MEpedia - User contributions [en]

MEpedia:How to contribute

2018-12-16T20:11:49Z

Bill:test edit

Contribute to MEpedia today! Anyone can create pages, write content, add links/citations, fact-check, or even just fix typos. Everyone has something to offer, whatever your skills & experience, even if you have never edited a wiki (like Wikipedia) before. Get involved and help the patient community identify all of the best and most important resources for our disease and its research, treatment and history.

To get started, read our [[Editorial Guidelines]] and find more information about how to edit MEpedia below. Please make sure to join our contributor community, the MEpedia [http://facebook.com/groups/218347055598647 Facebook Group]. You can also follow MEPedia [https://www.facebook.com/mepedia/ on Facebook], [https://twitter.com/MEencyclopedia Twitter] and subscribe to us on [https://www.reddit.com/r/MEAction Reddit].

Pages that are a [[red link]] have not been created yet and need to be populated – a full list of these pages [[Special:WantedPages|can be found here]]. Pages that have been created ([[Blue link|blue links]]) but need to be expanded are marked as stubs - a full list of all stubs [[:Category:Stubs|can be found here]]. We also have a [[MEpedia Suggestions#priority pages for expansion|list of priority pages for expansion]].

All we ask is that you read the guidelines (see below) before you edit.

Pages that have problems such as incorrect information, formatting issues, or a lack of citations are marked with a cleanup note. A full list of pages requiring cleanup [[:Category:All articles needing cleanup|can be found here]].

If a page needs deleting (or moving to rename it), you can add it to this category: [[:Category:Articles for deletion|Articles for deletion]]

Have any questions after reading the below? Email [mailto:mepedia@meaction.net mepedia@meaction.net].

== Getting started ==

=== Create an account ===
Before you start editing, you should [[Special:CreateAccount|create an account]] or [[Special:UserLogin|log in]]. Note, if you are not logged in when you make an edit or contribution to a page, your IP address will appear.

==Rules & Guidelines==

*[[Editorial Guidelines]]
*[[Science Guidelines]]
*[[MEpedia:Manual of Style]]

== Suggested tasks ==

===Five minute tasks===
Only have a five minute spoon to give? Here is a [[List of small tasks|list of small tasks]] you can help us with in roughly one to ten minutes of time.

=== Priority projects ===
Want to dive in deeper? Browse a [[MEpedia suggestions#Suggestions - High Priority|list of larger projects]] and page revisions.
== Roles ==
There are so many different roles contributors can play, at every level of cognitive ability or technical expertise. Every contributor can play one or more roles. All are important and help us grow and improve the project!

'''The Scientist:''' If you have a science background or a passion for science, we definitely need your expertise improving our medical and science pages and ensuring that all content is correct, accurate and cited. (Note: unlike Wikipedia, every fact presented on MEpedia does not need to be replicated or have appeared in a review article. However, the limitations of individual studies and the certainty of findings need to be properly contextualized and qualified. For more, see the [[Science Guidelines]])

'''The Translator:''' While many of the science pages will have highly technical information, useful to medical professionals and researchers, it's our goal that the opening section of every page (which usually comes before the table of contents) can provide a one to two paragraph summary that is accessible to as general audience as possible. As a page matures and contains a lot of information, The Translator can write an opening paragraph if none exists or improve the opening paragraph(s) to make it even more accessible.

''But you don't necessarily need to have a technical background to play any of these roles:''

'''The Historian:''' Help us improve our content on the history of [[Myalgic encephalomyelitis|ME]] and [[Chronic fatigue syndrome|CFS]] (and before it was either of these things, [[Icelandic disease|Icelandic Disease]] and [[Poliomyelitis|atypical polio]]). Bring to life the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of the past by digging into the newspaper and journal records and creating pages for individual outbreaks.

'''The Biographer:''' We have dozens of pages with biographies of scientists, clinicians, historical figures and activists with ME. These can always be improved and there are many people still missing. (See our categories for [[:Category:Famous people with ME, CFS, and/or FMS|famous people]], [[:Category:Researchers|researchers]], [[:Category:Clinicians|clinicians]], [[:Category:Advocates or allies|advocates]])

'''The Editor:''' As pages grow through the addition of new information, they can often become hard to navigate. Read our more developed pages and see whether they can be improved by breaking up very long sections into sub-sections, improving overall flow, organization and readability, or updating the opening paragraph to better reflect the way the page may have grown and changed.

'''The Link Collector:''' Sometimes you may not have the cognitive capacity or time to take an interesting article and writing it into an existing page. However, you can help simply by collecting links and pasting them on the "Discussion" page of a given article, with perhaps a sentence or two explaining its relevance, so that someone in the future can take that link and incorporate that into the page.

'''The Deep Sea Diver:''' You may not have an expertise in a particular area, but you decide to adopt a page you feel passionate about, and build it from the ground up, reading every reference you can find. It's a long, slow process but can be really gratifying to develop mastery over a specific topic!

'''The Photo Curator:''' Many of our pages could be improved simply through the addition of images and drawings. It's important to make sure you have permission to use the any photos you add , that they are in the public domain, or that they carry a Creative Commons license. See this category listing articles that need images or photos adding to them: [[:Category:Articles that need an image or photo]]. [https://wiki.creativecommons.org/wiki/Best_practices_for_attribution ''Best practices for attribution''] via [https://en.wikipedia.org/wiki/Creative_Commons Creative Commons]. See our examples: [https://me-pedia.org/wiki/File:HRQoL-journal.pone.0132421.g003.PNG Fig 3. Unadjusted means and medians compared to different conditions.], [https://me-pedia.org/wiki/File:Gaga.jpg Lady Gaga arriving at the Gaga: Five Foot Two press conference during the 2017 Toronto International Film Festival], [https://me-pedia.org/wiki/File:Cranial_Nerves.png Cranial Nerves], [https://me-pedia.org/wiki/File:Adam_Lowe.jpg Adam Lowe], [https://me-pedia.org/wiki/File:Epigenetics.jpg Epigenetics Mechanisms] and [https://me-pedia.org/wiki/File:MMC_Logo_2.JPG Millions Missing Canada].

'''The Bridge Builder:''' pick a [[Special:DeadendPages|dead end]] page and create internal links to related MEpedia content within the body of the page or by added pages to the "See also" section. Or, find an [[Special:LonelyPages|orphan page]] and link to it from existing pages.

'''The Expander:''' browse MEpedia's [[Special:ShortPages|shortest pages]] and help us lengthen them.

'''The Proofreader:''' Fix small typos and grammatical errors as you go. Or visit the [[Welcome to MEpedia|front page]] and hit "[[Special:Random|random]]" to be taken to a random article. Or see the list of [[Special:RecentChanges|recently updated pages]]. Read and correct mistakes.

'''The Citation Catcher:''' Many citations are simple links, without the proper article title, journal name, date or author information. Correcting citations are a great way to help us improve this project.

'''The Manual Writer:''' All of our support documentation could always be improved. Help us find ways to better explain the tools and guidelines behind MEpedia and help make them more accessible. To contribute in this way, consider starting a new thread in our [https://www.facebook.com/groups/218347055598647/ Facebook group] and making a suggestion.

'''The Community Organizer:''' Help us grow this project by growing the community around it. Invite friends to join our [https://www.facebook.com/groups/218347055598647/ Facebook group]. Act as a greeter, help folks feel welcome, answer questions as they arise.

'''The Outreacher:''' Help us build links between MEpedia and others. For example posting MEpedia articles to other M.E, community forums and asking for help improving them, sending links to MEpedia articles to scientists (e.g. the page about them) and asking them to update the page and confirm it is complete, asking researchers to read MEpedia pages related to their work and provide feedback on what needs adding, or asking M.E. blog writers to include MEpedia links in their articles so their readers can learn more.

'''The Supporter:''' Help MEpedia by helping, training and supporting its volunteer team. Help everyone learn how to edit pages, to do more advanced editing, and how to more effectively create content. Maybe you're a technologist who finds it easy to learn and teach others about wiki editing, or a technical writer who cannot commit to contribute much but can help others to write.

'''The News Reader:''' Help keep MEpedia fresh by updating its pages based on news you read. For example if you read a new article published by journalist David Tuller, make sure his page has been updated to include the latest article. Or if an announcement is made by the NIH or some other organization, update relevant pages to reflect the news.

See [[How_to_contribute#How_can_I_contribute.3F|even more ways to contribute]].

==A note on ME v. CFS==
We have separate pages for [[Myalgic Encephalomyelitis]], [[ME/CFS]] and [[Chronic Fatigue Syndrome]] as well as [[SEID]]. The convention is that the terminology used in an ME-pedia article should match the terminology used in the underlying source. Where there is a tension between the term used in the source and the definition (e.g., [[ME]] defined by the [[Oxford criteria]] or [[CFS]] defined by the [[Canadian Consensus Criteria]]), it may be useful for clarity to mention the definition used.

==How do I create a new page?==
Simply type in the title of your new page and hit "create page." You'll want to [[Special:Search|search]] the existing database of pages to make sure that your page or a similar page does not already exist.<inputbox>
type=create
break=no
</inputbox>
You can also browse our list of [[Special:WantedPages|"wanted" pages]] – pages that are linked to from existing pages, but don't yet exist.

==How do I edit existing pages?==

There are two types of editor on this wiki, the '''Visual editor''', which operates more like your word processing or email program, and the '''Source editor''', which uses a special kind of wiki code. Most users will prefer to use the Visual editor, but for more advance applications or if the Visual editor is "down" (as happens from time to time), the resources below will help you learn how to navigate both.

Look for the "edit" (Visual editor) or "edit source" (Source editor) links at the top of the page (to edit the whole page) and next to each section heading (to edit just that section).

After you've made your changes, scroll down to the 'Show Preview' section, add a comment, preview your changes, then save them.

=== Using the visual editor ===

To learn how to use the visual editor, please see Wikipedia's [https://www.mediawiki.org/wiki/Help:VisualEditor/User_guide visual editor user guide].

Note that the Visual Editor includes a facility to automatically insert full citations, by just specifying the link or doi to the source, see [https://www.mediawiki.org/wiki/VisualEditor/Design/Reference_Dialog#Auto-filled_Web_Citations Visual Editor Auto-filled Web Citations].

=== Using the source code editor ===
The source code editor is a more advanced way of editing MEpedia. See our tricks and tips on how to [[Using the source code editor|get started with the source code editor]].

== Article outlines, templates and includes==

=== Article outlines ===
A list of [[MEpedia article outlines|copy-and-paste outlines]] for new articles depending category.

=== Common templates and includes ===
{| class="wikitable"
!Template name
!Description / Function
!Source editor code
!Installation status
!Visual editor status
|-
|Cleanup needed
|Indicates articles that need cleanup and the reason why.
|<syntaxhighlight>
{{Cleanup|reason= |date= }}
</syntaxhighlight>
|Installed but could use cleaner visual (e.g., a box/outline around it). See Wikipedia's version and compare to MEpedia.
|Possible fields do not appear. Would be wonderful if there could be a handful of prefab reasons for cleanup that could allow for searching on those reasons (e.g., view all pages with citation issues, all pages requiring editing or reorganization, all pages that are too long, all pages not written in encyclopedic style, etc).
|-
|Stub article
|Indicates a very short article that is a "stub" waiting to be expanded.
|<syntaxhighlight>
{{stub}}
</syntaxhighlight>
|Installed but compared with Wikipedia's version.
|I don't know if Stub article take fields
|-
|Main
|Links a section of one page to the full article on another.
|<syntaxhighlight>
{{Main|page}}
</syntaxhighlight>
|Installed, but no formatting. See Wikipedia for example of how formatting should be displayed.
|Possible fields do not appear
|-
|Citation needed
|Indicates facts that require citations.
|<syntaxhighlight>
{{Citation needed}}
</syntaxhighlight>
|Installed but not working properly (may be missing a component).
|
|-
|All pages in a category
|Automatically displays all of the articles within the specified category
|<syntaxhighlight>
{{PagesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|All categories in a category
|Automatically displays all of the sub-categories within the specified category
|<syntaxhighlight>
{{CategoriesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|Mark an article as needing a photo or image adding to it
|Adds it to the category [[:Category:Articles that need an image or photo]]
|<syntaxhighlight>
{{NeedsImage}}
</syntaxhighlight>
|
|No explicit support
|-
|Mark a page as being a disambiguation page, linking to two or more articles that a word or term may refer to.
|
|<syntaxhighlight>
{{Disambiguation}}
</syntaxhighlight>
|
|No explicit support
|}

==Other ways to contribute==

===Make a suggestion===
Almost everyone working on MEpedia is sick, including bed-bound patients. Although we welcome suggestions please, please if you possibly can, create/edit the page yourself. It is very easy to add a new page or make an improvement – be bold! Together we are stronger as a community. If you REALLY can't edit the page, then you can go to the [[MEpedia suggestions]] page, click Edit, and add your suggestion to the list for someone else to consider implementing in future.

===Implement a suggestion===
If you want to contribute but aren't sure where to start, try looking at the [[MEpedia suggestions]] and consider implementing an improvement suggested by others.

===Create a new article===

To create a new article, simply search for the title of the article you wish to create. If a page does not already exist, you will see an option to create the page. Alternatively if you see a red link to the page, that means it does not yet exist. Just click the red link to create the page.

Once you have a blank editable article open, consider copying-and-pasting an outline into it for that type of article, so you have a set of headings to prompt writing. See [[MEpedia article outlines]]

Remember that articles must use strong citations. For example if you write "ME/CFS can be successfully treated with XYZ", you MUST provide a reference to evidence, ideally a high quality (randomized, placebo-controlled) published study. If there is no evidence, the wording must reflect this, for example "ME/CFS is sometimes treated using XYZ, but currently there is no good evidence for its use".

=== Expand a topic ===

Pages with blue links (as opposed to red) exist already, and can be proof-read, improved and extended. Remember statements need to be supported by the best available evidence or source, for example a published quote by a person, or a paper in a scientific journal.

=== Check our references ===

You can make sure facts are properly cited and references are in correct format.

We aim to serve a general audience, a research audience, and a patient audience. All entries should be cited and make clear to distinguish what has and has not been established by peer-reviewed research findings. Articles should aim to provide both a general overview of a specific topic as well as discuss its implications or applications in ME and CFS.

=== Correct typos ===

You can also copy-edit existing articles for typos and edit for clarity.

=== Clean-up poor pages ===
Some pages are inconsistently formatted, too long, are presented badly, need partially rewriting, or suffer from other problems. Those pages are marked as needing clean-up, and are listed under [[clean up list|all articles needing cleanup]].

===Mark pages as needing cleanup===
If you see a problem with a page, it needs clean-up, and you are not able to resolve it, mark the page as needing cleaning by adding a marker like this including a description of the problem:

''<nowiki>{{Cleanup | reason=the article is full of incorrect capitalization | date=August 2018}}</nowiki>''

For more details see [[Template:Cleanup|Cleanup]].

== Other Resources ==

* [[mw:Help:Editing|Help:Editing]]
* [[mw:Special:MyLanguage/Manual:Configuration_settings|Configuration settings list]]
* [[mw:Special:MyLanguage/Manual:FAQ MediaWiki|FAQ]]
* [https://lists.wikimedia.org/mailman/listinfo/mediawiki-announce MediaWiki release mailing list]
* [[mw:Special:MyLanguage/Localisation#Translation_resources|Localise MediaWiki for your language]]
* [[Power user/editor tips]]
* [[:Category:Fundamental | Categories browser]]

[[Category:MEpedia guidelines]]

MEpedia:How to contribute

2018-12-11T12:06:12Z

Bill:test video embed

MEpedia:How to contribute

2018-12-11T12:05:46Z

Bill:test video embed

<evlplayer id="player1" w="480" h="360" service="youtube" defaultid="KBKr4DHoRgE" />

Contribute to MEpedia today! Anyone can create pages, write content, add links/citations, fact-check, or even just fix typos. Everyone has something to offer, whatever your skills & experience, even if you have never edited a wiki (like Wikipedia) before. Get involved and help the patient community identify all of the best and most important resources for our disease and its research, treatment and history.

To get started, read our [[Editorial Guidelines]] and find more information about how to edit MEpedia below. Please make sure to join our contributor community, the MEpedia [http://facebook.com/groups/218347055598647 Facebook Group]. You can also follow MEPedia [https://www.facebook.com/mepedia/ on Facebook], [https://twitter.com/MEencyclopedia Twitter] and subscribe to us on [https://www.reddit.com/r/MEAction Reddit].

Pages that are a [[red link]] have not been created yet and need to be populated – a full list of these pages [[Special:WantedPages|can be found here]]. Pages that have been created ([[Blue link|blue links]]) but need to be expanded are marked as stubs - a full list of all stubs [[:Category:Stubs|can be found here]]. We also have a [[MEpedia Suggestions#priority pages for expansion|list of priority pages for expansion]].

All we ask is that you read the guidelines (see below) before you edit.

Pages that have problems such as incorrect information, formatting issues, or a lack of citations are marked with a cleanup note. A full list of pages requiring cleanup [[:Category:All articles needing cleanup|can be found here]].

If a page needs deleting (or moving to rename it), you can add it to this category: [[:Category:Articles for deletion|Articles for deletion]]

Have any questions after reading the below? Email [mailto:mepedia@meaction.net mepedia@meaction.net].

== Getting started ==

=== Create an account ===
Before you start editing, you should [[Special:CreateAccount|create an account]] or [[Special:UserLogin|log in]]. Note, if you are not logged in when you make an edit or contribution to a page, your IP address will appear.

==Rules & Guidelines==

*[[Editorial Guidelines]]
*[[Science Guidelines]]
*[[MEpedia:Manual of Style]]

== Suggested tasks ==

===Five minute tasks===
Only have a five minute spoon to give? Here is a [[List of small tasks|list of small tasks]] you can help us with in roughly one to ten minutes of time.

=== Priority projects ===
Want to dive in deeper? Browse a [[MEpedia suggestions#Suggestions - High Priority|list of larger projects]] and page revisions.
== Roles ==
There are so many different roles contributors can play, at every level of cognitive ability or technical expertise. Every contributor can play one or more roles. All are important and help us grow and improve the project!

'''The Scientist:''' If you have a science background or a passion for science, we definitely need your expertise improving our medical and science pages and ensuring that all content is correct, accurate and cited. (Note: unlike Wikipedia, every fact presented on MEpedia does not need to be replicated or have appeared in a review article. However, the limitations of individual studies and the certainty of findings need to be properly contextualized and qualified. For more, see the [[Science Guidelines]])

'''The Translator:''' While many of the science pages will have highly technical information, useful to medical professionals and researchers, it's our goal that the opening section of every page (which usually comes before the table of contents) can provide a one to two paragraph summary that is accessible to as general audience as possible. As a page matures and contains a lot of information, The Translator can write an opening paragraph if none exists or improve the opening paragraph(s) to make it even more accessible.

''But you don't necessarily need to have a technical background to play any of these roles:''

'''The Historian:''' Help us improve our content on the history of [[Myalgic encephalomyelitis|ME]] and [[Chronic fatigue syndrome|CFS]] (and before it was either of these things, [[Icelandic disease|Icelandic Disease]] and [[Poliomyelitis|atypical polio]]). Bring to life the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of the past by digging into the newspaper and journal records and creating pages for individual outbreaks.

'''The Biographer:''' We have dozens of pages with biographies of scientists, clinicians, historical figures and activists with ME. These can always be improved and there are many people still missing. (See our categories for [[:Category:Famous people with ME, CFS, and/or FMS|famous people]], [[:Category:Researchers|researchers]], [[:Category:Clinicians|clinicians]], [[:Category:Advocates or allies|advocates]])

'''The Editor:''' As pages grow through the addition of new information, they can often become hard to navigate. Read our more developed pages and see whether they can be improved by breaking up very long sections into sub-sections, improving overall flow, organization and readability, or updating the opening paragraph to better reflect the way the page may have grown and changed.

'''The Link Collector:''' Sometimes you may not have the cognitive capacity or time to take an interesting article and writing it into an existing page. However, you can help simply by collecting links and pasting them on the "Discussion" page of a given article, with perhaps a sentence or two explaining its relevance, so that someone in the future can take that link and incorporate that into the page.

'''The Deep Sea Diver:''' You may not have an expertise in a particular area, but you decide to adopt a page you feel passionate about, and build it from the ground up, reading every reference you can find. It's a long, slow process but can be really gratifying to develop mastery over a specific topic!

'''The Photo Curator:''' Many of our pages could be improved simply through the addition of images and drawings. It's important to make sure you have permission to use the any photos you add , that they are in the public domain, or that they carry a Creative Commons license. See this category listing articles that need images or photos adding to them: [[:Category:Articles that need an image or photo]]. [https://wiki.creativecommons.org/wiki/Best_practices_for_attribution ''Best practices for attribution''] via [https://en.wikipedia.org/wiki/Creative_Commons Creative Commons]. See our examples: [https://me-pedia.org/wiki/File:HRQoL-journal.pone.0132421.g003.PNG Fig 3. Unadjusted means and medians compared to different conditions.], [https://me-pedia.org/wiki/File:Gaga.jpg Lady Gaga arriving at the Gaga: Five Foot Two press conference during the 2017 Toronto International Film Festival], [https://me-pedia.org/wiki/File:Cranial_Nerves.png Cranial Nerves], [https://me-pedia.org/wiki/File:Adam_Lowe.jpg Adam Lowe], [https://me-pedia.org/wiki/File:Epigenetics.jpg Epigenetics Mechanisms] and [https://me-pedia.org/wiki/File:MMC_Logo_2.JPG Millions Missing Canada].

'''The Bridge Builder:''' pick a [[Special:DeadendPages|dead end]] page and create internal links to related MEpedia content within the body of the page or by added pages to the "See also" section. Or, find an [[Special:LonelyPages|orphan page]] and link to it from existing pages.

'''The Expander:''' browse MEpedia's [[Special:ShortPages|shortest pages]] and help us lengthen them.

'''The Proofreader:''' Fix small typos and grammatical errors as you go. Or visit the [[Welcome to MEpedia|front page]] and hit "[[Special:Random|random]]" to be taken to a random article. Or see the list of [[Special:RecentChanges|recently updated pages]]. Read and correct mistakes.

'''The Citation Catcher:''' Many citations are simple links, without the proper article title, journal name, date or author information. Correcting citations are a great way to help us improve this project.

'''The Manual Writer:''' All of our support documentation could always be improved. Help us find ways to better explain the tools and guidelines behind MEpedia and help make them more accessible. To contribute in this way, consider starting a new thread in our [https://www.facebook.com/groups/218347055598647/ Facebook group] and making a suggestion.

'''The Community Organizer:''' Help us grow this project by growing the community around it. Invite friends to join our [https://www.facebook.com/groups/218347055598647/ Facebook group]. Act as a greeter, help folks feel welcome, answer questions as they arise.

'''The Outreacher:''' Help us build links between MEpedia and others. For example posting MEpedia articles to other M.E, community forums and asking for help improving them, sending links to MEpedia articles to scientists (e.g. the page about them) and asking them to update the page and confirm it is complete, asking researchers to read MEpedia pages related to their work and provide feedback on what needs adding, or asking M.E. blog writers to include MEpedia links in their articles so their readers can learn more.

'''The Supporter:''' Help MEpedia by helping, training and supporting its volunteer team. Help everyone learn how to edit pages, to do more advanced editing, and how to more effectively create content. Maybe you're a technologist who finds it easy to learn and teach others about wiki editing, or a technical writer who cannot commit to contribute much but can help others to write.

'''The News Reader:''' Help keep MEpedia fresh by updating its pages based on news you read. For example if you read a new article published by journalist David Tuller, make sure his page has been updated to include the latest article. Or if an announcement is made by the NIH or some other organization, update relevant pages to reflect the news.

See [[How_to_contribute#How_can_I_contribute.3F|even more ways to contribute]].

==A note on ME v. CFS==
We have separate pages for [[Myalgic Encephalomyelitis]], [[ME/CFS]] and [[Chronic Fatigue Syndrome]] as well as [[SEID]]. The convention is that the terminology used in an ME-pedia article should match the terminology used in the underlying source. Where there is a tension between the term used in the source and the definition (e.g., [[ME]] defined by the [[Oxford criteria]] or [[CFS]] defined by the [[Canadian Consensus Criteria]]), it may be useful for clarity to mention the definition used.

==How do I create a new page?==
Simply type in the title of your new page and hit "create page." You'll want to [[Special:Search|search]] the existing database of pages to make sure that your page or a similar page does not already exist.<inputbox>
type=create
break=no
</inputbox>
You can also browse our list of [[Special:WantedPages|"wanted" pages]] – pages that are linked to from existing pages, but don't yet exist.

==How do I edit existing pages?==

There are two types of editor on this wiki, the '''Visual editor''', which operates more like your word processing or email program, and the '''Source editor''', which uses a special kind of wiki code. Most users will prefer to use the Visual editor, but for more advance applications or if the Visual editor is "down" (as happens from time to time), the resources below will help you learn how to navigate both.

Look for the "edit" (Visual editor) or "edit source" (Source editor) links at the top of the page (to edit the whole page) and next to each section heading (to edit just that section).

After you've made your changes, scroll down to the 'Show Preview' section, add a comment, preview your changes, then save them.

=== Using the visual editor ===

To learn how to use the visual editor, please see Wikipedia's [https://www.mediawiki.org/wiki/Help:VisualEditor/User_guide visual editor user guide].

Note that the Visual Editor includes a facility to automatically insert full citations, by just specifying the link or doi to the source, see [https://www.mediawiki.org/wiki/VisualEditor/Design/Reference_Dialog#Auto-filled_Web_Citations Visual Editor Auto-filled Web Citations].

=== Using the source code editor ===
The source code editor is a more advanced way of editing MEpedia. See our tricks and tips on how to [[Using the source code editor|get started with the source code editor]].

== Article outlines, templates and includes==

=== Article outlines ===
A list of [[MEpedia article outlines|copy-and-paste outlines]] for new articles depending category.

=== Common templates and includes ===
{| class="wikitable"
!Template name
!Description / Function
!Source editor code
!Installation status
!Visual editor status
|-
|Cleanup needed
|Indicates articles that need cleanup and the reason why.
|<syntaxhighlight>
{{Cleanup|reason= |date= }}
</syntaxhighlight>
|Installed but could use cleaner visual (e.g., a box/outline around it). See Wikipedia's version and compare to MEpedia.
|Possible fields do not appear. Would be wonderful if there could be a handful of prefab reasons for cleanup that could allow for searching on those reasons (e.g., view all pages with citation issues, all pages requiring editing or reorganization, all pages that are too long, all pages not written in encyclopedic style, etc).
|-
|Stub article
|Indicates a very short article that is a "stub" waiting to be expanded.
|<syntaxhighlight>
{{stub}}
</syntaxhighlight>
|Installed but compared with Wikipedia's version.
|I don't know if Stub article take fields
|-
|Main
|Links a section of one page to the full article on another.
|<syntaxhighlight>
{{Main|page}}
</syntaxhighlight>
|Installed, but no formatting. See Wikipedia for example of how formatting should be displayed.
|Possible fields do not appear
|-
|Citation needed
|Indicates facts that require citations.
|<syntaxhighlight>
{{Citation needed}}
</syntaxhighlight>
|Installed but not working properly (may be missing a component).
|
|-
|All pages in a category
|Automatically displays all of the articles within the specified category
|<syntaxhighlight>
{{PagesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|All categories in a category
|Automatically displays all of the sub-categories within the specified category
|<syntaxhighlight>
{{CategoriesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|Mark an article as needing a photo or image adding to it
|Adds it to the category [[:Category:Articles that need an image or photo]]
|<syntaxhighlight>
{{NeedsImage}}
</syntaxhighlight>
|
|No explicit support
|-
|Mark a page as being a disambiguation page, linking to two or more articles that a word or term may refer to.
|
|<syntaxhighlight>
{{Disambiguation}}
</syntaxhighlight>
|
|No explicit support
|}

==Other ways to contribute==

===Make a suggestion===
Almost everyone working on MEpedia is sick, including bed-bound patients. Although we welcome suggestions please, please if you possibly can, create/edit the page yourself. It is very easy to add a new page or make an improvement – be bold! Together we are stronger as a community. If you REALLY can't edit the page, then you can go to the [[MEpedia suggestions]] page, click Edit, and add your suggestion to the list for someone else to consider implementing in future.

===Implement a suggestion===
If you want to contribute but aren't sure where to start, try looking at the [[MEpedia suggestions]] and consider implementing an improvement suggested by others.

===Create a new article===

To create a new article, simply search for the title of the article you wish to create. If a page does not already exist, you will see an option to create the page. Alternatively if you see a red link to the page, that means it does not yet exist. Just click the red link to create the page.

Once you have a blank editable article open, consider copying-and-pasting an outline into it for that type of article, so you have a set of headings to prompt writing. See [[MEpedia article outlines]]

Remember that articles must use strong citations. For example if you write "ME/CFS can be successfully treated with XYZ", you MUST provide a reference to evidence, ideally a high quality (randomized, placebo-controlled) published study. If there is no evidence, the wording must reflect this, for example "ME/CFS is sometimes treated using XYZ, but currently there is no good evidence for its use".

=== Expand a topic ===

Pages with blue links (as opposed to red) exist already, and can be proof-read, improved and extended. Remember statements need to be supported by the best available evidence or source, for example a published quote by a person, or a paper in a scientific journal.

=== Check our references ===

You can make sure facts are properly cited and references are in correct format.

We aim to serve a general audience, a research audience, and a patient audience. All entries should be cited and make clear to distinguish what has and has not been established by peer-reviewed research findings. Articles should aim to provide both a general overview of a specific topic as well as discuss its implications or applications in ME and CFS.

=== Correct typos ===

You can also copy-edit existing articles for typos and edit for clarity.

=== Clean-up poor pages ===
Some pages are inconsistently formatted, too long, are presented badly, need partially rewriting, or suffer from other problems. Those pages are marked as needing clean-up, and are listed under [[clean up list|all articles needing cleanup]].

===Mark pages as needing cleanup===
If you see a problem with a page, it needs clean-up, and you are not able to resolve it, mark the page as needing cleaning by adding a marker like this including a description of the problem:

''<nowiki>{{Cleanup | reason=the article is full of incorrect capitalization | date=August 2018}}</nowiki>''

For more details see [[Template:Cleanup|Cleanup]].

== Other Resources ==

* [[mw:Help:Editing|Help:Editing]]
* [[mw:Special:MyLanguage/Manual:Configuration_settings|Configuration settings list]]
* [[mw:Special:MyLanguage/Manual:FAQ MediaWiki|FAQ]]
* [https://lists.wikimedia.org/mailman/listinfo/mediawiki-announce MediaWiki release mailing list]
* [[mw:Special:MyLanguage/Localisation#Translation_resources|Localise MediaWiki for your language]]
* [[Power user/editor tips]]
* [[:Category:Fundamental | Categories browser]]

[[Category:MEpedia guidelines]]

MEpedia:How to contribute

2018-12-11T12:04:21Z

Bill:test video embed

{{#ev:youtube|KBKr4DHoRgE}}

Contribute to MEpedia today! Anyone can create pages, write content, add links/citations, fact-check, or even just fix typos. Everyone has something to offer, whatever your skills & experience, even if you have never edited a wiki (like Wikipedia) before. Get involved and help the patient community identify all of the best and most important resources for our disease and its research, treatment and history.

To get started, read our [[Editorial Guidelines]] and find more information about how to edit MEpedia below. Please make sure to join our contributor community, the MEpedia [http://facebook.com/groups/218347055598647 Facebook Group]. You can also follow MEPedia [https://www.facebook.com/mepedia/ on Facebook], [https://twitter.com/MEencyclopedia Twitter] and subscribe to us on [https://www.reddit.com/r/MEAction Reddit].

Pages that are a [[red link]] have not been created yet and need to be populated – a full list of these pages [[Special:WantedPages|can be found here]]. Pages that have been created ([[Blue link|blue links]]) but need to be expanded are marked as stubs - a full list of all stubs [[:Category:Stubs|can be found here]]. We also have a [[MEpedia Suggestions#priority pages for expansion|list of priority pages for expansion]].

All we ask is that you read the guidelines (see below) before you edit.

Pages that have problems such as incorrect information, formatting issues, or a lack of citations are marked with a cleanup note. A full list of pages requiring cleanup [[:Category:All articles needing cleanup|can be found here]].

If a page needs deleting (or moving to rename it), you can add it to this category: [[:Category:Articles for deletion|Articles for deletion]]

Have any questions after reading the below? Email [mailto:mepedia@meaction.net mepedia@meaction.net].

== Getting started ==

=== Create an account ===
Before you start editing, you should [[Special:CreateAccount|create an account]] or [[Special:UserLogin|log in]]. Note, if you are not logged in when you make an edit or contribution to a page, your IP address will appear.

==Rules & Guidelines==

*[[Editorial Guidelines]]
*[[Science Guidelines]]
*[[MEpedia:Manual of Style]]

== Suggested tasks ==

===Five minute tasks===
Only have a five minute spoon to give? Here is a [[List of small tasks|list of small tasks]] you can help us with in roughly one to ten minutes of time.

=== Priority projects ===
Want to dive in deeper? Browse a [[MEpedia suggestions#Suggestions - High Priority|list of larger projects]] and page revisions.
== Roles ==
There are so many different roles contributors can play, at every level of cognitive ability or technical expertise. Every contributor can play one or more roles. All are important and help us grow and improve the project!

'''The Scientist:''' If you have a science background or a passion for science, we definitely need your expertise improving our medical and science pages and ensuring that all content is correct, accurate and cited. (Note: unlike Wikipedia, every fact presented on MEpedia does not need to be replicated or have appeared in a review article. However, the limitations of individual studies and the certainty of findings need to be properly contextualized and qualified. For more, see the [[Science Guidelines]])

'''The Translator:''' While many of the science pages will have highly technical information, useful to medical professionals and researchers, it's our goal that the opening section of every page (which usually comes before the table of contents) can provide a one to two paragraph summary that is accessible to as general audience as possible. As a page matures and contains a lot of information, The Translator can write an opening paragraph if none exists or improve the opening paragraph(s) to make it even more accessible.

''But you don't necessarily need to have a technical background to play any of these roles:''

'''The Historian:''' Help us improve our content on the history of [[Myalgic encephalomyelitis|ME]] and [[Chronic fatigue syndrome|CFS]] (and before it was either of these things, [[Icelandic disease|Icelandic Disease]] and [[Poliomyelitis|atypical polio]]). Bring to life the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of the past by digging into the newspaper and journal records and creating pages for individual outbreaks.

'''The Biographer:''' We have dozens of pages with biographies of scientists, clinicians, historical figures and activists with ME. These can always be improved and there are many people still missing. (See our categories for [[:Category:Famous people with ME, CFS, and/or FMS|famous people]], [[:Category:Researchers|researchers]], [[:Category:Clinicians|clinicians]], [[:Category:Advocates or allies|advocates]])

'''The Editor:''' As pages grow through the addition of new information, they can often become hard to navigate. Read our more developed pages and see whether they can be improved by breaking up very long sections into sub-sections, improving overall flow, organization and readability, or updating the opening paragraph to better reflect the way the page may have grown and changed.

'''The Link Collector:''' Sometimes you may not have the cognitive capacity or time to take an interesting article and writing it into an existing page. However, you can help simply by collecting links and pasting them on the "Discussion" page of a given article, with perhaps a sentence or two explaining its relevance, so that someone in the future can take that link and incorporate that into the page.

'''The Deep Sea Diver:''' You may not have an expertise in a particular area, but you decide to adopt a page you feel passionate about, and build it from the ground up, reading every reference you can find. It's a long, slow process but can be really gratifying to develop mastery over a specific topic!

'''The Photo Curator:''' Many of our pages could be improved simply through the addition of images and drawings. It's important to make sure you have permission to use the any photos you add , that they are in the public domain, or that they carry a Creative Commons license. See this category listing articles that need images or photos adding to them: [[:Category:Articles that need an image or photo]]. [https://wiki.creativecommons.org/wiki/Best_practices_for_attribution ''Best practices for attribution''] via [https://en.wikipedia.org/wiki/Creative_Commons Creative Commons]. See our examples: [https://me-pedia.org/wiki/File:HRQoL-journal.pone.0132421.g003.PNG Fig 3. Unadjusted means and medians compared to different conditions.], [https://me-pedia.org/wiki/File:Gaga.jpg Lady Gaga arriving at the Gaga: Five Foot Two press conference during the 2017 Toronto International Film Festival], [https://me-pedia.org/wiki/File:Cranial_Nerves.png Cranial Nerves], [https://me-pedia.org/wiki/File:Adam_Lowe.jpg Adam Lowe], [https://me-pedia.org/wiki/File:Epigenetics.jpg Epigenetics Mechanisms] and [https://me-pedia.org/wiki/File:MMC_Logo_2.JPG Millions Missing Canada].

'''The Bridge Builder:''' pick a [[Special:DeadendPages|dead end]] page and create internal links to related MEpedia content within the body of the page or by added pages to the "See also" section. Or, find an [[Special:LonelyPages|orphan page]] and link to it from existing pages.

'''The Expander:''' browse MEpedia's [[Special:ShortPages|shortest pages]] and help us lengthen them.

'''The Proofreader:''' Fix small typos and grammatical errors as you go. Or visit the [[Welcome to MEpedia|front page]] and hit "[[Special:Random|random]]" to be taken to a random article. Or see the list of [[Special:RecentChanges|recently updated pages]]. Read and correct mistakes.

'''The Citation Catcher:''' Many citations are simple links, without the proper article title, journal name, date or author information. Correcting citations are a great way to help us improve this project.

'''The Manual Writer:''' All of our support documentation could always be improved. Help us find ways to better explain the tools and guidelines behind MEpedia and help make them more accessible. To contribute in this way, consider starting a new thread in our [https://www.facebook.com/groups/218347055598647/ Facebook group] and making a suggestion.

'''The Community Organizer:''' Help us grow this project by growing the community around it. Invite friends to join our [https://www.facebook.com/groups/218347055598647/ Facebook group]. Act as a greeter, help folks feel welcome, answer questions as they arise.

'''The Outreacher:''' Help us build links between MEpedia and others. For example posting MEpedia articles to other M.E, community forums and asking for help improving them, sending links to MEpedia articles to scientists (e.g. the page about them) and asking them to update the page and confirm it is complete, asking researchers to read MEpedia pages related to their work and provide feedback on what needs adding, or asking M.E. blog writers to include MEpedia links in their articles so their readers can learn more.

'''The Supporter:''' Help MEpedia by helping, training and supporting its volunteer team. Help everyone learn how to edit pages, to do more advanced editing, and how to more effectively create content. Maybe you're a technologist who finds it easy to learn and teach others about wiki editing, or a technical writer who cannot commit to contribute much but can help others to write.

'''The News Reader:''' Help keep MEpedia fresh by updating its pages based on news you read. For example if you read a new article published by journalist David Tuller, make sure his page has been updated to include the latest article. Or if an announcement is made by the NIH or some other organization, update relevant pages to reflect the news.

See [[How_to_contribute#How_can_I_contribute.3F|even more ways to contribute]].

==A note on ME v. CFS==
We have separate pages for [[Myalgic Encephalomyelitis]], [[ME/CFS]] and [[Chronic Fatigue Syndrome]] as well as [[SEID]]. The convention is that the terminology used in an ME-pedia article should match the terminology used in the underlying source. Where there is a tension between the term used in the source and the definition (e.g., [[ME]] defined by the [[Oxford criteria]] or [[CFS]] defined by the [[Canadian Consensus Criteria]]), it may be useful for clarity to mention the definition used.

==How do I create a new page?==
Simply type in the title of your new page and hit "create page." You'll want to [[Special:Search|search]] the existing database of pages to make sure that your page or a similar page does not already exist.<inputbox>
type=create
break=no
</inputbox>
You can also browse our list of [[Special:WantedPages|"wanted" pages]] – pages that are linked to from existing pages, but don't yet exist.

==How do I edit existing pages?==

There are two types of editor on this wiki, the '''Visual editor''', which operates more like your word processing or email program, and the '''Source editor''', which uses a special kind of wiki code. Most users will prefer to use the Visual editor, but for more advance applications or if the Visual editor is "down" (as happens from time to time), the resources below will help you learn how to navigate both.

Look for the "edit" (Visual editor) or "edit source" (Source editor) links at the top of the page (to edit the whole page) and next to each section heading (to edit just that section).

After you've made your changes, scroll down to the 'Show Preview' section, add a comment, preview your changes, then save them.

=== Using the visual editor ===

To learn how to use the visual editor, please see Wikipedia's [https://www.mediawiki.org/wiki/Help:VisualEditor/User_guide visual editor user guide].

Note that the Visual Editor includes a facility to automatically insert full citations, by just specifying the link or doi to the source, see [https://www.mediawiki.org/wiki/VisualEditor/Design/Reference_Dialog#Auto-filled_Web_Citations Visual Editor Auto-filled Web Citations].

=== Using the source code editor ===
The source code editor is a more advanced way of editing MEpedia. See our tricks and tips on how to [[Using the source code editor|get started with the source code editor]].

== Article outlines, templates and includes==

=== Article outlines ===
A list of [[MEpedia article outlines|copy-and-paste outlines]] for new articles depending category.

=== Common templates and includes ===
{| class="wikitable"
!Template name
!Description / Function
!Source editor code
!Installation status
!Visual editor status
|-
|Cleanup needed
|Indicates articles that need cleanup and the reason why.
|<syntaxhighlight>
{{Cleanup|reason= |date= }}
</syntaxhighlight>
|Installed but could use cleaner visual (e.g., a box/outline around it). See Wikipedia's version and compare to MEpedia.
|Possible fields do not appear. Would be wonderful if there could be a handful of prefab reasons for cleanup that could allow for searching on those reasons (e.g., view all pages with citation issues, all pages requiring editing or reorganization, all pages that are too long, all pages not written in encyclopedic style, etc).
|-
|Stub article
|Indicates a very short article that is a "stub" waiting to be expanded.
|<syntaxhighlight>
{{stub}}
</syntaxhighlight>
|Installed but compared with Wikipedia's version.
|I don't know if Stub article take fields
|-
|Main
|Links a section of one page to the full article on another.
|<syntaxhighlight>
{{Main|page}}
</syntaxhighlight>
|Installed, but no formatting. See Wikipedia for example of how formatting should be displayed.
|Possible fields do not appear
|-
|Citation needed
|Indicates facts that require citations.
|<syntaxhighlight>
{{Citation needed}}
</syntaxhighlight>
|Installed but not working properly (may be missing a component).
|
|-
|All pages in a category
|Automatically displays all of the articles within the specified category
|<syntaxhighlight>
{{PagesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|All categories in a category
|Automatically displays all of the sub-categories within the specified category
|<syntaxhighlight>
{{CategoriesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|Mark an article as needing a photo or image adding to it
|Adds it to the category [[:Category:Articles that need an image or photo]]
|<syntaxhighlight>
{{NeedsImage}}
</syntaxhighlight>
|
|No explicit support
|-
|Mark a page as being a disambiguation page, linking to two or more articles that a word or term may refer to.
|
|<syntaxhighlight>
{{Disambiguation}}
</syntaxhighlight>
|
|No explicit support
|}

==Other ways to contribute==

===Make a suggestion===
Almost everyone working on MEpedia is sick, including bed-bound patients. Although we welcome suggestions please, please if you possibly can, create/edit the page yourself. It is very easy to add a new page or make an improvement – be bold! Together we are stronger as a community. If you REALLY can't edit the page, then you can go to the [[MEpedia suggestions]] page, click Edit, and add your suggestion to the list for someone else to consider implementing in future.

===Implement a suggestion===
If you want to contribute but aren't sure where to start, try looking at the [[MEpedia suggestions]] and consider implementing an improvement suggested by others.

===Create a new article===

To create a new article, simply search for the title of the article you wish to create. If a page does not already exist, you will see an option to create the page. Alternatively if you see a red link to the page, that means it does not yet exist. Just click the red link to create the page.

Once you have a blank editable article open, consider copying-and-pasting an outline into it for that type of article, so you have a set of headings to prompt writing. See [[MEpedia article outlines]]

Remember that articles must use strong citations. For example if you write "ME/CFS can be successfully treated with XYZ", you MUST provide a reference to evidence, ideally a high quality (randomized, placebo-controlled) published study. If there is no evidence, the wording must reflect this, for example "ME/CFS is sometimes treated using XYZ, but currently there is no good evidence for its use".

=== Expand a topic ===

Pages with blue links (as opposed to red) exist already, and can be proof-read, improved and extended. Remember statements need to be supported by the best available evidence or source, for example a published quote by a person, or a paper in a scientific journal.

=== Check our references ===

You can make sure facts are properly cited and references are in correct format.

We aim to serve a general audience, a research audience, and a patient audience. All entries should be cited and make clear to distinguish what has and has not been established by peer-reviewed research findings. Articles should aim to provide both a general overview of a specific topic as well as discuss its implications or applications in ME and CFS.

=== Correct typos ===

You can also copy-edit existing articles for typos and edit for clarity.

=== Clean-up poor pages ===
Some pages are inconsistently formatted, too long, are presented badly, need partially rewriting, or suffer from other problems. Those pages are marked as needing clean-up, and are listed under [[clean up list|all articles needing cleanup]].

===Mark pages as needing cleanup===
If you see a problem with a page, it needs clean-up, and you are not able to resolve it, mark the page as needing cleaning by adding a marker like this including a description of the problem:

''<nowiki>{{Cleanup | reason=the article is full of incorrect capitalization | date=August 2018}}</nowiki>''

For more details see [[Template:Cleanup|Cleanup]].

== Other Resources ==

* [[mw:Help:Editing|Help:Editing]]
* [[mw:Special:MyLanguage/Manual:Configuration_settings|Configuration settings list]]
* [[mw:Special:MyLanguage/Manual:FAQ MediaWiki|FAQ]]
* [https://lists.wikimedia.org/mailman/listinfo/mediawiki-announce MediaWiki release mailing list]
* [[mw:Special:MyLanguage/Localisation#Translation_resources|Localise MediaWiki for your language]]
* [[Power user/editor tips]]
* [[:Category:Fundamental | Categories browser]]

[[Category:MEpedia guidelines]]

MediaWiki:Common.css

2018-12-11T11:50:09Z

Bill:Change text

/* CSS placed here will be applied to all skins */

#p-logo {
height: 225px;
}

#p-logo a, #p-logo a:hover {
height: 225px;
}

#p-navigation {
position: relative !important;
top: 0 !important;
}

#p-tb {
position: relative !important;
top: 10px !important;
}

/* We need to fix for MonoBook but not Modern or Cologne Blue skins which don't show the logo
.skin-monobook #p-navigation, .skin-vector #p-navigation {
top: 105px !important;
}
*/

/* Lifted from https://en.wikipedia.org/wiki/MediaWiki:Common.css */
/* Infobox template style */
.infobox {
border: 1px solid #a2a9b1;
border-spacing: 3px;
background-color: #f8f9fa;
color: black;
/* @noflip */
margin: 0.5em 0 0.5em 1em;
padding: 0.2em;
/* @noflip */
float: right;
/* @noflip */
clear: right;
font-size: 88%;
line-height: 1.5em;
}
.infobox caption {
font-size: 125%;
font-weight: bold;
padding: 0.2em;
text-align: center;
}
.infobox td,
.infobox th {
vertical-align: top;
/* @noflip */
text-align: left;
}
.infobox.bordered {
border-collapse: collapse;
}
.infobox.bordered td,
.infobox.bordered th {
border: 1px solid #a2a9b1;
}
.infobox.bordered .borderless td,
.infobox.bordered .borderless th {
border: 0;
}

.infobox.sisterproject {
width: 20em;
font-size: 90%;
}

.infobox.standard-talk {
border: 1px solid #c0c090;
background-color: #f8eaba;
}
.infobox.standard-talk.bordered td,
.infobox.standard-talk.bordered th {
border: 1px solid #c0c090;
}

/* styles for bordered infobox with merged rows */
.infobox.bordered .mergedtoprow td,
.infobox.bordered .mergedtoprow th {
border: 0;
border-top: 1px solid #a2a9b1;
/* @noflip */
border-right: 1px solid #a2a9b1;
}

.infobox.bordered .mergedrow td,
.infobox.bordered .mergedrow th {
border: 0;
/* @noflip */
border-right: 1px solid #a2a9b1;
}

/* Styles for geography infoboxes, eg countries,
country subdivisions, cities, etc. */
.infobox.geography {
border-collapse: collapse;
line-height: 1.2em;
font-size: 90%;
}

.infobox.geography td,
.infobox.geography th {
border-top: 1px solid #a2a9b1;
padding: 0.4em 0.6em 0.4em 0.6em;
}
.infobox.geography .mergedtoprow td,
.infobox.geography .mergedtoprow th {
border-top: 1px solid #a2a9b1;
padding: 0.4em 0.6em 0.2em 0.6em;
}

.infobox.geography .mergedrow td,
.infobox.geography .mergedrow th {
border: 0;
padding: 0 0.6em 0.2em 0.6em;
}

.infobox.geography .mergedbottomrow td,
.infobox.geography .mergedbottomrow th {
border-top: 0;
border-bottom: 1px solid #a2a9b1;
padding: 0 0.6em 0.4em 0.6em;
}

.infobox.geography .maptable td,
.infobox.geography .maptable th {
border: 0;
padding: 0;
}

.hatnote{
padding-left: 1.6em;
margin-bottom: 0.5em;
}

table.ambox{
margin: 0 10%;
border: 1px solid #a2a9b1;
border-left: 10px solid #36c;
background: #fbfbfb;
box-sizing: border-box;
}

table.ambox-style{
border-left: 10px solid #fc3;
}

#n-donate a{
background-color: #0BA7CD;
padding: 3px;
border-radius: 2px;
color:white !important;
font-weight: 600 !important;
box-shadow: 2px 2px #888888;
cursor: pointer;
}

/**Add Text before donate button**/
li#n-donate::before {
content: "Did this page help you?";
display: block;
border-top: solid #0000006b 0.5px;
padding-top: 10px;
color: #0ba7cdbf;
font-size: 14px;
font-style: italic;
margin-bottom: 10px;
}

/**Add text after donate button*/
li#n-donate::after {
content: "Help us grow MEpedia";
display: block;
padding-top: 15px;
color: #0ba7cdbf;
font-size: 14px;
font-style: italic;
}

MediaWiki:Sidebar

2018-11-28T19:45:08Z

Bill:Update sidebar

MediaWiki:Donate

2018-11-28T19:44:10Z

Bill:Donate button

DONATE

MediaWiki:Donate-url

2018-11-28T19:43:37Z

Bill:create page for donation URL

https://www.meaction.net/donate/

MediaWiki:Common.css

2018-11-28T19:43:07Z

Bill:Donate button

/* CSS placed here will be applied to all skins */

#p-logo {
height: 225px;
}

#p-logo a, #p-logo a:hover {
height: 225px;
}

#p-navigation {
position: relative !important;
top: 0 !important;
}

#p-tb {
position: relative !important;
top: 10px !important;
}

/* We need to fix for MonoBook but not Modern or Cologne Blue skins which don't show the logo
.skin-monobook #p-navigation, .skin-vector #p-navigation {
top: 105px !important;
}
*/

/* Lifted from https://en.wikipedia.org/wiki/MediaWiki:Common.css */
/* Infobox template style */
.infobox {
border: 1px solid #a2a9b1;
border-spacing: 3px;
background-color: #f8f9fa;
color: black;
/* @noflip */
margin: 0.5em 0 0.5em 1em;
padding: 0.2em;
/* @noflip */
float: right;
/* @noflip */
clear: right;
font-size: 88%;
line-height: 1.5em;
}
.infobox caption {
font-size: 125%;
font-weight: bold;
padding: 0.2em;
text-align: center;
}
.infobox td,
.infobox th {
vertical-align: top;
/* @noflip */
text-align: left;
}
.infobox.bordered {
border-collapse: collapse;
}
.infobox.bordered td,
.infobox.bordered th {
border: 1px solid #a2a9b1;
}
.infobox.bordered .borderless td,
.infobox.bordered .borderless th {
border: 0;
}

.infobox.sisterproject {
width: 20em;
font-size: 90%;
}

.infobox.standard-talk {
border: 1px solid #c0c090;
background-color: #f8eaba;
}
.infobox.standard-talk.bordered td,
.infobox.standard-talk.bordered th {
border: 1px solid #c0c090;
}

/* styles for bordered infobox with merged rows */
.infobox.bordered .mergedtoprow td,
.infobox.bordered .mergedtoprow th {
border: 0;
border-top: 1px solid #a2a9b1;
/* @noflip */
border-right: 1px solid #a2a9b1;
}

.infobox.bordered .mergedrow td,
.infobox.bordered .mergedrow th {
border: 0;
/* @noflip */
border-right: 1px solid #a2a9b1;
}

/* Styles for geography infoboxes, eg countries,
country subdivisions, cities, etc. */
.infobox.geography {
border-collapse: collapse;
line-height: 1.2em;
font-size: 90%;
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List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis

2018-08-18T00:20:36Z

Bill:fix main template

[[Myalgic encephalomyelitis]] is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

== Nervous system ==

=== Central nervous system ===
{{Main article |page_name =Central nervous system}}
* increased [[Ventricular system|ventricular]] [[lactate]]<ref name=":5">{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=Apr 2009|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: anin vivo3.0 T1H MRS imaging study|url=https://onlinelibrary.wiley.com/doi/full/10.1002/nbm.1315|journal=NMR in Biomedicine|language=en|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|issn=0952-3480}}</ref><ref>{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=Jul 2010|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/20661876|journal=NMR in biomedicine|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref><ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=Sep 2012|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology|url=https://www.ncbi.nlm.nih.gov/pubmed/22281935|journal=NMR in biomedicine|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=PMC3896084|pmid=22281935}}</ref><ref>{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017-01-02|title=Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1280114?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=PMC5754037|pmid=29308330}}</ref>
* neuroinflammation<ref>{{Cite journal|last=Nakatomi|first=Yasuhito|last2=Mizuno|first2=Kei|last3=Ishii|first3=Akira|last4=Wada|first4=Yasuhiro|last5=Tanaka|first5=Masaaki|last6=Tazawa|first6=Shusaku|last7=Onoe|first7=Kayo|last8=Fukuda|first8=Sanae|last9=Kawabe|first9=Joji|date=2014-06-01|title=Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study|url=http://jnm.snmjournals.org/content/55/6/945|journal=Journal of Nuclear Medicine|language=en|volume=55|issue=6|pages=945–950|doi=10.2967/jnumed.113.131045|issn=0161-5505|pmid=24665088}}</ref>
* reduced [[Grey matter|grey]]<ref name=":6">{{Cite journal|last=Puri|first=B K|last2=Jakeman|first2=P M|last3=Agour|first3=M|last4=Gunatilake|first4=K D R|last5=Fernando|first5=K A C|last6=Gurusinghe|first6=A I|last7=Treasaden|first7=I H|last8=Waldman|first8=A D|last9=Gishen|first9=P|date=Jul 2012|title=Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study|url=https://www.birpublications.org/doi/full/10.1259/bjr/93889091|journal=The British Journal of Radiology|language=en|volume=85|issue=1015|pages=e270–e273|doi=10.1259/bjr/93889091|issn=0007-1285|pmc=PMC3474083|pmid=22128128}}</ref> and [[white matter]]<ref>{{Cite journal|last=Shan|first=Zack Y.|last2=Kwiatek|first2=Richard|last3=Burnet|first3=Richard|last4=Del Fante|first4=Peter|last5=Staines|first5=Donald R.|last6=Marshall-Gradisnik|first6=Sonya M.|last7=Barnden|first7=Leighton R.|date=2016-04-28|title=Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study|url=https://onlinelibrary.wiley.com/doi/full/10.1002/jmri.25283|journal=Journal of Magnetic Resonance Imaging|language=en|volume=44|issue=5|pages=1301–1311|doi=10.1002/jmri.25283|issn=1053-1807|pmc=PMC5111735|pmid=27123773}}</ref><ref name=":6" />

=== Autonomic nervous system ===
{{Main article |page_name =Autonomic nervous system}}
* Orthostatic intolerance<ref>Gerwin Morris, Michael Maes, see citations 12 through 27 in [http://www.biomedcentral.com/1741-7015/11/205 "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics"] ''BMC Medicine'', 17 September 2013</ref><ref>{{Cite journal|last=Miwa|first=K|date=Jul 2015|title=Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle|url=https://www.ncbi.nlm.nih.gov/pubmed/24736946|journal=Heart and Vessels|volume=30|issue=4|pages=484–489|via=}}</ref>

=== Peripheral nervous system ===
{{Main article |page_name =Peripheral nervous system}}

== Muscular system ==
{{Main article |page_name =Muscle}}
*[[mitochondria]]l abnormalities found via [[muscle biopsy]] including: mitochondrial degeneration<ref>{{Cite journal|last=Behan|first=W. M. H.|last2=More|first2=I. A. R.|last3=Behan|first3=P. O.|date=Dec 1991|title=Mitochondrial abnormalities in the postviral fatigue syndrome|url=https://link.springer.com/article/10.1007/BF00294431|journal=Acta Neuropathologica|language=en|volume=83|issue=1|pages=61–65|doi=10.1007/bf00294431|issn=0001-6322}}</ref>, deletions of mitochondrial DNA <ref name=":0">{{Cite journal|date=1996-04-19|title=Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.sciencedirect.com/science/article/abs/pii/0304394096125593|journal=Neuroscience Letters|language=en|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940}}</ref><ref>{{Cite journal|last=Zhang|first=C.|last2=Baumer|first2=A.|last3=Mackay|first3=I. R.|last4=Linnane|first4=A. W.|last5=Nagley|first5=P.|date=Apr 1995|title=Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/7633428|journal=Human Molecular Genetics|volume=4|issue=4|pages=751–754|issn=0964-6906|pmid=7633428}}</ref>, the reduction of mitochondrial activity<ref name=":0" />
*Increased urinary [[creatine]] excretion during relapses<ref>{{Cite journal|last=Albrecht|first=Robert|date=March 21, 1964|title=Epidemic Neuromyasthenia Outbreak in a Convent in New York State|url=https://www.ncbi.nlm.nih.gov/pubmed/14100144|journal=Journal of the American Medical Association|volume=187|pages=904-907|via=}}</ref>
*Increased [[creatine kinase]] ([[postviral fatigue syndrome]])
*Persistence of [[enterovirus]]es in muscle tissue<ref name=":1">{{Cite journal|last=Gow|first=J. W.|last2=Behan|first2=W. M. H.|last3=Simpson|first3=K.|last4=McGarry|first4=F.|last5=Keir|first5=S.|last6=Behan|first6=P. O.|date=1994-01-01|title=Studies on Enterovirus in Patients with Chronic Fatigue Syndrome|url=https://academic.oup.com/cid/article-abstract/18/Supplement_1/S126/316946|journal=Clinical Infectious Diseases|language=en|volume=18|issue=Supplement_1|pages=S126–S129|doi=10.1093/clinids/18.Supplement_1.S126|issn=1537-6591}}</ref><ref name=":2">{{Cite journal|last=Cunningham|first=Louise|last2=Bowles|first2=N. E.|last3=Lane|first3=R. J. M.|last4=Dubowitz|first4=V.|last5=Archard|first5=L. C.|date=1990|title=Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA|url=http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-71-6-1399|journal=Journal of General Virology|volume=71|issue=6|pages=1399–1402|doi=10.1099/0022-1317-71-6-1399}}</ref><ref name=":3">{{Cite journal|last=Archard|first=L C|last2=Bowles|first2=N E|last3=Behan|first3=P O|last4=Bell|first4=E J|last5=Doyle|first5=D|date=1988-06-01|title=Postviral Fatigue Syndrome: Persistence of Enterovirus RNA in Muscle and Elevated Creatine Kinase

,

Postviral Fatigue Syndrome: Persistence of Enterovirus RNA in Muscle and Elevated Creatine Kinase|url=https://doi.org/10.1177/014107688808100608|journal=Journal of the Royal Society of Medicine|language=en|volume=81|issue=6|pages=326–329|doi=10.1177/014107688808100608|issn=0141-0768|pmc=PMC1291623|pmid=3404526}}</ref><ref name=":4">{{Cite journal|last=Gow|first=J. W.|last2=Behan|first2=W. M.|last3=Clements|first3=G. B.|last4=Woodall|first4=C.|last5=Riding|first5=M.|last6=Behan|first6=P. O.|date=1991-03-23|title=Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome.|url=https://www.bmj.com/content/302/6778/692|journal=BMJ|language=en|volume=302|issue=6778|pages=692–696|doi=10.1136/bmj.302.6778.692|issn=0959-8138|pmid=1850635}}</ref>
*abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells<ref name="BrownAE2015">{{Citation
| last1 = Brown | first1 = Audrey E | authorlink1 = Audrey Brown
| last2 = Jones | first2 = David E | authorlink2 = David Jones
| last3 = Walker | first3 = Mark | authorlink3 = Mark Walker
| last4 = Newton | first4 = Julia L | authorlink4 = Julia Newton
| title = Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells
| journal = PLoS One | volume = 10 | issue = 4
| date = 2 Apr 2015
| pmid = 25836975 | doi = 10.1371/journal.pone.0122982
| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982
}}</ref><ref name="Wellness20150420">{{citation
| last1 = Dobberstein | first1 = Linda J. | authorlink1 =
| title = Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia
| journal = Wellness Resources
| date = 20 Apr 2015
| url = http://www.wellnessresources.com/health/articles/master_enzyme_switch_deactivated_in_chronic_fatigue_syndrome_and_fibromyalg/
}}</ref>

== Immune system ==
{{Main article |page_name =Immune system}}
=== Immune dysregulation ===
* [[Natural killer cell]] function is reduced<ref>{{Cite journal|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|date=Apr 2014|issn=1460-2377|pmid=24343819|pages=233–242|volume=26|issue=4|doi=10.1093/intimm/dxt068|first=Ekua Weba|last=Brenu|first2=Teilah K.|last2=Huth|first3=Sharni L.|last3=Hardcastle|first4=Kirsty|last4=Fuller|first5=Manprit|last5=Kaur|first6=Samantha|last6=Johnston|first7=Sandra B.|last7=Ramos|first8=Don R.|last8=Staines|first9=Sonya M.|last9=Marshall-Gradisnik}}</ref><ref>{{Cite journal|last=Victoria Scott|first=David Strayer|date=2015|title=Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity|url=https://www.omicsonline.org/open-access/low-nk-cell-activity-in-chronic-fatigue-syndrome-cfs-and-relationship-to-symptom-severity-2155-9899-1000348.php?aid=59415|journal=Journal of Clinical & Cellular Immunology|language=En|volume=06|issue=04|doi=10.4172/2155-9899.1000348|issn=2155-9899}}</ref>
* [[Cytokine]] dysregulation<ref name="Montoya, 2017">{{citation
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya
| last2 = Holmes | first2 = Tyson H. | authorlink2 =
| last3 = Anderson | first3 = Jill N. | authorlink3 =
| last4 = Maecker | first4 = Holden T. | authorlink4 =
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 =
| last6 = Valencia | first6 = Ian J. | authorlink6 =
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger
| last9 = Tato | first9 = Cristina M. | authorlink9 =
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis
| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients
| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158
| date = 2017
| pmid =
| doi = 10.1073/pnas.1710519114
}}</ref><ref>[http://www.meaction.net/2015/12/07/study-finds-evidence-of-downregulated-immune-system-in-mecfs-patients Study finds evidence of downregulated immune system in ME/CFS patients - MEAtcion - Landi, et al.]</ref><ref>[http://microbediscovery.org/2017/04/04/new-research-discovers-evidence-of-atypical-classical-mecfs/ New Research Discovers Evidence of Atypical & Classical ME/CFS - The Microbe Discovery Project - Apr 4, 2017]</ref>
* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>
* increased [[mast cell]] populations<ref>{{Cite journal|last=Rönnberg|first=E|last2=Calounova|first2=G|last3=Pejler|first3=G|date=June 2017|title=Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pubmed/27362406|journal=Asian Pac J Allergy Immunol|volume=35|issue=2|pages=75-81|via=}}</ref>
* elevated anti-cholinergic [[Muscarinic acetylcholine receptor|muscarinic]], Β-adrenergic<ref>{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>, [[phosphatidylinositol]]<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=Dec 2007|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://www.ncbi.nlm.nih.gov/pubmed/18063934|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref> and [[serotonin]]<ref>{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=2013-09-05|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=https://www.ncbi.nlm.nih.gov/pubmed/23664637|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref> [[antibodies]]

=== Chronic infection ===
* [[Enterovirus]]: Persistence of [[enterovirus]]es in muscle tissue<ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" />; brain<ref name="McGarry19942">{{citation
| last1 = McGarry | first1 = Frances | authorlink1 = Frances McGarry
| last2 = Gow | first2 = John | authorlink2 = John Gow
| last3 = Behan | first3 = Peter O | authorlink3 = Peter O Behan
| title = Enterovirus in the Chronic Fatigue Syndrome
| journal = Annals of Internal Medicine | volume = 120| issue = 11| pages = 972–973
| date = 1 Jun 1994
| doi = 10.7326/0003-4819-120-11-199406010-00020
| url = http://www.ncbi.nlm.nih.gov/pubmed/8172448
}}</ref>; and gut<ref name="ChiaJKS2016">{{Citation
| last1 = Chia | first1 = JKS | authorlink1 = John Chia
| last2 = Chia | first2 = AY | authorlink2 = Andrew Chia
| title = Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach
| journal = Journal of Clinical Pathology | volume = 61| issue = 1| pages = 43–48
| date = 1 Jan 2008
| pmid = 17872383 | doi = 10.1136/jcp.2007.050054
| url = http://jcp.bmj.com/content/61/1/43
}}</ref>; increased detection of viral RNA via PCR; increased [[Antibody|antibodies]]
* [[Herpesvirus]]:

== Lymphatic system ==

== Cardiovascular system ==

{{Main article|page_name =Cardiovascular system}}{{Main article|page_name =Cardiac problems in ME/CFS}}

=== Heart ===
* Smaller than normal [[left ventricle]] of the [[heart]],<ref name=":8">Miwa K., [http://www.ncbi.nlm.nih.gov/pubmed/24736946 "Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle"] ''Heart Vessels'', July 2015</ref><ref>Hollingsworth K.G [http://onlinelibrary.wiley.com/enhanced/doi/10.1111/j.1365-2796.2011.02429.x/ "Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging"] ''J Intern Med'' 2012; 271: 264–270.</ref><ref name="Olimulder, 2016">{{Citation
| last1 = Olimulder | first1 = M.A.G.M. | authorlink1 =
| last2 = Galjee | first2 = M.A. | authorlink2 =
| last3 = Wagenaar | first3 = L.J. | authorlink3 =
| last4 = van Es | first4 = J. | authorlink4 =
| last5 = van der Palen | first5 = J. | authorlink5 =
| last6 = Visser | first6 = F. C. | authorlink6 =
| last7 = Vermeulen | first7 = R.C.W. | authorlink7 =
| last8 = von Birgelen | first8 = C. | authorlink8 =
| title = Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging
| journal = Netherlands Heart Journal
| date = 2016
| doi = 10.1007/s12471-016-0885-8
}}</ref><ref>[http://openheart.bmj.com/content/3/1/e000381.long Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study]</ref> [[small heart syndrome]],<ref name=":8" /> and low [[Cardiovascular system|cardiac]] output.<ref>Miwa K., Fujita M., [http://www.ncbi.nlm.nih.gov/pubmed/19881233 "Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome"] ''Intern Med'', 2009;48(21):1849-54</ref>
* Mean age of death from heart failure of [[CFS]] patients is 58.7 years as compared to 83.1 years for the general population.<ref>Jason LA, Corradi K, Gress S, Williams S, Torres-Harding S, [http://www.ncbi.nlm.nih.gov/pubmed/16844674 "Causes of death among patients with chronic fatigue syndrome"] ''Health Care Women Int.'', 27(7): 615-626. 2006</ref>
=== Circulation ===
* reduced blood flow to the brain and heart<ref>{{Cite journal|last=Patrick Neary|first=J.|last2=Roberts|first2=Andy D. W.|last3=Leavins|first3=Nina|last4=Harrison|first4=Michael F.|last5=Croll|first5=James C.|last6=Sexsmith|first6=James R.|date=Nov 2008|title=Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1475-097X.2008.00822.x|journal=Clinical Physiology and Functional Imaging|volume=28|issue=6|pages=364–372|doi=10.1111/j.1475-097x.2008.00822.x|issn=1475-0961}}</ref><ref>{{Cite journal|last=Peterson|first=P K|last2=Sirr|first2=S A|last3=Grammith|first3=F C|last4=Schenck|first4=C H|last5=Pheley|first5=A M|last6=Hu|first6=S|last7=Chao|first7=C C|date=Mar 1994|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>

=== Blood vessels ===

=== Blood ===
* reduced [[blood]] volume<ref>{{Cite journal|last=Hurwitz|first=BE|last2=Coryell|first2=VT|last3=Parker|first3=M|last4=Martin|first4=P|last5=LaPerriere ....|first5=A|last6=Bilsker|first6=MS|date=|title=Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function|url=http://www.clinsci.org/content/118/2/125|journal=Clinical Science|volume=118|issue=2|pages=125-135|via=}}</ref><ref>{{Cite journal|last=Streeten|first=DHP|last2=Bell|first2=D|date=1998|title=Circulating Blood Volume in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n01_02|journal=Journal of Chronic Fatigue Syndrome|volume=4|pages=3-11|via=}}</ref>
* abnormally shaped of [[Red blood cell|red blood cells]]<ref name="Simpson1989">{{Citation
| last1 = Simpson | first1 = LO | authorlink1 = Leslie Simpson
| title = Nondiscocytic erythrocytes in myalgic encephalomyelitis
| journal = The New Zealand Medical Journal | volume = 102 | issue = 864 | page = 126-127
| date = 1989
| pmid = 2927808
| doi =
}}</ref><ref>{{Cite journal|last=Richards|first=RS|last2=Wang|first2=L|last3=Jelinek|first3=H|date=Jan 2007|title=Erythrocyte oxidative damage in chronic fatigue syndrome|url=https://www.sciencedirect.com/science/article/pii/S0188440906002992|journal=Archives of Medical Research|volume=38|issue=1|pages=94-98|via=}}</ref>
* reduced oxygen uptake in [[hemoglobin]]<ref>{{Cite journal|last=Miller|first=Ruth R|last2=Reid|first2=W Darlene|last3=Mattman|first3=Andre|last4=Yamabayashi|first4=Cristiane|last5=Steiner|first5=Theodore|last6=Parker|first6=Shoshana|last7=Gardy|first7=Jennifer|last8=Tang|first8=Patrick|last9=Patrick|first9=David M|date=2015-05-20|title=Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case–control study|url=http://doi.org/10.1186/s12967-015-0527-8|journal=Journal of Translational Medicine|language=En|volume=13|issue=1|doi=10.1186/s12967-015-0527-8|issn=1479-5876|pmc=PMC4438583|pmid=25990639}}</ref>

== Digestive system ==

=== Gastrointestinal tract ===
{{Main article |page_name =Gastrointestinal tract}}
* lower levels of ''[[Bifidobacteria]]'', ''[[Escherichia coli]]'' and higher levels of [[aerobic bacteria]].<ref>{{Cite journal|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=http://www.medical-hypotheses.com/article/S0306-9877(03)00096-3/abstract|journal=Medical Hypotheses|date=Jun 2003|issn=0306-9877|pages=915–923|volume=60|issue=6|doi=10.1016/S0306-9877(03)00096-3|language=English|first=Alan C|last=Logan|first2=A|last2=Venket Rao|first3=Dinaz|last3=Irani}}</ref>, in particular ''[[Enterococcus]]'' and ''[[Streptococcus]]'' species<ref>{{Cite journal|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=http://www.ncbi.nlm.nih.gov/pubmed/19567398|journal=In Vivo (Athens, Greece)|date=Jul 2009|issn=0258-851X|pmid=19567398|pages=621–628|volume=23|issue=4|first=John R.|last=Sheedy|first2=Richard E. H.|last2=Wettenhall|first3=Denis|last3=Scanlon|first4=Paul R.|last4=Gooley|first5=Donald P.|last5=Lewis|first6=Neil|last6=McGregor|first7=David I.|last7=Stapleton|first8=Henry L.|last8=Butt|first9=Kenny L.|last9=DE Meirleir}}</ref>
* higher levels of enterococcus bacteria in CFS patients were associated with more severe neurological and cognitive dysfunction<ref>https://getinfo.de/en/search/id/BLCP%3ACN055885616/%60Bacterial-Colonosis-in-Patients-with-Persistent/</ref>
* Significantly increased proportions of Firmicutes<ref>{{Cite journal|title=High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.sciencedirect.com/science/article/pii/S1075996413000929|journal=Anaerobe|date=2013-08-01|issn=1075-9964|pages=50–56|volume=22|doi=10.1016/j.anaerobe.2013.06.002|language=en}}</ref><ref name=":7">{{Cite journal|last=Giloteaux|first=Ludovic|last2=Goodrich|first2=Julia K.|last3=Walters|first3=William A.|last4=Levine|first4=Susan M.|last5=Ley|first5=Ruth E.|last6=Hanson|first6=Maureen R.|date=2016-06-23|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918027/|journal=Microbiome|volume=4|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=PMC4918027|pmid=27338587}}</ref> and Bacteroides<ref name=":7" />
* CFS patients may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at high rates.<ref name="Pimentel2000">{{Citation
| last1 = Pimentel | first1 = M | authorlink1 = Mark Pimentel
| last2 = Hallegua | first2 = D | authorlink2 = David Hallegua
| last3 = Chow | first3 = EJ | authorlink3 = Evelyn Chow
| last4 = Wallace | first4 = D | authorlink4 = Daniel Wallace
| last5 = Bonorris | first5 = G | authorlink5 = George Bonorris
| last6 = Lin | first6 = HC | authorlink6 = Henry Lin
| display-authors = 3
| title = Eradication of small intestinal bacterial overgrowth decreases symptoms in chronic fatigue syndrome: A double blind, randomized study
| journal = Gastroenterology | volume = 118| issue = 4| pages = –414
| date = 1 Apr 2000
| doi = 10.1016/S0016-5085(00)83765-8
| url = http://www.gastrojournal.org/article/S0016508500837658/abstract
}}</ref>
* Higher levels of serum [[Immunoglobulin A|IgA]] and [[Immunoglobulin M|IgM]] against [[lipopolysaccharides]] (LPS), a major component of the outer membrane of [[gram negative bacteria]], indicating translocation. <ref>http://www.jad-journal.com/article/S0165-0327(06)00355-7/abstract</ref> Serum IgA was significantly correlated to the severity of illness.

=== Liver ===
* Reduced [[liver]] volume<ref>{{Cite journal|title=Liver volume is lower and associates with resting and dynamic blood pressure variability in chronic fatigue syndrome|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1488525|journal=Fatigue: Biomedicine, Health & Behavior|date=2018-06-18|issn=2164-1846|pages=141–152|volume=6|issue=3|doi=10.1080/21641846.2018.1488525|language=en|first=Pawel|last=Zalewski|first2=Andreas|last2=Finkelmeyer|first3=James|last3=Frith|first4=Laura|last4=Maclachlan|first5=Andrew|last5=Blamire|first6=Julia L.|last6=Newton}}</ref>

== Nutrition ==
* low red blood cell [[magnesium]]<ref name="cfs_and_blood_mg">{{Citation
| last1 = I.M.
| first1 = Cox
| authorlink1 =
| last2 = M.J.
| first2 = Campbell
| authorlink2 =
| last3 = D.
| first3 = Dowson
| authorlink3 =
| display-authors =
| title = Red blood cell magnesium and chronic fatigue syndrome
| journal = The Lancet
| year = 1991
| pmid = 1672392
| doi = 10.1016/0140-6736(91)91371-Z
}}</ref>

== Metabolism ==

=== Cellular respiration ===
* errors in [[cellular respiration]] including a reduction in [[glycolysis]],<ref>{{Cite journal|last=Armstrong|first=Christopher W.|last2=McGregor|first2=Neil R.|last3=Lewis|first3=Donald P.|last4=Butt|first4=Henry L.|last5=Gooley|first5=Paul R.|date=2015-05-30|title=Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients|url=https://link.springer.com/article/10.1007/s11306-015-0816-5|journal=Metabolomics|language=en|volume=11|issue=6|pages=1626–1639|doi=10.1007/s11306-015-0816-5|issn=1573-3882}}</ref> including impaired [[pyruvate dehydrogenase]]<ref>{{Cite journal|last=Fluge|first=Øystein|last2=Mella|first2=Olav|last3=Bruland|first3=Ove|last4=Risa|first4=Kristin|last5=Dyrstad|first5=Sissel E.|last6=Alme|first6=Kine|last7=Rekeland|first7=Ingrid G.|last8=Sapkota|first8=Dipak|last9=Røsland|first9=Gro V.|date=2016-12-22|title=Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/28018972|journal=JCI insight|volume=1|issue=21|pages=e89376|doi=10.1172/jci.insight.89376|issn=2379-3708|pmc=PMC5161229|pmid=28018972}}</ref>
* increased [[lactic acid]]<ref name="Plioplys1995">{{citation
| last1 = Plioplys | first1 = AV | authorlink1 =
| last2 = Plioplys | first2 = S | authorlink2 =
| title = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates
| journal = Neuropsychobiology | date = 1995 | volume = 32 | issue = 3 | page = 132-8
| pmid = 8544970
| url = http://www.ncbi.nlm.nih.gov/pubmed/8544970
}}</ref><ref name="LaneRJ1998">{{citation
| last1 = Lane | first1 = R J | authorlink1 = Russell Lane
| last2 = Barrett | first2 = M C | authorlink2 = Michael Barrett
| last3 = Taylor | first3 = D J | authorlink3 = Doris Taylor
| last4 = Kemp | first4 = G J | authorlink4 = Graham Kemp
| last5 = Lodi | first5 = R | authorlink5 = Raffaele Lodi
| title = Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle
| journal = Neuromuscul Disord | volume = 1998 May;8 | issue = 3-4 | page = 204-9
| date = May 1998
| pmid = 9631403
| url = http://www.ncbi.nlm.nih.gov/pubmed/9631403
}}</ref><ref name="JonesDE2010">{{citation
| last1 = Jones | first1 = David EJ | authorlink1 = David Jones
| last2 = Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth
| last3 = Taylor | first3 = Renee R | authorlink3 = Renee Taylor
| last4 = Blamire | first4 = Andrew M | authorlink4 = Andrew Blamire
| last5 = Newton | first5 = Julia L | authorlink5 = Julia Newton
| title = Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome
| journal = J Intern Med | volume = 267 | issue = 4 | page = 394-401
| date = Apr 2010
| pmid = 20433583 | doi = 10.1111/j.1365-2796.2009.02160.x
| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02160.x/abstract
}}</ref><ref name="LengertN2015">{{citation
| last1 = Lengert | first1 = Nicor | authorlink1 = Nicor Lengert
| last2 = Drossel | first2 = Barbara | authorlink2 = Barbara Drossel
| title = In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome
| journal = Biophysical Chemistry | volume = 202 | page = 21–31
| date = Jul 2015
| pmid = 25899994 | doi = 10.1016/j.bpc.2015.03.009
| url = http://www.sciencedirect.com/science/article/pii/S0301462215000630
}}</ref><ref name=":5" />
* reduction in metabolites reflecting a slowed metabolism.<ref>{{Cite journal|last=Naviaux|first=Robert K.|last2=Naviaux|first2=Jane C.|last3=Li|first3=Kefeng|last4=Bright|first4=A. Taylor|last5=Alaynick|first5=William A.|last6=Wang|first6=Lin|last7=Baxter|first7=Asha|last8=Nathan|first8=Neil|last9=Anderson|first9=Wayne|date=2016-09-13|title=Metabolic features of chronic fatigue syndrome|url=http://www.pnas.org/content/113/37/E5472|journal=Proceedings of the National Academy of Sciences|language=en|volume=113|issue=37|pages=E5472–E5480|doi=10.1073/pnas.1607571113|issn=0027-8424|pmid=27573827}}</ref>

=== Exercise ===
* reduced pain threshold<ref name="Whiteside, 2004">{{Citation
| last1 = Whiteside | first1 = Alan | authorlink1 =
| last2 = Hansen | first2 = Stig | authorlink2 =
| last3 = Chaudhuri | first3 = Abhijit | authorlink3 = Abhijit Chaudhuri
| title = Exercise lowers pain threshold in chronic fatigue syndrome
| journal = Pain | volume = 109 | issue = 3 | page = 497-9
| date = 2004
| pmid = 15157711
| doi = 10.1016/j.pain.2004.02.029
}}</ref>
* translocation of bacteria<ref name="ShuklaS2015">{{citation
| last1 = Shukla | first1 = Sanjay K | authorlink1 = Sanjay Shukla
| last2 = Cook | first2 = Dane | authorlink2 = Dane Cook
| last3 = Meyer | first3 = Jacob | authorlink3 = Jacob Meyer
| last4 = Vernon | first4 = Suzanne D | authorlink4 = Suzanne Vernon
| last5 = Le | first5 = Thao | authorlink5 = Thao Le
| last6 = Clevidence | first6 = Derek | authorlink6 = Derek Clevidence
| last7 = Robertson | first7 = Charles E | authorlink7 = Charles Robertson
| last8 = Schrodi | first8 = Steven J | authorlink8 = Steven Schrodi
| last9 = Yale | first9 = Steven | authorlink9 = Steven Yale
| last10 = Frank | first10= Daniel N | authorlink10= Daniel Frank
| display-authors = 3
| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
| journal = PLoS ONE
| date = 18 Dec 2015
| pmid = 26683192 | doi = 10.1371/journal.pone.0145453
| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453
}}</ref>
* loss of capacity to recover from acidosis on repeat exercise.<ref name="JonesDE2012">{{citation
| last1 = Jones | first1 = David EJ | authorlink1 = David Jones
| last2 = Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth
| last3 = Jakovljevic | first3 = Djordje G | authorlink3 = Djordje Jakovljevic
| last4 = Fattakhova | first4 = Gulnar | authorlink4 = Gulnar Fattakhova
| last5 = Pairman | first5 = Jessie | authorlink5 = Jessie Pairman
| last6 = Blamire | first6 = Andrew M | authorlink6 = Andrew Blamire
| last7 = Trenell | first7 = Michael I | authorlink7 = Michael Trenell
| last8 = Newton | first8 = Julia L | authorlink8 = Julia Newton
| display-authors = 3
| title = Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome
| journal = Eur J Clin Invest | volume = 2012 Feb;42 | issue = 2 | page = 186-94
| date = 12 Jul 2011
| pmid = 21749371 | doi = 10.1111/j.1365-2362.2011.02567.x
| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2011.02567.x/abstract
}}</ref>
* increased expression of sensory, adrenergic and immune genes following [[muscle]] exertion<ref name="LightAR2009">{{citation
| last1 = Light | first1 = Alan R | authorlink1 = Alan Light
| last2 = White | first2 = Andrea T | authorlink2 = Andrea White
| last3 = Hughen | first3 = Ronald W | authorlink3 = Ronald Hughen
| last4 = Light | first4 = Kathleen C | authorlink4 = Kathleen Light
| title = Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects
| journal = J Pain | volume = 2009 Oct;10 | issue = 10 | page = 1099-112
| date = 31 Jul 2009
| pmid = 19647494 | doi = 10.1016/j.jpain.2009.06.003
| url = http://www.jpain.org/article/S1526-5900(09)00574-4/abstract
}}</ref><ref name="LightAR2011">{{citation
| last1 = Light | first1 = Alan R | authorlink1 = Alan Light
| last2 = Bateman | first2 = Lucinda | authorlink2 = Lucinda Bateman
| last3 = Jo | first3 = D | authorlink3 = Daehyun Jo
| last4 = Hughen | first4 = Ronald W | authorlink4 = Ronald Hughen
| last5 = Vanhaitsma | first5 = TA | authorlink5 = Timothy VanHaitsma
| last6 = White | first6 = Andrea T | authorlink6 = Andrea White
| last7 = Light | first7 = Kathleen C | authorlink7 = Kathleen Light
| display-authors = 3
| title = Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome
| journal = J Intern Med | volume = 2012 271 | issue = 1 | page = 64-81
| date = 13 Jul 2011
| pmid = 21615807 | doi = 10.1111/j.1365-2796.2011.02405.x
| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/abstract
}}</ref><ref name="WhiteAT2012">{{citation
| last1 = White | first1 = Andrea T | authorlink1 = Andrea White
| last2 = Light | first2 = Alan R | authorlink2 = Alan Light
| last3 = Hughen | first3 = Ronald W | authorlink3 = Ronald Hughen
| last4 = VanHaitsma | first4 = Timothy A | authorlink4 = Timothy VanHaitsma
| last5 = Light | first5 = Kathleen C | authorlink5 = Kathleen Light
| title = Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls
| journal = Psychosom Med | volume = 2012 Jan;74 | issue = 1 | page = 46-54
| date = 30 Dec 2011
| pmid = 22210239 | doi = 10.1097/PSY.0b013e31824152ed
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/
}}</ref>
* decreased [[oxygen]] utilization<ref>{{Cite journal|last=Vermeulen|first=Ruud CW|last2=Vermeulen van Eck|first2=Ineke WG|date=2014|title=Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome|url=https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-20|journal=Journal of Translational Medicine|language=En|volume=12|issue=1|pages=20|doi=10.1186/1479-5876-12-20|issn=1479-5876|pmc=PMC3903040|pmid=24456560}}</ref>

== See also ==
* [[myalgic encephalomyelitis]]

== Learn more ==
* [http://www.meaction.net/wp-content/uploads/2015/05/ME2FCFS-RESEARCH-SUMMARY-Jamie-Seltzer.pdf #MEAction ME/CFS Research Summary]

==References==
<references />

History of myalgic encephalomyelitis and chronic fatigue syndrome

2018-08-18T00:20:00Z

Bill:fix main template

[[Myalgic encephalomyelitis]] has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical polio. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called "Akureyri Disease" or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

== 19th century ==
Several descriptions of illness resembling those of chronic fatigue syndrome have been reported for at least two hundred years.<ref>{{cite journal|vauthors=Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G|date=February 2009|title=Immunological aspects of chronic fatigue syndrome|url=|journal=Autoimmun Rev|volume=8|issue=4|pages=287–91|doi=10.1016/j.autrev.2008.08.003|pmid=18801465}}</ref> In the 19th century, neurologist [[George Miller Beard]] popularised the concept of [[neurasthenia]], with symptoms including fatigue, anxiety, headache, impotence, neuralgia and depression.<ref>{{cite journal|last=Beard|first=G|authorlink=George Miller Beard|year=1869|title=Neurasthenia, or nervous exhaustion|journal=The [[Boston Medical and Surgical Journal]]|pages=217–221}}</ref> This concept remained popular well into the 20th century, eventually coming to be seen as a behavioural rather than physical condition, with a diagnosis that excluded postviral syndromes. Neurasthenia has largely been abandoned as a medical diagnosis.<ref name="pmid 10583715">{{cite journal|vauthors=Evangard B, Schacterie RS, Komaroff AL|date=Nov 1999|title=Chronic fatigue syndrome: new insights and old ignorance|url=http://www3.interscience.wiley.com/cgi-bin/fulltext/119095441/PDFSTART|journal=Journal of Internal Medicine|volume=246|issue=5|pages=455–469|doi=10.1046/j.1365-2796.1999.00513.x|pmid=10583715|accessdate=June 25, 2009}}</ref> The [[ICD-10]] system of the [[World Health Organization]] now categorizes neurasthenia under (F48 Other neurotic disorders) which specifically excludes chronic fatigue syndrome.<ref name="Who Neurasthenia">{{Cite web|url=http://apps.who.int/classifications/apps/icd/icd10online/index.htm?gf40.htm+|title=ICD-10|author=WHO|year=2007|accessdate=October 9, 2009|chapter=Chapter V Mental and behavioural disorders (F00-F99)}}</ref>

==Epidemic myalgic encephalomyelitis (1930s-1960s) ==
{{Main article |page_name = Epidemic myalgic encephalomyelitis}}

In 1938, [[Alexander Gilliam]] described an illness that resembled [[poliomyelitis]], interviewing patients and reviewing records of one of several clusters which had occurred in Los Angeles, United States in 1934.<ref name="Gilliam38">{{cite journal|last=Gilliam|first=AG|year=1938|title=Epidemiological study on an epidemic, diagnosed as poliomyelitis, occurring among the personnel of Los Angeles County General Hospital during the summer of 1934,|journal=United States Treasury Department Public Health Service Public Health Bulletin|location=Washington, DC|publisher=[[United States Government Printing Office]]|volume=240|pages=1–90}}</ref> The [[1934 Los Angeles atypical polio outbreak|Los Angeles County Hospital outbreak]] included all or most of its nurses and doctors.<ref name="ISBN 078902196X">{{cite book|title=Medical Etiology, Assessment, and Treatment of Chronic Fatigue and Malaise|author=Roberto Patarca-Montero|publisher=Haworth Press|year=2004|isbn=0-7890-2196-X|pages=6–7|oclc=}}</ref> Gilliam called the outbreak "atypical [[wikipedia:Poliomyelitis|poliomyelitis]]" and described the symptoms as: rapid muscle weakness, vasomotor instability, clonic twitches and cramps, ataxia, severe pain (usually aggravated by exercise), neck and back stiffness, menstrual disturbance and dominant sensory involvement.

Novices and convent candidates at a Wisconsin convent were diagnosed with "encephalitis" in 1936. Two towns in Switzerland had outbreaks of "abortive poliomyelitis" in 1937, and 73 Swiss soldiers were given the same diagnosis in 1939. Outbreaks in Iceland were called "[[1948-49 Akureyri outbreak|Akureyri disease]]" or "simulating poliomyelitis" and were later called "[[Icelandic disease|Iceland disease]]." 800 people in [[1949-53 Adelaide outbreak|Adelaide, Australia]] became ill during 1949-1951 with a disease "resembling poliomyelitis." Two smaller clusters in the United States during 1950 were diagnosed as "[[Epidemic neuromyasthenia]]" and "resembling Iceland disease simulating acute anterior poliomyelitis." Additional outbreaks of poliomyelitis-like "mystery diseases" occurred from the 1950s through the 1980s, in Denmark, the United States, South Africa, and Australia, among others.<ref name="ISBN 078902196X" />

Several outbreaks of a polio-resembling illness occurred in Britain in the 1950s.<ref name="Ramsay-RF">{{cite book|title=Postviral Fatigue Syndrome. The saga of Royal Free disease|author=A. Melvin Ramsay|publisher=Gower|year=1986|isbn=0-906923-96-4|location=London}}</ref> A [[1955 Royal Free Hospital outbreak|1955 outbreak at the Royal Free Hospital Group]] was later called ''Royal Free disease'' or ''benign myalgic encephalomyelitis''.<ref name="pmid13472002">{{cite journal|year=1957|title=An outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955|journal=Br Med J|volume=2|issue=5050|pages=895–904|doi=10.1136/bmj.2.5050.895|pmc=1962472|pmid=13472002}}</ref><ref name="Acheson1956">{{cite journal|author=(No authors listed)|year=1956|title=A new clinical entity?|journal=Lancet|volume=270|issue=6926|pages=789–90|doi=10.1016/S0140-6736(56)91252-1|pmid=13320887}}</ref> After the Royal Free Hospital outbreak, a disorder with similar symptoms was found among the general population and the epidemic form came to be considered the exception.{{Citation needed|date=August 2007}} Pathology findings, both in [[wikipedia:Monkey|monkeys]]<ref>{{cite journal|vauthors=Pellew RA, Miles JA|date=September 1955|title=Further investigations on a disease resembling poliomyelitis seen in Adelaide|url=|journal=Med. J. Aust.|volume=2|issue=13|pages=480–2|pmid=13272481}}</ref> and in rare human [[wikipedia:Casualty_(person)|casualties]],<ref>{{Cite journal|last=Wallis|first=AL|year=1957|title=An investigation into an unusual illness seen in epidemic and sporadic form in a general practice in Cumberland in 1955 and subsequent years|format=M.D. Thesis|publisher=Edinburgh University}}</ref> led to the conclusion that the disorder was caused by [[inflammation]] of the brain and the [[spinal cord]], particularly the [[afferent]] nerve roots, perhaps with [[neuroimmune]] etiology.<ref>{{cite journal|last1=Richardson|first1=J|year=2002|title=Myalgic encephalomyelitis: guidelines for doctors|url=http://www.prohealth.com/library/showarticle.cfm?libid=9926|journal=Journal of Chronic Fatigue Syndrome|volume=10|issue=1|pages=65–80|doi=10.1300/j092v10n01_06|name-list-format=vanc}}</ref>

==Mass hysteria (1960s-1970s) ==
In the 1960s and 1970s, chronic fatigue symptoms were often attributed to chronic brucellosis, but typically people were seen as having psychiatric disorders, in particular depression.<ref name="ISBN 078902196X" /> Epidemic cases of benign myalgic encephalomyelitis were called [[mass hysteria]] by psychiatrists McEvedy and Beard in 1970,<ref>{{cite journal|vauthors=McEvedy CP, Beard AW|year=1970|title=Concept of Benign Myalgic Encephalomyelitis|url=|journal=British Medical Journal|volume=1|issue=5687|pages=11–5|doi=10.1136/bmj.1.5687.11|pmc=1700895|pmid=5411596}}</ref> provoking criticism in letters to the editor of the British Medical Journal by outbreak researchers, attending physicians, and physicians who fell ill.<ref name="PMID5370039">{{cite journal|author=Scott BD|date=January 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=1|issue=5689|pages=170–175|doi=10.1136/bmj.1.111.170|pmc=1699088|pmid=5370039}}</ref><ref name="Compston">{{cite journal|author1=N. D. Compston|author2=H. E. Dimsdale|author3=A. M. Ramsay|author4=A. T. Richardson|date=February 1970|title=Epidemic malaise|journal=Br Med J|volume=1|issue=5692|pages=362–363|doi=10.1136/bmj.1.5692.362-a|pmc=1699022|pmid=}}</ref><ref name="Acheson">{{cite journal|author=E. D. Acheson|date=February 1970|title=Epidemic Malaise|journal=Br Med J|volume=1|issue=5692|pages=363–4|doi=10.1136/bmj.1.5692.363-b|pmc=1698971|pmid=}}</ref><ref name="PMID5435167">{{cite journal|author=Gosling PH|date=February 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=1|issue=5694|pages=499–500|doi=10.1136/bmj.1.5694.499-b|pmc=1699452|pmid=5435167}}</ref><ref name="PMID5435168">{{cite journal|author=Purke GJ|date=February 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=1|issue=5694|pages=500|doi=10.1136/bmj.1.5694.500|pmc=1699458|pmid=5435168}}</ref><ref name="PMID5435169">{{cite journal|author=Hopkins EJ|date=February 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=1|issue=5694|pages=500–1|doi=10.1136/bmj.1.5694.500-a|pmc=1699426|pmid=5435169}}</ref><ref name="PMID5435170">{{cite journal|author=Galpine JF|date=February 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=1|issue=5694|pages=501|doi=10.1136/bmj.1.5694.501|pmc=1699416|pmid=5435170}}</ref><ref name="PMID5420612">{{cite journal|author=Poskanzer DC|date=May 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=2|issue=5706|pages=420–1|doi=10.1136/bmj.2.5706.420-b|pmc=1700311|pmid=5420612}}</ref><ref name="PMID4316803">{{cite journal|author=Parish JG|date=July 1970|title=Epidemic malaise|url=|journal=Br Med J|volume=3|issue=5713|pages=47–8|doi=10.1136/bmj.3.5713.47-c|pmc=1700986|pmid=4316803}}</ref> The psychiatrists were faulted for not adequately investigating the patients they described,<ref name="hooper_pathol_06">{{cite journal|author=Hooper M|year=2006|title=Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research|journal=J Clin Pathol|volume=60|issue=5|pages=466–71|doi=10.1136/jcp.2006.042408|pmc=1994528|pmid=16935967}}[http://jcp.bmj.com/cgi/content/abstract/jcp.2006.042408v2 <nowiki>[1]</nowiki>]</ref> and their conclusions have been refuted.<ref name="pmid 10583715" /><ref name="pmid 3128374">{{cite journal|vauthors=David AS, Wessely S, Pelosi AJ|date=March 1988|title=Postviral fatigue syndrome: time for a new approach|url=|journal=Br Med J (Clin Res Ed)|volume=296|issue=6623|pages=696–9|doi=10.1136/bmj.296.6623.696|pmc=2545306|pmid=3128374}}</ref><ref name="pmid2294610">{{cite journal|vauthors=Stricklin A, Sewell M, Austad C|date=January 1990|title=Objective measurement of personality variables in epidemic neuromyasthenia patients|url=|journal=S. Afr. Med. J.|volume=77|issue=1|pages=31–4|pmid=2294610}}</ref> In 1978 a symposium held at the Royal Society of Medicine (RSM) concluded that ''epidemic myalgic encephalomyelitis'' was a distinct disease entity with a clear organic basis.<ref name="pmid647324">{{cite journal|author=[No authors listed]|date=June 3, 1978|title=Epidemic myalgic encephalomyelitis|journal=Br Med J|volume=1|issue=6125|pages=1436–7|doi=10.1136/bmj.1.2791.1436-a|pmc=1604957|pmid=647324}}</ref>

==Chronic fatigue syndrome (1980s & 1990s) ==
The illness gained national attention in the United States when the popular magazine ''Hippocrates'' ran a cover story of an [[1984 Incline Village chronic fatigue syndrome outbreak|epidemic at Lake Tahoe, Nevada]], in the mid-1980s.<ref name="Osler'sWeb">{{cite book|title=Osler's Web: inside the labyrinth of the chronic fatigue syndrome epidemic|last=Johnson|first=Hilary|publisher=Penguin Books|year=1996|isbn=0-595-34874-2|location=New York|pages=24}}</ref> The designation Chronic Epstein-Barr Virus was in use in the U.S.,<ref name="pmid2578266">{{cite journal|vauthors=Jones J, Ray C, Minnich L, Hicks M, Kibler R, Lucas D|year=1985|title=Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies|journal=Ann Intern Med|volume=102|issue=1|pages=1–7|doi=10.7326/0003-4819-102-1-|pmid=2578266}}</ref><ref name="pmid2578268">{{cite journal|vauthors=Straus S, Tosato G, Armstrong G, Lawley T, Preble O, Henle W, Davey R, Pearson G, Epstein J, Brus I|year=1985|title=Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection|journal=Ann Intern Med|volume=102|issue=1|pages=7–16|doi=10.7326/0003-4819-102-1-7|pmid=2578268}}</ref> but the magazine used the term "[[Raggedy Ann Syndrome]]" to note the fatigue and loss of muscle power patients felt.<ref name="Hippocrates">{{Cite journal|author=Day W|year=1987|title=Raggedy Ann syndrome|journal=Hippocrates|pages=July/August, cover story}}</ref>

Researchers investigating the Lake Tahoe cluster did not find evidence that EBV was involved, and they proposed the name ''[[chronic fatigue syndrome]]'', describing the main symptom of the illness.<ref name="isbn0-19-263049-0">{{cite book|url=https://books.google.com/books?id=_LqAIK616lgC&pg=PA14&lpg=PA14&dq=chronic+fatigue+syndrome+was+coined+in+1988+by+the+centers+for+disease+control|title=Chronic Fatigue Syndrome (CFS/ME): TheFacts|author1=Sharpe, Michael|author2=Frankie Campling|publisher=Oxford Press|year=2000|isbn=0-19-263049-0|location=Oxford|pages=14, 15|oclc=|accessdate=April 2, 2008}}</ref><ref name="isbn0801879426">{{cite book|title=Emerging Illnesses and Society|vauthors=Packard RM, Berkelman RL, Brown PJ, Frumkin H|publisher=JHU Press|year=2004|isbn=0-8018-7942-6|pages=[https://books.google.com/books?id=EGNFPZrKIKMC&pg=PA156&dq=cdc+lake+tahoe+1988 156]}}</ref> They published the first working case definition for CFS in 1988.<ref name="Holmes1988">{{cite journal|vauthors=Holmes G, Kaplan J, Gantz N, Komaroff A, Schonberger L, Straus S, Jones J, Dubois R, Cunningham-Rundles C, Pahwa S|year=1988|title=Chronic fatigue syndrome: a working case definition|journal=Ann Intern Med|volume=108|issue=3|pages=387–9|doi=10.7326/0003-4819-108-3-387|pmid=2829679}}</ref> Research increased considerably, and more so after the criteria were relaxed in 1994.<ref>{{cite journal|author=Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A; International Chronic Fatigue Syndrome Study Group|year=1994|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study|journal=Ann. Intern. Med.|volume=121|issue=12|pages=953–9|doi=10.7326/0003-4819-121-12-199412150-00009|pmid=7978722}}</ref>

In 1990, researchers presented evidence they found [[DNA]] sequences very similar to the human [[HTLV-II retrovirus]] in some CFS patients, at a conference in Kyoto, Japan.<ref name="DOI 10.1126">{{Cite journal|author=Palca J|date=September 14, 1990|title=Does a retrovirus explain fatigue syndrome puzzle?|url=http://www.sciencemag.org/cgi/pdf_extract/249/4974/1240|journal=Science|volume=249|issue=4974|pages=1240–12|bibcode=1990Sci...249.1240P|doi=10.1126/science.2399461|pmid=2399461}}</ref><ref name="NYT">{{cite news|url=https://query.nytimes.com/gst/fullpage.html?sec=health&res=9C0CE3DD1430F936A3575AC0A966958260|title=Virus found that may be linked to a debilitating fatigue ailment|last=Altman|first=Lawrence K.|date=September 5, 1990|work=The New York Times|accessdate=February 24, 2009}}</ref> Their study was later published in the Proceedings of the National Academy of Sciences.<ref name="pmid 1672770">{{cite journal|author=DeFreitas E|author2=Hilliard B|author3=Cheney PR|last4=Bell|first4=DS|last5=Kiggundu|first5=E|last6=Sankey|first6=D|last7=Wroblewska|first7=Z|last8=Palladino|first8=M|last9=Woodward|first9=JP|display-authors=3|date=April 1991|title=Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1672770|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=88|issue=7|pages=2922–6|bibcode=1991PNAS...88.2922D|doi=10.1073/pnas.88.7.2922|pmc=51352|pmid=1672770|name-list-format=vanc}}</ref> A reporter on Prime Time Live stated the announcement made headlines all over the world. The CDC first ignored their findings,<ref name="PTL">{{cite video|people=Sam Donaldson, Nancy Snyderman, Paul Cheney, David Bell, Elaine DeFreitas, Hillary Johnson, PWC's, Paul Pollard, Mrs. Dailor, Philip Lee|title=Sick & Tired|medium=Television|publisher=ABC News|url=http://abcnewsstore.go.com/webapp/wcs/stores/servlet/DSIProductDisplay?catalogId=11002&storeId=20051&productId=2013126&langId=-1&categoryId=100024|date=March 27, 1996}}</ref> then later conducted a study and published a paper that refuted the hypothesis.<ref name="Retroviral">{{cite journal|date=March 1993|title=Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00019881.htm|journal=[[Morbidity and Mortality Weekly Report]]|publisher=[[U.S. Centers for Disease Control and Prevention]] (CDC)|volume=42|issue=10|pages=183, 189–90|pmid=8446093|accessdate=February 23, 2009}}</ref>

In the United Kingdom, the Chief Medical Officer Kenneth Calman requested a report from the medical Royal Colleges in 1996. This led to the publication of a joint report in which the term "chronic fatigue syndrome" was found to be most representative.<ref>{{cite book|title=Chronic fatigue syndrome; Report of a joint working group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners|author=Royal Colleges of Physicians, Psychiatrists and General Practitioners|publisher=Royal College of Physicians of London|year=1996|isbn=1-86016-046-8|location=London, UK}}</ref> This was followed in 2002 by a further report by the new CMO, Liam Donaldson.<ref name="CMOrept2002">{{cite web|url=http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840|title=A report of the CFS/ME working group: report to the chief medical officer of an independent working group.|author=CFS/ME Working Group|year=2002|publisher=Department of Health|location=London}}</ref>

The U.S. [[Centers for Disease Control & Prevention]] (CDC) recognized CFS as a serious illness, and launched a campaign in June 2006 to raise public and medical awareness about it.<ref name="CDCBasic">{{cite web|url=https://www.cdc.gov/cfs/cfsbasicfacts.htm|title=Chronic fatigue syndrome basic facts|date=May 9, 2006|publisher=Centers for Disease Control and Prevention|accessdate=February 7, 2008}}</ref><ref name="CDC-awareness">{{cite web|url=https://www.cdc.gov/cfs/PSAs/Gerberding-launch.pdf|title=Address at CFS awareness campaign launch|last=Gerberding|date=June 7, 2008|publisher=Department of Health and Human Services. Centers for Disease Control and Prevention|format=pdf}}</ref>

== XMRV ==
A 2009 study published in the journal ''Science'' reported an association between a retrovirus [[wikipedia:Xenotropic_murine_leukemia_virus-related_virus|xenotropic murine leukemia virus-related virus]] (XMRV) and CFS. The editors of ''Science'' subsequently attached an "Editorial Expression of Concern" to the report to the effect that the validity of the study "''is now seriously in question"''.<ref>{{cite journal|author=Alberts B|year=2011|title=Editorial Expression of Concern|journal=Science|volume=333|issue=6038|page=35|bibcode=2011Sci...333...35A|doi=10.1126/science.1208542|pmid=21628391}}</ref> and in September 2011, the authors published a "Partial Retraction" of their 2009 findings;<ref name="pmid21940859">{{cite journal|author=Silverman RH, Das Gupta J, Lombardi VC, Ruscetti FW, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Mikovits JA|last2=Das Gupta|last3=Lombardi|last4=Ruscetti|last5=Pfost|last6=Hagen|last7=Peterson|last8=Ruscetti|last9=Bagni|date=September 2011|title=Partial Retraction|journal=Science|volume=334|issue=6053|pages=176|bibcode=2011Sci...334..176S|doi=10.1126/science.1212182|pmid=21940859|last10=Petrow-Sadowski|last11=Gold|last12=Dean|last13=Mikovits}}</ref> this was followed by a full retraction by the magazine’s Editor in Chief, after the authors failed to agree on a full retraction statement.<ref>{{cite journal|author=Alberts B|year=2011|title=Retraction|journal=Science|volume=334|issue=6063|page=1636|bibcode=2011Sci...334.1636A|doi=10.1126/science.334.6063.1636-a|pmid=22194552}}</ref> Also in September 2011, the Blood XMRV Scientific Research Working Group published a report, which concluded ''"that currently available XMRV/P-MLV assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from CFS patients and controls (2, 4), cannot reproducibly detect direct virus markers (RNA, DNA, or culture) or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive (all but one with a diagnosis of CFS) or healthy blood donors."''<ref>{{cite journal|author=Simmons G, Glynn SA, Komaroff AL, Mikovits JA, Tobler LH, Hackett J, Tang N, Switzer WM, Heneine W, Hewlett IK, Zhao J, Lo SC, Alter HJ, Linnen JM, Gao K, Coffin JM, Kearney MF, Ruscetti FW, Pfost MA, Bethel J, Kleinman S, Holmberg JA, Busch MP|last2=Glynn|last3=Komaroff|last4=Mikovits|last5=Tobler|last6=Hackett Jr|last7=Tang|last8=Switzer|last9=Heneine|year=2011|title=Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study|journal=Science|volume=334|issue=6057|pages=814–7|bibcode=2011Sci...334..814S|doi=10.1126/science.1213841|pmc=3299483|pmid=21940862|author24=Blood XMRV Scientific Research Working Group (SRWG)|last10=Hewlett|last11=Zhao|last12=Lo|last13=Alter|last14=Linnen|last15=Gao|last16=Coffin|last17=Kearney|last18=Ruscetti|last19=Pfost|last20=Bethel|last21=Kleinman|last22=Holmberg|last23=Busch}}</ref> In December 2011, the ''Proceedings of the [[wikipedia:National_Academy_of_Sciences|National Academy of Sciences]]'' published a similar retraction for an August 2010 paper.<ref>{{cite journal|author=Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R, Alter HJ|last2=Pripuzova|last3=Li|last4=Komaroff|last5=Hung|last6=Wang|last7=Alter|year=2011|title=Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors|journal=Proceedings of the National Academy of Sciences|volume=109|issue=1|page=346|bibcode=2012PNAS..109..346.|doi=10.1073/pnas.1119641109|pmc=3252929|pmid=22203980}}</ref> Some members of the patient community, who had viewed the XMRV findings as a source of hope for a possible cure, initially reacted negatively when the papers were called into question. One UK researcher reported verbal abuse after publishing an early paper indicating that the XMRV studies were flawed.<ref>{{cite web|url=https://www.theguardian.com/society/2011/aug/21/chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Chronic fatigue syndrome researchers face death threats from militants|date=2011-08-21|accessdate=2014-02-02|newspaper=The Guardian}}</ref>

== Institute of Medicine Report ==
{{Main article | page_name =Institute of Medicine report}}

February 15, 2015, The [[National Academy of Medicine]] (known as the [[Institute of Medicine]] or [[IOM]] until June 2015) published a report on ME/CFS, ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness''<ref name="IOM2015MECFS">{{citation
| last1 = Institute of Medicine (USA)
| last2 = Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| display-authors =
| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| date = 10 February 2015
| url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
}}</ref> proposing a new name – [[systemic exertion intolerance disease]] – and a new diagnostic criteria. It has since influenced government policy on the disease in the United States and around the world.{{Citation needed}}

The proposed name proved to be highly unpopular and has not been widely adopted by government agencies or researchers and proposed criteria captured an overlapping but different subset of patients than stricter criteria like the [[International Consensus Criteria]] or the [[Canadian Consensus Criteria]]. Despite some positive impacts, its recommendations have remained controversial among many patients and advocacy groups.

== See also ==

* [[Epidemic myalgic encephalomyelitis]]
* [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]

== References ==
<references />

Epidemic myalgic encephalomyelitis

2018-08-18T00:19:44Z

Bill:fix main template

[[File:Nurses at the Los Angeles County Hospital, 1934.png|thumb|400x400px|Nurses who became ill during an [[1934 Los Angeles atypical polio outbreak|outbreak of "atypical polio"]] at the Los Angeles County Hospital in 1934.]]
There have been [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|at least 75 documented outbreaks]] of [[myalgic encephalomyelitis]] and [[chronic fatigue syndrome]] since the 1930s. The true number of clusters and outbreaks is likely much higher. Many of these outbreaks occurred in institutions like hospitals and schools, and frequently coincided with outbreaks of [[poliomyelitis]].

The first recorded outbreak of epidemic was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and the most recent putative outbreak was in Arizona in 1996.

Prior to the 1980s, while no infectious was ever isolated, the outbreaks were widely thought to be caused by an virus related to [[poliovirus]], i.e., by another, yet-to-be-unidentified [[enterovirus]]. After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village outbreak]] in 1984, [[herpesviruses]] and in particular, [[Epstein-Barr virus]] was posited as the cause.
==History==
{{Main article|page_name =List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks}}

The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical polio. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called "Akureyri Disease" or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

== Onset ==
The incubation period was generally estimated at 4 to 8 days.<ref name=":4" /><ref name=":0" /><ref name=":6">{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/13320872|title=The Lancet|last=Sigurdsson|first=B|date=May 1956|journal=Clinical findings six years after outbreak of Akureyri disease|volume=270|pages=766-7|via=}}</ref> The illness generally began with a prodromal period of flu-like symptoms, symptoms of an [[upper respiratory tract infection]], low-grade fever, [[sore throat]] or [[Gastrointestinal system|gastrointestinal]] distress<ref name=":7" /><ref name=":11" /><ref name=":5" />, followed by a symptom complex involving [[muscle weakness]], [[muscle fatiguability]] and [[central nervous system]] involvement in a significant proportion of cases.<ref name=":0" /><ref name="Shelokov, 1957" />

== Symptoms ==
Reported symptoms could vary considerably from outbreak to outbreak. Common symptoms included:

* [[muscle fatigability|muscle fatiguability]]
* [[muscle weakness]] / [[paresis]]<ref name=":8">{{Cite journal|url=http://journals.co.za/content/m_samj/31/21/AJA20785135_45533|title=A disease resembling poliomyelitis; report of an outbreak in Johannesburg|last=Jackson|first=B|date=May 1957|journal=South African Medical Journal|volume=31|pages=514 - 517|via=}}</ref><ref name=":9">{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/13642847|title=Epidemic myalgic encephalomyelopathy: the Durban outbreak|last=Hill|first=RC|date=April 4, 1959|journal=The Lancet|volume=1|pages=689-693|via=}}</ref> (10-80%<ref name="Acheson, 1959" /> of cases), commonly occurring in the legs<ref name=":6" /><ref name=":7">Dr R.A. Pellew, [http://www.cabdirect.org/abstracts/19522700678.html;jsessionid=AA4534CA199AC800732B3877608F5CE0 "A Clinical Description of a Disease resembling Poliomyelitis, seen in Adelaide, 1949-1951"] ''Medical Journal of Australia'', Medical Journal of Australia 1951, June 30 Vol. 1 No. 26 pp. 944-6</ref>
* ataxia
* [[myalgia]]<ref name=":6" /><ref name=":8" /> and [[neuralgia]]
* severe [[headache]]<ref name=":7" /><ref name=":8" /><ref name=":9" />
* stiffness of the neck and spine<ref name=":6" /><ref name=":7" /><ref name=":8" /><ref name=":9" />
* tender lymph nodes, spleen and/or liver
* cognitive symptoms including impaired memory<ref name=":6" /> and concentration<ref name=":9" />
* sleep disturbances<ref name=":9" />
* sensory symptoms including sensitivity to [[Photophobia|light]] and sound, [[Paresthesia|paraesthesiae]]<ref name=":6" /><ref name=":8" /><ref name=":9" />, [[hyperaesthesiae]]
* autonomic symptoms such as tachychardia, coldness of the extremities, sweating
* [[post-exertional malaise]], worsening of symptoms with exertion<ref name=":6" /><ref name="Shelokov, 1957" /><ref name=":9" /><ref name=":1">{{Cite journal|last=Albrecht|first=Robert|date=March 21, 1964|title=Epidemic Neuromyasthenia Outbreak in a Convent in New York State|url=https://www.ncbi.nlm.nih.gov/pubmed/14100144|journal=Journal of the American Medical Association|volume=187|pages=904-907|via=}}</ref><ref name="Poskanzer, 19572" />("fatigue on walking short distances and on the least exertion was prominent"<ref name=":0" />)

== Findings ==

Findings varied considerably based on the technology of the time and what tests physicians attending to these outbreaks chose or were able to run:

* Low-grade [[fever]]<ref name=":6" /><ref name=":8" /><ref name=":1" /><ref name=":9" />
* Abnormal [[electromyogram]] showing generalized, mild, lower motor neuron changes indicative of a [[radiculopathy]]
* Muscle weakness measured via quantitative muscular-testing<ref name="Shelokov, 1957">{{Citation
| last1 = Shelokov | first1 = Alexis | authorlink1 =
| last2 = Habel | first2 = Karl | authorlink2 =
| last3 = Verder | first3 = Elizabeth | authorlink3 =
| last4 = Welsh | first4 = William | authorlink4 =
| title = Epidemic Neuromyasthenia — An Outbreak of Poliomyelitis-like Illness in Student Nurses
| journal = New England Journal of Medicine | volume = 1957 | issue = 257 | page = 345-355
| date = August 1957
| doi = 10.1056/NEJM195708222570801
}}</ref>
* Normal or minimal [[cerebrospinal fluid]] findings<ref name=":6" /><ref name="Shelokov, 1957" /><ref name=":9" /><ref>{{Cite journal|url=https://www.sciencedirect.com/science/article/pii/S0033350657800225|title=Encephalomyelitis simulating poliomyelitis|last=Ramsay|first=Melvin|date=May 26, 1956|journal=The Lancet|volume=270|pages=761-764|via=|last2=O'Sullivan|first2=E}}</ref>
* Normal or mildly increased [[erythrocyte sedimentation rate]]<ref name=":8" /><ref name=":9" /><ref name=":11" />
* Mild increase in white blood cell count<ref name=":9" />
* [[Autonomic nervous system]] dysfunction, [[Hypothalamus|hypothalamic]] dysfunction
* [[Postural orthostatic tachycardia syndrome|Orthostatic tachycardia]]<ref name=":9" />
* Ulnar neuritis, neuropathy or lesion<ref name=":4" /><ref>{{Cite journal|last=Levine|first=PH|date=January 1994|title=Epidemic neuromyasthenia and chronic fatigue syndrome: epidemiological importance of a cluster definition|url=https://www.ncbi.nlm.nih.gov/pubmed/8148446|journal=Clinical Infectious Diseases|volume=18|pages=S16-20|via=}}</ref><ref name=":2">{{Cite journal|last=White|first=D|last2=Burtch|first2=Robert|date=July 1, 1954|title=Iceland Disease: A New Infection Simulating Acute Anterior Poliomyelitis|url=http://n.neurology.org/content/4/7/506.short|journal=Neurology|volume=4|pages=|via=}}</ref>
* Microscopic infiltration of nerve roots with [[lymphocytes]] and [[Mononuclear cell|mononuclear cells]]; patchy damage to the myelin sheaths and axon swellings (in monkeys infected with unidentified virus from the [[1949-53 Adelaide outbreak|Adelaide]] outbreak)
* Raised urinary [[creatine]] excretion<ref name=":1" /><ref name=":2" />
* abnormally high [[lactic dehydrogenase]] and [[glutamic oxaloacetic transaminase]]<ref name=":11" />

In the majority of early epidemics, no viral or bacterial infectious agent was successfully cultured.<ref name=":6" /><ref name=":8" /><ref name=":9" /> In a small number of epidemics [[Coxsackie B]]<ref name="Fegan1983">{{Citation
| last1 = Fegan | first1 = KG | authorlink1 = KG Fegan
| last2 = Behan | first2 = PO | authorlink2 = Peter Behan
| last3 = Bell | first3 = EJ | authorlink3 = Eleanor Bell
| title = Myalgic encephalomyelitis — report of an epidemic
| journal = J R Coll Gen Pract | volume = 33| issue = 251| pages = 335–337
| date = 1 Jun 1983
| pmid = 6310104
| url = http://bjgp.org/content/33/251/335
}}</ref><ref name="Calder1984">{{Citation
| last1 = Calder | first1 = BD | authorlink1 = BD Calder
| last2 = Warnock | first2 = PJ | authorlink2 = PJ Warnock
| title = Coxsackie B infection in a Scottish general practice
| journal = Jrnl Royal Coll Gen Pract | volume = 34| issue = 258| pages = 15–19
| date = Jan 1984
| pmid = 6319691
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/
}}</ref> or [[Bethesda-Ballerup paracolon organism]]<ref name="Shelokov, 1957" /> were found, although the latter was found . In others, infection of animal models with samples from patients results in identifiable nervous system damage on autopsy and in one case, [[myocarditis]], in spite of being unable to identify the agent.<ref name=":0" /><ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/13272481|title=Further Investigations on a Disease Resembling Poliomyelitis Seen in Adelaide|last=Pellew|first=R.A.A.|date=September 24, 1955|journal=The Medical Journal of Australia|volume=2|pages=480-2|via=}}</ref>

==Epidemiology==
Many of these outbreaks occurred at institutions for example, hospitals<ref name="Shelokov, 1957" /><ref name="Gilliam, 1936-38" /><ref name=":9" />, schools, army bases or convents. The pattern of spread suggested a highly infectious agent that spread person to person, rather than through contaminated food or drink or exposure to a single toxic agent.<ref name=":0">{{Cite journal|last=Parish|first=JG|date=1978|title=Early outbreaks of 'epidemic neuromyasthenia'|url=https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54|pages=711-7|via=}}</ref><ref name="Gilliam, 1936-38">{{Citation
| last1 = Gilliam | first1 = A.G. | authorlink1 =
| title = Epidemiological Study Of An Epidemic, Diagnosed As Poliomyelitis, Occurring Among The Personnel Of The Los Angeles County General Hospital During The Summer Of 1934
| journal = Public health bulletin, 1936-1938 | volume = no.231-240 | issue = | page =
| date = 1938
| pmid =
| url = http://babel.hathitrust.org/cgi/pt?id=mdp.39015022082260;view=1up;seq=617
}}</ref><ref name="Poskanzer, 19572" /><ref name=":9" />

Outbreaks tended to begin in the summer months, with most initial cases reported from April to September in the Northern hemisphere, October to March in the Southern hemisphere.<ref name="Acheson, 1959" /><ref name=":9" />

In outbreaks involving both medical personnel and the general community, medical personnel had a higher attack rate and/or greater central nervous system involvement.<ref name="Poskanzer, 19572" /> A similar pattern was seen in hospital outbreaks, where those in roles that involved more frequent or intimate contact with patients or those working in an infectious disease ward were more affected than other hospital staff.<ref name=":0" /><ref name="Gilliam, 1936-38" /> A large proportion of recorded outbreaks have taken place in hospital settings.<ref name="Acheson, 1959" />

In many outbreaks including [[1934 Los Angeles atypical polio outbreak|Los Angeles]], [[Akureyri]], [[1953 Maryland outbreak|Rockville, MD]], [[1955 Royal Free Hospital outbreak|Royal Free Hospital]], and [[1956 Punta Gorda outbreak|Punta Gorda, Florida]], women were affected at higher rates.<ref name=":4" /><ref name=":0" /><ref name="Shelokov, 1957" /><ref name="Gilliam, 1936-38" /><ref name="Acheson, 1959">{{Citation
| last1 = Acheson | first1 = E.D. | authorlink1 =
| title = The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia
| journal = American Journal of Medicine | volume = 26 | issue = 4 | page = 569–595
| date = 1959
| pmid =
| url = http://www.name-us.org/defintionspages/DefinitionsArticles/Acheson1959.pdf
}}</ref><ref name="Poskanzer, 1957">{{Citation
| last1 = Poskanzer | first1 = David C. | authorlink1 =
| last2 = Henderson | first2 = Donald A. | authorlink2 =
| last3 = Kunkle | first3 = E. Charles | authorlink3 =
| last4 = Kalter | first4 = Seymour S. | authorlink4 =
| last5 = Clement | first5 = Walter B. | authorlink5 =
| last6 = Bond | first6 = James O. | authorlink6 =
| title = Epidemic Neuromyasthenia — An Outbreak in Punta Gorda, Florida
| journal = New England Journal of Medicine | volume = 1957 | issue = 257 | page = 356-364
| date = 1957
| pmid = 13464939
| doi = 10.1056/NEJM195708222570802
| url = http://www.nejm.org/doi/full/10.1056/NEJM195708222570802
}}</ref><ref name=":3" /><ref name=":5">Levine PH, Snow PG, Ranum BA, Paul C, Holmes MJ. (1997). Epidemic neuromyasthenia and chronic fatigue syndrome in west Otago, New Zealand. A 10-year follow-up. ''Archives of Internal Medicine, 157''(7), 750-754. doi:10.1001/archinte.157.7.750 Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9125006 on 17 Jul 2016</ref><ref name=":8" /> In other outbreaks, including the 1949-1953 [[1949-53 Adelaide outbreak|Adelaide]] outbreak and an outbreak in [[1955 North of England outbreak|northern England in 1955]], a 1:1 gender ratio was reported.<ref name=":0" /><ref name=":5" /> In hospital epidemics, young female nurses were disproportionately affected, but this may have been due to risk factors like higher repeated exposure to the same infection during an epidemic<ref name=":0" /> and in some outbreaks, gender-segregated living quarters.<ref name=":3">[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital]</ref> However, the higher ratio of women were also reported in outbreaks in the general population.<ref name="Acheson, 1959" /> In Akureyri, while the incidence among adults was higher for females, there was no significant difference in incidence between sexes among those under twenty.<ref name=":4">{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/14771044|title=A disease epidemic in Iceland simulating poliomyelitis|last=Sigurdsson|first=B|date=September 1950|journal=American Journal of Hygiene|volume=52|pages=222-38|via=}}</ref> This comports with patterns of age and sex distribution in sporadic cases.{{Citation needed}}

In most outbreaks, those most affected tended to be adults in their twenties,<ref name=":0" /><ref name="Gilliam, 1936-38" /><ref name=":1" /><ref name=":9" /> although cases of young children and adults as old as 80 have been recorded in outbreaks.<ref name="Acheson, 1959" /> In Akureyri, the highest attack rate was among ages 15-19.<ref name=":6" />

Melvin Ramsay observed an absence of cases among sedentary people, and postulated that this might explain why hospital staff frequently became affected, while patients in hospital rarely did.<ref name=":11">{{Cite journal|last=Ramsay|first=A. Melvin|date=November 1978|title='Epidemic neuromyasthenia' 1955-1978|url=https://www.ncbi.nlm.nih.gov/pubmed/746017|journal=Postgraduate Medical Journal|volume=54|pages=718-721|via=}}</ref>

{| class="wikitable"
!Outbreak
!Type
!Peak months
!Percent female
!Most affected age group
!Attack rate
|-
|[[1934 Los Angeles atypical polio outbreak|1934 Los Angeles]]
|Institution
|May to December
|75%
|< 30 years
|4.5%
|-
|[[1937 Erstfeld outbreak|1937 Erstfeld]]
|Institution
|July
|NA (all male soldier)
|
|14%
|-
|[[1948-49 Akureyri outbreak|1948-49 Akureyri]]
|Community
|Winter
|50% (< age 20), 70% ( > age 20) <ref name=":6" />
|15-19 years<ref name=":6" />
|6.7% (town), 0.8% (rural)<ref name=":6" />
|-
|[[1949-53 Adelaide outbreak|1949-53 Adelaide]]
|Community
|Winter (August)
|50%
|
|
|-
|[[1950 Louisville outbreak|1950 Louisville]]
|Institution
|October
|NA (mainly female nurses)
|
|23%
|-
|[[1953 Maryland outbreak|1953 Maryland]]
|Institution
|July
|NA (mainly female nurses)
|
|13.7%
|-
|[[1954 Johannesburg outbreak|1954 Johannesburg]]
|Community
|August to March
|72%<ref name=":8" />
|
|
|-
|[[1955 Dalston outbreak|1955 Dalston]]
|Community
|January
|50%<ref name=":10">{{Cite book|title=An investigation into an unusual disease seen in epidemic and sporadic form in a general practice in Cumberland in 1955 and subsequent years, M.D. Thesis|last=Wallis|first=A. L.|publisher=University of Edinburgh|year=1957|isbn=|location=|pages=}}</ref>
|
|13.9%<ref name=":10" />
|-
|[[1955 Durban outbreak|1955 Durban]]
|Institution
|late summer (February)
|NA (mainly female nurses)
|< 25 years
|
|-
|[[1955 Royal Free Hospital outbreak|1955 London]]
|Institution
|July to November
|
|
|
|-
|[[1956 Punta Gorda outbreak|1956 Punta Gorda]]
|Mixed
|mid-March to June
|74%<ref name="Poskanzer, 19572" />
|20-49 years<ref name="Poskanzer, 19572" />
|6.1%<ref name="Poskanzer, 19572" /> (community), 42% (hospital)
|-
|[[1961 New York State outbreak|1961 New York State]]
|Institution
|July to January
|NA (all female nuns)
|< 30 years
|37.7%
|}

== Pathophysiology ==
Due to paucity of objective findings, very little was known about the [[pathophysiology]] of the disease. Several investigators postulated damage to the [[hypothalamus]]<ref name=":11" /> owing to the symptoms of orthostatic tachycardia, abnormal glucose regulation, circulatory impairment, and problems with temperature regulation.

== Prognosis ==

Although many patients improved over time, in follow-up studies, a large percentage were still ill months to years later. Many case studies note long periods of convalescence with relapses following exertion<ref name=":6" /><ref name="Shelokov, 1957" /><ref name=":9" /><ref name=":1" /><ref name="Poskanzer, 19572">{{Citation
| last1 = Poskanzer | first1 = David C. | authorlink1 =
| last2 = Henderson | first2 = Donald A. | authorlink2 =
| last3 = Kunkle | first3 = E. Charles | authorlink3 =
| last4 = Kalter | first4 = Seymour S. | authorlink4 =
| last5 = Clement | first5 = Walter B. | authorlink5 =
| last6 = Bond | first6 = James O. | authorlink6 =
| title = Epidemic Neuromyasthenia — An Outbreak in Punta Gorda, Florida
| journal = New England Journal of Medicine | volume = 1957 | issue = 257 | page = 356-364
| date = 1957
| pmid = 13464939
| doi = 10.1056/NEJM195708222570802
| url = http://www.nejm.org/doi/full/10.1056/NEJM195708222570802
}}</ref> or before or during [[Menstrual cycle|menstrual periods]].<ref name="Shelokov, 1957" /><ref name=":1" /><ref name="Poskanzer, 19572" />

{| class="wikitable"
!Outbreak
!Time after outbreak
!Subjective recovery rate
!Objective recovery rate
|-
|[[1948-49 Akureyri outbreak]]
|7 years
|13%<ref name=":6" />
|31%<ref name=":6" />
|-
|[[1953 Maryland outbreak]]
|5 months
|0%<ref name="Shelokov, 1957" />
|
|-
|[[1955 Durban outbreak]]
|3 years
|
|89%*<ref name=":9" />
|-
|[[1961 New York State outbreak]]
|1 year
|
|35%<ref name=":1" />
|}
<nowiki>*</nowiki>Follow-up was with those patients considered disabled. Others may have been more mildly affected.

==Relationship to polio==
Prior to the poliovirus vaccine, several [[outbreaks]] of what later came to be called [[myalgic encephalomyelitis]] coincided with confirmed outbreaks of [[poliomyelitis]] including the [[1934 Los Angeles atypical polio outbreak|1934 Los Angeles outbreak]], the [[1948-49 Akureyri outbreak|1948 Akureyri, Iceland outbreak]], and 1949 outbreak in [[1949-53 Adelaide outbreak|Adelaide, Australia]].<ref name=":7" /> Many outbreaks were initially misinterpreted as clusters of [[poliomyelitis]] or [[abortive poliomyelitis]], hence one of [[ME]]'s earliest names, [[atypical polio]]. It is not known whether there is a direct relationship between polio outbreaks and ME or if outbreaks of ME were more likely to be reported when public health authorities were already mobilized for an earlier crisis.

No serological evidence of polio was ever found in these outbreaks and the ultimate pattern of the outbreaks differed in significant ways, chief among them the higher attack rate, the tendency to affect adults rather than children, and the higher [[morbidity]] than poliomyelitis but no [[mortality]].<ref name=":0" /><ref name="Acheson, 1959" /> Findings in several outbreaks seemed to suggest that symptoms were caused by an [[enterovirus]] distinct from but related to polio: findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio, i.e., the rise in cases during summer months.<ref name=":0" /><ref name="Acheson, 1959" />

There is indirect evidence of cross-immunity between [[poliovirus]] and the unidentified virus or viruses in epidemic myalgic encephalomyelitis outbreaks. After the Akureyri outbreak, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to the poliovirus.<ref name=":0" /><ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/13515219|title=Response to poliomyelitis vaccination|last=Sigurdsson|first=B|date=February 15, 1958|journal=The Lancet|volume=1|pages=370-1|via=}}</ref> During the [[1949-53 Adelaide outbreak|outbreak in Adelaide]], cases of classic poliomyelitis dropped by 43%.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542300/ "Poliomyelitis in 1953"] ''Bulletin of the World Health Organization.'' 1955;12(4):595-649.</ref>

== Controversy ==
In 1970, a paper by Colin P. McEvedy and AW Beard claimed that the [[1955 Royal Free Hospital outbreak]] was actually [[mass hysteria]].<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700894/ Royal Free epidemic of 1955: a reconsideration. 1970 PubMed.gov]</ref><ref>[https://www.telegraph.co.uk/news/health/12033810/Its-time-for-doctors-to-apologise-to-their-ME-patients.html It’s time for doctors to apologise to their ME patients by Dr. Charles Shepherd - The Telegraph]</ref>

== Outbreaks of the 1980s and 1990s ==
The case reports of the 1980s and 1990s differed substantially from those of earlier decades. Whereas reports from the 1930s-1960s focused heavily on neurological and muscle symptoms and findings, and compared and contrasted the disease to poliomyelitis, reports of the 1980s focused far more heavily on fatigue and the possible relationship to [[herpesviruses]].

== See also ==

* [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks]]
* [[Enterovirus]]
* [[Non-cytolytic enterovirus]]

== Learn more==

*"[https://www.newyorker.com/magazine/1965/11/27/in-the-bughouse In the Bughouse]," ''The New Yorker'' by Berton Roueché.
*[https://www.amazon.com/Oslers-Web-Labyrinth-Syndrome-Epidemic/dp/0595348742 ''Osler's Web''] by Hillary Johnson

== References ==
<references />
[[Category:Outbreaks]]

Thyroid gland

2018-08-18T00:19:21Z

Bill:fix main template

The '''thyroid''' is an [[endocrine]] gland in the neck. It secretes [[thyroid hormones]], which regulate the body's rate of [[metabolism]], and calcitonin, a protein that assists in calcium balance. The production of thyroid hormones is stimulated by [[thyrotropin]] or Thyroid Stimulating Hormone (TSH), which is produced by the [[pituitary]].

==Types of thyroid hormones==
{{Main article|page_name =Thyroid hormones}}

[[Triiodothyronine]] and [[thyroxine]] are the two main forms of [[thyroid hormones]]. Thyroid hormones are partially comprised of [[iodine]] and a deficiency of [[iodine]] in the diet can lead to decreased production of these hormones. If left uncorrected the thyroid tissue can enlarge, resulting in a pronounced swelling in the neck, called a 'simple goitre.'<ref>https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024712/</ref>

==Notable studies==
*2018, Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study<ref name="Ruiz-Núñez, 2018"/> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869352/ Full Text)]

==Learn more==
*[https://www.thyroid.org/ American Thyroid Association webpage]

==See also==
*[[Thyroid disease]]
*[[Thyroid hormones]]
*[[Hormones]]
*[[:Category:Hormones|List of hormones]]
*[[Triiodothyronine]]
*[[Thyroxine]]
*[[Thyroid-stimulating hormone]]

==References==
<references>
<ref name="Ruiz-Núñez, 2018">
{{Citation
| last1 = Ruiz-Núñez | first1 = Begoña | authorlink1 =
| last2 = Tarasse | first2 = Rabab | authorlink2 =
| last3 = Vogelaar | first3 = Emar F. | authorlink3 =
| last4 = Janneke Dijck-Brouwer | first4 = D. A. | authorlink4 =
| last5 = Muskiet | first5 = Frits A. J. | authorlink5 =
| title = Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study
| journal = Frontiers in Endocrinology | volume = 9 | issue = | page = 97
| date = 2018
| pmid = 29615976
| doi = 10.3389/fendo.2018.00097
}}
</ref>
</references>
[[Category:Body systems]]
[[Category:Endocrine system]]

Thyroid hormone

2018-08-18T00:19:11Z

Bill:fix main template

'''Thyroid hormones''' are a group of [[hormones]] produced and released by the [[thyroid gland]], namely [[triiodothyronine]] (T3) and [[thyroxine]] (T4). They are primarily responsible for regulation of metabolism, and thus act on nearly every cell in the body.

Thyroid hormone production is regulated by the [[pituitary gland]], which releases [[thyroid stimulating hormone]] (TSH).

Over production of thyroid hormones ([[hyperthyroidism]]) can accelerate your body's metabolism causing sudden weight loss, a rapid or irregular heartbeat, sweating, nervousness or irritability, and other symptoms.<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/hyperthyroidism/symptoms-causes/syc-20373659|title=Hyperthyroidism - Symptoms and causes|work=Mayo Clinic|access-date=2018-07-31|language=en}}</ref> Under production of thyroid hormones ([[hypothyroidism]]) can lower your body's metabolism causing obesity, fatigue, muscle weakness, thinning hair, slowed heart rate, depression and other symptoms.<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/hypothyroidism/symptoms-causes/syc-20350284|title=Hypothyroidism - Symptoms and causes|work=Mayo Clinic|access-date=2018-07-31|language=en}}</ref>

==Types of thyroid hormones==

===Thyroxine (T4) (90%)===

[[Thyroxine]] (abbreviated as [[T4]]) accounts for 90% of the hormone produced by the thyroid gland. It is physiological inactive and must be converted to T3 in the liver and kidneys.

===Triiodothyronine (T3) (9%)===

[[Triiodothyronine]] (abbreviated as [[T3]]) is the active form of the hormone. Only 9% of the thyroid hormone produced by the thyroid glad is T3. The rest of the physiologically required T3 is converted from T4 within liver and kidney cells by [[deiodinases]], which are [[selenium]]-dependent enzymes. Selenium sufficiency is therefore important for the proper conversion of T4 to T3. Genetic differences can deiodinase production and therefore conversion ability.

===Reverse T3 (rT3) (0.9%) ===
Reverse T3 is an isomer of T3, that is it has the same chemical formula but a different shape and is physiologically inactive. It is also made from T4 and plays a role in [[euthyroid sick syndrome]], where rT3 levels are elevated in presence of normal T4 and TSH levels.

===Diiodothyronine (T2) ===
The physiological functions of [[diiodothyronine]] (T2), including [[3,5-diiodo-L-thyronine]], are less well-understood.

== Production ==

=== Central ===

=== Peripheral ===
T4 is a [[prohormone]] and a reservoir for the biologically active T3. T<sub>4</sub> is converted to T3 by deiodinase enzymes.

There are three types of deiodinase enzymes:

* '''Type 1 (D1)''' deiodinates T4 to the biologically active T3 as well as the hormonally inactive and possibly inhibitory rT3. Breaks down rT3 into T2. Encoded by ''DIO1'' gene''.'' In humans, it is found in liver, kidney, thyroid, and pituitary.<ref name=":0">{{Cite journal|last=Medici|first=Marco|date=March 2017|title=Genetics of thyroid function|url=https://www-sciencedirect-com/science/article/pii/S1521690X17300301|journal=Best Practice & Research Clinical Endocrinology & Metabolism|volume=31|pages=129-142|via=}}</ref>
* '''Type 2 (D2)''' converts T4 into T3, and breaks down rT3 into T2. Encoded by ''DIO2'' gene''.'' In humans, it is found in skeletal muscle, central nervous system, pituitary, thyroid, heart, and brown adipose tissue.<ref name=":0" />
* '''Type 3 (D3)''' produces rT3 from T4, and breaks down T3 into T2. Encoded by ''DIO3'' gene''.'' In humans, it has been found in the central nervous system and placenta in adults and in many additional tissues in the fetus.<ref name=":0" />

=== Genetic factors ===
It is estimated that 40–65% of the inter-individual variation in serum TSH and FT4 levels is determined by genetic factors.<ref name=":0" /> Genetic factors may influence individual variation in the ability to convert T4 to T3. Several SNPs of the ''[[DIO1]]'' gene'','' which encodes for the D1 enzyme, and ''[[DIO2]]'' gene, which encodes for the D2 enzyme, have been studied.

==== D1O1 ====
'''rs2235544''': The homozygous mutant allele (C:C) is associated decreased deiodinase function, resulting in a lower FT3/FT4 ratio, lower T3 and high T4 compared to wild type.<ref name=":0" /><ref>{{Cite journal|last=Panicker|first=V|date=August 2008|title=A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine|url=https://www.ncbi.nlm.nih.gov/pubmed/18492748?dopt=Abstract|journal=Journal of Clinical Endocrinology Metabolism|volume=93|pages=3075-81|via=}}</ref>

==== D2O2 ====
'''rs225014''': Also known as [[Thr92Ala]], represents a variant in the deiodinase, iodothyronine, type II DIO2 gene on chromosome 14. A study of 102 patients pre- and post- total thyroidectomy showed that after receiving T4-only hormone replacement, 34% of patients had lower reduced Free T3 levels (FT3) than they had pre-surgery. Those with [[mutant]] alleles of [[Thr92Ala]] had lower levels of Free T3 hormone than [[wild type]] (Thr/Thr) / (T;T) patients. The percentage of reduced post-surgery FT3 levels was directly correlated with the presence and severity of the polymorphism: 58.3% in homozygous (Ala/Ala) / (C;C) patients vs 36.5% in heterozygous (Thr/Ala) / (T;C) subjects.<ref>{{Cite journal|last=Castagna|first=Maria|date=May 2017|title=DIO2 Thr92Ala Reduces Deiodinase-2 Activity and Serum-T3 Levels in Thyroid-Deficient Patients|url=https://academic.oup.com/jcem/article/102/5/1623/2966904|journal=The Journal of Clinical Endocrinology & Metabolism|volume=102|pages=1623–1630|via=}}</ref>

'''rs12885300:''' In a study of patients after thyroidectomy, patients with appeared to have an "have an altered set point of the hypothalamus-pituitary-thyroid axis" with a weaker negative feedback of FT4 on TSH in patients with homozygous mutant alleles (C;C).<ref>{{Cite journal|last=Hoftijzer|first=HC|date=September 2011|title=The type 2 deiodinase ORFa-Gly3Asp polymorphism (rs12885300) influences the set point of the hypothalamus-pituitary-thyroid axis in patients treated for differentiated thyroid carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/21715540?dopt=Abstract|journal=Journal of Clinical Endocrinology and Metabolism|volume=96|pages=1527-33|via=}}</ref>

== Transport ==
Thyroxine binding globulin is a transport protein responsible for carrying T4 and T3 in the bloodstream.
== Function and metabolic effects ==

Thyroid hormones are essential for regulating a number of biological processes, including growth, neurodevelopment, carbohydrate metabolism, oxygen consumption and protein synthesis.

=== Mitochondrial function ===
T3 plays an important role in the regulation of [[Mitochondria|mitochondrial]] function as well as in [[mitochondrial biogenesis]]<ref>{{Cite journal|last=Weitzel|first=Joachim|date=May 4, 2004|title=Regulation of Mitochondrial Biogenesis by Thyroid Hormone|url=https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/eph8802506|journal=Experimental Physiology|volume=|pages=|via=}}</ref>. T3 rapidly stimulates an increase in [[cellular respiration]] within minutes to hours after hormone treatment. One to several days after hormone treatment, changes in gene expression as well as direct binding of hormone to receptors induces mitochondrial biogenesis and changes to mitochondrial mass. T3 stimulates the expression of an inner membrane mitochondrial protein called [[uncoupling protein]], resulting in increased inner membrane proton leak. It also induces changes in phospholipid turnover. [[Adenosine triphosphate|ATP]] synthesis and turnover reactions are also affected.<ref>{{Cite journal|last=Harper|first=ME|last2=Seifert|first2=EL|date=February 2008|title=Thyroid hormone effects on mitochondrial energetics|url=https://www.ncbi.nlm.nih.gov/pubmed/18279015|journal=Thyroid|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Wrutniak-Cabello|first=C|date=February 2001|title=Thyroid Hormone action in mitochondria|url=https://www.ncbi.nlm.nih.gov/pubmed/11174855|journal=Journal of Molecular Endocrinology|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Cioffi|first=Frederica|date=15 October 2013|title=Thyroid hormones and mitochondria: With a brief look at derivatives and analogues|url=https://www.sciencedirect.com/science/article/pii/S030372071300244X|journal=Molecular and Cellular Endocrinology|volume=379|pages=51-61|via=}}</ref>

Uncoupling protein is responsible for [[thermogenesis]], which is why [[hyperthyroidism]] results in excess heat while [[hypothyroidism]] results in cold intolerance.

=== Citric acid cycle ===
T3 increases [[oxygen]]<ref>{{Cite journal|last=Bray|first=G.A.|date=August 1, 1969|title=Effect of diet and triiodothyronine on the activity of sn-glycerol-3-phosphate dehydrogenase and on the metabolism of glucose and pyruvate by adipose tissue of obese patients|url=https://www.jci.org/articles/view/106107|journal=The Journal of Clinical Investigation|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Bray|first=G.A.|date=August 1971|title=Effects of Triiodothyronine, Growth Hormone and Anabolic Steroids on Nitrogen Excretion and Oxygen Consumption of Obese Patients|url=https://academic.oup.com/jcem/article-abstract/33/2/293/2716425|journal=The Journal of Clinical Endocrinology & Metabolism|volume=33|pages=293–300|via=}}</ref><ref>{{Cite journal|last=Oh|first=Soomee|date=December 1, 1994|title=Early Treatment of Obese (ob/ob) Mice with Triiodothyronine Increases Oxygen Consumption and Temperature and Decreases Body Fat Content|url=http://journals.sagepub.com/doi/abs/10.3181/00379727-207-43814|journal=Experimental Biology and Medicine|volume=207|pages=260-267|via=}}</ref>, [[glucose]] and [[pyruvate]]<ref>{{Cite journal|last=Paradise|first=Giuseppe|date=August 17, 1988|title=Effect of hyperthyroidism on the transport of pyruvate in rat-heart mitochondria|url=https://www.sciencedirect.com/science/article/pii/0005272888901107|journal=Biochimica et Biophysica Acta (BBA) - Bioenergetics|volume=935|pages=79-86|via=}}</ref><ref>{{Cite journal|last=Leary|first=DC|date=October 1996|title=Direct Effects of 3, 5, 3′-Triiodothyronine and 3, 5-Diiodothyronine on Mitochondrial Metabolism in the GoldfishCarassius auratus|url=https://www.sciencedirect.com/science/article/pii/S0016648096901410|journal=General and Comparative Endocrinology|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Novitsky|first=D|date=January 1988|title=Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy|url=https://europepmc.org/abstract/med/3336918|journal=Transplantation|volume=45|pages=32-36|via=}}</ref> utilization, shifting [[metabolism]] from an [[anaerobic]] to more [[aerobic]] state.

T2 also plays a role in regulating energy metabolism, although its role is less studied. 3,5-diiodo-L-thyronine influences resting metabolic rate.<ref>{{Cite journal|last=Goglia|first=Fernando|date=June 1999|title=Action of thyroid hormones at the cellular level: the mitochondrial target|url=https://www.sciencedirect.com/science/article/pii/S0014579399006420|journal=FEBS Letters|volume=452|pages=115-120|via=}}</ref>

=== Cholesterol ===
Triiodothyronine reduces cholesterol.

== Testing ==
Standard commercial laboratory testing for thyroid hormones is via [[immunoassay]]. However, these tests are shown to be unreliable in the low-normal and high-normal range when compared to [[mass spectrometry]].<ref>{{Cite web|url=https://www.youtube.com/watch?v=tF_C_na9l2I|title=Steve Soldin & NIH team develop UltraHigh Sensitivity Method for FT3/FT4 Hormones with IONICS 3Q 320|last=|first=|date=January 9, 2015|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> In addition, most clinicians do not test for [[reverse T3]].

== Thyroid disease ==
{{Main article |page_name = Thyroid disease}}

=== Hypothyrodism ===
Hypothyrodism is when the thyroid produces excess levels of hormone. It can have a number of causes including:

* [[Hashimoto's thyroiditis]]

=== Hyperthyrodism ===
[[Hyperthyroidism]] is when the thyroid produces excess levels of hormone. It can have a number of causes including:

* [[Graves' disease]], an autoimmune disorder

=== Low T3 Syndrome ===
Also known as [[euthyroid sick syndrome]], Low T3 syndrome is characterized by decreased serum T3 and/or thyroxin (T4) levels, increased reverse T3 (rT3), and no significant increase in TSH. Low T3 syndrome is often seen in cases of acute and chronic illness, including myocardial infarction, fasting, starvation and [[sepsis]]. There is no evidence that supplementation with T3 is of benefit.

== Nutrition ==
Sufficient iodine, selenium, and iron are crucial for normal thyroid hormone function. Thyroid hormones are partially comprised of [[iodine]] and a deficiency of [[iodine]] in the diet can lead to decreased production of these [[hormones]]. If left uncorrected the thyroid tissue can enlarge, resulting in a pronounced swelling in the neck, called a 'simple goitre.'<ref>https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024712/</ref> [[Selenium]] is required for the production of deiodinase enzymes, and thus the conversion of T4 to T3. Iron is needed for heme-dependent thyroid peroxidase.

==Hormone replacement==

Patients with [[hypothyrodism]] may need hormone replacement. The standard replacement therapy is [[Levothyroxine]], a synthetic form of T4. However, some patients on Levothyroxine report continuing symptoms of hypothyrodism despite normal laboratory results, owing to poor conversion of T4 to T3. In these cases, patients may add a T3 replacement hormone drug, such as [[Cytomel]], or [[Armour thyroid]], which is whole desiccated thyroid glandular from pigs.

==Role in other human disease==

=== Chronic Fatigue Syndrome ===
A study of 99 patients with a diagnosis of [[Chronic Fatigue Syndrome]] found similar levels of TSH to healthy controls but lower free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), %TT3 (4.7%), deiodinase activity, secretory capacity of the thyroid gland, lower 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3). "Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state."<ref name="Ruiz-Núñez, 2018" />

=== Fibromyalgia ===
A series of small N trials found significant improvement in symptoms in euthyroid patients given T3.<ref>{{Cite journal|last=Lowe|first=John C.|date=1996-08-10|title=Results of an Open Trial of T3Therapy with 77 Euthyroid Female Fibromyalgia Patients|url=https://www.tandfonline.com/doi/abs/10.1300/J425v02n01_04?journalCode=wzcb20|journal=Clinical Bulletin of Myofascial Therapy|language=en|volume=2|issue=1|pages=35–37|doi=10.1300/j425v02n01_04|issn=1089-4195}}</ref><ref>{{Cite journal|last=Lowe|first=John C.|last2=Garrison|first2=Richard L.|last3=Reichman|first3=Alan|last4=Yellin|first4=Jackie|date=1997-08-15|title=Triiodothyronine (T3) Treatment of Euthyroid Fibromyalgia|url=https://www.tandfonline.com/doi/abs/10.1300/J425v02n04_05|journal=Clinical Bulletin of Myofascial Therapy|language=en|volume=2|issue=4|pages=71–88|doi=10.1300/j425v02n04_05|issn=1089-4195}}</ref><ref>{{Cite journal|last=Lowe|first=John C.|last2=Garrison|first2=Richard L.|last3=Reichman|first3=Alan J.|last4=Yellin|first4=Jackie|last5=Thompson|first5=Mervianna|last6=Kaufman|first6=Daniel|date=1996-10-08|title=Effectiveness and Safety of T3(Triiodothyronine) Therapy for Euthyroid Fibromyalgia|url=https://www.tandfonline.com/doi/abs/10.1300/J425v02n02_04|journal=Clinical Bulletin of Myofascial Therapy|language=en|volume=2|issue=2-3|pages=31–57|doi=10.1300/j425v02n02_04|issn=1089-4195}}</ref><ref>{{Cite journal|last=Lowe|first=Jhon C.|last2=Reichman|first2=Alan J.|last3=Yellin|first3=Jackie|date=1996-10-08|title=The Process of Change During T3Treatment for Euthyroid Fibromyalgia|url=https://www.tandfonline.com/doi/abs/10.1300/J425v02n02_07|journal=Clinical Bulletin of Myofascial Therapy|language=en|volume=2|issue=2-3|pages=91–124|doi=10.1300/j425v02n02_07|issn=1089-4195}}</ref>

=== Small intestinal bacterial overgrowth ===
In one study, 54% of patients with hypothyroidism tested positive for [[small intestinal bacterial overgrowth]] (SIBO) as compared to 5% of controls.<ref>{{Cite journal|last=Lauritano|first=Ernesto Cristiano|date=November 1, 2007|title=Association between Hypothyroidism and Small Intestinal Bacterial Overgrowth|url=https://academic.oup.com/jcem/article/92/11/4180/2598186|journal=The Journal of Clinical Endocrinology & Metabolism|volume=92|pages=4180–4184|via=}}</ref> SIBO is also associated with Levothyroxine usage,<ref>{{Cite journal|last=Brechmann|first=Thorsten|date=February 2017|title=Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296200/|journal=World Journal of Gastroenterology|volume=23|pages=842–852|via=}}</ref> possibly owing to the secondary hypothyroidism seen in patients who are poor converters.

==Notable studies==

*2018, Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study<ref name="Ruiz-Núñez, 2018" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869352/ Full Text)]

==Learn more==

*[https://www.thyroid.org/ American Thyroid Association webpage]

==See also==

*[[Thyroid gland]]
*[[Hormones]]
*[[:Category:Hormones|List of hormones]]
*[[Triiodothyronine]]
*[[Thyroxine]]
*[[Thyroid disease]]

==References==
<references>
<ref name="Ruiz-Núñez, 2018">{{Citation
| last1 = Ruiz-Núñez | first1 = Begoña | authorlink1 =
| last2 = Tarasse | first2 = Rabab | authorlink2 =
| last3 = Vogelaar | first3 = Emar F. | authorlink3 =
| last4 = Janneke Dijck-Brouwer | first4 = D. A. | authorlink4 =
| last5 = Muskiet | first5 = Frits A. J. | authorlink5 =
| title = Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study
| journal = Frontiers in Endocrinology | volume = 9 | issue = | page = 97
| date = 2018
| pmid = 29615976
| doi = 10.3389/fendo.2018.00097
}}
</ref>
</references>

[[Category:Neurotransmitters and hormones]]
[[Category:Hormones]]

Diagnostic biomarker

2018-08-18T00:19:05Z

Bill:fix main template

A '''diagnostic biomarker''' refers to a biological parameter that aids the diagnosis of a disease and may serve in determining disease progression and/or success of treatment. It may be a laboratory, radiological, genetic, anatomical, physiological or other finding that helps to differentiate one disease from others. In 2001, the World Health Organization (WHO), in coordination with the United Nations and the International Labor Organization, has defined a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease.”<ref name="WHO, 2001" /> The Biomarkers Consortium, a major public-private biomedical research partnership, uses the 2001 [[National Institutes of Health]] Biomarkers Definitions Working Group definition: "Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to therapeutic intervention."<ref name="NIH, 2001" />

Presently, [[myalgic encephalomyelitis]]/[[chronic fatigue syndrome]] (ME/CFS) patients are diagnosed based on well-defined clinical criteria, for example, please see the Proposed Diagnostic Criteria Chart section of the [[Institute of Medicine report]]. Diagnosis also includes a process of exclusion of other causes of fatigue which can result in a delay of diagnosis.<ref name="IOM2015MECFS" />

Potential diagnostic biomarkers for [[ME/CFS]] are being explored by many researchers in the field. Below is a list of some that have been considered. They are alphabetically ordered so as not to imply some may be more promising than others.

== Activin B ==
A 2017 study that used the [[Canadian Consensus Criteria]] concludes: "Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients."<ref name="Lidbury, 2017" />

==Allantoin==
A 2015 metabolic profiling study of female [[ME/CFS]] subjects by Armstrong, et al, showed an increase in allantoin in the urine collected as a first-void urine sample, i.e., collected upon arising. Allantoin has been considered a reliable indicator of exercise-induced oxidative stress in humans. Other studies have shown indications of oxidative stress in ME/CFS<ref name="Morris, Mar2014" /> "but this is the first to report of allantoin as a marker and the first to suggest a pathway linking ATP degradation and oxidative stress."<ref name="Armstrong, 2015" />

Obstacle for use: The findings in this published study need to be validated through replication by other studies using a more heterogeneous [[ME/CFS]] population.

==Brain imaging==
''{{main article|page_name =Brain imaging}}''

Using advanced [[brain imaging]], [[Michael Zeineh | Zeineh]], et.al., found that there was right arcuate fasciculus (FA) abnormality in [[CFS]] patients. "Bilateral white matter atrophy is present in CFS...Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS."<ref name="Zeineh, 2015" />

Obstacle for use: The specialized radiological equipment needed for this test is usually only available in facilities engaged in research. Radiologists would need to be trained to interpret the scans to identify the unique features present in [[ME/CFS]] brains.

==CellTrend diagnostic test==
Cell-Trend bases its test on the theory that a subset of 20-30% of all patients suffering from [[ME/CFS]] have developed elevated levels of three auto-antibodies, i.e., auto-antibodies against the b2-adrenergic receptor, auto-antibodies against the muscarinic cholinergic receptor 3 (M3) and auto-antibodies against the muscarinic cholinergic receptor 4 (M4).<ref>http://www.celltrend.de/cfs-diagnostics.html</ref><ref name="Loebel, 2016" />

Obstacle for use: Only detects a subset 20-30%. Not widely accepted. Patients pay the test cost.

==Combination of M-wave, TBars, and CD26==
A 2016 study in France by Fenouillet, et al, examined 36 ME/CFS cases and 11 healthy controls with regard to three biological variables:
a) post-exercise M-wave - a measurement after electrical stimulation of muscle nerves which coordinates with muscle fatigue
b) TBARS variations - a plasma marker which represents excessive oxidative stress response to exercise, and
c) CD26-expression at rest - a protein potentially related to inflammation, which was found to decrease in CFS patients.
Although the researchers set out to explore physiological and biological abnormalities that could be indicative of the etiology, "striking differences" in the results between patients and controls lead them to believe that this combination could be used to identify patients with ME/CFS and help to distinguish ME/CFS patients from fibromyalgia patients.<ref name="Fenouillet, 2016" />

Obstacle for use: The findings in this published study need to be validated through replication by other studies.

==Cytokine expression==
''{{main article|page_name =Cytokine}}''

Several researchers are exploring if [[cytokine]] expression in ME/CFS is a unique enough signature to be used as a diagnostic marker.<ref name="Russell, 2016" /><ref name="Peterson, 2015" /><ref name="Hornig, 2016" /><ref name="Montoya, 2017" />

[[Cytokine]] expression changes in ME/CFS related to length of illness, with some cytokines levels increasing and some decreasing dependent on illness duration. Russell, et al, focused on a subset of three cytokines, IL-1α, 6 and 8, in plasma samples and concluded that: "Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration [the] sub-groups produced ME/CFS classification accuracies of 75–88%."<ref name="Russell, 2016" />

Obstacle for use: Since cytokine expression changes in ME/CFS related to progression of the illness, the validity of potentially useful markers may be obscured by such variation.<ref name="Russell, 2016" />

In 2016, Landi, et al, "observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and [[Vascular endothelial growth factor|Vascular Endothelial Growth Factor]] A (VEGF-A) in ME/CFS patients" but not in patients of other chronic illnesses with fatigue as a symptom. This three cytokine pattern is being studied further as a potential biomarker for [[ME/CFS]].<ref name="Landi, 2016" />

In 2018, Moneghetti, et al, compared the results of cytokine profiles 18 hours post exercise for [[ME/CFS]] patients vs healthy patients matched for cardiac structure and exercise capacity. They found that the most discriminatory cytokines detected post exercise in [[ME/CFS]] patients were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1. They concluded that cytokine profiling following exercise may help differentiate patients with [[ME/CFS]] from sedentary controls.<ref name="Moneghetti, 2018" />

Obstacle for use: These studies need to be duplicated with other patient cohorts to assure the results are specific enough for an accurate diagnosis of [[ME/CFS]].

==Dysfunction of TCA and urea cycles==
A 2016 study in Japan, by Yamano, et al, looked at the differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles in [[CFS]] patients versus healthy controls: "CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma."<ref name="Yamano, 2016" />

Obstacle for use: The specialized laboratory equipment needed for this test is usually only available in facilities engaged in research. The findings in this published study need to be validated through replication by other studies.

==EBV-encoded DNA polymerase and EBV-encoded dUTPase==
In 2012, Dr [[Ronald Glaser]] and Dr [[A Martin Lerner]], et al, discovered that the proteins, [[Epstein-Barr virus]]-encoded DNA polymerase and [[Epstein-Barr virus]]-encoded dUTPase, were present in the blood sera of an [[EBV]] subset of [[CFS]] patients, but was negative in sera of controls.<ref name="Lerner, 2012" />

Obstacle for use: These were preliminary findings that need to be are corroborated by studies with a larger number of [[EBV]] subset [[CFS]] patients.

==Electrical Impedance==
Experimentation is also being carried out at the [[End ME/CFS Project]] with the [[Open Medicine Foundation]] to test if a metabolic testing device using new nanofabricated technology that measures electrical impedance could be used to develop a simple diagnostic test for [[myalgic encephalomyelitis]]/[[chronic fatigue syndrome]] ([[ME/CFS]]). Blood from patients with [[ME/CFS]] causes a rapid and significant rise in electrical impedance when placed in this device, whereas blood from healthy people does not. The device is inexpensive and gives a real-time assay. This nanofabricated technology has the potential to be place in a hand-held device and disseminate to physician's offices for use as a test during medical visits.<ref>https://www.youtube.com/watch?v=sGBXXlQO49g</ref>

Obstacle for use: The technology is still very new and needs further testing. If the technology works, development into an inexpensive, easily disseminated, handheld device is necessary.

==Extracellular Vesicles==
A 2018 study from Spain reported that extracellular vesicles (EVs) were significantly smaller as measured by protein cargo, size distribution and concentration, and the amount of EV-enriched fraction was significantly higher in the blood serum of CFS/ME patients versus healthy controls. Extracellular vesicles are secreted from both healthy cells and cells undergoing apoptosis (i.e., cell death) and play a role in intercellular communication.<ref name="Castro-Marrero, 2018" />

Obstacle for use: The study population consisted of 10 Spanish CFS/ME patients and 5 matched healthy controls. This study would need to be reproduced in larger populations to verify statistic significance.

==Gut [[microbiome]]==
In a 2016 study done by Giloteaux, [[Maureen Hanson | Hanson]], et al, the gut bacterial [[microbiome]] of 48 [[ME/CFS]] patients and 39 healthy controls was examined by sequencing regions of 16S ribosomal ribonucleic acid (rRNA) genes that allow identification of the different types of bacteria present in the stool as well as inflammatory markers from serum. "Bacterial diversity was decreased in the [[ME/CFS]] specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum...Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as [[ME/CFS]] with a cross-validation accuracy of 82.93%."<ref name="Giloteaux, 2016" />

==Immunosignatures==
Immunosignaturing is a medical diagnostic test which uses arrays of random-sequence peptides (i.e., linked amino acids) to measure specific antibodies circulating in the blood. The [[Nevada Center for Biomedical Research]] in Reno, Nevada, USA has identified a unique Immunosignature (IMS) comprised of a subset of 25 peptides that differentiates the blood serum from people with [[ME]] compared to controls with 92.9% specificity and 97.6% sensitivity. [[ME]] patients met both the [[ICC]] and [[Fukuda criteria]].<ref name="Singh, 2016" />

==Metabolomics==
''{{main article|page_name =Metabolomics}}''

[[Robert Naviaux | Naviaux]], et al, at the University of California, San Diego School of Medicine reported in 2016 "that targeted, broad-spectrum [[metabolomics]] of plasma not only revealed a characteristic chemical signature but also revealed an unexpected underlying biology." The researchers found that [[Chronic Fatigue Syndrome]] patients
had an average of 40 metabolic abnormalities. From these, a set of 8 metabolites were identified in male patients and a set of 13 metabolites in females that performed well together as a diagnostic test. Both sets gave a 95% Confidence Interval. The eight metabolites selected for males were phosphatidyl choline PC(16:0/16:0), glucosylceramide GC(18:1/16:0), 1-P5C, FAD, pyroglutamic acid (also known as 5-oxoproline), 2-hydroxyisocaproic acid (HICA), l-serine, and lathosterol. The 13 metabolites selected for females were THC(18:1/24:0), phosphatidyl choline PC(16:0/16:0), hydroxyproline, ceramide(d18:1/22:2), lathosterol, adenosine, phosphatidylinositol PI(16:0/16:0), FAD, 2-octenoylcarnitine, phosphatidyl choline plasmalogen PC(22:6/P18:0), phosphatidyl choline PC(18:1/22:6), 1-P5C, and CDCA. There are several metabolites that appear on both the males and female lists.<ref name="Naviaux, 2016" />

Obstacle for use: The specialized laboratory equipment needed for this test is usually only available in facilities engaged in research.

==MicroRNA (miRNA)==
Very simply stated, microRNA (miRNA) are molecules involved in gene expression. They are different from mRNA which stands for messenger RNA. A 2016 study by [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150904 Petty, et al] found that "four upregulated miRNA were suitable markers to resolve CFS/ME subjects from a matched control cohort."<ref name="Petty, 2016" /> A 2012 study by [https://www.ncbi.nlm.nih.gov/pubmed/22572093 Brenu, et al] found the expression of eight specific miRNAs "significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls" and one specific miRNA was significantly downregulated in "both the NK and CD8(+)T cells in the CFS/ME sufferers."<ref name="Brenu, 2012" />

In 2015, [[Griffith University]] filed for a [https://www.google.co.uk/patents/WO2016023077A1?cl=en&dq=sonya+marshall-gradisnik patent for a biological marker] (Patent Publication number WO2016023077 A1) for the diagnosis and management of [[ME]] and [[CFS]]. [[Sonya Marshall-Gradisnik]] and [[Ekua Brenu]] are listed as the inventors. The patent application states: "The present invention resides broadly in the use of at least one miRNA as a biological marker for identifying or diagnosing a subject having [[CFS]] and/or [[ME]]."<ref>https://www.google.co.uk/patents/WO2016023077A1?cl=en&dq=sonya+marshall-gradisnik</ref> In 2016, Griffith University's Professor [[Donald Staines]] and Professor [[Sonya Marshall-Gradisnik]] announced that they have been awarded a $4-million grant to be administered during the next five years that will enable them to continue research into developing a diagnostic test for ME/CFS.<ref>http://www.goldcoastbulletin.com.au/lifestyle/gold-coast-team-getting-closer-to-discovering-test-for-chronic-fatigue-syndrom/news-story/1627b3fcc41c53efac927200a53cc756</ref>

Obstacle for use: Although the science of using the detection of different miRNAs for disease confirmation is exploding, it is still in its infancy. There are no established baseline data for miRNAs among normal individuals which would be necessary for using miRNA levels as biomarkers.<ref name="Tonge, 2016" /> The findings in the study published in March 2016 need to be validated through replication by other studies. The [[Griffith University]] test has not been released for public use to date.

==[[Natural killer cell]] function==
Numerous studies of [[Chronic Fatigue Syndrome]] have found evidence of reduced [[natural killer cell]] function.<ref name="Barker1994" /><ref name="WhitesideTL1998" /><ref name="BrenuEW2014" /><ref name="FletcherMA2002" /><ref name="BrenuEW2012" /> Some studies have showed natural killer cell function correlates with illness severity.<ref name="OjoAmaize1994" /> One study found increased differentiation in NK cells.<ref name="HuthTK2016" />

Obstacles for use: Specialized lab equipment not available in average laboratories; blood specimen must be tested within 48 hours of draw and must remain at between 59°-98.6°F or 15°-37°C<ref>http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=34184X&labCode=QDV</ref> so special considerations are needed in transporting blood specimens to specialized labs. Reduced [[natural killer cell]] function can be seen with other immune-related conditions,<ref>Orange, J. S. (2013). Natural killer cell deficiency. The Journal of Allergy and Clinical Immunology, 132(3), 515–526. http://doi.org/10.1016/j.jaci.2013.07.020</ref> so this test would need to be paired with other clinical or laboratory findings to make a definitive diagnosis.

==Orosomucoid==
Orosomucoid (ORM) is a protein which has many biological activities including modulating immunity. In 2016, a study with Yang, et al, showed that the serum level of ORM in individuals with [[chronic fatigue syndrome]] was consistently elevated compared with that from healthy volunteers. The serum cortisol level in these same [[CFS]] patients was moderately decreased, indicating that "ORM increase is not a direct result of stress response."<ref name="Yang, 2016" />

Orosomucoid 2 is one of the proteins [[James Baraniuk |Baraniuk]], et al, found in a unique CFS – related proteome when studying pooled cerebrospinal fluid of CFS patients.<ref name="Baraniuk, 2005" />

Obstacles in use: Further testing needed for confirmation.

==Plasma neuropeptide Y==
Plasma levels of neuropeptide Y (NPY), a neurotransmitter in high quantity in the brain, are reported to be elevated in complex multi-symptom illnesses associated with immunologic dysfunction. [[Mary Ann Fletcher | Fletcher]], et al, did a study believed to be "the first in the CFS literature to report that plasma NPY is elevated [in ME/CFS] compared to healthy controls and to a fatigued comparison group, GWI [Gulf War Illness] patients. The significant correlations of NPY with stress, negative mood, general health, depression and cognitive function strongly suggest that this peptide be considered as a biomarker to distinguish subsets of CFS."<ref name="Fletcher, 2010" />

Obstacles in use: NPY is elevated in other immune illnesses such as [[rheumatoid arthritis]] (RA) and systemic lupus erythematosus (SLE). NPY varies greatly between individuals and is interdependent on other cellular and molecular components and must be viewed with data from other biomarkers.<ref name="Fletcher, 2010" />

==Proteome in cerebrospinal fluid==
Analysis of the proteome (complement of proteins) in cerebrospinal fluid specimens by [[James Baraniuk | Baraniuk]], et al, in 2005, showed one, consistent CFS-related proteome compared to a group with Gulf War Illness and to controls. They found the presence of 10 proteins in cerebrospinal fluid that were shared by patients with [[CFS]], but were not detected in control samples."<ref name="Baraniuk, 2005" />

A similar study of proteome analysis of cerebrospinal fluid was done in 2011 by Schutzer, et al. His group compared the pooled cerebrospinal fluid specimens of patients with [[chronic fatigue syndrome]] to patients with Neurologic Post Treatment Lyme disease (nPTLS) and to healthy controls. The cerebrospinal fluid proteome of the three groups were markedly unique for each group. Although nPTLS and [[CFS]] have similar clinical presentations, the researchers were able to distinguish the two syndromes from each other via data analysis.<ref name="Schutzer, 2011" />

Obstacles in use: The specialized laboratory equipment needed for this test is usually only available in facilities engaged in research. The samples were pooled specimens. The presence of these proteins in one patient may be too small for average laboratory equipment to detect. Specific proteins to be used for a biomarker have not been identified. Cerebral spinal fluid samples are obtained via spinal taps which are considered invasive and come with potential side effects.

==Ratio of active:inactive PKR==
In 2018, E.C. Sweetman discovered, during work for his doctorate thesis, that a changed ratio of active:inactive Protein Kinase R (PKR) in people with ME/CFS vs age-gender matched controls could potentially be used as a diagnostic biomarker. Protein Kinase R (PKR) is an innate antiviral immune response protein. Upon measuring an antibody against a non-phosphorylated PKR fragment and an antibody against a Thr-446 phosphorylated PKR peptide, an increased ratio of phosphorylated PKR to non-phosphorylated inactive PKR was detected ME/CFS patients.<ref>Sweetman, E. C. (2018). Comprehensive molecular analysis of different classes of molecules in a Myalgic Encephalomyelitis/Chronic Fatigue Syndrome pilot study group, and investigation of RNA-activated Protein Kinase R (PKR) as a diagnostic biomarker (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/7834</ref>

Obstacles in use: Further testing needed for confirmation; test would need to be adapted from a research setting to a clinical setting for wide availability.

==Saliva proteins ACON and ATPB==
Using whole saliva, Ciregia, et al, 2016, found two proteins, aconitate hydratase (ACON) and ATP synthase subunit beta (ATPB), were upregulated in CFS. When these two proteins were tested in combination, they gave a ROC curve with sensitivity of 93% and specificity of 70%, in a twin study where one twin was healthy and one had CFS. A second cohort of unrelated CFS patients and healthy controls, likewise proved ACON and ATPB as promising biomarkers.<ref name="Ciregia, 2016" />

==Short QT interval==
''{{main article|page_name =Short QT interval}}''

"Automated measurement of QTc [QT corrected] in clinical practise has potential utility as a diagnostic biomarker in CFS."<ref name="Scott, 2012" />

The electrocardiographic QT interval is shorter in patients with ME/CFS than those of the general population.<ref name="Scott, 2012" /> The only exception is in those who have a rare genetic illness, Short QT syndrome. Differentiation is easy to determine because those with Short QT syndrome also have tall and peaked T waves,<ref>https://en.wikipedia.org/wiki/Short_QT_syndrome</ref> whereas the T waves are normal in [[PwME]]. Modern computer-based ECG machines are programed to correct the QT interval in relation to heart rate, because a number of medical conditions illicit a prolonged QT interval.<ref>https://en.wikipedia.org/wiki/QT_interval</ref>

Obstacles for use: medical personnel education needed to recognize this finding on the EKG finding as indicative of [[ME/CFS]]; modern computer-based EKG machine needed.

==Two-day cardiopulmonary exercise testing==
''{{main article|page_name =Two-day cardiopulmonary exercise testing}}''

[[Two-day cardiopulmonary exercise testing]] or [[2-day CPET]] is an accepted, reliable test for [[post-exertional malaise]] (PEM), one of the cardinal symptoms that distinguishes between individuals with and without [[ME/CFS]].<ref name="Davenport, 2011" />

Obstacles for use: The [[2-day CPET]] "carries substantial risk for these patients as it may worsen their condition."<ref name="IOM2015MECFS" /> A single day CPET is a common test used as a cardiac stress test and therefore the equipment is widely available at medical centers, however, medical personnel would need to be educated on how to interpret a [[2-day CPET]] test for [[ME/CFS]] diagnosis.

==Others==
Other biomarkers being researched:
*Dr. Kevin Conley and Dr. David Maughan, University of Washington, Seattle, Washington, USA are studying the abnormal response of the muscle metabolites, NADP+/NADPH, as a molecular marker in [[ME/CFS]] patients before and after fatiguing exercise by using advanced, non-invasive magnetic resonance spectroscopy (MRS).<ref>[http://solvecfs.org/promising-non-invasive-diagnostic-testing-project-seeks-to-detect-mecfs/ Promising Non-invasive Diagnostic Testing Project Seeks to Detect ME/CFS - Solve ME/CFS]</ref>
*Dr. Isabel Barao hypothesizes that FcR (a protein found on the surface of certain cells) dysfunction in immune cells is a risk factor for the development of [[ME/CFS]]. The [[Bateman Horne Center]], the National Cancer Institute (NCI) at [[NIH]], and Roche Pharmaceuticals, are examining polymorphisms and mutations of FcgRs in NK cells of ME/CFS patients and their associations to antibody-dependent cell-mediated cytotoxicity (ADCC) capability and disease pathology.<ref>[https://batemanhornecenter.org/uncovering-biomarkers-fcg-receptors/ Uncovering Biomarkers FCG Receptors - Bateman Horne Center]</ref>
*the presence of salivary [[Human herpesvirus 6]] (HHV6) and [[Human herpesvirus 7]] (HHV7) biomarkers to distinguish physiological fatigue from pathological fatigue<ref name="Aoki, 2016" />
*visible and near-infrared (Vis-NIR) spectroscopy of patients' thumbs are being explored in Japan as a non-invasive test for CFS<ref name="Sakudo, 2016" /><ref name="Sakudo, 2012" />

==Learn more==
*2012, Biomarkers for chronic fatigue.<ref name="Klimas, 2012" />
*2014, Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging Biomarkers. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052724/ (FULL TEXT)]<ref name="Fischer, 2014" />
*March 3, 2016, [https://meaustralia.net/2016/03/03/study-proposes-new-name-definition-and-biomarkers/ "Study proposes new name, definition and biomarkers for chronic fatigue syndrome"] in ''ME Australia'' by Sasha Nimmo
*March 30, 2016, [https://meaustralia.net/2016/03/30/march-a-busy-month-for-biomarker-discoveries/ "Three new chronic fatigue syndrome and ME biomarker discoveries"] in ''ME Australia'' by Sasha Nimmo
*2017, [https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view "What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?"] [[Solve ME/CFS Initiative]] explains Biomarkers in medicine for diagnosis and treatment.

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[[Category:Tests]]
[[Category:Core topics]]

AIM ImmunoTech

2018-08-18T00:18:25Z

Bill:fix main template

[[File:Hemispherx logo.gif|right|250px]]
'''Hemispherx Biopharma''' is a small American pharmaceutical company that produces the drug [[Ampligen]]. Corporate headquarters are in Orlando, Florida (formerly in Philadelphia, PA) and the main manufacturing and research facility is in New Brunswick, NJ.<ref>https://www.bizjournals.com/philadelphia/news/2018/01/31/heb-hemispherx-corporate-hq-philly-orlando-amplige.amp.html</ref> A second manufacturing plant is in use in Spokane, Washington.

In addition to Ampligen® (rintatolimid), Hemispherx produces Alferon N Injection® and Alferon® LDO (Low Dose Oral). To date, only Alferon N Injection® has [[FDA]] approval. Ampligen® and Alferon® LDO are not FDA-approved and are considered experimental.<ref>http://www.hemispherx.net/</ref>

In Jan 2018, [[Thomas Equels]], chief executive officer of Hemispherx Biopharma, released a letter instructing every Hemispherx employee to watch the documentary [[Unrest]] and urged their affiliates and stockholders to do the same, in an effort to share information about [[ME/CFS]], one of the primary disease targets for their drug Ampligen.<ref>http://b2icontent.irpass.cc/2265/173159.pdf?AWSAccessKeyId=1Y51NDPSZK99KT3F8VG2&Expires=1517512463&Signature=fjTaGeTPvUEZjsqbc5NOXGztYqA%3D</ref>

==Change in leadership==

In Feb 2016, Dr. [[William Carter]], then Chairman and CEO, was terminated by the board of directors of Hermispherx Biopharma, who cited that part of the reason was a strong financial austerity plan. William M. Mitchell, M.D., Ph.D. was promoted in house as his replacement.<ref>http://www.bizjournals.com/philadelphia/news/2016/02/19/philly-biotech-hemispherx-fires-ceo-william-carter.html</ref>

In June 2016, the law suit was resolved between Dr. Carter and Hemispherx regarding the wrongful termination claim. As part of the settlement, the intellectual property rights, including the patent for Ampligen and Alferon, are irrevocably assigned to to Hemispherx.<ref>http://www.bizjournals.com/philadelphia/news/2016/06/07/hemispherx-gets-ip-rights-from-fired-ceo-carter.html</ref>

==Management==
*[[Thomas Equels|Thomas K. Equels]], M.S., J.D. - Executive Vice Chairman, Chief Executive Officer, President, Secretary & General Counsel
*Adam Pascale, CPA - Chief Financial Officer
*[[David Strayer | David R. Strayer]], M.D. - Chief Scientific & Medical Officer
*Wayne Springate - Senior Vice President of Operations

==Board of directors==
*[[William Mitchell | William M. Mitchell]], M.D., Ph.D. - Chairman of the Board
*Thomas K. Equels, M.S., J.D. - Executive Vice Chairman, Chief Executive Officer, President, Secretary, & General Counsel
*Peter W. Rodino III, Esq.- Lead Director

==Marketing history==
''{{main article|page_name =Marketing History of Ampligen}}''

==Online presence==
*[http://www.hemispherx.net/ Website]
*[https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0000946644 SEC filings - Hemispherx Biompharma]

==Talks and interviews==
*2016, [https://www.youtube.com/watch?v=RVwAHIjNkb4&feature=youtu.be Small Cap Nation - ME/CFS (Updated)] ([[Thomas Equels]])

==Learn more==
*[https://en.wikipedia.org/wiki/Hemispherx_Biopharma Wikipedia - Hemispherx Biopharma]
*[https://en.wikipedia.org/wiki/Rintatolimod Wikipedia - Rintatolimod]
*[http://simmaronresearch.com/2016/05/hemispherx-ampligen-approval-chronic-fatigue-syndrome-top-priority/ http://simmaronresearch.com/2016/05/hemispherx-ampligen-approval-chronic-fatigue-syndrome-top-priority/]
*2016, [https://www.benzinga.com/general/biotech/16/12/8851721/hemispherx-biopharma-ceo-explains-chronic-fatigue-syndrome-and-how-the Hemispherx BioPharma CEO Explains Chronic Fatigue Syndrome And How The Company Is Treating It]<ref>{{citation |last= Hasse|first= Javier|date= 30 December 2016|title= Hemispherx BioPharma CEO Explains Chronic Fatigue Syndrome And How The Company Is Treating It|url= https://www.benzinga.com/general/biotech/16/12/8851721/hemispherx-biopharma-ceo-explains-chronic-fatigue-syndrome-and-how-the|newspaper= Benzinga|location= Detroit Michigan|access-date= }}</ref>
*2016, [http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f Executive Informational Overview by Crystal Research Associates]<ref name="Crystal, 2016"/>
*2016, [http://www.streetinsider.com/Corporate+News/Hemispherx+Biopharma+%28HEB%29+Comments+on+Recent+Meeting+with+NIH+for+MECFS+Research+Advancement/11408291.html Hemispherx Biopharma (HEB) Comments on Recent Meeting with NIH for ME/CFS Research Advancement] (see also [[NIH Post-Infectious ME/CFS Study]])
*2016, [http://www.cortjohnson.org/forums/threads/ampligen-co-inventor-head-of-hemispherx-biopharma-fired-implications-for-me-cfs-drug-unclear.3729/ Ampligen Co-Inventor / Head of Hemispherx Biopharma Fired: Implications for ME/CFS Drug Unclear]
*2014, [http://investorshub.advfn.com/boards/read_msg.aspx?message_id=96215994 Investor's post about HEB's rocky history]

==See also==
*[[Ampligen]]
*[[Marketing History of Ampligen]]
*[[William Carter]]
*[[David Strayer]]
*[[William Mitchell]]
*[[Thomas Equels]]

==References==
<references>
<ref name="Crystal, 2016">{{citation
| author = Crystal Research Associates
| title = Hemispherx Biopharma, Inc.
| type = Executive Informational Overview
| date = 27 Nov 2016
| url = http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f
}}</ref>
</references>

[[Category:Pharmaceutical companies]]

Postural orthostatic tachycardia syndrome

2018-08-18T00:18:13Z

Bill:fix main template

'''Postural orthostatic tachycardia syndrome''' aka '''POTS''' aka '''postural tachycardia syndrome''' is a condition in which a change from the supine position (lying horizontally) to an upright position causes an abnormally large increase in [[heart rate]], called [[tachycardia]]. Other symptoms of an orthostatic nature — occurring in response to upright posture — may accompany the [[tachycardia]].<ref>{{Cite journal|last=Mar|first=Philip L.|last2=Raj|first2=Satish R.|date=2014|title=Neuronal and hormonal perturbations in postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24982638|journal=Frontiers in Physiology|volume=5|pages=220|doi=10.3389/fphys.2014.00220|issn=1664-042X|pmc=|pmid=24982638|via=}}</ref> It is a form of [[orthostatic intolerance]] (OI). Accompanying the heart rate acceleration, other symptoms, such as headaches, fatigue, sweating, nausea, fainting and dizziness may occur. POTS is associated with an increase in heart rate from the lying to upright position of greater than 30 beats per minute, or a heart rate of greater than 120 beats per minute within 10 minutes of standing. The [[autonomic nervous system]] is in charge of heart rate and blood pressure but it has become disregulated.<ref>{{Cite news|url=http://www.potsuk.org/|title=PoTS - Postural Tachycardia Syndrome|last=|first=|work=PoTS UK|access-date=2018-08-16|language=en|date=|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite news|url=http://www.potsuk.org/what_is_pots2|title=PoTS - Postural Tachycardia Syndrome - What is POTS?|last=|first=|work=PoTS UK|access-date=2018-08-16|language=en|date=|archive-url=|archive-date=|dead-url=}}</ref>

=Signs and symptoms=
The following symptoms are common in POTS<ref>{{Cite web|url=http://standinguptopots.org/learning/pots-symptoms|title=Symptoms of Postural Orthostatic Tachycardia Syndrome (POTS)|last=|first=|date=July 9, 2018|website=Standing Up to POTS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>:

* [[Dizziness]]/ [[lightheadedness]]
* [[Headache]]s and [[migraines]]
* [[Cognitive impairment]] / [[brain fog]]
* [[Sleep abnormalities]]
* [[Neuropathic pain]]
* [[Fatigue]]
* [[Blood pooling]] in the extremities
* [[Sensory sensitivity]]
* [[Abdominal pain]], [[gastroparesis]], or rapid [[gastric emptying]]

=Testing=
Assessing orthostatic blood pressure can be done in a physician's office by measuring the patient's blood pressure while lying down, sitting, and standing at standardized time increments. Dr. [[Lucinda Bateman]] uses a modified orthostatic blood pressure assessment called the [[NASA 10-minute Lean Test]], a variant of a test used by NASA researchers to test for orthostatic intolerance following space flight. The NASA 10-minute Lean Test is less taxing on the patient and can be done in any physician's office. Instructions are available for printout for both [https://batemanhornecenter.org/wp-content/uploads/2016/09/NASA-Lean-Test-Instructions-1.pdf healthcare providers] and [https://batemanhornecenter.org/wp-content/uploads/2016/09/NASA-Lean-Patient-Preparation-Instructions-1.pdf patients].<ref>{{Cite news|url=https://batemanhornecenter.org/assess-orthostatic-intolerance/|title=Simple Way to Assess Orthostatic Intolerance - Bateman Horne Center|last=Bateman|first=Lucinda|date=2016-09-27|work=Bateman Horne Center|access-date=2018-08-16|archive-url=|archive-date=|dead-url=|publisher=Sep 27, 2016|language=en-US}}</ref>

If the results of the standard orthostatic blood pressure assessment are inconclusive, a [[tilt table test]] can be used for diagnosis.<ref>{{Cite news|url=http://myheart.net/pots-syndrome/diagnosis-tests/|title=How Doctors Diagnose & Test for POTS • MyHeart|work=MyHeart|access-date=2018-08-16|language=en-US}}</ref>

=Treatment=
A 2012 study [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390096/ Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review]<ref name=":0" /> concluded:

:"The pathophysiology of POTS is complex and the result of a number of separate mechanisms producing a common pattern of symptoms. The large number of clinical manifestations that characterize this disorder and the wide range of medications available, plus the clear evidence that certain medications and treatment strategies work in some, but not all POTS patients, demonstrates that POTS is a range of disorders requiring comprehensive investigation and characterisation to guide selection of the most appropriate treatment. The recent consensus statement will help to direct further research into the underlying conditions that lead to POTS."
The following treatments were identified:
*[[Diet]]
*[[Exercise]] (contraindicated in patients with co-morbid [[myalgic encephalomyelitis]])
*[[Sodium chloride]] 0.9% ([[Normal saline]])
*[[Beta-blocker]]s
*[[Fludrocortisone]]
*[[Ivabradine]]
*[[Erythropoietin]]
*[[Pyridostigmine]] bromide
*[[Vasoconstrictor]]s
*[[NSAID]]s
*Others such as methyldopa and antidepressants<ref name=":0">{{Cite journal|last=Abed|first=Howraa|last2=Ball|first2=Patrick A|last3=Wang|first3=Le-Xin|date=2012|title=Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390096/|journal=Journal of Geriatric Cardiology : JGC|volume=9|issue=1|pages=61–67|doi=10.3724/SP.J.1263.2012.00061|issn=1671-5411|pmid=22783324|via=}}</ref>

=Related conditions =
===ME/CFS ===
POTS can be a co-morbid condition in [[ME/CFS]] patients.<ref>{{Cite web|url=https://www.youtube.com/watch?v=o4OqNPZoqVs|title=POTS in ME/CFS|last=|first=|date=Aug 2, 2014|website=YouTube|publisher=Freedom From ME - The Optimum Health Clinic|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-08-12}}</ref> Estimates on the prevalence of POTS among [[ME/CFS]] patients varies widely. In a 2008 study done in the UK by the Northern CFS/ME Clinical Network, using the [[Fukuda criteria]], 27% of the study population had POTS compared with 9% in the control population.<ref>{{Cite journal|last=Hoad|first=A.|last2=Spickett|first2=G.|last3=Elliott|first3=J.|last4=Newton|first4=J.|date=2008|title=Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18805903|journal=QJM: monthly journal of the Association of Physicians|volume=101|issue=12|pages=961–965|doi=10.1093/qjmed/hcn123|issn=1460-2393|pmid=18805903|via=}}</ref>

A 2011 study, by the Vanderbilt Autonomic Dysfunction Center (Vanderbilt University School of Medicine, Nashville, TN, U.S.A.), reported that 64% of the POTS population in the study also met the [[Centers for Disease Control & Prevention]] criteria for [[chronic fatigue syndrome]].<ref>{{Cite journal|last=Okamoto|first=Luis E.|last2=Raj|first2=Satish R.|last3=Peltier|first3=Amanda|last4=Gamboa|first4=Alfredo|last5=Shibao|first5=Cyndya|last6=Diedrich|first6=André|last7=Black|first7=Bonnie K.|last8=Robertson|first8=David|last9=Biaggioni|first9=Italo|date=2012-02-01|title=Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203411/|journal=Clinical Science (London, England : 1979)|volume=122|issue=Pt 4|pages=183–192|doi=10.1042/CS20110200|issn=0143-5221|pmid=21906029|via=}}</ref>

The proposed [[SEID]] criteria requires that either [[orthostatic intolerance]] (of which POTS is one type) or [[cognitive dysfunction]] for a diagnosis. However, the diagnosis of POTS alone does not automatically support a [[ME/CFS]] diagnosis and cannot be used as a [[diagnostic biomarker]] to determine ME/CFS. POTS can occur independent from ME/CFS, and, likewise, ME/CFS can occur without the symptomatology of POTS.

A September 2016 study in the Netherlands by Roerink, et al, found that patients with CFS who fulfilled the [[SEID]] criteria did not have a prevalence of POTS different from that in the overall CFS population. In adults with CFS, the prevalence of POTS was low, between 6% - 18% (depending on age), was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome.<ref name="Roerink, 2016" />

=== Ehlers Danlos Syndrome ===
{{main article|page_name =Ehlers-Danlos syndrome}}

==Symptom recognition==
POTS is a well documented symptom in [[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/6#114|journal=The National Academies Press|language=en|volume=|pages=114|at=Box 4-3|doi=10.17226/19012|via=NAP.edu}}</ref>, the [[Canadian Consensus Criteria]] (CCC) which diagnoses ME/CFS,<ref>{{Cite web|url=http://me-pedia.org/wiki/Canadian_Consensus_Criteria#Definition|title=Canadian Consensus Criteria - MEpedia|website=me-pedia.org|language=en|access-date=2018-08-16}}</ref> and the [[International Consensus Criteria]] (ICC) for diagnosing Myalgic encephalomyelitis.<ref>{{Cite web|url=http://me-pedia.org/wiki/International_Consensus_Criteria#D._Energy_production.2Ftransportation_impairments:_At_least_one_symptom|title=International Consensus Criteria - MEpedia|website=me-pedia.org|language=en|access-date=2018-08-16}}</ref>

== Studies ==
*2008, [http://www.ncbi.nlm.nih.gov/pubmed/18805903 Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome]<ref name="Hoad, 2008" />
*2012, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390096/ Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review]<ref>{{Cite journal|last=Abed|first=Howraa|last2=Ball|first2=Patrick A|last3=Wang|first3=Le-Xin|date=2012|title=Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390096/|journal=Journal of Geriatric Cardiology : JGC|volume=9|issue=1|pages=61–67|doi=10.3724/SP.J.1263.2012.00061|issn=1671-5411|pmid=22783324|via=}}</ref>
*2013, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896080/ What is brain fog? An evaluation of the symptom in postural tachycardia syndrome]<ref name="Ross, 2013" />
*2014, [http://hic.sagepub.com/content/2/1/2324709614527812.full Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”]<ref>{{Cite journal|last=Tomljenovic|first=Lucija|last2=Colafrancesco|first2=Serena|last3=Perricone|first3=Carlo|last4=Shoenfeld|first4=Yehuda|date=2014-03-13|title=Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”|url=http://journals.sagepub.com/doi/full/10.1177/2324709614527812|journal=Journal of Investigative Medicine High Impact Case Reports|language=en|volume=2|issue=1|pages=232470961452781|doi=10.1177/2324709614527812|issn=2324-7096|pmid=26425598|via=}}</ref>
*2014, [http://www.ncbi.nlm.nih.gov/pubmed/24206536 Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort]<ref name="Reynolds2014" />
*2016, Is Postural Orthostatic Tachycardia a Useful Diagnostic Marker in Chronic Fatigue Syndrome Patients?<ref>{{Cite journal|last=Roerink|first=M.E.|last2=Lenders|first2=J.W.M|last3=Schmits|first3=I.C.|last4=Pistorius|first4=A.|last5=Knoop|first5=H.|last6=van der Meer|first6=J.W.M.|date=2016|title=Is Postural Orthostatic Tachycardia a Useful Diagnostic Marker in Chronic Fatigue Syndrome Patients?|url=http://www.jpsychores.com/article/S0022-3999(16)30280-X/abstract|journal=Journal of Psychosomatic Research|language=English|volume=85|pages=78|doi=10.1016/j.jpsychores.2016.03.193|issn=0022-3999|via=}}</ref>[http://www.jpsychores.com/article/S0022-3999%2816%2930280-X/abstract (Abstract)]
*2016, [http://onlinelibrary.wiley.com/doi/10.1111/joim.12564/full Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome]<ref name="Roerink, 2016" />
*2018, Managing fatigue in postural tachycardia syndrome (PoTS): The Newcastle approach<ref name="Strassheim, 2018" /> [https://www.ncbi.nlm.nih.gov/pubmed/29519643 (Abstract)]

==Learn more==
*[http://www.potsuk.org/ POTS UK website]
*Sep 2010, [https://www.youtube.com/watch?v=5iF30TVLaRE Mangaging Orthostatic Intolerance]<ref>{{Cite web|url=https://www.youtube.com/watch?v=5iF30TVLaRE|title=Managing Orthostatic Intolerance|last=|first=|date=Sep 1, 2010|website=YouTube|publisher=SolveCFS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/26967958 Recognizing postural orthostatic tachycardia syndrome]<ref>{{Cite journal|last=Pavlik|first=Daniel|last2=Agnew|first2=Donna|last3=Stiles|first3=Lauren|last4=Ditoro|first4=Rachel|date=2016|title=Recognizing postural orthostatic tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26967958|journal=JAAPA: official journal of the American Academy of Physician Assistants|volume=29|issue=4|pages=17–23|doi=10.1097/01.JAA.0000481398.76099.09|issn=1547-1896|pmid=26967958|via=}}</ref>
*2016, [http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/ The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained?]<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/|title=The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained? - Health Rising|last=Johnson|first=Cort|date=2016-07-04|work=Health Rising|access-date=2018-08-16|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==See also==

*[[Tilt table test]]

== References ==
<references>
<ref name="Hoad, 2008">{{Citation
| last1 = Hoad | first1 = A. | authorlink1 =
| last2 = Spickett | first2 = Gavin | authorlink2 =
| last3 = Elliott | first3 = J. | authorlink3 =
| last4 = Newton | first4 = Julia | authorlink4 = Julia Newton
| title = Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.
| journal = QJM: monthly journal of the Association of Physicians | volume = 101 | issue = 12 | page = 961-5
| date = 2008
| pmid = 18805903
| doi = 10.1093/qjmed/hcn123
}}
</ref>
<ref name="Reynolds2014">{{citation
| last1 = Reynolds | first1 = GK | authorlink1 =
| last2 = Lewis | first2 = Donald P | authorlink2 = Donald Lewis
| last3 = Richardson | first3 = AM | authorlink3 =
| last4 = Lidbury | first4 = Brett A | authorlink4 = Brett Lidbury
| display-authors =
| title = Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort
| journal = Journal of Internal Medicine | volume = Volume 275, Issue 4 | pages = 409–417
| date = April 2014
| pmid = 24206536 | doi = 10.1111/joim.12161
| url = http://onlinelibrary.wiley.com/doi/10.1111/joim.12161/abstract
}}</ref>
<ref name="Roerink, 2016">{{Cite journal|last=Roerink|first=M. E.|last2=Lenders|first2=J. W. M.|last3=Schmits|first3=I. C.|last4=Pistorius|first4=A. M. A.|last5=Smit|first5=J. W.|last6=Knoop|first6=H.|last7=van der Meer|first7=J. W. M.|date=2016-10-02|title=Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome|url=https://doi.org/10.1111/joim.12564|journal=Journal of Internal Medicine|language=en|volume=281|issue=2|pages=179–188|doi=10.1111/joim.12564|issn=0954-6820}}
</ref>
<ref name="Ross, 2013">{{Citation
| last1 = Ross | first1 = A. J. | authorlink1 =
| last2 = Medow | first2 = M. S. | authorlink2 = Marvin Medow
| last3 = Rowe | first3 = P. C. | authorlink3 = Peter Rowe
| last4 = Stewart | first4 = J. M. | authorlink4 =
| title = What is brain fog? An evaluation of the symptom in postural tachycardia syndrome.
| journal = Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society | volume = 23 | issue = 6 | page = 305–311
| date = 2013
| doi = 10.1007/s10286-013-0212-z
}}
</ref>
<ref name="Strassheim, 2018">{{Citation
| last1 = Strassheim | first1 = V | authorlink1 =
| last2 = Welford | first2 = J | authorlink2 =
| last3 = Ballantine | first3 = R | authorlink3 =
| last4 = Newton | first4 = JL | authorlink4 = Julia Newton
| title = Managing fatigue in postural tachycardia syndrome (PoTS): The Newcastle approach.
| journal = Autonomic Neuroscience | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autneu.2018.02.003
}}
</ref>
</references>
[[Category:Diagnoses]]
[[Category:Comorbidities]]
[[Category:Signs and symptoms]]
[[Category:Cardiac signs and symptoms]]

Myalgic encephalomyelitis

2018-08-18T00:17:34Z

Bill:fix main template

'''Myalgic Encephalomyelitis''' (ME) is a chronic, [[inflammatory]], physically and [[neurological|neurologically]] disabling disease that presents with symptoms involving multiple bodily systems. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[autonomic nervous system]] (ANS), [[immune system]], [[cardiovascular system]], [[endocrine system]], [[digestive system]], and [[musculoskeletal system]].<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic forms since at least the 1930s.

A hallmark symptom of ME is [[Post-exertional malaise|post-exertional malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical effort.<ref name=":0">[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - NIH]</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref name=":3">[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":4">[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":5">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref name=":6">[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and easy [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. [[Autonomic nervous system]] dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]], [[Orthostatic intolerance|orthostatic hypotension]], [[cold intolerance]] and [[heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], sound, [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain).

Among adults, ME is more common in women than men. New onset has been observed in children and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>

There are no approved pharmacological treatments for ME anywhere in the world, except in [[Argentina]], which has approved the immunomodulator [[Ampligen]] for [[ME/CFS]] as off August 23, 2016.<ref>{{Cite news|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|work=GlobeNewswire News Room|access-date=2018-08-12|language=en-US|first=Hemispherx Biopharma,|last=Inc.|date=Aug 23, 2016|archive-url=|archive-date=|dead-url=}}</ref>
== History ==

{{Main article | page_name =History of myalgic encephalomyelitis and chronic fatigue syndrome}}

ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

==Disease Name==

{{Main article |page_name = Names of myalgic encephalomyelitis and chronic fatigue syndrome}}
* ''Myalgic adj. - of or relating to [[myalgia]].'' Is [[muscle pain]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myalgic|title=myalgic|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Encephalo'': Refers to the [[brain]].<ref>{{Cite news|url=https://medical-dictionary.thefreedictionary.com/encephalo-|title=encephalo-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Myel'': Relating to the [[spinal cord]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myel-|title=myel-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Itis'': [[Inflammation]].<ref>{{Cite news|url=https://www.thefreedictionary.com/-itis|title=Itis|work=TheFreeDictionary.com|access-date=2018-08-12|last=|first=|date=|archive-url=|archive-date=|dead-url=}}</ref>
The name myalgic encephalomyelitis<ref>{{Cite news|url=https://www.verywell.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis: Chronic Fatigue Syndrome's Other Name|last=Dellwo|first=Adrienne|date=Jul 23, 2018|work=Verywell Health|access-date=2018-08-12|archive-url=|archive-date=|dead-url=}}</ref> was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital]</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign myalgic encephalomyelitis, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], and [[systemic exertion intolerance disease]]. This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome|chronic fatigue syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref> Most government agencies and researchers around the world use the term [[ME/CFS]].{{Citation needed}}

== Onset ==
Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the [[central nervous system]]. It is this second phase, persistent phase that is most ME.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In others, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold.
==Signs and Symptoms==

Symptoms can range from mild to very severe and can include:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*[[low-grade fever]], [[Temperature dysregulation|temperature instability]]
*[[post-exertional malaise]]
*[[Cognitive dysfunction]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[Headache]]
*[[myalgia|myalgia (muscle pain)]]
*[[neuralgia|neuralgia (nerve pain)]]
*[[ataxia|ataxia (coordination difficulties)]]
*[[gastrointestinal]] symptoms
*[[sleep dysfunction]]
*neck and back or spinal cord stiffness
*sensitivity to [[Light sensitivity|light]], [[Hyperacusis|sound]] and/or [[Allodynia|touch]]
*sensitivity to [[Temperature sensitivity|heat or cold]]

</div>

Symptoms presentation and severity can vary considerably day to day and even hour to hour.<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> Overexertion can make all symptoms worse, the effects are often delayed and may not be seen within 24 hours.<ref>[http://www.investinme.org/landerP5.shtml What is ME - Invest in ME Research]</ref> <ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> The US [[National Institutes of Health]] notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome]</ref>

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by physical or cognitive activity beyond a patient's limits, which typically entails anaerobic activity <ref>{{Cite web|url=https://www.me-pedia.org/wiki/Unrest|title=Unrest - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

=== Post-exertional malaise ===
{{Main article | page_name =Post-exertional malaise}}
A core symptom, [[Post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" /><ref name=":6" />

== Clinical Findings ==
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*reaction to physical and mental activity and sensory input
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]]
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*high titers to specific infection
*low red blood cell [[magnesium]]

</div>
==Diagnosis==

{{Main article | page_name =Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}

There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.

=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely most heterogenous definition. (The US [[Institute of Medicine report]] called for its complete retirement<ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped]</ref>). The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, [[brucellosis]], or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

"The later course of ME is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

==Clinical Subtypes==
There are no standard subtypes. Some researchers and clinicians have proposed distinguishing between a relapsing-remitting and progressive course.{{Citation needed}} However, it is difficult to distinguish between natural variation in the population of ME patients who might share a common disease process but owing to individual, genetic, or environmental differences, have different symptom clusters or disease course versus heterogeneity created by imprecise criteria and misdiagnosis.<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref>[http://me-ireland.com/genes2.pdf Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online]</ref>

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

==Pathophysiology==
{{Main article | page_name =List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
{{Main article |page_name =Central nervous system}}Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

=== Autonomic nervous system ===
{{Main article |page_name =Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |page_name =Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |page_name =Muscle}}

=== Immune system ===
{{Main article |page_name =Immune system}}

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].

=== Cardiovascular ===
Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

=== Gastrointestinal system ===
{{Main article |page_name =Gastrointestinal system}}

== Sex Differences ==
{{Main article |page_name = Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome]] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

==Risk Factors and Potential Causes==

{{Main article | page_name =Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>[http://via.library.depaul.edu/csh_etd/117/ Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University]</ref><ref>[http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis Vagus nerve infection hypothesis - MEpedia]</ref><ref>[http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm Chronic Fatigue Syndrome - Cleveland Clinic]</ref><ref>[https://www.ncbi.nlm.nih.gov/pubmed/26475444/ Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed]</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26604026 Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed]</ref><ref>[http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome]</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>[https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948 Klimas ME/CFS Genes Study - Face Book - Video]</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in allergy and more likely to attack the body.<ref>[http://www.sciencedirect.com/science/article/pii/S1043466614006024 Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect]</ref><ref>[http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF]</ref>

===Viruses===

{{Main article |page_name = Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>[https://www.ncbi.nlm.nih.gov/pubmed/2841461 Coxsackie B viruses and myalgic encephalomyelitis.]</ref><ref>[http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/ Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS]</ref> <ref>[https://www.ncbi.nlm.nih.gov/pubmed/22927850 Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.]</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===

{{Main article |page_name = Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[Lyme disease]]. Another bacterium that has been implicated in ME is [[Chlamydia pneumoniae]].<ref>[http://med.stanford.edu/chronicfatiguesyndrome/infections/chlamydia/chlamydia-experts.html Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative]</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>[http://www.nytimes.com/health/guides/test/csf-oligoclonal-banding/overview.html CSF Oligoclonal Banding - NY Times]</ref>

The [[Vagus nerve infection hypothesis]] accounts for why so many different infectious onsets could be responsible. The vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>

==Treatments==

{{Main article |page_name = Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no cure for ME and no country as approved any pharmacological treatment for the disease except, [[Argentina]] which has approved [[Ampligen]] for the treatment of [[chronic fatigue syndrome]]. However the effectiveness of Ampligen is under dispute<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|title=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|website=www.bizjournals.com|access-date=2018-08-12}}</ref>. Other off label medications have been used with varying effectiveness in some patients.<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Valganciclovir|title=Valganciclovir - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref><ref>{{Cite web|url=https://www.me-pedia.org/wiki/Oxymatrine|title=Oxymatrine - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

Treatments being trialled include an antiviral drug called [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and an immune system modulator drug called [[Rituximab]].<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref>

==Epidemiology==

{{Main article |page_name = Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>[http://www.hfme.org/methemedicalfacts.htm Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?]</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> In children the sex ratio is approximately equal.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

== Co-morbidities ==
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions,<ref>{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-08-12}}</ref> and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and [[idiopathic intracranial hypertension|intracranial hypertension]] (IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== See also ==

*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
<references />

UK CFS/ME Research Collaborative

2018-08-18T00:16:42Z

Bill:/* Conference */ fix

The '''UK CFS/ME Research Collaborative''' (CMRC) is a UK group of researchers and [[ME/CFS]] patient groups led by Professor [[Stephen Holgate]].<ref>[http://www.meassociation.org.uk/2013/10/uk-mecfs-research-collaborative-executive-board-minutes-of-meeting-held-on-7-october-2013/ "UK ME/CFS Research Collaborative executive board | summary of meeting held on 7 October 2013"]</ref> Its launch in 2013 was covered by the [[Science Media Centre]].<ref>[http://www.sciencemediacentre.org/chronic-fatigue-syndrome-unravelling-the-controversy/ Chronic Fatigue Syndrome – unraveling the controversy]</ref>

Membership is open to researchers, health care professionals, charities and patients. Associate membership is free, enabling patients to receive updates & take part in sessions at the conference.<ref>[http://www.meassociation.org.uk/research2015/cfsme-research-collaborative/cmrc-executive-committee-becoming-a-member/ Becoming a member]</ref> Patient groups represented include the [[ME Association]], [[Action for ME]] and the [[Association of Young People with ME]].

In May 2017, [[ME Research UK]], who had previously been a member, announced, via Facebook, that they had withdrawn their membership.<ref>[ME Research UK & UK CFS/ME Research Collaborative ME Research UK - Facebook]</ref>

A number of patient groups and charities have declined to join. These include [[Invest in ME]], [[Tymes Trust]], and the [[25 Percent ME Group]].

== Aims ==
The collaborative was set up with the intention of:
*providing a mechanism for M.E. charities, researchers and clinicians to work together in a coordinated and collaborative way,
*increasing awareness of M.E. within the research community,
*highlighting priorities for research funding to assist funders such as the [[Medical Research Council]]
*increasing funding for M.E. research.

==The Grand Challenge==
The [[Grand Challenge]] is a UK study announced in 2015 and aiming to collect a large sample size (10,000+) of data from people with M.E.

==Criticism==

The collaborative has been criticised for not using [[post-exertional malaise]] as a mandatory symptom in research.<ref>[http://www.stonebird.co.uk/CMRC.pdf Compromise is not acceptable - By: Stonebird]</ref><ref>[http://www.meassociation.org.uk/2015/10/post-exertional-malaise-in-mecfs-medical-research-council-announces-new-neuroimaging-research-16-october-2015/ Post-exertional malaise in ME/CFS | Medical Research Council announces new neuroimaging research | 16 October 2015 - ME Association - Dr. Charles Shepherd]</ref><ref>[http://www.shoutoutaboutme.com/advocacy/whats-wrong-with-the-uk-cfsme-research-collaborative/ Rocky Start for CFS/ME Collaborative - Shout Out About ME - By: Russell Logan]</ref><ref>[http://phoenixrising.me/archives/16786 Launch of inclusive UK CFS/ME Research Collaborative - By: Simon McGrath]</ref> [[Invest in ME]] compared the Collaborative unfavourably with their own [[Invest in ME International ME Conference]],<ref>[http://www.investinme.org/IIME-Newslet-1304-01.htm "A tale of two collaboratives"]</ref> whilst the [[Tymes Trust]] raised issues about rules on debating controversial issues.<ref>[https://www.facebook.com/tymestrust/posts/1494167207535083 "BEHIND THE SCENES: SETTING UP THE UK CFS/ME RESEARCH COLLABORATIVE (UK CMRC)"]</ref>

The [[25 Percent ME Group]] stated in declining membership, "It is wholly unacceptable for people with chronic fatigue and mental health issues to be included in research for [[Myalgic Encephalomyelitis]] and for people with [[Myalgic Encephalomyelitis]] to be used for [[Chronic Fatigue]] research."<ref>[http://www.25megroup.org/info_news.html#CMRC STATEMENT FROM THE 25% ME GROUP REGARDING THE CFS/ME RESEARCH COLLABORATIVE CHARTER (CMRC) MAY 2013]</ref>

The involvement of the [[Science Media Centre]] has also been questioned. See [[Science Media Centre]]: [http://me-pedia.org/wiki/Science_Media_Centre#Criticism Criticism].

==Conference==
''{{main article|page_name =CFS/ME Research Collaborative Conference}}''

==Minutes==
*[https://www.meassociation.org.uk/wp-content/uploads/CMRC-Draft-Minutes-10.07.18.pdf DRAFT Minutes of UK CFS/ME Research Collaborative Executive Board Meeting 10 July 2018]
*[https://www.actionforme.org.uk/uploads/images/2018/05/Draft_Chair_approved_mins_24.4.18.pdf DRAFT Minutes of UK CFS/ME Research Collaborative Executive Board Meeting, 24 April 2018]
*[https://www.actionforme.org.uk/uploads/pdfs/draft-crmc-minutes-15-01-16.pdf DRAFT Minutes of CMRC Minutes of CMRC Meeting Meeting Meeting 15 January 2016]
*[https://www.actionforme.org.uk/uploads/pdfs/CMRC-draft-minutes-111115.pdf DRAFT Minutes of CMRC Meeting 11 November 2015]

==Executive Board - 2018==
(As per [[ME Association]] website.<ref>[http://www.meassociation.org.uk/research/cfsme-research-collaborative/cmrc-executive-committee-becoming-a-member/ CMRC Executive Board and Becoming a Member - ME Association]</ref>)
===Executive board members:===
*Chair, Professor [[Stephen Holgate]], (University of Southampton)
*Deputy Chair, Professor [[Chris Ponting]] (Section Head, Biomedical Genomics, Chair of Medical Bioinformatics MRC/University of Edinburgh)

*Professor [[Patrick Chinnery]] (MRC Mitochondrial Biology Unit, and Dept. of Clinical Neurosciences, Cambridge University),
*Dr [[Joanna Elson]] (Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle),
*Dr [[Neil Harrison]] (Wellcome Clinician Scientist and Reader in Neuropsychiatry, Research Lead for the Department of Neuroscience, Sussex University),
*Prof [[Paul Little]] (Professor of Primary Care Research within Medicine, University of Southampton),
*Professor [[Carmine Pariante]] (Biological Psychiatry and Head of section, King’s College London),
*Professor [[Colin Smith]] (Functional Genomics, Brighton University),
*[[Sonya Chowdhury]], CEO, Action for M.E.
*Dr [[Charles Shepherd]], Hon. Medical Adviser, The [[ME Association]]
*Chris Macdonald/Craig Bullock (Arthritis Research UK),
*CMRC Patient Reference Group,
*Michael Dalrymple (MRC-Technology),
*Mark Edwards (Lay member with pharma/industry experience),<ref>[https://uk.linkedin.com/in/edwardsmark2? Mark Edwards - Linked In]</ref>
*Lars Erwig (Senior Director Discovery Medicine, GSK),
*Mark Jones (UCB Pharma),

===Official observers:===
*Ana Atunes-Martin (Programme Manager for population sciences and public health, MRC),
*Dr [[Gabrielle Murphy]] (BACME),
*Representative from the [[National Institute for Health Research]] (NIHR).

==Executive Board - 2017==
*[[Stephen Holgate]] (Chair)
*[[Esther Crawley]] (Vice-Chair)
*[[Sonya Chowdhury]], CEO, Action for ME
*James Brodie – GWPharma
*Mike Dalrymple (MRCT)
*Mark Edwards – EMIG
*Mark J Edwards
*[[Zoe Gotts]], Northumbria University
*Neeha Isaar-Brown, [[Medical Research Council]]
*Mark Jones - UCB
*Claire Kidgell
*Paul Little, Southampton University
*[[Gabrielle Murphy]]
*Jen McKendrick
*[[Julia Newton]], Newcastle University
*Carmine Pariante
*Hugh Perry, Southampton University
*Chris Ponting
*[[Charles Shepherd]], [[ME Association]]
*Raliza Stoyanova
*Edward Sykes, [[Science Media Centre]]
*Allison Wallace, Wellcome Trust observer
*Des Walsh
*Mary-Jane Willow, [[Association of Young People with M.E.]]

==Online presence==
*[https://www.actionforme.org.uk/research/uk-cfsme-collaborative/ UK CFS/M.E. Research Collaborative] (hosted by [[Action for ME]])

==Learn more==
*2016, [http://phoenixrising.me/archives/27889 The Power and Pitfalls of Omics: [[George Davey Smith]]’s storming talk at ME/CFS conference (Pt 1 of 2)]
*2016, [https://www.actionforme.org.uk/news/ceo-blog-prof-george-davey-smith-on-the-grand-challenge/ CEO blog: Prof [[George Davey Smith]] on the [[Grand Challenge]]]
*2013, [http://www.meresearch.org.uk/news/uk-research-collaborative/ UK Research Collaborative]
*2013, [http://www.meassociation.org.uk/research2015/cfsme-research-collaborative/ CFS/ME Research Collaborative]

==See also==
*[[Grand Challenge]]

==References==
<references>
</references>
[[Category:Research initiatives]]
[[Category:British research initiatives]]

Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome

2018-08-18T00:16:21Z

Bill:fix main template

Worldwide, an estimated 15 to 20 million people{{Citation needed}} have [[myalgic encephalomyelitis]]. It is more prevalent in women than men and affects children as young as X and adults as old as X. In 80% of causes, the onset follows an acute infection.

==Incidence and Prevalence==

The prevalence rate is projected at 0.2%<ref name=":0" /><ref name=":5" />-0.4%<ref name="Jason, 1999" /><ref>{{Cite news|url=https://mecfsresearchreview.me/2018/06/11/analysis-of-data-from-500000-individuals-in-uk-biobank-demonstrates-an-inherited-component-to-me-cfs/|title=Analysis of data from 500,000 individuals in UK Biobank demonstrates an inherited component to ME/CFS|date=2018-06-11|work=ME/CFS Research Review|access-date=2018-08-11|language=en-US}}</ref> although estimates vary widely due to different definitions and sampling methods used<ref>{{Cite journal|last=Johnston|first=Samantha|last2=Brenu|first2=Ekua W.|last3=Staines|first3=Donald|last4=Marshall-Gradisnik|first4=Sonya|date=2013|title=The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/23576883|journal=Clinical Epidemiology|volume=5|pages=105–110|doi=10.2147/CLEP.S39876|issn=1179-1349|pmc=3616604|pmid=23576883}}</ref>.

Estimated incidence rates – generally, the number of new cases in a single year – vary from 0.025%<ref name=":2">{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=Håberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://www.ncbi.nlm.nih.gov/pubmed/25274261|journal=BMC medicine|volume=12|pages=167|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmc=4189623|pmid=25274261}}</ref> to 0.3% of the population.

=== Incidence and prevalence by country ===

{| class="wikitable"
!Country
!Incidence
!Prevalence rate
!Total number
|-
|Australia
|
|
|242,000 people have CFS (of which 94,000 meet a narrower definition for ME).<ref>''Emerge Quarterly Journal'', AUTUMN 2016 - Vol 36 - No 1, page 14, Mar 2016</ref>
|-
|United Kingdom
|0.015%<ref name=":0">{{Cite journal|last=Nacul|first=LC|date=July 2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|url=https://www.ncbi.nlm.nih.gov/pubmed/21794183|journal=BMC Medicine|volume=9|pages=91|via=}}</ref>
|0.03-0.19%<ref name=":0" />
|250,000{{Citation needed}}
|-
|United States
|
|
|836,000 to 2.5 million{{Citation needed}}
|-
|The Netherlands
|
|0,11%<ref>Bazelmans E, Vercoulen J.H.M.M, Galama J.M.D, Van Weel, C, Van Der Meer J.W.M, Bleijenberg G. (1997). [https://www.ntvg.nl/system/files/publications/1997115200001a.pdf Prevalentie van het chronische-vermoeidheidssyndroom en het primaire-fibromyalgiesyndroom in Nederland.] Nederlands Tijdschrift voor Geneeskunde; 141: 1520-1523. </ref><ref>Versluis R.G.J.A, De Waal M.W.M, Opmeer C, Petri H, Springer M.P. (1997). [https://www.ntvg.nl/system/files/publications/1997115230001a.pdf Prevalentie van het chronische-vermoeidheidssyndroom in 4 huisartspraktijken in de regio Leiden.] Nederlands Tijdschrift voor Geneeskunde; 141(31): 1523-26. </ref>
|30.000-40.000<ref>[https://www.gezondheidsraad.nl/sites/default/files/grpublication/kernadvies_me_cvs_1.pdf Gezondheidsraad. ME/CVS. Den Haag: Gezondheidsraad, 2018; publicatienr. 2018/07.]</ref>
|}

=== Incidence and prevalence by definition ===
{| class="wikitable"
!Method
!12-month incidence
!Prevalence rate
|-
|[[Postviral fatigue syndrome]] (ICD-10-CM G93.3 in a national health registry in Norway)
|0.025%<ref>{{Cite journal|last=Magnus|first=P|date=November 17, 2015|title=Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine|url=https://www.ncbi.nlm.nih.gov/pubmed/26475444|journal=Vaccine|volume=33|pages=6173-7|via=}}</ref> (NO)
|–
|-
|[[Fukuda criteria|Fukuda Criteria (CDC-1994 definition]])
|
|0.19%<ref name=":0" /> (UK), 0.24%<ref name=":5">{{Cite journal|last=Reyes|first=Michele|date=July 14, 2003|title=Prevalence and Incidence of Chronic Fatigue Syndrome in Wichita, Kansas|url=https://www.ncbi.nlm.nih.gov/pubmed/12860574|journal=JAMA Internal Medicine|volume=163|pages=1530-1536|via=}}</ref> (US. Kansas), 0.42%<ref name="Jason, 1999" /> (US, Chicago),
|-
|[[Canadian Consensus Criteria]] (CCC)
|
|0.11%<ref name=":0" /> (UK)
|-
|Empirical definition (Reeves criteria)
|
|2,54%<ref>{{Cite journal|last=Reeves|first=William C.|last2=Jones|first2=James F.|last3=Maloney|first3=Elizabeth|last4=Heim|first4=Christine|last5=Hoaglin|first5=David C.|last6=Boneva|first6=Roumiana S.|last7=Morrissey|first7=Marjorie|last8=Devlin|first8=Rebecca|date=2007-06-08|title=Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia|url=https://www.ncbi.nlm.nih.gov/pubmed/17559660|journal=Population Health Metrics|volume=5|pages=5|doi=10.1186/1478-7954-5-5|issn=1478-7954|pmc=1904178|pmid=17559660}}</ref>
|-
|[[Epidemiological Case Definition]] (ECD)
|
|0.03%<ref name=":0" /> (UK)
|-
|
|0.015%<ref name=":0" /> (UK)
|
|-
|Diagnoses reported by general practitioners and pediatricians in the Netherlands (criteria unspecified)
|0.012%<ref name=":1">{{Cite journal|last=Nijhof|first=Sanne|date=April 2011|title=Adolescent Chronic Fatigue Syndrome: Prevalence, Incidence, and Morbidity|url=http://pediatrics.aappublications.org/content/early/2011/04/18/peds.2010-1147|journal=Pediatrics|volume=|pages=|via=}}</ref> (NL, 10-18 year olds)
|0.11%<ref name=":1" /> (NL, 10-18 year olds)
|}

== Sex ==

{{Main article | page_name =Sex differences in myalgic encephalomyelitis}}

[[File:Age and Gender distribution.png|thumb|Age and gender distribution of ME/CFS.<ref name=":2" />]]
Numerous studies have found the rates of [[ME/CFS]] to be substantially higher in adult women than in men, with estimates ranging from 75-85%.<ref name="Jason, 1999" /><ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=Håberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://www.ncbi.nlm.nih.gov/pubmed/25274261|journal=BMC medicine|volume=12|pages=167|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmc=4189623|pmid=25274261}}</ref><ref>{{Cite book|title=Ciba Foundation Symposium 173 ‐ Chronic Fatigue Syndrome|last=Gunn|first=Walter|publisher=|year=1993|isbn=|location=|pages=|chapter=Epidemiology of Chronic Fatigue Syndrome: The Centers for Disease Control Study}}</ref>

A higher preponderance of women has also been noted in numerous [[outbreaks]] including [[1934 Los Angeles atypical polio outbreak|Los Angeles]], [[Akureyri]], [[1953 Maryland outbreak|Rockville, MD]], [[1955 Royal Free Hospital outbreak|Royal Free Hospital]], and [[1956 Punta Gorda outbreak|Punta Gorda, Florida]].<ref name=":02">{{Cite journal|last=Parish|first=JG|date=1978|title=Early outbreaks of 'epidemic neuromyasthenia'|url=https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54|pages=711-7|via=}}</ref><ref name="Shelokov, 1957">{{Citation
| last1 = Shelokov | first1 = Alexis | authorlink1 =
| last2 = Habel | first2 = Karl | authorlink2 =
| last3 = Verder | first3 = Elizabeth | authorlink3 =
| last4 = Welsh | first4 = William | authorlink4 =
| title = Epidemic Neuromyasthenia — An Outbreak of Poliomyelitis-like Illness in Student Nurses
| journal = New England Journal of Medicine | volume = 1957 | issue = 257 | page = 345-355
| date = August 1957
| doi = 10.1056/NEJM195708222570801
}}</ref><ref name="Gilliam, 1936-38">{{Citation
| last1 = Gilliam | first1 = A.G. | authorlink1 =
| title = Epidemiological Study Of An Epidemic, Diagnosed As Poliomyelitis, Occurring Among The Personnel Of The Los Angeles County General Hospital During The Summer Of 1934
| journal = Public health bulletin, 1936-1938 | volume = no.231-240 | issue = | page =
| date = 1938
| pmid =
| url = http://babel.hathitrust.org/cgi/pt?id=mdp.39015022082260;view=1up;seq=617
}}</ref><ref name="Acheson, 1959">{{Citation
| last1 = Acheson | first1 = E.D. | authorlink1 =
| title = The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia
| journal = American Journal of Medicine | volume = 26 | issue = 4 | page = 569–595
| date = 1959
| pmid =
| url = http://www.name-us.org/defintionspages/DefinitionsArticles/Acheson1959.pdf
}}</ref><ref name="Poskanzer, 1957">{{Citation
| last1 = Poskanzer | first1 = David C. | authorlink1 =
| last2 = Henderson | first2 = Donald A. | authorlink2 =
| last3 = Kunkle | first3 = E. Charles | authorlink3 =
| last4 = Kalter | first4 = Seymour S. | authorlink4 =
| last5 = Clement | first5 = Walter B. | authorlink5 =
| last6 = Bond | first6 = James O. | authorlink6 =
| title = Epidemic Neuromyasthenia — An Outbreak in Punta Gorda, Florida
| journal = New England Journal of Medicine | volume = 1957 | issue = 257 | page = 356-364
| date = 1957
| pmid = 13464939
| doi = 10.1056/NEJM195708222570802
| url = http://www.nejm.org/doi/full/10.1056/NEJM195708222570802
}}</ref><ref name=":3">{{Cite journal|date=1957-10-19|title=An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/|journal=British Medical Journal|volume=2|issue=5050|pages=895–904|issn=0007-1447|pmc=1962472|pmid=13472002}}</ref><ref name=":4">{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/14771044|title=A disease epidemic in Iceland simulating poliomyelitis|last=Sigurdsson|first=B|date=September 1950|journal=American Journal of Hygiene|volume=52|pages=222-38|via=}}</ref> In some cases, this was thought to do with the occupational hazard of nursing, but this female-skewed sex ratio was also found in several outbreaks among the general population. However, in other outbreaks, including the 1949-1953 [[1949-53 Adelaide outbreak|Adelaide]] outbreak and an outbreak in [[1955 North of England outbreak|northern England in 1955]], a 1:1 gender ratio was reported.<ref name=":02" /> In Akureyri, a significantly higher incidence rate was found among adult women but not in patients under twenty.<ref name=":4" />

== Age ==
New cases of myalgic encephalomyelitis have been in children as young as eight and adults in their eighties. In terms of ''incidence'', a study in [[Norway]] found two age peaks, one between 10 and 19 years and a second peak between 30 and 39 years.<ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=Håberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://www.ncbi.nlm.nih.gov/pubmed/25274261|journal=BMC medicine|volume=12|pages=167|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmc=4189623|pmid=25274261}}</ref> In terms of ''prevalence'', Jason found that individuals in the 40- to 49-year-old age range exhibited the highest prevalence rates of CFS.<ref name="Jason, 1999" />

== Race and ethnicity ==
In 1999, a community-based study by Dr [[Leonard Jason]], et al, performed in the Chicago area found that individuals who identified as people of color exhibited higher rates of CFS than whites, with Latino participants demonstrating the highest CFS prevalence.<ref name="Jason, 1999" />

== Socioeconomic characteristics ==
The prevalence of CFS was highest among skilled workers and lowest among professionals.<ref name="Jason, 1999" />

== Severity ==

[[File:HRQoL-journal.pone.0132421.g003.PNG|200px|thumb|right|Comparison of disability for ME/CFS and other conditions]]

People with ME/CFS are more disabled and socially marginalized than for most other chronic illnesses.<ref>Falk Hvidberg et al, [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132421 The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)], ''PLOS One'', 5 Jul 2015.</ref>

Around 25 per cent of people with ME/CFS will have a mild form and be able to get to school or work either part-time or full-time, while reducing other activities. About 50 per cent will have a moderate to severe form of ME/CFS and not be able to get to school or work. Another 25 per cent will experience severe ME/CFS and have to stay at home or in bed.{{Citation needed}}

In the US, 50-75% of patients with [[ME/CFS]] cannot work.{{Citation needed}}

== Risk factors ==

=== Genetics ===

{{Main article|page_name =Genetics of chronic fatigue syndrome}}

5% of children of mothers with ME/CFS later developed the illness.<ref>http://www.njcfsa.org/wp-content/uploads/2010/09/Pregnancy-in-Women-with-ME-CFS.pdf</ref>

=== Infection ===
Infection is a major risk factor for the development of [[post-viral fatigue syndrome]], [[chronic fatigue syndrome]], and [[myalgic encephalomyelitis.]]

== Prognosis ==

On average, many people with ME/CFS will improve in the first five years, but others may mainly stay at home or in bed, or may suffer relapses throughout their lives.{{Citation needed}}

==Mortality==

One study found no increased risk of all cause mortality or mortality from [[cancer]] but an increased risk of suicide. Suicide risk was increased 6.85 compared to the general population.<ref>{{Cite journal|last=Roberts|first=Emmert|last2=Wessely|first2=Simon|last3=Chalder|first3=Trudie|last4=Chang|first4=Chin-Kuo|last5=Hotopf|first5=Matthew|date=Apr 2016|title=Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01223-4/abstract|journal=The Lancet|language=English|volume=387|issue=10028|pages=1638–1643|doi=10.1016/S0140-6736(15)01223-4|issn=0140-6736}}</ref> It was based on a cohort that used multiple clinical criteria, including the [[Oxford criteria]].<ref>[https://jcoynester.wordpress.com/2016/02/16/bad-stats-non-sequitur-conclusions-in-lancet-chronic-fatigue-syndromesuicide-study/ Interpretive jiggery-pokery in The Lancet A tale of a convenience sample with inconvenient serious limitations.] Quick Thoughts, a blog by James Coyne, February 16, 2016</ref> A Spanish study found a suicide risk of 12.75% versus 2.3% in the general population.<ref>{{Cite news|url=https://afectadasporlosrecortessanitarios.wordpress.com/2016/05/11/risk-of-suicide-due-to-neglect-amongst-pwme/|title=RISK OF SUICIDE DUE TO NEGLECT AMONGST PWME|date=2016-05-11|work=Plataforma de Afectadas por los Recortes Sanitarios - La PARS|access-date=2018-08-10|language=es-ES}}</ref>

A 2006 study by Leonard Jason found that ME/CFS patients died of cancer, heart failure and suicide at considerable younger age than the general population. For example while the median age of death for cancer in the US was 72, the average age at which ME/CFS patients died of cancer was 47. And while the average age of heart failure in the general population was 83, it was only 58 in the ME/CFS sample.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Corradi|first2=Karina|last3=Gress|first3=Sara|last4=Williams|first4=Sarah|last5=Torres-Harding|first5=Susan|date=Aug 2006|title=Causes of death among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16844674|journal=Health Care for Women International|volume=27|issue=7|pages=615–626|doi=10.1080/07399330600803766|issn=0739-9332|pmid=16844674}}</ref>

.

== Learn more ==
*[[Pediatric]]
*[[Prognosis]]

== See also ==

* [[Sex differences in myalgic encephalomyelitis]]

==References==
<references>
<ref name="Jason, 1999">{{Citation
| last1 = Jason | first1 = LA | authorlink1 = Leonard Jason
| last2 = Richman | first2 = JA | authorlink2 =
| last3 = Rademaker | first3 = AW | authorlink3 =
| last4 = Jordan | first4 = KM | authorlink4 = Karen Jordan
| last5 = Plioplys | first5 = AV | authorlink5 =
| last6 = Taylor | first6 = RR | authorlink6 = Renee Taylor
| last7 = McCready | first7 = W | authorlink7 =
| last8 = Huang | first8 = C | authorlink8 =
| last9 = Plioplys | first9 = S | authorlink9 =
| title = A Community-Based Study of Chronic Fatigue Syndrome
| journal = Arch Intern Med | volume = 159 | issue = 18 | page = 2129-2137
| date = 1999
| pmid =
| doi = 10.1001/archinte.159.18.2129
}}
</ref>
</references>

[[Category:Triggers and risk factors]]
[[Category:Core topics]]

Microbiome

2018-08-18T00:15:48Z

Bill:fix main template

The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and gut. [[Dysbiosis]] or an imbalance in this community may play a role in the [[pathophysiology]] of [[chronic fatigue syndrome]].

==Anatomical areas==

===Gut flora===

The gut microbiome is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010" /> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharides]] from the cell walls of commensal bacteria. Increased IgA response was associated with increased [[serum IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref name="Logan2003" /> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.<ref>[[Reference needed]]</ref>

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicutes]] ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the stress response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis]] is introduced. [[Escherichia coli]] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, [https://www.ncbi.nlm.nih.gov/pubmed/19567398 Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome]<ref name="Sheedy2009" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016"/>
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref name="Giloteaux2016" />
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017"/> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]?<ref name="Newberry, 2018"/>

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nose microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

==References==
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<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150| issue = 3| pages = 470–480| last1 = Koren| first1 = Omry| last2 = Goodrich| first2 = Julia K.| last3 = Cullender| first3 = Tyler C.| last4 = Spor| first4 = Aymé| last5 = Laitinen| first5 = Kirsi| last6 = Bäckhed| first6 = Helene Kling| last7 = Gonzalez| first7 = Antonio| last8 = Werner| first8 = Jeffrey J.| last9 = Angenent| first9 = Largus T.| last10 = Knight| first10 = Rob| last11 = Bäckhed| first11 = Fredrik| last12 = Isolauri| first12 = Erika| last13 = Salminen| first13 = Seppo| last14 = Ley| first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03| pmid = 22863002}}</ref>

<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37| issue = 9| pages = 1369–1378| last1 = Dinan| first1 = Timothy G.| last2 = Cryan| first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| accessdate = 2016-12-13| date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>

<ref name="Giloteaux2016">{{Citation| doi = 10.1186/s40168-016-0171-4| issn = 2049-2618| volume = 4| pages = 30| last1 = Giloteaux| first1 = Ludovic| authorlink1 = Ludovic Giloteaux |last2 = Goodrich| first2 = Julia K.| last3 = Walters| first3 = William A.| last4 = Levine| first4 = Susan M.| last5 = Ley| first5 = Ruth E.| last6 = Hanson| first6 = Maureen R.| title = Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome| journal = Microbiome| accessdate = 2016-12-13| date = 2016| url = http://dx.doi.org/10.1186/s40168-016-0171-4}}</ref>

<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22| pages = 50–56| last1 = Frémont| first1 = Marc| last2 = Coomans| first2 = Danny| last3 = Massart| first3 = Sebastien| last4 = De Meirleir| first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe| date = August 2013| pmid = 23791918}}</ref>

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[[Category:Body systems]]
[[Category:Microbiome]]

Immune system

2018-08-18T00:15:34Z

Bill:fix main template

The '''immune system''' is primarily formed by the [[innate immune system]] which we are born with, and the [[adaptive immune system]] which learns how to fight pathogens (for example from vaccines, or infections we contract).

==Innate immune system==
[[Innate immune system]]

===Barriers===

[[Mucosal immune system]]

===Inflammation===

===Complement===

===Leukocytes===

===Natural killer cells===

{{Main|page_name =Natural killer cell}}

==Adaptive immune system==
[[Adaptive immune system]]

===Lymphocytes===

===Immunological memory===

==Immunodeficiency==

==Autoimmunity==

ME/CFS patients have anti-cholinergic [[Muscarinic acetylcholine receptor|muscarinic]], Β-adrenergic<ref>{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref>, [[phosphatidylinositol]]<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivanka|last3=Leunis|first3=Jean-Claude|date=Dec 2007|title=Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression|url=https://www.ncbi.nlm.nih.gov/pubmed/18063934|journal=Neuro Endocrinology Letters|volume=28|issue=6|pages=861–867|issn=0172-780X|pmid=18063934}}</ref> and [[serotonin]]<ref>{{Cite journal|last=Maes|first=Michael|last2=Ringel|first2=Karl|last3=Kubera|first3=Marta|last4=Anderson|first4=George|last5=Morris|first5=Gerwyn|last6=Galecki|first6=Piotr|last7=Geffard|first7=Michel|date=5 Sep 2013|title=In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation|url=https://www.ncbi.nlm.nih.gov/pubmed/23664637|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref> [[antibodies]] when compared to healthy controls.

==Hypersensitivity==

{{Main|page_name =Immunological hypersensitivity}}

==Chronic fatigue syndrome==

There is evidence of immune dysregulation in [[chronic fatigue syndrome]].

Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

==Learn more==
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)

==See also==
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]
*[[Adaptive immune system]]

==References==
<references />
[[Category:Body systems]]

Viral onset hypothesis

2018-08-18T00:15:18Z

Bill:/* Outbreaks */ fix

{{Cleanup | reason=citations needed (see discussion page) | date=November 2015}}
Many [[Myalgic Encephalomyelitis]] and [[Chronic Fatigue Syndrome]] patients report falling ill after an acute viral infection.<ref>Reference needed</ref> Many different viruses have been researched as possible etiological agents.

==Disease onset==
Some think there is a single, novel viral agent as yet undiscovered.

Others think many different viruses can initiate and sustain the disease. Viruses implicated in disease onset include [[herpesviruses]] such as [[Epstein-Barr virus]] or [[HHV-6]], [[enteroviruses]] such as [[coxsackie]] or even [[influenza]] (the [[flu]]).

For patients who trace their illness to a viral onset, there are several hypotheses for how the viral trigger initiates and perpetuates the disease.

===Chronic infection===
Some think that there may be a low grade, chronic infection whereby the initial virus continues to provoke an immune response, especially in key areas such as the gastrointestinal tract, muscle, and the brain, brainstem, and spinal cord.

===Autoimmune disease===
Some think that symptoms are caused by an inflammatory process that is triggered by an initial infection and continues even after the initial virus is no longer replicating. It is possible that [[ME/CFS]] is an [[autoimmune disease|autoimmune]] response that can be triggered by many different infections.

===Viral reactivation===
Still others think that an immune deficiency allows otherwise common or benign viruses to replicate.

===Dysbiosis===
Viral infection triggers [[dysbiosis]] leading to alterations in the [[immune system]] and [[gut-brain axis]] and causing the symptoms of the disease.

==Outbreaks==
:''{{main|page_name =List of outbreaks}}''

There have been dozens of reported clusters and outbreaks of ME, which all suggest a role of either a communicable pathogen or in some cases, a toxic agent.

==See also==
*[[Vagus nerve infection hypothesis]]
*[[Bacterial disease onset]]

==References==
<references>

</references>

[[Category:Medical hypotheses]]
[[Category:Triggers and risk factors]]
[[Category:Virology]]

Gastrointestinal system

2018-08-18T00:14:31Z

Bill:fix main template

The '''gastrointestinal system''' is an organ system which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. It consists of the esophagus, stomach, and intestines, and is divided into the upper and lower gastrointestinal tracts.

[[Autonomic nervous system]] dysfunction of the gut, [[dysmotility]], [[dysbiosis]], and potentially, gut [[pathogen]]s, are all thought to contribute to the symptoms of [[ME]].

== Evidence of gastrointestinal dysfunction in CFS ==

=== Dysbiosis ===

{{main|page_name =Dysbiosis}}

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. On average, ME/CFS patients have lower levels of ''[[Bifidobacteria]]'', ''[[Escherichia coli]]'' and higher levels of [[aerobic bacteria]]. <ref>{{Cite journal|last=Logan|first=Alan C|last2=Venket Rao|first2=A|last3=Irani|first3=Dinaz|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=http://www.medical-hypotheses.com/article/S0306-9877(03)00096-3/abstract|journal=Medical Hypotheses|language=English|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|issn=0306-9877}}</ref>, in particular ''[[Enterococcus]]'' and ''[[Streptococcus]]'' species<ref>{{Cite journal|last=Sheedy|first=John R.|last2=Wettenhall|first2=Richard E. H.|last3=Scanlon|first3=Denis|last4=Gooley|first4=Paul R.|last5=Lewis|first5=Donald P.|last6=McGregor|first6=Neil|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|last9=DE Meirleir|first9=Kenny L.|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=http://www.ncbi.nlm.nih.gov/pubmed/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|issn=0258-851X|pmid=19567398}}</ref>. The latter produce [[D-lactate]], a form of lactic acid only produced by non-human cells that is poorly metabolized in humans. [[D lactate]] is associated with a wide variety of cognitive and neurological symptoms, such as in patients who suffer from [[D lactate acidosis]]. A study found that higher levels of enterococcus bacteria in CFS patients were associated with more severe neurological and cognitive dysfunction<ref>https://getinfo.de/en/search/id/BLCP%3ACN055885616/%60Bacterial-Colonosis-in-Patients-with-Persistent/</ref>.

CFS patients may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at high rates.{{Citation needed}}

One hypothesized consequence of dysobiosis is an overproduction of [[hydrogen sulfide]] (H2S) by pathogenic bacteria. H2S can inhibit [[mitochondria]]l respiration by blocking [[cytochrome c oxidase]].{{Citation needed}}

A study of Norwegian and Belgian patients found significantly decreased proportions of [[Firmicutes]] genera ''[[Holdemania]]'' and increased proportions of [[Bacteroidetes]] genera ''[[Alistipes]]'' in the Norwegian but not the Belgian sample. Significantly increased proportions of [[Firmicutes]] genera ''[[Lactonifactor]]'' were found in both.<ref>{{Cite journal|date=2013-08-01|title=High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.sciencedirect.com/science/article/pii/S1075996413000929|journal=Anaerobe|language=en|volume=22|pages=50–56|doi=10.1016/j.anaerobe.2013.06.002|issn=1075-9964}}</ref>.

=== Intestinal permeability ===

{{main|page_name =Intestinal permeability}}

In a healthy digestive tract, the intestinal walls provide a tight, selective barrier to allow the absorption of nutrients prevent the entry of bacteria or pathogens. However, in CFS patients, there is evidence of increased [[intestinal permeability]] or "leaky gut." Intestinal permeability can allow for the [[translocation]] of bacteria across the mucosal lining and inside the blood stream.

One study found higher levels of serum [[Immunoglobulin A|IgA]] and [[Immunoglobulin M|IgM]] against [[lipopolysaccharides]] (LPS), a major component of the outer membrane of [[gram negative bacteria]], indicating translocation.<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=Apr 2007|title=Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability|url=http://www.jad-journal.com/article/S0165-0327(06)00355-7/abstract|journal=Journal of Affective Disorders|language=English|volume=99|issue=1-3|pages=237–240|doi=10.1016/j.jad.2006.08.021|issn=0165-0327}}</ref> Serum IgA was significantly correlated to the severity of illness.

=== Malabsorption ===

==Learn more==
*[[Gastroparesis]]
*[[Irritable bowel syndrome]]

==See also==
*[[Antibiotics]]
*[[Fecal bacteriotherapy]]
*[[Helminthic therapy]]
*[[Hygiene hypothesis]]
*[[Microbiome]]
*[[Probiotics]]

==References==
<references />
[[Category:Body systems]]
[[Category:Digestive system]]

Exercise

2018-08-18T00:14:18Z

Bill:fix main template

Exercise is any movement or activity considered to contribute to general health and well-being. Exercise may be recommended as part of a wellness regimen in chronic illness.<ref>{{Cite journal|last=Pederson|first=B.K.|last2=Saltin|first2=B.|date=2006|title=Evidence for prescribing exercise as therapy in chronic disease
|url=https://www.essa.org.au/wp-content/uploads/2015/06/Chronic-disease_Review-2006.pdf|journal=Scand J Med Sci Sports|volume=16(Suppl 1)|pages=3-63|via=}}</ref> <ref>{{Cite journal|last=Hovanec|first=Nina|last2=Bellemore|first2=Derek|last3=Kuhnow|first3=Jason|last4=Miller|first4=Felicia|last5=van Vloten|first5=Alexi|last6=Vandervoort|first6=Anthony A.|date=3 March 2015|title=Exercise Prescription Considerations for Individuals with Multiple Chronic Diseases: Systematic Review|url=https://www.omicsonline.org/open-access/exercise-prescription-considerations-for-individuals-with-multiple-chronic-diseases-systematic-review-2167-7182-1000201.php?aid=41826|journal=J Gerontol Geriatr Res|volume=4:201|pages=|via=}}<nowiki></ref> However, [[Post-exertional malaise|exercise intolerance]] is a central feature of ME/CFS, and patients show multiple documented abnormal responses to exercise. Rather than increase health and well-being, ME/CFS patients report that increased activity has reduced their physical and cognitive capacity over time, sometimes permanently.<ref>{{Cite web|url=http://www.meassociation.org.uk/wp-content/uploads/2015-ME-Association-Illness-Management-Report-No-decisions-about-me-without-me-30.05.15.pdf|title=ME Association illness management report: no decisions about me without me|last=ME Association|first=|date=May 2015|website=ME Association|archive-url=|archive-date=|dead-url=|access-date=25 April 2018}}</ref>

==Physiological effects of exercise==

Exercise causes a variety of temporary physiological changes in healthy people. This includes an increase in respiratory rate, heart rate, and blood pressure in order to keep up with higher energy demands.<ref name=":0">{{Cite journal|last=Burton|first=Deborah Anne|last2=Stokes|first2=Keith|last3=Hall|first3=George M|date=December 1, 2004|title=Physiological effects of exercise|url=https://academic.oup.com/bjaed/article/4/6/185/314696|journal=Continuing Education in Anaesthesia Critical Care & Pain|publisher=|volume=4|issue=6|pages=185-8|via=BJA Education}}</ref> The chemical reactions that break down nutrients -- [[glycolysis]], the [[Citric Acid Cycle|Krebs Cycle]], and the [[electron transport chain]] -- move more rapidly to liberate energy, and blood flow to muscles should increase. In healthy individuals, the amount of oxygen and carbon dioxide present in the blood should not alter significantly.<ref name=":0" />

===Immune system===

In healthy people, exercise induces a variety of temporary changes to immune markers. Immediately after exercise, [[natural killer cell]] activity is decreased and [[Leukotriene]] B4 (LTB4) increase, along with the LTB4/PGE2 ratio. Exercise elevates levels of [[prostaglandin]] E2 (PGE2) for up to five days.<ref name="GrayJB1994" />

=== Infection ===
Several studies of a mouse model of [[Coxsackie B3]] [[myocarditis]] have found that exercise increases the virulence of the infection and results in poorer outcomes.<ref name=":4">Cabinian AE, Kiel RJ, Smith F, Ho KL, Khatib R, Reyes MR. Modification of exercise-aggravated coxsackie virus B3 murine myocarditis by T-lymphocyte suppression in an inbred model. J. Lab. Clin. Med. 1990; 115: 454– 62.</ref><ref name=":5">Kiel RJ, Smith FE, Chason J, Khatib R, Reyes MD. Coxsackie B3 myocarditis in C3H/HeJ mice: Description of an inbred model and the effect of exercise on the virulence. Eur. J. Epidemiol. 1989; 5: 248– 67.</ref><ref name=":6">{{Cite journal|last=Ilbäck|first=NG|date=June 1989|title=Exercise in coxsackie B3 myocarditis: Effects on heart lymphocyte subpopulations and the inflammatory reaction|url=https://www.ncbi.nlm.nih.gov/pubmed/2543197|journal=American Heart Journal|volume=117|pages=1298-302|via=}}</ref><ref name=":7">{{Cite journal|last=Gatmaitan|first=Bienvenido|date=June 1, 1970|title=Augmentation of the Virulence of Murine Coxsackie Virus B-3 Myocardiopathy by Exercise|url=http://jem.rupress.org/content/131/6/1121|journal=Journal of Experimental Medicine|volume=131|pages=1121|via=}}</ref><ref name=":8">{{Cite journal|last=Reyes|first=MP|date=February 1976|title=Interferon and neutralizing antibody in sera of exercised mice with coxsackievirus B-3 myocarditis|url=https://www.ncbi.nlm.nih.gov/pubmed/1250870|journal=Proceedings of the Society for Experimental Biology and Medicine|volume=151|pages=333-8|via=}}</ref>

===Neurotransmitters===

[[Acetylcholine]], an important [[neurotransmitter]] that regulates immune response and muscle strength, decreases during exercise.

== Effects of exercise in Chronic Fatigue Syndrome ==

===Post Exertional Malaise===

[[File:2010 VanNess Post exertional worsening of symptoms chart.png|right|frame|Post-exertional worsening of symptoms, VanNess et al 2010.png|377x377px]]
[[File:2015 IOM report PEM chart.png|right|frame|PEM chart from the 2015 Institute of Medicine report|378x378px]]

[[ME]] patients who exercise are likely to experience [[Post-exertional malaise]] which is a worsening of symptoms following physical, cognitive, or sensory exertion.

Read the main page: '''[[Post-exertional malaise]]'''.

===Pain threshold===

Pain thresholds, or the point at which a stimulus becomes painful, drop in people with [[CFS]] (as per the [[Fukuda criteria]]) after graded exercise. In healthy controls, pain thresholds rise. This phenomenon has been attributed to a dysfunction of the central anti-[[nociceptive]] mechanism in [[CFS]] patients.<ref name="Whiteside, 2004" />

===Immune System===
[[Histamine]], a chemical that is released in response to cellular damage and inflammation, is released during exercise in healthy individuals. The histamine dilates blood vessels in order to deliver nutrients to working muscles.<ref>{{Cite journal|last=Romero|first=S.A.|last2=Hocker|first2=A.D.|last3=Magnum|first3=J.E.|last4=Luttrell|first4=M.J.|last5=Turnbull|first5=D.W. ...|last6=Halliwill|first6=J.R.|date=2016|title=Evidence of a broad histamine footprint on the human exercise transcriptome|url=http://doi.org/10.1113/JP272177|journal=The Journal of Physiology|volume=594|issue=17|pages=5009-5023|via=}}</ref> However, patients with ME may experience increased histamine release due to increased mast cell populations.<ref>{{Cite journal|last=Rönnberg|first=E|last2=Calounova|first2=G|last3=Pejler|first3=G|date=June 2017|title=Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pubmed/27362406|journal=Asian Pac J Allergy Immunol|volume=35|issue=2|pages=75-81|via=}}</ref>

===Microbiome===

A small study of ten CFS patients found significant changes in the composition of the [[microbiome]] and increased bacterial translocation (movement from the [[intestine]] into the [[blood|bloodstream]]) following exercise. The study found increased ''[[Clostridium]]'' in the blood fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="ShuklaS2015" />

=== Musculature ===

Exercise has also been found to induce both early and excessive lactic acid formation in the [[muscle fatigability|muscles]]<ref name="Plioplys1995" /> with reduced intracellular concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref name="McCully1996" /> Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by [[deconditioning]].<ref name="LaneRJ1998" /> There is evidence of abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.<ref name="JonesDE2010" /><ref name="LengertN2015" />

There is also evidence of loss of capacity to recover from acidosis on repeat exercise.<ref name="JonesDE2012" />

Finally, there is evidence of abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.<ref name="BrownAE2015" /><ref name="Wellness20150420" />
[[File:Light2011-geneexpression-figure3.jpg|right|frame|Gene expression changes following moderate exercise (Light et al, 2011)|516x516px]]
=== Gene expression ===

There is evidence of increased expression of certain genes following muscular exertion.<ref name="LightAR2009" /><ref name="LightAR2011" /><ref name="WhiteAT2012" /> A 2011 study found that moderate exercise in CFS increased the expression of 13 genes (sensory, adrenergic and 1 cytokine) for 48 hours, and the increases correlated with fatigue and pain levels.<ref name="LightAR2011" /> (see graph at right)

=== Second day exercise test ===
{{Main article|page_name =Two-day cardiopulmonary exercise testing}}

The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by [[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise"<ref name="VanNess2007" /> A repeat study in 2013 confirmed these results.<ref name="SnellCR2013" />

In a confirmation study, Doctor [[Betsy Keller]] found that patients could not repeat their performance on a second cardiopulmonary exercise test performed a day after the first.<ref name="KellerBA2014" />

A review by [[Jo Nijs|Nijs]] et al. found that multiple studies showed reduced peak heart rate, reduced endurance, reduced peak work rate, reduced peak oxygen uptake, lower blood lactate values, and an increased respiratory exchange ratio;<ref name="Nijs2014" /> see 'Oxidative impairment', below.

It is important to note that CPET testing oxygen uptake (VO2), carbon dioxide output (VCO2), tidal volume (VT), blood pressure, oxygen saturation, and other objective measures, and cannot be invalidated with inadequate effort.

===Oxidative impairment===

DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing;<ref name="DeBecker2000" /><ref name="Vanness2003" /> Fulle et al (2000) demonstrated oxidative damage to DNA.<ref name="Fulle2000" />; and Wong et al (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.<ref name="Wong1992" />

== Graded exercise ==
{{main|page_name =Graded exercise therapy}}
Graded exercise therapy, or the incremental increase in physical activity over time, is a controversial treatment for ME/CFS, due to exercise intolerance being a central feature of the disease. See the main page for more.

==Talks & Interviews==

*2016, [https://www.youtube.com/watch?v=FXN6f53ba6k Dr. Mark Van Ness, "Expanding Physical Capability in ME/CFS" Part 1 (of 2)] ([[Mark VanNess]])
*2016, [https://www.youtube.com/watch?v=7BceGgEdMpA Dr. Mark Van Ness, "Expanding Physical Capability in ME/CFS" Part 2 (of 2)] ([[Mark VanNess]])
*2015, [https://www.youtube.com/watch?v=F1PP21TmUPs 72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman]<ref name="Bateman20151103interview" /> ([[Lucinda Bateman]], [[Science for Patients]])
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One]<ref name="VanNess20140205video" /> ([[Mark VanNess]])
*2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)] ([[Lucinda Bateman]])
*2012, [https://www.youtube.com/watch?v=nL49DwGRs30 Clinical exercise testing in CFS/ME research and treatment] ([[Christopher Snell]])
*2012, [https://www.youtube.com/watch?v=kCO3pAbSq3I MECFS Alert Episode 32: Staci Stevens, Director of the Pacific Fatigue Lab] ([[Staci Stevens]], [[ME/CFS Alert]])
*2012, [https://www.youtube.com/watch?v=B20H1u1LjCE&feature=youtu.be Top 10 Things You Should Know About Post-Exertional Relapse] ([[Staci Stevens]])
*2010, [http://www.hhs.gov/advcomcfs/meetings/presentations/presentation_10132010_snell-stevens.pdf Slide presentation to CFSAC] ([[Staci Stevens]], [[CFSAC]])
*2009, [https://www.youtube.com/watch?v=vqy4gVNh0rI Staci Steven speaking to CFSAC meeting] ([[Staci Stevens]])

==Studies==

*[https://www.ncbi.nlm.nih.gov/pubmed/27187093 2016, Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis]
*2016, [[Cochrane|Cochrane meta-analysis]]
*2011, [[PACE trial]]

==Learn more==

*Oct 2, 2017 - [https://www.npr.org/sections/health-shots/2017/10/02/554369327/for-people-with-chronic-fatigue-syndrome-more-exercise-isnt-better For People With Chronic Fatigue Syndrome, More Exercise Isn't Better - by Michaeleen Doucleff for ''Shots: Health News From NPR'']
*Aug 12, 2016 - [http://solvecfs.org/neuromuscular-strain-in-mecfs-research-study-conclusion/ Neuromuscular Strain in ME/CFS – Research Study Conclusion] in [[Solve ME/CFS Initiative]] Newsletter
*Jul 6, 2016 - [https://meaustralia.net/2016/07/06/australian-metabolomics-study-of-young-women/ Australian metabolomics study of young women with ME/CFS (CCC)] by Sasha Nimmo for ''ME Australia''
*Feb 10, 2016 - [http://www.prohealth.com/library/showarticle.cfm?libid=25096 Lost in Translation - The ME-Polio Connection and the Dangers of Exercise] by [[Nancy Blake]] for ''[[ProHealth]]''<ref name="ProHealth20160210" />
*Jan 2016 - [http://www.hindawi.com/journals/jar/2016/2497348/ Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome] by Gina Rutherford, Philip Manning, and [[Julia Newton|Julia L. Newton]]<ref name="RutherfordG2016" />
*Dec 19, 2015 - [https://cfsremission.wordpress.com/2015/12/19/exercise-alteration-of-the-cfs-microbiome/ Exercise alteration of the CFS Microbiome] from [[CFS Remission]] blog
*April 2015 - [https://www.omicsonline.org/open-access/objective-evidence-of-postexertional-malaise-in-myalgic-encephalomyelitis-and-chronic-fatigue-syndrome-2161-0673-1000159.pdf Objective Evidence of Post-exertional “Malaise” in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by Frank N.M. Twisk
*Nov 7, 2015 - [http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by [[Frank Twisk|Frank N.M. Twisk]], and [[Keith Geraghty|Keith J. Geraghty]]<ref name="TwiskF2015" /> and
*Jan 17, 2015 - [http://sallyjustme.blogspot.co.uk/2015/01/dr-vanness-on-recent-press-reports.html Dr. VanNess on recent press reports] by Sally Burch in [[Just ME]] blog<ref name="BurchS20150117" />
*2014 - [https://www.youtube.com/watch?v=kbaW4JKkin4 ME/CFS and Exercise: VO2 Max Testing with Nancy Klimas M.D. - PREVIEW] (this is a preview of a pay-per-view video)
*May 16, 2014 - [http://www.deseretnews.com/article/865603384/Sufferers-of-chronic-fatigue-fibromyalgia-have-hope-in-new-diagnostic-tool.html Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool] by Wendy Leonard for ''Deseret News''<ref name="DeseretNews20140516" />
*Autumn 2011 - [http://www.meresearch.org.uk/our-research/completed-studies/acidosis/ Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case–control study], an essay for [[ME Research UK]]
*2011 - [https://www.youtube.com/watch?v=Suq0dPMUbOk ME/CFS and Exercise: The VO2 Max Based Exercise Program, A Personal View] by [[Dan Moricoli]]

== See also ==

*[[Two-day cardiopulmonary exercise testing]]
*[[Graded exercise therapy]]
*[[Muscle fatigability]]
*[[Mitochondria]]
*[[Deconditioning]]
*[[Post-exertional malaise]]
*[[Body by Science]]

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| date = 18 Dec 2015
| pmid = 26683192 | doi = 10.1371/journal.pone.0145453
| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453
}}</ref>
<ref name="SnellCR2013">{{citation
| last1 = Snell | first1 = Christopher R | authorlink1 = Christopher Snell
| last2 = Stevens | first2 = Staci R | authorlink2 = Staci Stevens
| last3 = Davenport | first3 = Todd E | authorlink3 = Todd Davenport
| last4 = VanNess | first4 = J Mark | authorlink4 = Mark VanNess
| title = Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome
| journal = Physical Therapy (APTA) | volume = 93 | issue = 11 | page = 1484-1492
| date = 31 Oct 2013
| pmid = 23813081 | doi = 10.2522/ptj.20110368
| url = https://academic.oup.com/ptj/article-lookup/doi/10.2522/ptj.20110368
}}</ref>
<ref name="TwiskF2015">{{citation
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| last2 = Geraghty | first2 = Keith J | authorlink2 = Keith Geraghty
| title = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
| journal = Jacobs Journal of Physiology | volume = 2015, 1(2): 007
| date = 11 Jul 2015
| url = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf
}}</ref>
<ref name="Vanness2003">{{citation
| last1 = VanNess | first1 = JM | authorlink1 = Mark VanNess
| last2 = Snell | first2 = CR | authorlink2 = Christopher Snell
| last3 = Strayer | first3 = DR | authorlink3 = David Strayer
| last4 = Dempsey | first4 = L | authorlink4 = Line Dempsey
| last5 = Stevens | first5 = SR | authorlink5 = Staci Stevens
| title = Subclassifying chronic fatigue syndrome through exercise testing
| journal = Medicine and Science in Sports and Exercise | issn = 0195-9131| volume = 35| issue = 6| pages = 908–913
| date = June 2003
| pmid = 12783037 | doi = 10.1249/01.MSS.0000069510.58763.E8
| url = https://www.researchgate.net/profile/Mark_Van_Ness/publication/10728803_Subclassifying_chronic_fatigue_syndrome_through_exercise_testing/links/0c96051793fc9a83e4000000.pdf
}}</ref>
<ref name="VanNess2007">{{citation
| last1 = VanNess | first1 = J Mark | authorlink1 = Mark VanNess
| last2 = Snell | first2 = Christopher R | authorlink2 = Christopher Snell
| last3 = Stevens | first3 = Staci R | authorlink3 = Staci Stevens
| title = Diminished Cardiopulmonary Capacity During Post-Exertional Malaise
| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 2 | page = 77-85
| date = 2007
| doi = 10.1300/J092v14n02_07
| url = http://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07
}}</ref>
<ref name="VanNess20140205video">{{citation
| last1 = VanNess | first1 = J Mark | authorlink1 = Mark VanNess
| title = Video: A Realistic Approach to Exercise and Rehabilitation in ME/CFS
| date = 5 Feb 2014 | location = Bristol Watershed
| url = https://www.youtube.com/watch?v=q_cnva7zyKM
}}</ref>
<ref name="Wellness20150420">{{citation
| last1 = Dobberstein | first1 = Linda J. | authorlink1 =
| title = Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia
| journal = Wellness Resources
| date = 20 Apr 2015
| url = http://www.wellnessresources.com/health/articles/master_enzyme_switch_deactivated_in_chronic_fatigue_syndrome_and_fibromyalg/
}}</ref>
<ref name="WhiteAT2012">{{citation
| last1 = White | first1 = Andrea T | authorlink1 = Andrea White
| last2 = Light | first2 = Alan R | authorlink2 = Alan Light
| last3 = Hughen | first3 = Ronald W | authorlink3 = Ronald Hughen
| last4 = VanHaitsma | first4 = Timothy A | authorlink4 = Timothy VanHaitsma
| last5 = Light | first5 = Kathleen C | authorlink5 = Kathleen Light
| title = Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls
| journal = Psychosom Med | volume = 2012 Jan;74 | issue = 1 | page = 46-54
| date = 30 Dec 2011
| pmid = 22210239 | doi = 10.1097/PSY.0b013e31824152ed
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/
}}</ref>
<ref name="Whiteside, 2004">{{Citation
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| last3 = Chaudhuri | first3 = Abhijit | authorlink3 = Abhijit Chaudhuri
| title = Exercise lowers pain threshold in chronic fatigue syndrome
| journal = Pain | volume = 109 | issue = 3 | page = 497-9
| date = 2004
| pmid = 15157711
| doi = 10.1016/j.pain.2004.02.029
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<ref name="Wong1992">{{citation
| last1 = Wong | first1 = R | authorlink1 = Roger Wong
| last2 = Lopaschuk | first2 = G | authorlink2 = Gary Lopaschuk
| last3 = Zhu | first3 = G | authorlink3 = Gang Zhu
| last4 = Walker | first4 = D | authorlink4 = Dorothy Walker
| last5 = Catellier | first5 = D | authorlink5 = Dianne Catellier
| last6 = Burton | first6 = D | authorlink6 = David Burton
| last7 = Teo | first7 = K | authorlink7 = Koon Teo
| last8 = Collins-Nakai | first8 = R | authorlink8 = Ruth Collins-Nakai
| last9 = Montague | first9 = T | authorlink9 = Terrence Montague
| display-authors = 3
| title = Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy
| journal = Chest | issn = 0012-3692| volume = 102| issue = 6| pages = 1716–1722
| date = Dec 1992
| pmid = 1446478 | doi = 10.1378/chest.102.6.1716
| url = http://www.sciencedirect.com/science/article/pii/S0012369216408469
}}</ref>
</references>

[[Category:Potential treatments]]
[[Category:Tests]]

Probiotic

2018-08-18T00:13:03Z

Bill:fix main template

Probiotics are microorganisms that are believed to provide health benefits when consumed.

=Health effects=
*Some bacteria species have been shown to inhibit pathogens in the gut<ref>[http://www.hindawi.com/journals/jpr/2011/610769/tab1/ Hindawi - List of probiotics tested on different eukaryotic pathogens]</ref> through competition or by producing their own [[antibiotic]]s.
*Probiotics can reduce histamines levels, or increase them.<ref>[https://cfsremission.wordpress.com/2014/05/20/probiotics-and-histamines/ CFS Remission - Probiotics and histamines]</ref>
*CFS Remission - Survey of Probiotics Responses<ref>[https://cfsremission.wordpress.com/2016/07/10/first-survey-results-on-probiotics/ CFS Remission - Survey of Probiotics Responses]</ref>

=Efficacy=
Probiotics should be taken with or immediately before a meal, ideally with 1-2% milk.<ref>[https://cfsremission.wordpress.com/2015/11/10/when-to-take-probiotics-an-actual-study/ CFS Remission - When to take probiotics? - an actual study]</ref>.

=Evidence for Commercial Probiotics=

==[[Mutaflor]]==

[[E. Coli Nissle 1917]]<ref>[https://cfsremission.wordpress.com/2014/04/16/my-favorite-probiotic-e-coli-nissle-1917-mutaflor/ CFS Remission - My favorite probiotic: E. Coli Nissle 1917 (Mutaflor)]</ref>

==[[Symbioflor-2]]==

[[E. Coli G1-G10 6 species]]<ref>[https://cfsremission.wordpress.com/2016/03/01/symbioflor-2-another-e-coli-probiotic/ CFS Remission - Symbioflor-2: Another E. Coli Probiotic]</ref>

== Prescript Assist ==

[[Prescript Assist]] is a commercial probiotic containing 28 soil based bacteria.<ref>[https://cfsremission.wordpress.com/treatment/microflora-and-autoimmune-illnesses/changing-microfloras-by-probiotics/prescript-assist-broad-spectrum-probiotic-prebiotic-complex/ CFS Remission - Prescript-Assist Broad Spectrum Probiotic Prebiotic Complex]</ref>

==Miyarisan==

[[Miyarisan]] is a Japanese probiotic containing [[clostridium butyricum]],<ref>[https://cfsremission.wordpress.com/2015/10/19/miyarisan-clostridium-butyricum-revisited/ CFS Remission - Miyarisan clostridium butyricum revisited]</ref> a species that consumes [[lactic acid]] and produces [[butyrate]].<ref>Reference needed</ref>

==Advanced Orthomolecular Research AOR, Advanced Series, Probiotic-3==
[[Clostridium butyricum]], [[Streptococcus faecalis]], [[Bacillus mesentericus]]<ref>[https://cfsremission.wordpress.com/2014/05/12/a-new-probiotic-advanced-orthomolecular-research-aor-advanced-series-probiotic-3/ CFS Remission - A new probiotic: Advanced Orthomolecular Research AOR, Advanced Series, Probiotic-3]</ref>

==Align==
[[Bifidobacterium infantis]] 35624<ref>[https://cfsremission.wordpress.com/treatment/microflora-and-autoimmune-illnesses/changing-microfloras-by-probiotics/align-bifidobacterium-infantis-35624-a-demonstrated-probiotic-for-ibs/ CFS Remission - Align – Bifidobacterium infantis 35624 – a demonstrated probiotic for IBS]</ref><ref>[https://cfsremission.wordpress.com/2013/07/16/bifidobacteriun-infantis-another-interesting-probiotic/ CFS Remission - Bifidobacteriun Infantis – another interesting probiotic]</ref>

==Culturelle==
[[Lactobacillus Rhamnosus]] GG<ref>[https://cfsremission.wordpress.com/treatment/microflora-and-autoimmune-illnesses/changing-microfloras-by-probiotics/lactobacillus-rhamnosis-one-of-the-good-ones/ CFS Remission - Lactobacillus Rhamnosis: One of the good ones...]</ref>

==Bifido|Maximus==
[[Bifidobacterium longum]], [[Bifidobacterium infantis]], [[Lactobacillus rhamnosus]], [[Lactobacillus salivarius]], [[Lactobacillus gasseri]]<ref>[https://cfsremission.wordpress.com/2015/11/08/bifidomaximus-histamine-free-and-d-lactate-free-probiotic-review/ CFS Remission - Bifido|Maximus Histamine-Free and D-Lactate Free Probiotic – Review]</ref>

''See also [[Bifidobacteria]]''

==Enterogermina==
[[Bacillus clausii]] <ref>[https://cfsremission.wordpress.com/2015/10/22/enterogermina-four-bacillus-clausii-strains/ CFS Remission - Enterogermina – Four Bacillus clausii strains]</ref>

==Yakult==
[[Lactobacillus casei]] Shirota

==DanActive==
[[Lactobacillus casei]] Danone

==Bioflorin==
[[Enterococcus faecium]] SF 68<ref>[https://cfsremission.wordpress.com/2015/10/21/bioflorin-enterococcus-faecium-sf-68/ CFS Remission - Bioflorin – Enterococcus faecium SF 68]</ref>

==BioGaia==
[[Lactobacillus reuteri]]<ref>[https://cfsremission.wordpress.com/2013/07/13/lactobacillus-reuteri-and-recommendations-on-how-to-take-it/ CFS Remission - Lactobacillus Reuteri and recommendations on how to take it]</ref><ref>[https://cfsremission.wordpress.com/treatment/microflora-and-autoimmune-illnesses/changing-microfloras-by-probiotics/lactobacillus-reuteri-for-b12-production/ CFS Remission - Lactobacillus Reuteri for B12 production]</ref> = Produces B12

= Suspected to be effective but lacking studies =
[[GeneralBiotics Equilibrium]]<ref>[https://cfsremission.wordpress.com/2016/03/18/generalbiotics-probiotics/ CFS Remission - GeneralBiotics probiotics]</ref> 115 strains - none are lactobacillus or bifidobacteria.

= Commercial probiotics without evidence =
These are likely harmful because they are known to kill E.Coli that is very low in CFS patients.

==Common Yogurts==
[[Lactobacillus Acidophilus]]<ref name="cfsr1">[https://cfsremission.wordpress.com/2013/07/04/should-cfs-patients-use-lactobacillus-acidophilus-probably-not/ CFS Remission - Should CFS Patients use Lactobacillus Acidophilus? - Probably not]</ref>

==Typical Probiotics sold in Health Food Stores==
[[Lactobacillus Acidophilus]]<ref name="cfsr1" /> - often kill off the bacteria that was greatly reduced by CFS. Further unbalance the microbiome.

==Megasporebiotic==
Not sufficient research published<ref>[https://cfsremission.wordpress.com/2015/10/24/megasporebiotic-preliminary-review/ CFS Remission - Megasporebiotic – Preliminary Review]</ref>

==GcMAF Bravo ==
"“Streptococci, lactobacilli, bifidobacteria, lactococci, yeasts” - no research, no details of strains<ref>[https://cfsremission.wordpress.com/2013/09/29/gcmaf-bravo-probiotic-a-review/ CFS Remission - GcMAF – Bravo Probiotic – a review]</ref>

=Species and Strains=

== Evidence for specific strains ==

===Bifidobacteria===

{{main|page_name =Bifidobacteria}}
Cost per Billion CFU can vary from 1 cent to $1.62.<ref>[https://cfsremission.wordpress.com/2015/12/01/bifidobacteria-probiotics-best-bang-for-the-buck/ CFS Remission - Bifidobacteria probiotics – best bang for the buck!]</ref> A recent study found 15/16 commercial offerings in California were mislabeled (i.e. different strain than listed).<ref>[https://cfsremission.wordpress.com/2015/11/26/commercial-bifidobacteria-probiotics/ CFS Remission - Commercial Bifidobacteria probiotics]</ref>

==== Bifidobacterium infantis 35624 ====

One study found that 6-8 weeks of [[Bifidobacterium infantis]] supplementation reduced [[C-reactive protein]], [[Tumor necrosis factor alpha|TNF-alpha]] and [[Interleukin 6|IL-6]] levels in CFS patients.<ref name="Groeger2013" /> Another found that ''B. infantis'' boosted [[serotonin]] levels in the brain.<ref>Reference needed</ref>

===Lactobacillus===
{{main|page_name =Lactobacillus}}

==Notable studies==
*2018, Are probiotic treatments useful on [[fibromyalgia]] syndrome or [[chronic fatigue syndrome]] patients? A systematic review.<ref>Roman P, Carrillo-Trabalón F, Sánchez-Labraca N, Cañadas F, Estévez AF, Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review. Benef Microbes. 2018 Apr 26:1-10. doi: 10.3920/BM2017.0125.</ref> [https://www.ncbi.nlm.nih.gov/pubmed/29695180 (Abstract)]
*2018, A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and [[Irritable Bowel Syndrome]] in [[ME|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)]].<ref name="Corbitt, 2018"/> [https://www.ncbi.nlm.nih.gov/pubmed/29464501 (Abstract)]

==Learn more==
*2016, [http://www.cortjohnson.org/blog/2016/01/07/probiotics-cure-my-chronic-fatigue-syndrome/ Probiotics cured my chronic fatigue syndrome] ([[Cort Johnson]], January 7)
*2013, [http://www.cortjohnson.org/blog/2013/06/13/a-person-with-chronic-fatigue-syndrome-recovers-and-a-gut-series-begins/ A Person with Chronic Fatigue Syndrome Recovers and….a Gut Series Begins]

== See also ==
*[[Prebiotics]]
*[[Gastrointestinal system]]
*[[Microbiome]]
*[[CFS Remission]]
*[[Ken Lassesen's model]]

==References==
<references>
<ref name="Corbitt, 2018">
{{Citation
| last1 = Corbitt | first1 = M | authorlink1 =
| last2 = Campagnolo | first2 = N | authorlink2 =
| last3 = Staines | first3 = D | authorlink3 = Donald Staines
| last4 = Marshall-Gradisnik | first4 = S | authorlink4 = Sonya Marshall-Gradisnik
| title = A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
| journal = Probiotics Antimicrob Proteins | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1007/s12602-018-9397-8
}}
</ref>
<ref name="Groeger2013">{{Citation| doi = 10.4161/gmic.25487| issn = 1949-0984| volume = 4| issue = 4| pages = 325–339| last1 = Groeger| first1 = David| last2 = O'Mahony| first2 = Liam| last3 = Murphy| first3 = Eileen F.| last4 = Bourke| first4 = John F.| last5 = Dinan| first5 = Timothy G.| last6 = Kiely| first6 = Barry| last7 = Shanahan| first7 = Fergus| last8 = Quigley| first8 = Eamonn M. M.| title = Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut| journal = Gut Microbes| date = August 2013| pmid = 23842110}}</ref>

</references>

[[Category:Potential treatments]]
[[Category:Supplements]]
[[Category:Probiotics]]

Poliovirus

2018-08-18T00:11:37Z

Bill:fix main template

'''Poliovirus''' is an [[enterovirus]]. It is the cause of the paralytic disease known as [[poliomyelitis]]."<ref>[http://www.virology.ws/2004/08/18/poliovirus/ Poliovirus - Virology Blog]</ref>

== Metabolic effects ==
A study of poliovirus found that polio infection rapidly decreases (45% decrease) cellular oxygen consumption (and thus energy production through [[cellular respiration]]) by inhibiting [[succinate dehydrogenase]] (55% decrease in activity) and blocking mitochondrial electron transport at or between complexes I and III.<ref>{{Cite journal|last=Koundouris|first=A|date=May 2000|title=Poliovirus Induces an Early Impairment of Mitochondrial Function by Inhibiting Succinate Dehydrogenase Activity|url=https://www.ncbi.nlm.nih.gov/pubmed/10814509|journal=Biochemical and Biophysical Research Communications|volume=271|pages=610-4|via=}}</ref>

== Relationship to myalgic encephalomyelitis ==
Prior to the poliovirus vaccine, several [[outbreaks]] of what later came to be called [[myalgic encephalomyelitis]] coincided with confirmed outbreaks of [[poliomyelitis]] including the [[1934 Los Angeles atypical polio outbreak|1934 Los Angeles outbreak]], the [[1948-49 Akureyri outbreak|1948 Akureyri, Iceland outbreak]], and 1949 outbreak in [[1949-53 Adelaide outbreak|Adelaide, Australia]]. Many outbreaks were initially misinterpreted as clusters of [[poliomyelitis]] or [[abortive poliomyelitis]], hence one of [[ME]]'s earliest names, [[atypical polio]]. It is not known whether there is a direct relationship between polio outbreaks and ME or if outbreaks of ME were more likely to be reported when public health authorities were already mobilized for an earlier crisis.

No serological evidence of polio was ever found in these outbreaks and the ultimate pattern of the outbreaks differed in significant ways, chief among them, the tendency to affect adults rather than children, and to result in higher [[morbidity]] than poliomyelitis but no [[mortality]].<ref name=":02">{{Cite journal|last=Parish|first=JG|date=1978|title=Early outbreaks of 'epidemic neuromyasthenia'|url=https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54|pages=711-7|via=}}</ref> Findings in several outbreaks seemed to suggest that symptoms were caused by an [[enterovirus]] distinct from but related to polio including findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio.<ref name=":02" />
== Cross-immunity ==
It is theorized that exposure to one enterovirus may confer partial immunity or improved immune response to another enteroviruses. One study compared schoolchildren in [[Estonia]], who were inoculated with the Sabin, live attenuated virus polio vaccine, to [[Finland|Finnish]] schoolchildren, who were inoculated with the Salk, inactivated vaccine.<ref>{{Cite journal|last=Juhela|first=S|date=July 1999|title=Comparison of enterovirus-specific cellular immunity in two populations of young children vaccinated with inactivated or live poliovirus vaccines|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905481/|journal=Clinical & Experimental Immunology|volume=117|pages=100–105|via=}}</ref> Estonian children had stronger [[T cell]] responses to [[coxsackievirus B4]] and poliovirus type 1, and stronger expression of [[IFN-γ]] when exposed to poliovirus challenge as compared to Finnish children. Finnish children have weaker cellular immunity against enteroviruses at the age of 9 months compared with Estonian children at the same age. (Finland has a rate of [[Type 1 diabetes]] three times the rate of Estonia. Coxsackie B4 has been associated with Type 1 diabetes.) An unintended consequence of widespread polio vaccination may have been impaired immunity to other enteroviruses, such as [[Coxsackievirus|Coxsackie]] and [[echoviruses]].

There is indirect evidence of cross-immunity between [[poliovirus]] and the unidentified virus or viruses in epidemic myalgic encephalomyelitis outbreaks. After the 1948-1949 [[1948-49 Akureyri outbreak|Akureyri outbreak]] in Iceland, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to poliomyelitis virus.<ref name=":02" /><ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/13515219|title=Response to poliomyelitis vaccination|last=Sigurdsson|first=B|date=February 15, 1958|journal=The Lancet|volume=1|pages=370-1|via=}}</ref> During the 1949-1953 [[1949-53 Adelaide outbreak|outbreak in Adelaide]], cases of classic poliomyelitis dropped by 43%.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542300/ "Poliomyelitis in 1953"] ''Bulletin of the World Health Organization.'' 1955;12(4):595-649.</ref>

== Post-polio syndrome ==
{{Main article | page_name =Post-polio syndrome}}

== See also ==

*[[Epidemic myalgic encephalomyelitis]]
*[[List of outbreaks]]
*[[Enterovirus]]
*[[Non-cytolytic enterovirus]]

== References ==

[[Category:Infectious agents]]
[[Category:Triggers and risk factors]]
<references />

Enterovirus

2018-08-18T00:09:19Z

Bill:fix main template

Seventy-one types of '''enteroviruses''' have been discovered. Among these are [[Coxsackie A]] viruses, [[Coxsackie B]] viruses, [[Echoviruses|echoviruses]] and [[Poliovirus|polioviruses]].

The majority of enteroviral infections are subclinical and unlike [[Herpesvirus|herpesvirus]]es, usually leave the body after an effective [[Immune system|immune]] response. However, they are also the most common cause of [[meningitis]] (responsible for 85-90% of cases{{Citation needed}}), and can cause [[myocarditis]] and chronic or life-threatening conditions in certain populations,<ref name="Rotbart2001" /> such as in patients with X-linked agammaglobulinemia (XLA). Most children are exposed to at least one enterovirus by the age of 12 months.<ref>{{Cite journal|last=Juhela|first=S|date=July 1999|title=Comparison of enterovirus-specific cellular immunity in two populations of young children vaccinated with inactivated or live poliovirus vaccines|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905481/|journal=Clinical & Experimental Immunology|volume=117|pages=100–105|via=}}</ref>

Enteroviruses have a tropism for [[muscle]] cells and have been linked to [[myalgic encephalomyelitis]] and [[chronic fatigue syndrome]], as well as [[Type 1 Diabetes]].

== Poliovirus ==
{{Main article | page_name = Poliovirus}}
Poliovirus is the cause of the paralytic disease known as [[poliomyelitis]]."<ref>[http://www.virology.ws/2004/08/18/poliovirus/ Poliovirus - Virology Blog]</ref>

== Coxsackievirus ==
{{Main article | page_name =Coxsackievirus}}

== Coxsackie A viruses ==
{{Main article | page_name =Coxsackie A virus}}

== Coxsackie B viruses ==
{{Main article | page_name =Coxsackie B virus}}

[[Coxsackie B]] (also written coxsackievirus B) is a group of six types of [[enterovirus]], causing symptoms ranging from gastrointestinal distress to [[pericarditis]] and [[myocarditis]]. Symptoms of infection with viruses in the Coxsackie B grouping include [[fever]], [[headache]], [[sore throat]], gastrointestinal distress, extreme fatigue as well as [[Chest pain|chest]] and [[muscle pain]]. It can also lead to spasms in arms and legs. Numerous studies have found evidence of persistent infection of Coxsackie B in the [[blood]], [[muscle]], [[gut]] and [[brain]] in a subset of patients with diagnosed with myalgic encephalomyelitis and chronic fatigue syndrome.<ref>{{Cite journal|last=Landay|first=AL|date=September 1991|title=Chronic fatigue syndrome: clinical condition associated with immune activation|url=https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name=":02">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref><ref name="Fegan1983">{{Citation
| last1 = Fegan | first1 = KG | authorlink1 = KG Fegan
| last2 = Behan | first2 = PO | authorlink2 = Peter Behan
| last3 = Bell | first3 = EJ | authorlink3 = Eleanor Bell
| title = Myalgic encephalomyelitis — report of an epidemic
| journal = J R Coll Gen Pract | volume = 33| issue = 251| pages = 335–337
| date = 1 Jun 1983
| pmid = 6310104
| url = http://bjgp.org/content/33/251/335
}}</ref><ref name="Calder1984">{{Citation
| last1 = Calder | first1 = BD | authorlink1 = BD Calder
| last2 = Warnock | first2 = PJ | authorlink2 = PJ Warnock
| title = Coxsackie B infection in a Scottish general practice
| journal = Jrnl Royal Coll Gen Pract | volume = 34| issue = 258| pages = 15–19
| date = Jan 1984
| pmid = 6319691
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/
}}</ref><ref>{{Cite journal|last=Yousef|first=G.E.|date=January 1988|title=CHRONIC ENTEROVIRUS INFECTION IN PATIENTS WITH POSTVIRAL FATIGUE SYNDROME|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7595406|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref><ref name=":03">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Gow|first=JW|date=|title=Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1850635|journal=British Medical Journal|volume=|pages=|via=}}</ref>

== Echovirus ==
{{Main article | page_name =Echovirus}}

==Persistent infection==

{{Main article|page_name =Non-cytolytic enterovirus}}

Some researchers believe that enteroviruses establish a persistent, intracellular, non-cytolytic infection, that is an infection that does not involve the destruction of infected cells. [[Non-cytolytic enterovirus|Non-cytolytic]] infection is difficult to measure in the serum as viral particles remain in the cell walls of tissues.

The molecular mechanisms of non-cytolytic infection were examined in a small study comparing [[Coxsackievirus B2|Coxsackie B2]] virus cultured ''in vitro'' to RNA extracted via [[muscle biopsy]] from eight patients with a [[chronic fatigue syndrome]] diagnosis. All patients had symptoms of [[muscle fatiguability]]. Four of these samples tested positive for enteroviral RNA. In all four patients with enteroviral-specific RNA, the enteroviral RNA had equal amounts of [[positive sense]] and [[negative sense]] RNA. By contrast, CVB2 virus in culture produced positive sense RNA at a ratio of 100:1. An equal ratio of positive to negative sense RNA would inhibit the translation of virus-specific gene products, explaining the failure to attract a response from the host [[immune system]], and my account for how CVB2 could establish a persistent infection in these four patients.<ref>{{Cite journal|last=Cunningham|first=Louise|date=1990|title=Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA|url=http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-71-6-1399|journal=Journal of General Virology|volume=71|pages=1399-1402|via=}}</ref>

Models of persistent infection of the heart<ref>Chapman N.M., Kim K.S. (2008) Persistent Coxsackievirus Infection: Enterovirus Persistence in Chronic Myocarditis and Dilated Cardiomyopathy. In: Tracy S., Oberste M.S., Drescher K.M. (eds) Group B Coxsackieviruses. Current Topics in Microbiology and Immunology, vol 323. Springer, Berlin, Heidelberg</ref> and brain<ref>{{Cite journal|last=Feuer|first=Ralph|date=September 2009|title=Viral Persistence and Chronic Immunopathology in the Adult Central Nervous System following Coxsackievirus Infection during the Neonatal Period|url=http://jvi.asm.org/content/83/18/9356.short|journal=Journal of Virology|volume=83|pages=9356-9369|via=}}</ref> have also been studied in mice and in [[thyroid carcinoma]].

== Metabolic effects ==
A study of poliovirus found that polio infection rapidly decreases cellular oxygen consumption (and thus energy production through [[cellular respiration]]) by inhibiting [[succinate dehydrogenase]] and blocking [[Mitochondria|mitochondrial]] electron transport.<ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/10814509|title=Poliovirus Induces an Early Impairment of Mitochondrial Function by Inhibiting Succinate Dehydrogenase Activity|last=Koundouris|first=A|date=May 2000|journal=Biochemical and Biophysical Research Communications|volume=271|pages=610-4|via=}}</ref>

== Myalgic Encephalomyelitis ==

Ever since the historic outbreaks of ME in the 1930s-1950s, enteroviruses, especially [[Coxsackie B]] viruses, have been [[Enteroviral infection hypothesis|posited]] as a key etiological factor in [[Myalgic encephalomyelitis|myalgic encephalomyelitis]]. These frequently coincided with outbreaks of [[polio]], another enterovirus. Findings in several outbreaks seemed to suggest that symptoms were caused by a virus distinct from but related to polio including findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio.<ref name=":0">{{Cite journal|last=Parish|first=JG|date=1978|title=Early outbreaks of 'epidemic neuromyasthenia'|url=https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54|pages=711-7|via=}}</ref>

There is no consensus regarding the direct evidence for enteroviral persistence in [[ME]] patients, in part to different methods of testing and types of tissue samples. Several researchers have indicated that they have failed to find evidence of enteroviruses in the blood and cerebrospinal fluid of ME patients,{{Citation needed}} whereas others maintain that a persistent infection can only be directly measured in tissue samples, for example [[Muscle biopsy|muscle biopsies]], stomach biopsies, or brain tissue.

Some studies have found evidence of enteroviral infection in [[Muscle biopsy|muscle biopsies]] in a subset of patients, while others have failed to replicate those results.<ref name="McArdle1996" /><ref name="Lindh1996" /><ref name="Archard1988" />

Several studies have patients with ME to have persistently elevated levels of Coxsackie B IgM or IgG antibodies, circulating immune complexes containing viral antigen, or presence of enterovirus by PCR or culture, all indicating the possible presence of a persistent infection.<ref>{{Cite journal|last=Landay|first=AL|date=September 1991|title=Chronic fatigue syndrome: clinical condition associated with immune activation|url=https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name=":05">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref> Others studies failed to find a difference in rates of positivity between patients and controls. Differences in study outcomes may be due to the criteria used to define study cohorts as well as the techniques used.

=== Blood testing ===
Elevated Coxsackie B antibodies have been found in patients in at least two ME outbreaks.<ref name="Fegan19832">{{Citation
| last1 = Fegan | first1 = KG | authorlink1 = KG Fegan
| last2 = Behan | first2 = PO | authorlink2 = Peter Behan
| last3 = Bell | first3 = EJ | authorlink3 = Eleanor Bell
| title = Myalgic encephalomyelitis — report of an epidemic
| journal = J R Coll Gen Pract | volume = 33| issue = 251| pages = 335–337
| date = 1 Jun 1983
| pmid = 6310104
| url = http://bjgp.org/content/33/251/335
}}</ref><ref name="Calder19842">{{Citation
| last1 = Calder | first1 = BD | authorlink1 = BD Calder
| last2 = Warnock | first2 = PJ | authorlink2 = PJ Warnock
| title = Coxsackie B infection in a Scottish general practice
| journal = Jrnl Royal Coll Gen Pract | volume = 34| issue = 258| pages = 15–19
| date = Jan 1984
| pmid = 6319691
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/
}}</ref> In a retrospective cohort study<ref name="Dowsett19902">{{Citation
| last1 = Dowsett | first1 = EG | authorlink1 = Elizabeth Dowsett
| last2 = Ramsay | first2 = AM | authorlink2 = Melvin Ramsay
| last3 = McCartney | first3 = RA | authorlink3 = Robert McCartney
| last4 = Bell | first4 = EJ | authorlink4 = Eleanor Bell
| title = Myalgic encephalomyelitis--a persistent enteroviral infection?
| journal = Postgraduate Medical Journal | volume = 66| issue = 777| pages = 526–530
| date = 1 Jul 1990
| pmid = 2170962 | doi = 10.1136/pgmj.66.777.526
| url = http://pmj.bmj.com/content/66/777/526
}}</ref> by [[Melvin Ramsay]] and [[Elizabeth Dowsett]], 31% of the patients were found to have elevated enteroviral IgM antibody levels. Sixteen of these patients were retested annually over three years and all showed persistently elevated Coxsackie B neutralizing antibody levels and intermittently positive enteroviral IgM, suggesting a persistent infection was present.

Similarly, a study of of 76 patients with [[postviral fatigue syndrome]] (PVFS) found that 76% had detectible [[IgM]] responses to enteroviruses. 22% had positive cultures (compared to 7% controls) and [[VP1 antigen]] was detected in 51%, all pointing to a chronic infection in many post-viral patients.<ref>{{Cite journal|last=Yousef|first=G.E.|date=January 1988|title=CHRONIC ENTEROVIRUS INFECTION IN PATIENTS WITH POSTVIRAL FATIGUE SYNDROME|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=|pages=|via=}}</ref> However, a larger study in Scotland of 243 PVFS patients and matched controls found no difference in IgM and IgG positivity between patients and controls.<ref>{{Cite journal|last=Miller|first=N A|date=1991|title=Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome|url=https://www.bmj.com/content/302/6769/140.short|journal=The British Medical Journal|volume=|pages=|via=}}</ref>

=== PCR ===
In a study of serum samples from 100 CFS patients and 100 healthy controls, 42% of patients were positive for Coxsackie B sequences by PCR, compared to only 9% of the comparison group.<ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7595406|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref>

Also using PCR, a study of 236 patients by [[John Chia]] found enteroviral RNA in 48% of patients as compared to 8% of controls.To date, Chia reports finding enteroviral RNA in 35% of 518 patients.<ref name=":04">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref>

=== Muscle biopsy ===
Several [[muscle biopsy]] studies have also found the presence of Coxsackie B RNA sequences in CFS patients as compared to controls. A study of 60 [[Postviral fatigue syndrome|post-viral fatigue syndrome]] patients found 53% had enteroviral RNA in [[muscle]] compared to 15% of controls.<ref>{{Cite journal|last=Gow|first=JW|date=|title=Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1850635|journal=British Medical Journal|volume=|pages=|via=}}</ref> However, a follow-up study comparing CFS patients to patients with other neuromuscular disorders failed to find a statistically significant difference.<ref>{{Cite journal|last=Gow|first=JW|date=1994|title=Studies on enterovirus in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8148439/|journal=Clin Infect Dis.|volume=18|pages=S126-9|via=}}</ref>

=== Gut biopsy ===
Research by [[John Chia]] and his son, [[Andrew Chia]] has looked for enteroviruses in gut biopsies. 82% of samples were positive for [[viral capsid protein 1]] (VP1), compared to 20% of controls. Enteroviral RNA was detected in 37% of biopsy samples, compared to 4.7% of controls. They posit that a subset of [[Chronic Fatigue Syndrome]] patients have a chronic enteroviral infection.<ref name="ChiaJKS2016" />

=== Brain autopsy ===

== Other conditions ==

=== Type 1 Diabetes ===
Several studies have suggested a relationship between Coxsackie B4 and the onset of [[Type 1 diabetes]].<ref>{{Cite journal|last=Gamble|first=D. R.|last2=Taylor|first2=K. W.|last3=Cumming|first3=H.|date=1973-11-03|title=Coxsackie Viruses and Diabetes Mellitus|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1587352/|journal=British Medical Journal|volume=4|issue=5887|pages=260–262|issn=0007-1447|pmc=1587352|pmid=4753237}}</ref><ref>{{Cite journal|last=Ylipaasto|first=P.|last2=Klingel|first2=K.|last3=Lindberg|first3=A. M.|last4=Otonkoski|first4=T.|last5=Kandolf|first5=R.|last6=Hovi|first6=T.|last7=Roivainen|first7=M.|date=2004-02-01|title=Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells|url=http://link.springer.com/article/10.1007/s00125-003-1297-z|journal=Diabetologia|language=en|volume=47|issue=2|pages=225–239|doi=10.1007/s00125-003-1297-z|issn=0012-186X}}</ref><ref>{{Cite journal|last=Bason|first=Caterina|last2=Lorini|first2=Renata|last3=Lunardi|first3=Claudio|last4=Dolcino|first4=Marzia|last5=Giannattasio|first5=Alessandro|last6=d’Annunzio|first6=Giuseppe|last7=Rigo|first7=Antonella|last8=Pedemonte|first8=Nicoletta|last9=Corrocher|first9=Roberto|date=2013-02-28|title=In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057729|journal=PLOS ONE|language=en|volume=8|issue=2|pages=e57729|doi=10.1371/journal.pone.0057729|issn=1932-6203|pmc=3585221|pmid=23469060}}</ref>

A study of patients with Type 1 [[Diabetes]] found that [[Coxsackie B4]] was found to infect the β cells in the pancreatic islets of the pancreas and cause inflammation mediated by [[natural killer cell]]s.<ref>http://www.pnas.org/content/104/12/5115.full</ref>

=== Gastroparesis ===
A very small observational study found that nine out of ten patients with symptoms of [[gastroparesis]] had positive gastric biopsies for enterovirus.<ref name="BarkinJA, 20162">{{Citation
| last1 = Barkin | first1 = JA | authorlink1 =
| last2 = Czul | first2 = F | authorlink2 =
| last3 = Barkin | first3 = JS | authorlink3 =
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Rey | first5 = IR | authorlink5 = Irma Rey
| last6 = Moshiree | first6 = B | authorlink6 =
| title = Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis
| journal = Digestive Diseases and Sciences | volume = 61 | issue = 8 | page = 2344-50
| date = 2016
| pmid = 27344315
| doi = 10.1007/s10620-016-4227-x
}}</ref>
== Treatment ==

There are no FDA-approved treatments for enteroviruses. The drug [[Pleconaril]] has been shown to have activity against a number of enteroviruses<ref name="Rotbart2001" /><ref name="Pevear1999" /><ref name="Bauer2002" /><ref name="Groarke1999" /><ref name="Abzug2016" /> but has not been approved by the [[FDA]].

Treatment usually involves supporting the immune response particularly in those with documented immune dysfunction. Dr. Chia treats his patients with enteroviral infection with [[Equilibrant]], [[gammaglobulin]] and [[interferon]].<ref name="evmed-treatment" />

==Published Studies==

*2016, A study on brain tissue samples from a deceased ME patient found evidence of enterovirus specific genomic sequences and enteroviral protein in the patient's cerebral cortex.<ref name="Richardson2016" />
*2016, A study on stomach tissue samples from CFS patients found that 82% of patients have evidence of chronic enterovirus infection of the stomach.<ref name="ChiaJKS2016" />
*2010, A longitudinal study found that a percentage of patients presenting to emergency care with acute enterovirus infection would go on to develop symptoms of ME and CFS and had demonstrable evidence of viral persistence.<ref name="ChiaJKS2010" />
*1996, A Swedish study using the [[Fukuda criteria]] was unable to find evidence of any persistent enteroviral infection in fecal samples, [[Muscle biopsy|muscle biopsies]], or cerebrospinal fluid.<ref name="Lindh1996" />
*1995, In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group.<ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of Coxsackie B neutralization and enteroviral PCR in chronic fatigue patients|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.1890460404|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref>
*1994, A second postmortem tissue study found positive enterovirus PCR sequences in the [[muscle]], heart, brain stem, and hypothalamus of a deceased ME patient.<ref name="McGarry1994" />
*1990, Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. "This suggests that entrovirus pesistence in [[muscle]] is due to a defect in control of viral RNA synthesis."<ref name="Cunningham, 1990" />
*1990, A retrospective cohort study found that 31% of ME patients had elevated enteroviral IgM antibody levels. Sixteen of these patients were retested annually over three years and all showed persistently elevated [[Coxsackie B]] neutralizing antibody levels and intermittently positive enteroviral IgM, indicating the possibility of a persistent infection.<ref name="Dowsett1990" />
*1988, A study of 76 postviral fatigue patients and 30 controls found significantly higher numbers of positive cultures and IgM responses to enteroviruses.<ref>{{Cite journal|last=Yousef|first=G.E.|date=23 Jan 1988|title=Chronic Enterovirus Infection in Patients with Postviral Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=331|pages=146-150|via=}}</ref>
*1988, In one study, enterovirus-specific RNA three standard deviations greater than controls was found in [[Muscle biopsy|muscle biopsies]] of 20% of ME patients studied.<ref name="Archard1988" />

==Talks & interviews==

*2016, [https://youtu.be/mZdG2otpC3w - 86. ‪ME and the role of enteroviruses / ME en de rol van enterovirussen - Dr. Byron Hyde‬, MD]

==Learn More==
*[[List of enterovirus infection studies]]

*[http://www.anapsid.org/cnd/diffdx/polio1.html ME/CFS and Polio], chapter from book "ME: The New Plague", Jane Colby.<ref name="ColbyJ1996" />

==See Also==

* [[Non-cytolytic enterovirus]]
* [[List of enterovirus infection studies]]
* [[Enteroviral infection hypothesis]]
* [[Post-mortem brain studies]]
*[[Coxsackie B]]
*[[John Chia]]
*[[John Richardson]]
*[[James Mowbray]]
*[[Irving Spurr]]

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[[Category:Infectious agents]]
[[Category:Virology]]

Enterovirus

2018-08-18T00:07:15Z

Bill:/* Poliovirus */ edit via new change of Main template

Seventy-one types of '''enteroviruses''' have been discovered. Among these are [[Coxsackie A]] viruses, [[Coxsackie B]] viruses, [[Echoviruses|echoviruses]] and [[Poliovirus|polioviruses]].

The majority of enteroviral infections are subclinical and unlike [[Herpesvirus|herpesvirus]]es, usually leave the body after an effective [[Immune system|immune]] response. However, they are also the most common cause of [[meningitis]] (responsible for 85-90% of cases{{Citation needed}}), and can cause [[myocarditis]] and chronic or life-threatening conditions in certain populations,<ref name="Rotbart2001" /> such as in patients with X-linked agammaglobulinemia (XLA). Most children are exposed to at least one enterovirus by the age of 12 months.<ref>{{Cite journal|last=Juhela|first=S|date=July 1999|title=Comparison of enterovirus-specific cellular immunity in two populations of young children vaccinated with inactivated or live poliovirus vaccines|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905481/|journal=Clinical & Experimental Immunology|volume=117|pages=100–105|via=}}</ref>

Enteroviruses have a tropism for [[muscle]] cells and have been linked to [[myalgic encephalomyelitis]] and [[chronic fatigue syndrome]], as well as [[Type 1 Diabetes]].

== Poliovirus ==
{{Main article | page_name = Poliovirus}}
Poliovirus is the cause of the paralytic disease known as [[poliomyelitis]]."<ref>[http://www.virology.ws/2004/08/18/poliovirus/ Poliovirus - Virology Blog]</ref>

== Coxsackievirus ==
{{Main article | Coxsackievirus}}

== Coxsackie A viruses ==
{{Main article | Coxsackie A virus}}

== Coxsackie B viruses ==
{{Main article | Coxsackie B virus}}

[[Coxsackie B]] (also written coxsackievirus B) is a group of six types of [[enterovirus]], causing symptoms ranging from gastrointestinal distress to [[pericarditis]] and [[myocarditis]]. Symptoms of infection with viruses in the Coxsackie B grouping include [[fever]], [[headache]], [[sore throat]], gastrointestinal distress, extreme fatigue as well as [[Chest pain|chest]] and [[muscle pain]]. It can also lead to spasms in arms and legs. Numerous studies have found evidence of persistent infection of Coxsackie B in the [[blood]], [[muscle]], [[gut]] and [[brain]] in a subset of patients with diagnosed with myalgic encephalomyelitis and chronic fatigue syndrome.<ref>{{Cite journal|last=Landay|first=AL|date=September 1991|title=Chronic fatigue syndrome: clinical condition associated with immune activation|url=https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name=":02">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref><ref name="Fegan1983">{{Citation
| last1 = Fegan | first1 = KG | authorlink1 = KG Fegan
| last2 = Behan | first2 = PO | authorlink2 = Peter Behan
| last3 = Bell | first3 = EJ | authorlink3 = Eleanor Bell
| title = Myalgic encephalomyelitis — report of an epidemic
| journal = J R Coll Gen Pract | volume = 33| issue = 251| pages = 335–337
| date = 1 Jun 1983
| pmid = 6310104
| url = http://bjgp.org/content/33/251/335
}}</ref><ref name="Calder1984">{{Citation
| last1 = Calder | first1 = BD | authorlink1 = BD Calder
| last2 = Warnock | first2 = PJ | authorlink2 = PJ Warnock
| title = Coxsackie B infection in a Scottish general practice
| journal = Jrnl Royal Coll Gen Pract | volume = 34| issue = 258| pages = 15–19
| date = Jan 1984
| pmid = 6319691
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/
}}</ref><ref>{{Cite journal|last=Yousef|first=G.E.|date=January 1988|title=CHRONIC ENTEROVIRUS INFECTION IN PATIENTS WITH POSTVIRAL FATIGUE SYNDROME|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7595406|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref><ref name=":03">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Gow|first=JW|date=|title=Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1850635|journal=British Medical Journal|volume=|pages=|via=}}</ref>

== Echovirus ==
{{Main article | Echovirus}}

==Persistent infection==

{{Main article|Non-cytolytic enterovirus}}

Some researchers believe that enteroviruses establish a persistent, intracellular, non-cytolytic infection, that is an infection that does not involve the destruction of infected cells. [[Non-cytolytic enterovirus|Non-cytolytic]] infection is difficult to measure in the serum as viral particles remain in the cell walls of tissues.

The molecular mechanisms of non-cytolytic infection were examined in a small study comparing [[Coxsackievirus B2|Coxsackie B2]] virus cultured ''in vitro'' to RNA extracted via [[muscle biopsy]] from eight patients with a [[chronic fatigue syndrome]] diagnosis. All patients had symptoms of [[muscle fatiguability]]. Four of these samples tested positive for enteroviral RNA. In all four patients with enteroviral-specific RNA, the enteroviral RNA had equal amounts of [[positive sense]] and [[negative sense]] RNA. By contrast, CVB2 virus in culture produced positive sense RNA at a ratio of 100:1. An equal ratio of positive to negative sense RNA would inhibit the translation of virus-specific gene products, explaining the failure to attract a response from the host [[immune system]], and my account for how CVB2 could establish a persistent infection in these four patients.<ref>{{Cite journal|last=Cunningham|first=Louise|date=1990|title=Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA|url=http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-71-6-1399|journal=Journal of General Virology|volume=71|pages=1399-1402|via=}}</ref>

Models of persistent infection of the heart<ref>Chapman N.M., Kim K.S. (2008) Persistent Coxsackievirus Infection: Enterovirus Persistence in Chronic Myocarditis and Dilated Cardiomyopathy. In: Tracy S., Oberste M.S., Drescher K.M. (eds) Group B Coxsackieviruses. Current Topics in Microbiology and Immunology, vol 323. Springer, Berlin, Heidelberg</ref> and brain<ref>{{Cite journal|last=Feuer|first=Ralph|date=September 2009|title=Viral Persistence and Chronic Immunopathology in the Adult Central Nervous System following Coxsackievirus Infection during the Neonatal Period|url=http://jvi.asm.org/content/83/18/9356.short|journal=Journal of Virology|volume=83|pages=9356-9369|via=}}</ref> have also been studied in mice and in [[thyroid carcinoma]].

== Metabolic effects ==
A study of poliovirus found that polio infection rapidly decreases cellular oxygen consumption (and thus energy production through [[cellular respiration]]) by inhibiting [[succinate dehydrogenase]] and blocking [[Mitochondria|mitochondrial]] electron transport.<ref>{{Cite journal|url=https://www.ncbi.nlm.nih.gov/pubmed/10814509|title=Poliovirus Induces an Early Impairment of Mitochondrial Function by Inhibiting Succinate Dehydrogenase Activity|last=Koundouris|first=A|date=May 2000|journal=Biochemical and Biophysical Research Communications|volume=271|pages=610-4|via=}}</ref>

== Myalgic Encephalomyelitis ==

Ever since the historic outbreaks of ME in the 1930s-1950s, enteroviruses, especially [[Coxsackie B]] viruses, have been [[Enteroviral infection hypothesis|posited]] as a key etiological factor in [[Myalgic encephalomyelitis|myalgic encephalomyelitis]]. These frequently coincided with outbreaks of [[polio]], another enterovirus. Findings in several outbreaks seemed to suggest that symptoms were caused by a virus distinct from but related to polio including findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio.<ref name=":0">{{Cite journal|last=Parish|first=JG|date=1978|title=Early outbreaks of 'epidemic neuromyasthenia'|url=https://www.ncbi.nlm.nih.gov/pubmed/370810|journal=Postgraduate Medical Journal|volume=54|pages=711-7|via=}}</ref>

There is no consensus regarding the direct evidence for enteroviral persistence in [[ME]] patients, in part to different methods of testing and types of tissue samples. Several researchers have indicated that they have failed to find evidence of enteroviruses in the blood and cerebrospinal fluid of ME patients,{{Citation needed}} whereas others maintain that a persistent infection can only be directly measured in tissue samples, for example [[Muscle biopsy|muscle biopsies]], stomach biopsies, or brain tissue.

Some studies have found evidence of enteroviral infection in [[Muscle biopsy|muscle biopsies]] in a subset of patients, while others have failed to replicate those results.<ref name="McArdle1996" /><ref name="Lindh1996" /><ref name="Archard1988" />

Several studies have patients with ME to have persistently elevated levels of Coxsackie B IgM or IgG antibodies, circulating immune complexes containing viral antigen, or presence of enterovirus by PCR or culture, all indicating the possible presence of a persistent infection.<ref>{{Cite journal|last=Landay|first=AL|date=September 1991|title=Chronic fatigue syndrome: clinical condition associated with immune activation|url=https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name=":05">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref> Others studies failed to find a difference in rates of positivity between patients and controls. Differences in study outcomes may be due to the criteria used to define study cohorts as well as the techniques used.

=== Blood testing ===
Elevated Coxsackie B antibodies have been found in patients in at least two ME outbreaks.<ref name="Fegan19832">{{Citation
| last1 = Fegan | first1 = KG | authorlink1 = KG Fegan
| last2 = Behan | first2 = PO | authorlink2 = Peter Behan
| last3 = Bell | first3 = EJ | authorlink3 = Eleanor Bell
| title = Myalgic encephalomyelitis — report of an epidemic
| journal = J R Coll Gen Pract | volume = 33| issue = 251| pages = 335–337
| date = 1 Jun 1983
| pmid = 6310104
| url = http://bjgp.org/content/33/251/335
}}</ref><ref name="Calder19842">{{Citation
| last1 = Calder | first1 = BD | authorlink1 = BD Calder
| last2 = Warnock | first2 = PJ | authorlink2 = PJ Warnock
| title = Coxsackie B infection in a Scottish general practice
| journal = Jrnl Royal Coll Gen Pract | volume = 34| issue = 258| pages = 15–19
| date = Jan 1984
| pmid = 6319691
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/
}}</ref> In a retrospective cohort study<ref name="Dowsett19902">{{Citation
| last1 = Dowsett | first1 = EG | authorlink1 = Elizabeth Dowsett
| last2 = Ramsay | first2 = AM | authorlink2 = Melvin Ramsay
| last3 = McCartney | first3 = RA | authorlink3 = Robert McCartney
| last4 = Bell | first4 = EJ | authorlink4 = Eleanor Bell
| title = Myalgic encephalomyelitis--a persistent enteroviral infection?
| journal = Postgraduate Medical Journal | volume = 66| issue = 777| pages = 526–530
| date = 1 Jul 1990
| pmid = 2170962 | doi = 10.1136/pgmj.66.777.526
| url = http://pmj.bmj.com/content/66/777/526
}}</ref> by [[Melvin Ramsay]] and [[Elizabeth Dowsett]], 31% of the patients were found to have elevated enteroviral IgM antibody levels. Sixteen of these patients were retested annually over three years and all showed persistently elevated Coxsackie B neutralizing antibody levels and intermittently positive enteroviral IgM, suggesting a persistent infection was present.

Similarly, a study of of 76 patients with [[postviral fatigue syndrome]] (PVFS) found that 76% had detectible [[IgM]] responses to enteroviruses. 22% had positive cultures (compared to 7% controls) and [[VP1 antigen]] was detected in 51%, all pointing to a chronic infection in many post-viral patients.<ref>{{Cite journal|last=Yousef|first=G.E.|date=January 1988|title=CHRONIC ENTEROVIRUS INFECTION IN PATIENTS WITH POSTVIRAL FATIGUE SYNDROME|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=|pages=|via=}}</ref> However, a larger study in Scotland of 243 PVFS patients and matched controls found no difference in IgM and IgG positivity between patients and controls.<ref>{{Cite journal|last=Miller|first=N A|date=1991|title=Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome|url=https://www.bmj.com/content/302/6769/140.short|journal=The British Medical Journal|volume=|pages=|via=}}</ref>

=== PCR ===
In a study of serum samples from 100 CFS patients and 100 healthy controls, 42% of patients were positive for Coxsackie B sequences by PCR, compared to only 9% of the comparison group.<ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7595406|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref>

Also using PCR, a study of 236 patients by [[John Chia]] found enteroviral RNA in 48% of patients as compared to 8% of controls.To date, Chia reports finding enteroviral RNA in 35% of 518 patients.<ref name=":04">{{Cite journal|last=Chia|first=John|date=November 2005|title=The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref>

=== Muscle biopsy ===
Several [[muscle biopsy]] studies have also found the presence of Coxsackie B RNA sequences in CFS patients as compared to controls. A study of 60 [[Postviral fatigue syndrome|post-viral fatigue syndrome]] patients found 53% had enteroviral RNA in [[muscle]] compared to 15% of controls.<ref>{{Cite journal|last=Gow|first=JW|date=|title=Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1850635|journal=British Medical Journal|volume=|pages=|via=}}</ref> However, a follow-up study comparing CFS patients to patients with other neuromuscular disorders failed to find a statistically significant difference.<ref>{{Cite journal|last=Gow|first=JW|date=1994|title=Studies on enterovirus in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8148439/|journal=Clin Infect Dis.|volume=18|pages=S126-9|via=}}</ref>

=== Gut biopsy ===
Research by [[John Chia]] and his son, [[Andrew Chia]] has looked for enteroviruses in gut biopsies. 82% of samples were positive for [[viral capsid protein 1]] (VP1), compared to 20% of controls. Enteroviral RNA was detected in 37% of biopsy samples, compared to 4.7% of controls. They posit that a subset of [[Chronic Fatigue Syndrome]] patients have a chronic enteroviral infection.<ref name="ChiaJKS2016" />

=== Brain autopsy ===

== Other conditions ==

=== Type 1 Diabetes ===
Several studies have suggested a relationship between Coxsackie B4 and the onset of [[Type 1 diabetes]].<ref>{{Cite journal|last=Gamble|first=D. R.|last2=Taylor|first2=K. W.|last3=Cumming|first3=H.|date=1973-11-03|title=Coxsackie Viruses and Diabetes Mellitus|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1587352/|journal=British Medical Journal|volume=4|issue=5887|pages=260–262|issn=0007-1447|pmc=1587352|pmid=4753237}}</ref><ref>{{Cite journal|last=Ylipaasto|first=P.|last2=Klingel|first2=K.|last3=Lindberg|first3=A. M.|last4=Otonkoski|first4=T.|last5=Kandolf|first5=R.|last6=Hovi|first6=T.|last7=Roivainen|first7=M.|date=2004-02-01|title=Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells|url=http://link.springer.com/article/10.1007/s00125-003-1297-z|journal=Diabetologia|language=en|volume=47|issue=2|pages=225–239|doi=10.1007/s00125-003-1297-z|issn=0012-186X}}</ref><ref>{{Cite journal|last=Bason|first=Caterina|last2=Lorini|first2=Renata|last3=Lunardi|first3=Claudio|last4=Dolcino|first4=Marzia|last5=Giannattasio|first5=Alessandro|last6=d’Annunzio|first6=Giuseppe|last7=Rigo|first7=Antonella|last8=Pedemonte|first8=Nicoletta|last9=Corrocher|first9=Roberto|date=2013-02-28|title=In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057729|journal=PLOS ONE|language=en|volume=8|issue=2|pages=e57729|doi=10.1371/journal.pone.0057729|issn=1932-6203|pmc=3585221|pmid=23469060}}</ref>

A study of patients with Type 1 [[Diabetes]] found that [[Coxsackie B4]] was found to infect the β cells in the pancreatic islets of the pancreas and cause inflammation mediated by [[natural killer cell]]s.<ref>http://www.pnas.org/content/104/12/5115.full</ref>

=== Gastroparesis ===
A very small observational study found that nine out of ten patients with symptoms of [[gastroparesis]] had positive gastric biopsies for enterovirus.<ref name="BarkinJA, 20162">{{Citation
| last1 = Barkin | first1 = JA | authorlink1 =
| last2 = Czul | first2 = F | authorlink2 =
| last3 = Barkin | first3 = JS | authorlink3 =
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Rey | first5 = IR | authorlink5 = Irma Rey
| last6 = Moshiree | first6 = B | authorlink6 =
| title = Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis
| journal = Digestive Diseases and Sciences | volume = 61 | issue = 8 | page = 2344-50
| date = 2016
| pmid = 27344315
| doi = 10.1007/s10620-016-4227-x
}}</ref>
== Treatment ==

There are no FDA-approved treatments for enteroviruses. The drug [[Pleconaril]] has been shown to have activity against a number of enteroviruses<ref name="Rotbart2001" /><ref name="Pevear1999" /><ref name="Bauer2002" /><ref name="Groarke1999" /><ref name="Abzug2016" /> but has not been approved by the [[FDA]].

Treatment usually involves supporting the immune response particularly in those with documented immune dysfunction. Dr. Chia treats his patients with enteroviral infection with [[Equilibrant]], [[gammaglobulin]] and [[interferon]].<ref name="evmed-treatment" />

==Published Studies==

*2016, A study on brain tissue samples from a deceased ME patient found evidence of enterovirus specific genomic sequences and enteroviral protein in the patient's cerebral cortex.<ref name="Richardson2016" />
*2016, A study on stomach tissue samples from CFS patients found that 82% of patients have evidence of chronic enterovirus infection of the stomach.<ref name="ChiaJKS2016" />
*2010, A longitudinal study found that a percentage of patients presenting to emergency care with acute enterovirus infection would go on to develop symptoms of ME and CFS and had demonstrable evidence of viral persistence.<ref name="ChiaJKS2010" />
*1996, A Swedish study using the [[Fukuda criteria]] was unable to find evidence of any persistent enteroviral infection in fecal samples, [[Muscle biopsy|muscle biopsies]], or cerebrospinal fluid.<ref name="Lindh1996" />
*1995, In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group.<ref>{{Cite journal|last=Nairn|first=C|date=August 1995|title=Comparison of Coxsackie B neutralization and enteroviral PCR in chronic fatigue patients|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.1890460404|journal=Journal of Medical Virology|volume=|pages=|via=}}</ref>
*1994, A second postmortem tissue study found positive enterovirus PCR sequences in the [[muscle]], heart, brain stem, and hypothalamus of a deceased ME patient.<ref name="McGarry1994" />
*1990, Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. "This suggests that entrovirus pesistence in [[muscle]] is due to a defect in control of viral RNA synthesis."<ref name="Cunningham, 1990" />
*1990, A retrospective cohort study found that 31% of ME patients had elevated enteroviral IgM antibody levels. Sixteen of these patients were retested annually over three years and all showed persistently elevated [[Coxsackie B]] neutralizing antibody levels and intermittently positive enteroviral IgM, indicating the possibility of a persistent infection.<ref name="Dowsett1990" />
*1988, A study of 76 postviral fatigue patients and 30 controls found significantly higher numbers of positive cultures and IgM responses to enteroviruses.<ref>{{Cite journal|last=Yousef|first=G.E.|date=23 Jan 1988|title=Chronic Enterovirus Infection in Patients with Postviral Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S0140673688927225|journal=The Lancet|volume=331|pages=146-150|via=}}</ref>
*1988, In one study, enterovirus-specific RNA three standard deviations greater than controls was found in [[Muscle biopsy|muscle biopsies]] of 20% of ME patients studied.<ref name="Archard1988" />

==Talks & interviews==

*2016, [https://youtu.be/mZdG2otpC3w - 86. ‪ME and the role of enteroviruses / ME en de rol van enterovirussen - Dr. Byron Hyde‬, MD]

==Learn More==
*[[List of enterovirus infection studies]]

*[http://www.anapsid.org/cnd/diffdx/polio1.html ME/CFS and Polio], chapter from book "ME: The New Plague", Jane Colby.<ref name="ColbyJ1996" />

==See Also==

* [[Non-cytolytic enterovirus]]
* [[List of enterovirus infection studies]]
* [[Enteroviral infection hypothesis]]
* [[Post-mortem brain studies]]
*[[Coxsackie B]]
*[[John Chia]]
*[[John Richardson]]
*[[James Mowbray]]
*[[Irving Spurr]]

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| last4 = Bell | first4 = EJ | authorlink4 = Eleanor Bell
| title = Myalgic encephalomyelitis--a persistent enteroviral infection?
| journal = Postgraduate Medical Journal | volume = 66| issue = 777| pages = 526–530
| date = 1 Jul 1990
| pmid = 2170962 | doi = 10.1136/pgmj.66.777.526
| url = http://pmj.bmj.com/content/66/777/526
}}</ref>
<ref name="evmed-treatment">{{citation
| title = Treatments for Chronic Fatigue Syndrome
| type = webpage
| journal = EvMed Research
| url = http://www.evmedresearch.com/education/treatment.php
}}</ref>
<ref name="Groarke1999">{{Citation
| last1 = Groarke | first1 = James M
| last2 = Pevear | first2 = Daniel C
| title = Attenuated Virulence of Pleconaril-Resistant Coxsackievirus B3 Variants
| journal = Journal of Infectious Diseases | volume = 179| issue = 6| pages = 1538–1541
| date = 1 Jun 1999
| pmid = 10228078 | doi = 10.1086/314758
| url = http://jid.oxfordjournals.org/content/179/6/1538
}}</ref>
<ref name="Lindh1996">{{Citation
| last1 = Lindh | first1 = G
| last2 = Samuelson | first2 = A
| last3 = Hedlund | first3 = KO
| last4 = Evengård | first4 = B
| last5 = Lindquist | first5 = L
| last6 = Ehrnst | first6 = A
| title = No findings of enteroviruses in Swedish patients with chronic fatigue syndrome
| journal = Scandinavian Journal of Infectious Diseases | volume = 28| issue = 3| pages = 305–307
| date = 1996
| pmid = 8863367
| url = http://www.ncbi.nlm.nih.gov/pubmed/8863367
}}</ref>
<ref name="McArdle1996">{{Citation
| last1 = McArdle | first1 = A | authorlink1 =
| last2 = McArdle | first2 = F | authorlink2 =
| last3 = Jackson | first3 = MJ | authorlink3 =
| last4 = Page | first4 = SF | authorlink4 =
| last5 = Fahal | first5 = I | authorlink5 =
| last6 = Edwards | first6 = RH | authorlink6 =
| title = Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome
| journal = Clinical Science (London, England: 1979) | volume = 90| issue = 4| pages = 295–300
| date = Apr 1996
| pmid = 8777836 | doi = 10.1042/cs0900295
| url = http://www.ncbi.nlm.nih.gov/pubmed/8777836
}}</ref>
<ref name="McGarry1994">{{citation
| last1 = McGarry | first1 = Frances | authorlink1 = Frances McGarry
| last2 = Gow | first2 = John | authorlink2 = John Gow
| last3 = Behan | first3 = Peter O | authorlink3 = Peter O Behan
| title = Enterovirus in the Chronic Fatigue Syndrome
| journal = Annals of Internal Medicine | volume = 120| issue = 11| pages = 972–973
| date = 1 Jun 1994
| doi = 10.7326/0003-4819-120-11-199406010-00020
| url = http://www.ncbi.nlm.nih.gov/pubmed/8172448
}}</ref>
<ref name="Pevear1999">{{Citation
| last1 = Pevear | first1 = Daniel C
| last2 = Tull | first2 = Tina M
| last3 = Seipel | first3 = Martin E
| last4 = Groarke | first4 = James M
| title = Activity of Pleconaril against Enteroviruses
| journal = Antimicrobial Agents and Chemotherapy | volume = 43| issue = 9| pages = 2109–2115
| date = 1 Sep 1999
| pmid = 10471549
| url = http://aac.asm.org/content/43/9/2109
}}</ref>
<ref name="Richardson2016">{{Citation
| last = Richardson | first = J | authorlink1 = John Richardson
| title = Viral Isolation from Brain in Myalgic Encephalomyelitis
| journal = Journal of Chronic Fatigue Syndrome | volume = 9| issue = 3-4| pages = 15–19
| date = 1 Jan 2001
| doi = 10.1300/J092v09n03_03
| url = http://www.tandfonline.com/doi/abs/10.1300/J092v09n03_03
}}</ref>
<ref name="Rotbart2001">{{Citation
| last1 = Rotbart | first1 = HA | authorlink1 = Harley A Rotbart
| last2 = Webster | first2 = AD | authorlink2 = A. David Webster
| title = Treatment of Potentially Life-Threatening Enterovirus Infections with Pleconaril
| journal = Clinical Infectious Diseases| volume = 32| issue = 2| pages = 228–235
| date = 15 Jan 2001
| pmid = 11170912 | doi = 10.1086/318452
| url = http://cid.oxfordjournals.org/content/32/2/228
}}</ref>
</references>


[[Category:Infectious agents]]
[[Category:Virology]]

Template:Main article

2018-08-18T00:06:27Z

Bill:Add parameters in VE

<i><div role="note" class="hatnote navigation-not-searchable">Main article: [[{{{page_name}}}]]</div></i>
<noinclude>
{{documentation}}

<templatedata>
{
"params": {
"page_name": {}
}
}
</templatedata>
</noinclude>

Template:Main article

2018-08-18T00:04:42Z

Bill:fix

<i><div role="note" class="hatnote navigation-not-searchable">Main article: [{{canonicalurl:{{{page_name}}}}} {{{page_name}}}]</div></i>
<noinclude>
{{documentation}}

<templatedata>
{
"params": {
"1": {}
}
}
</templatedata>
</noinclude>

Template:Main article

2018-08-17T23:57:17Z

Bill:dsa

<i><div role="note" class="hatnote navigation-not-searchable">Main article: [/wiki/{{{page_name}}} {{{page_name}}}]</div></i>
<noinclude>
{{documentation}}

<templatedata>
{
"params": {
"1": {}
}
}
</templatedata>
</noinclude>

Template:Main article

2018-08-17T23:55:51Z

Bill:Make the template take only one parameter

<i><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/{{{page_name}}}" title="Poliovirus">Poliovirus</a></div></i>
<noinclude>
{{documentation}}

<templatedata>
{
"params": {
"1": {}
}
}
</templatedata>
</noinclude>

Template:Fix/category

2018-08-17T23:44:37Z

Bill:c character issue

<noinclude>{{pp-template|small=yes}}</noinclude>{{{cat|[[Category:All pages needing cleanup]]}}}{{#if:{{{cat-date|}}}
|[[{{{cat-date}}} {{#if:{{{date|}}}
|from {{{date}}}
}}]]{{#if:{{{date|}}}
|{{#ifexist:{{{cat-date}}} from {{{date}}}|
|[[Category:Articles with invalid date parameter in template]]
}}
}}
}}{{#if:{{{cat2|}}}|{{{cat2}}}}}{{#if:{{{cat-date2|}}}
|[[{{{cat-date2}}} {{#if:{{{date|}}}
|from {{{date}}}
}}]]{{#if:{{{date|}}}
|{{#ifexist:{{{cat-date2}}} from {{{date}}}|
|[[Category:Articles with invalid date parameter in template]]
}}
}}
}}{{#if:{{{cat3|}}}|{{{cat3}}}}}{{#if:{{{cat-date3|}}}
|[[{{{cat-date3}}} {{#if:{{{date|}}}
|from {{{date}}}
}}]]{{#if:{{{date|}}}
|{{#ifexist:{{{cat-date3}}} from {{{date}}}|
|[[Category:Articles with invalid date parameter in template]]
}}
}}
}}

Module:Hatnote

2018-08-09T21:45:49Z

Bill:update

--------------------------------------------------------------------------------
-- Module:Hatnote --
-- --
-- This module produces hatnote links and links to related articles. It --
-- implements the {{hatnote}} and {{format link}} meta-templates and includes --
-- helper functions for other Lua hatnote modules. --
--------------------------------------------------------------------------------

local libraryUtil = require('libraryUtil')
local checkType = libraryUtil.checkType
local mArguments -- lazily initialise [[Module:Arguments]]
local yesno -- lazily initialise [[Module:Yesno]]

local p = {}

--------------------------------------------------------------------------------
-- Helper functions
--------------------------------------------------------------------------------

local function getArgs(frame)
-- Fetches the arguments from the parent frame. Whitespace is trimmed and
-- blanks are removed.
mArguments = require('Module:Arguments')
return mArguments.getArgs(frame, {parentOnly = true})
end

local function removeInitialColon(s)
-- Removes the initial colon from a string, if present.
return s:match('^:?(.*)')
end

function p.findNamespaceId(link, removeColon)
-- Finds the namespace id (namespace number) of a link or a pagename. This
-- function will not work if the link is enclosed in double brackets. Colons
-- are trimmed from the start of the link by default. To skip colon
-- trimming, set the removeColon parameter to false.
checkType('findNamespaceId', 1, link, 'string')
checkType('findNamespaceId', 2, removeColon, 'boolean', true)
if removeColon ~= false then
link = removeInitialColon(link)
end
local namespace = link:match('^(.-):')
if namespace then
local nsTable = mw.site.namespaces[namespace]
if nsTable then
return nsTable.id
end
end
return 0
end

function p.formatPages(...)
-- Formats a list of pages using formatLink and returns it as an array. Nil
-- values are not allowed.
local pages = {...}
local ret = {}
for i, page in ipairs(pages) do
ret[i] = p._formatLink(page)
end
return ret
end

function p.formatPageTables(...)
-- Takes a list of page/display tables and returns it as a list of
-- formatted links. Nil values are not allowed.
local pages = {...}
local links = {}
for i, t in ipairs(pages) do
checkType('formatPageTables', i, t, 'table')
local link = t[1]
local display = t[2]
links[i] = p._formatLink(link, display)
end
return links
end

function p.makeWikitextError(msg, helpLink, addTrackingCategory, title)
-- Formats an error message to be returned to wikitext. If
-- addTrackingCategory is not false after being returned from
-- [[Module:Yesno]], and if we are not on a talk page, a tracking category
-- is added.
checkType('makeWikitextError', 1, msg, 'string')
checkType('makeWikitextError', 2, helpLink, 'string', true)
yesno = require('Module:Yesno')
title = title or mw.title.getCurrentTitle()
-- Make the help link text.
local helpText
if helpLink then
helpText = ' ([[' .. helpLink .. '|help]])'
else
helpText = ''
end
-- Make the category text.
local category
if not title.isTalkPage and yesno(addTrackingCategory) ~= false then
category = 'Hatnote templates with errors'
category = string.format(
'[[%s:%s]]',
mw.site.namespaces[14].name,
category
)
else
category = ''
end
return string.format(
'<strong class="error">Error: %s%s.</strong>%s',
msg,
helpText,
category
)
end

function p.disambiguate(page, disambiguator)
-- Formats a page title with a disambiguation parenthetical,
-- i.e. "Example" → "Example (disambiguation)".
checkType('disambiguate', 1, page, 'string')
checkType('disambiguate', 2, disambiguator, 'string', true)
disambiguator = disambiguator or 'disambiguation'
return string.format('%s (%s)', page, disambiguator)
end

--------------------------------------------------------------------------------
-- Format link
--
-- Makes a wikilink from the given link and display values. Links are escaped
-- with colons if necessary, and links to sections are detected and displayed
-- with " § " as a separator rather than the standard MediaWiki "#". Used in
-- the {{format hatnote link}} template.
--------------------------------------------------------------------------------

function p.formatLink(frame)
local args = getArgs(frame)
local link = args[1]
local display = args[2]
if not link then
return p.makeWikitextError(
'no link specified',
'Template:Format hatnote link#Errors',
args.category
)
end
return p._formatLink(link, display)
end

function p._formatLink(link, display)
checkType('_formatLink', 1, link, 'string')
checkType('_formatLink', 2, display, 'string', true)

-- Remove the initial colon for links where it was specified manually.
link = removeInitialColon(link)

-- Find whether a faux display value has been added with the {{!}} magic
-- word.
if not display then
local prePipe, postPipe = link:match('^(.-)|(.*)$')
link = prePipe or link
display = postPipe
end

-- Find the display value.
if not display then
local page, section = link:match('^(.-)#(.*)$')
if page then
display = page .. ' § ' .. section
end
end

-- Assemble the link.
if display then
return string.format(
'[[:%s|%s]]',
string.gsub(link, '|(.*)$', ''), --display overwrites manual piping
display
)
else
return string.format('[[:%s]]', link)
end
end

--------------------------------------------------------------------------------
-- Hatnote
--
-- Produces standard hatnote text. Implements the {{hatnote}} template.
--------------------------------------------------------------------------------

function p.hatnote(frame)
local args = getArgs(frame)
local s = args[1]
local options = {}
if not s then
return p.makeWikitextError(
'no text specified',
'Template:Hatnote#Errors',
args.category
)
end
options.extraclasses = args.extraclasses
options.selfref = args.selfref
return p._hatnote(s, options)
end

function p._hatnote(s, options)
checkType('_hatnote', 1, s, 'string')
checkType('_hatnote', 2, options, 'table', true)
options = options or {}
local classes = {'hatnote', 'navigation-not-searchable'}
local extraclasses = options.extraclasses
local selfref = options.selfref
if type(extraclasses) == 'string' then
classes[#classes + 1] = extraclasses
end
if selfref then
classes[#classes + 1] = 'selfref'
end
return string.format(
'<i><div role="note" class="%s">%s</div></i>',
table.concat(classes, ' '),
s
)
end

return p

Template:Main article

2018-08-09T21:44:10Z

Bill:u

{{#invoke:main|main}}<noinclude>
{{documentation}}

<templatedata>
{
"params": {
"1": {}
}
}
</templatedata>
</noinclude>

Template:Fix/category

2018-08-09T21:43:14Z

Bill:create template

Template:PagesInCategory

2018-08-09T21:42:18Z

Bill:update

<noinclude>This template is for listing all page members within a category. Use like <nowiki>{{PagesInCategory|myCategoryToListOut}} or with full arguments, {{PagesInCategory|myCategoryToListOut|columnCount=3|mode=ordered}} where "columnCount" is optional and can be any integer representing the number of columns, and "mode" which is also optional and can be "ordered", "unordered", "none", "gallery" (for images), "inline-bullets", or "inline"</nowiki>
</noinclude><includeonly>{{#invoke:CategoryList|main|{{{1|}}}|columnCount={{{columnCount|}}}|mode={{{mode|}}}}}</includeonly>
<noinclude>
<templatedata>
{
"params": {
"1": {},
"columnCount": {},
"mode": {}
}
}
</templatedata>
</noinclude>

Template:CategoriesInCategory

2018-08-09T21:41:52Z

Bill:update

<noinclude>This template is for listing all category members within a category. Use like <nowiki>{{CategoriesInCategory|myCategoryToListOut}} or with full arguments, {{CategoriesInCategory|myCategoryToListOut|columnCount=3|mode=ordered}} where "columnCount" is optional and can be any integer representing the number of columns, and "mode" which is also optional and can be "ordered", "unordered", "none", "gallery" (for images), "inline-bullets", or "inline"</nowiki>
</noinclude><includeonly>{{#invoke:CategoryList|categoriesInCategory|{{{1|}}}|columnCount={{{columnCount|}}}|mode={{{mode|}}}}}</includeonly>
<noinclude>
<templatedata>
{
"params": {
"1": {},
"columnCount": {},
"mode": {}
}
}
</templatedata>
</noinclude>

MediaWiki:Common.css

2018-08-09T21:41:28Z

Bill:update

Category:All articles with unsourced statements

2018-08-09T21:39:47Z

Bill:create category

Category:Articles with unsourced statements from unknown year

2018-08-09T21:39:16Z

Bill:create category

Template:Cleanup

2018-08-09T21:36:14Z

Bill:upgrade

{{ {{{|safesubst:}}}#invoke:Unsubst||$N=Cleanup |date=__DATE__ |$B=
{{#ifexpr:{{#expr:{{#iferror:{{#time:U|{{{date}}}}}|2000000000}}>=1341100800}}*{{#if:{{{reason|<noinclude>x</noinclude>}}}|0|1}}*{{#ifeq:{{{nocat}}}|true|0|1}}
|{{error|You must add a {{para|reason}} parameter to this Cleanup template - replace it with <code><nowiki>{{Cleanup|</nowiki>{{#if:{{{1|}}}|{{{1|}}}{{!}}|}}{{#if:{{{date|}}}|<nowiki>date=</nowiki>{{{date|}}}{{!}}}}<nowiki>reason=<Fill reason here>}}</nowiki></code>, or remove the Cleanup template.
{{clear}}
}}{{Category handler
|nocat = {{{nocat|}}}
|main = {{DMC|Cleanup tagged articles without a reason field|from|{{{date|}}}}}
}}
|{{main other
|{{ambox
| name = Cleanup
| subst = <includeonly>{{subst:</includeonly><includeonly>substcheck}}</includeonly>
| type = style
| class = ambox-Cleanup
| small = {{{small|}}}
| sect = {{{1|}}}
| issue = may '''require [[MEpedia:cleanup|cleanup]]''' to meet MEpedia's [[MEpedia:Manual of Style|quality standards]]. {{#if:{{{2|{{{reason|}}}}}}
|The specific problem is: '''{{{2|{{{reason}}}}}}'''.
}}
| talk = {{{talk|{{{talksection|}}}}}}
| fix = {{#if:{{{2|{{{reason|}}}}}}|
|No [[Template:Cleanup/doc|cleanup reason]] has been specified.
}} Please help [{{fullurl:{{FULLPAGENAME}}|veaction=edit}} improve this {{{1|{{SUBJECTSPACE formatted}}}}}] if you can.
| date = {{{date|}}}
| cat = Articles needing cleanup
| all = All articles needing cleanup
| cat2 = Cleanup tagged articles with{{#if:{{{2|{{{reason|}}}}}}||out}} a reason field
}}
|{{mbox
| demospace = {{{demospace|}}}
| type = style
| text = This {{{1|{{SUBJECTSPACE formatted}}}}} '''may require [[Wikipedia:cleanup|cleanup]] to meet Wikipedia's [[Wikipedia:Manual of Style|quality standards]]'''. {{#if:{{{2|{{{reason|}}}}}}
|The specific problem is: '''{{{2|{{{reason}}}}}}'''.
|No [[Template:Cleanup/doc|cleanup reason]] has been specified.
}} Please help [{{fullurl:{{FULLPAGENAME}}|veaction=edit}} improve this {{{1|{{SUBJECTSPACE formatted}}}}}] if you can{{#ifeq:{{SUBJECTSPACE}}|{{NAMESPACE}}
|; the [[{{TALKPAGENAME}}{{#if:{{{talksection|}}}|#{{{talksection}}}}}|talk page]] may contain suggestions.
|.
}}
}}
| demospace = {{{demospace|<noinclude>main</noinclude>}}}
}}{{Category handler
|page = {{SUBJECTPAGENAME}}
|nocat = {{{nocat|}}}
|category = {{DMC|Wikipedia categories needing cleanup|from|{{{date|}}}}}
|template = {{#ifeq:{{#titleparts:{{FULLPAGENAME}}|1}}|Template:Cleanup||{{DMC|Wikipedia templates needing cleanup|from|{{{date|}}}}}}}
|other = {{DMCA|Wikipedia pages needing cleanup|from|{{{date|}}}}}
}}
}}
}}<noinclude>
{{Documentation}}
<templatedata>
{
"params": {
"date": {
"autovalue": "{{subst:CURRENTMONTHNAME}} {{subst:CURRENTYEAR}}"
},
"reason": {
"type": "string",
"autovalue": "Describe cleanup needed"
}
},
"description": "Template to add a notice to a page that need a cleanup"
}
</templatedata>
</noinclude>

MEpedia:How to contribute

2018-07-31T04:22:49Z

Bill:Remove visual editor error warning.

Contribute to MEpedia today! Anyone can create pages, write content, add links/citations, fact-check, or even just fix typos. Everyone has something to offer, whatever your skills & experience, even if you have never edited a wiki (like Wikipedia) before. Get involved and help the patient community identify all of the best and most important resources for our disease and its research, treatment and history.

To get started, read our [[Editorial Guidelines]] and find more information about how to edit MEpedia below. Please make sure to join our contributor community, the MEpedia [http://facebook.com/groups/218347055598647 Facebook Group]. You can also follow MEPedia [https://www.facebook.com/mepedia/ on Facebook], [https://twitter.com/MEencyclopedia Twitter] and subscribe to us on [https://www.reddit.com/r/MEAction Reddit].

Pages that are a [[red link]] have not been created yet and need to be populated – a full list of these pages [[Special:WantedPages|can be found here]]. Pages that have been created ([[Blue link|blue links]]) but need to be expanded are marked as stubs - a full list of all stubs [[:Category:Stubs|can be found here]]. We also have a [[MEpedia Suggestions#priority pages for expansion|list of priority pages for expansion]].

All we ask is that you read the guidelines (see below) before you edit.

Pages that have problems such as incorrect information, formatting issues, or a lack of citations are marked with a cleanup note. A full list of pages requiring cleanup [[:Category:All articles needing cleanup|can be found here]].

Have any questions after reading the below? Email [mailto:mepedia@meaction.net mepedia@meaction.net].

== Getting started ==

=== Create an account ===
Before you start editing, you should [[Special:CreateAccount|create an account]] or [[Special:UserLogin|log in]]. Note, if you are not logged in when you make an edit or contribution to a page, your IP address will appear.

==Rules & Guidelines==

*[[Editorial Guidelines]]
*[[Science Guidelines]]
*[[MEpedia:Manual of Style]]

== Suggested tasks ==

===Five minute tasks===
Only have a five minute spoon to give? Here is a [[List of small tasks|list of small tasks]] you can help us with in roughly one to ten minutes of time.

=== Priority projects ===
Want to dive in deeper? Browse a [[MEpedia suggestions#Suggestions - High Priority|list of larger projects]] and page revisions.
== Roles ==
There are so many different roles contributors can play, at every level of cognitive ability or technical expertise. Every contributor can play one or more roles. All are important and help us grow and improve the project!

'''The Scientist:''' If you have a science background or a passion for science, we definitely need your expertise improving our medical and science pages and ensuring that all content is correct, accurate and cited. (Note: unlike Wikipedia, every fact presented on MEpedia does not need to be replicated or have appeared in a review article. However, the limitations of individual studies and the certainty of findings need to be properly contextualized and qualified. For more, see the [[Science Guidelines]])

'''The Translator:''' While many of the science pages will have highly technical information, useful to medical professionals and researchers, it's our goal that the opening section of every page (which usually comes before the table of contents) can provide a one to two paragraph summary that is accessible to as general audience as possible. As a page matures and contains a lot of information, The Translator can write an opening paragraph if none exists or improve the opening paragraph(s) to make it even more accessible.

''But you don't necessarily need to have a technical background to play any of these roles:''

'''The Historian:''' Help us improve our content on the history of [[Myalgic encephalomyelitis|ME]] and [[Chronic fatigue syndrome|CFS]] (and before it was either of these things, [[Icelandic Disease]] and [[atypical polio]]). Bring to life the [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of the past by digging into the newspaper and journal records and creating pages for individual outbreaks.

'''The Biographer:''' We have dozens of pages with biographies of scientists, clinicians, historical figures and activists with ME. These can always be improved and there are many people still missing. (See our categories for [[:Category:Famous people with ME, CFS, and/or FMS|famous people]], [[:Category:Researchers|researchers]], [[:Category:Clinicians|clinicians]], [[:Category:Advocates or allies|advocates]])

'''The Editor:''' As pages grow through the addition of new information, they can often become hard to navigate. Read our more developed pages and see whether they can be improved by breaking up very long sections into sub-sections, improving overall flow, organization and readability, or updating the opening paragraph to better reflect the way the page may have grown and changed.

'''The Link Collector:''' Sometimes you may not have the cognitive capacity or time to take an interesting article and writing it into an existing page. However, you can help simply by collecting links and pasting them on the "Discussion" page of a given article, with perhaps a sentence or two explaining its relevance, so that someone in the future can take that link and incorporate that into the page.

'''The Deep Sea Diver:''' You may not have an expertise in a particular area, but you decide to adopt a page you feel passionate about, and build it from the ground up, reading every reference you can find. It's a long, slow process but can be really gratifying to develop mastery over a specific topic!

'''The Photo Curator:''' Many of our pages could be improved simply through the addition of images and drawings. It's important to make sure you have permission to use the any photos you add , that they are in the public domain, or that they carry a Creative Commons license.

'''The Bridge Builder:''' pick a [[Special:DeadendPages|dead end]] page and create internal links to related MEpedia content within the body of the page or by added pages to the "See also" section. Or, find an [[Special:LonelyPages|orphan page]] and link to it from existing pages.

'''The Expander:''' browse MEpedia's [[Special:ShortPages|shortest pages]] and help us lengthen them.

'''The Proofreader:''' Fix small typos and grammatical errors as you go. Or visit the [[Welcome to MEpedia|front page]] and hit "[[Special:Random|random]]" to be taken to a random article. Or see the list of [[Special:RecentChanges|recently updated pages]]. Read and correct mistakes.

'''The Citation Catcher:''' Many citations are simple links, without the proper article title, journal name, date or author information. Correcting citations are a great way to help us improve this project.

'''The Manual Writer:''' All of our support documentation could always be improved. Help us find ways to better explain the tools and guidelines behind MEpedia and help make them more accessible. To contribute in this way, consider starting a new thread in our [https://www.facebook.com/groups/218347055598647/ Facebook group] and making a suggestion.

'''The Community Organizer:''' Help us grow this project by growing the community around it. Invite friends to join our [https://www.facebook.com/groups/218347055598647/ Facebook group]. Act as a greeter, help folks feel welcome, answer questions as they arise.

'''The Outreacher:''' Help us build links between MEpedia and others. For example posting MEpedia articles to other M.E, community forums and asking for help improving them, sending links to MEpedia articles to scientists (e.g. the page about them) and asking them to update the page and confirm it is complete, asking researchers to read MEpedia pages related to their work and provide feedback on what needs adding, or asking M.E. blog writers to include MEpedia links in their articles so their readers can learn more.

'''The Supporter:''' Help MEpedia by helping, training and supporting its volunteer team. Help everyone learn how to edit pages, to do more advanced editing, and how to more effectively create content. Maybe you're a technologist who finds it easy to learn and teach others about wiki editing, or a technical writer who cannot commit to contribute much but can help others to write.

'''The News Reader:''' Help keep MEpedia fresh by updating its pages based on news you read. For example if you read a new article published by journalist David Tuller, make sure his page has been updated to include the latest article. Or if an announcement is made by the NIH or some other organization, update relevant pages to reflect the news.

See [[How_to_contribute#How_can_I_contribute.3F|even more ways to contribute]].

==A note on ME v. CFS==
We have separate pages for [[Myalgic Encephalomyelitis]], [[ME/CFS]] and [[Chronic Fatigue Syndrome]] as well as [[SEID]]. The convention is that the terminology used in an ME-pedia article should match the terminology used in the underlying source. Where there is a tension between the term used in the source and the definition (e.g., [[ME]] defined by the [[Oxford criteria]] or [[CFS]] defined by the [[Canadian Consensus Criteria]]), it may be useful for clarity to mention the definition used.

==How do I create a new page?==
Simply type in the title of your new page and hit "create page." You'll want to [[Special:Search|search]] the existing database of pages to make sure that your page or a similar page does not already exist.<inputbox>
type=create
break=no
</inputbox>
You can also browse our list of [[Special:WantedPages|"wanted" pages]] – pages that are linked to from existing pages, but don't yet exist.

==How do I edit existing pages?==

There are two types of editor on this wiki, the '''Visual editor''', which operates more like your word processing or email program, and the '''Source editor''', which uses a special kind of wiki code. Most users will prefer to use the Visual editor, but for more advance applications or if the Visual editor is "down" (as happens from time to time), the resources below will help you learn how to navigate both.

Look for the "edit" (Visual editor) or "edit source" (Source editor) links at the top of the page (to edit the whole page) and next to each section heading (to edit just that section).

After you've made your changes, scroll down to the 'Show Preview' section, add a comment, preview your changes, then save them.

== Using the visual editor ==

To learn how to use the visual editor, please see Wikipedia's [https://www.mediawiki.org/wiki/Help:VisualEditor/User_guide visual editor user guide].

== Using the source code editor ==
The source code editor is a more advanced way of editing MEpedia. See our tricks and tips on how to [[Using the source code editor|get started with the source code editor]].

== Article outlines, templates and includes==

=== Article outlines ===
A list of [[MEpedia article outlines|copy-and-paste outlines]] for new articles depending category.

=== Common templates and includes ===
{| class="wikitable"
!Template name
!Description / Function
!Source editor code
!Installation status
!Visual editor status
|-
|Cleanup needed
|Indicates articles that need cleanup and the reason why.
|<syntaxhighlight>
{{Cleanup|reason= |date= }}
</syntaxhighlight>
|Installed but could use cleaner visual (e.g., a box/outline around it). See Wikipedia's version and compare to MEpedia.
|Possible fields do not appear. Would be wonderful if there could be a handful of prefab reasons for cleanup that could allow for searching on those reasons (e.g., view all pages with citation issues, all pages requiring editing or reorganization, all pages that are too long, all pages not written in encyclopedic style, etc).
|-
|Stub article
|Indicates a very short article that is a "stub" waiting to be expanded.
|<syntaxhighlight>
{{stub}}
</syntaxhighlight>
|Installed but compared with Wikipedia's version.
|I don't know if Stub article take fields
|-
|Main
|Links a section of one page to the full article on another.
|<syntaxhighlight>
{{Main|page}}
</syntaxhighlight>
|Installed, but no formatting. See Wikipedia for example of how formatting should be displayed.
|Possible fields do not appear
|-
|Citation needed
|Indicates facts that require citations.
|<syntaxhighlight>
{{Citation needed}}
</syntaxhighlight>
|Installed but not working properly (may be missing a component).
|
|-
|All pages in a category
|Automatically displays all of the articles within the specified category
|<syntaxhighlight>
{{PagesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|-
|All categories in a category
|Automatically displays all of the sub-categories within the specified category
|<syntaxhighlight>
{{CategoriesInCategory|category-name}}
</syntaxhighlight>
|Can be spread across columns, see examples.
|No explicit support
|}

==Other ways to contribute==

===Make a suggestion===
Almost everyone working on MEpedia is sick, including bed-bound patients. Although we welcome suggestions please, please if you possibly can, create/edit the page yourself. It is very easy to add a new page or make an improvement – be bold! Together we are stronger as a community. If you REALLY can't edit the page, then you can go to the [[MEpedia suggestions]] page, click Edit, and add your suggestion to the list for someone else to consider implementing in future.

===Implement a suggestion===
If you want to contribute but aren't sure where to start, try looking at the [[MEpedia suggestions]] and consider implementing an improvement suggested by others.

===Create a new article===

To create a new article, simply search for the title of the article you wish to create. If a page does not already exist, you will see an option to create the page. Alternatively if you see a red link to the page, that means it does not yet exist. Just click the red link to create the page.

Once you have a blank editable article open, consider copying-and-pasting an outline into it for that type of article, so you have a set of headings to prompt writing. See [[MEpedia article outlines]]

Remember that articles must use strong citations. For example if you write "ME/CFS can be successfully treated with XYZ", you MUST provide a reference to evidence, ideally a high quality (randomized, placebo-controlled) published study. If there is no evidence, the wording must reflect this, for example "ME/CFS is sometimes treated using XYZ, but currently there is no good evidence for its use".

=== Expand a topic ===

Pages with blue links (as opposed to red) exist already, and can be proof-read, improved and extended. Remember statements need to be supported by the best available evidence or source, for example a published quote by a person, or a paper in a scientific journal.

=== Check our references ===

You can make sure facts are properly cited and references are in correct format.

We aim to serve a general audience, a research audience, and a patient audience. All entries should be cited and make clear to distinguish what has and has not been established by peer-reviewed research findings. Articles should aim to provide both a general overview of a specific topic as well as discuss its implications or applications in ME and CFS.

=== Correct typos ===

You can also copy-edit existing articles for typos and edit for clarity.

=== Clean-up poor pages ===
Some pages are inconsistently formatted, too long, are presented badly, need partially rewriting, or suffer from other problems. Those pages are marked as needing clean-up, and are listed under [[clean up list|all articles needing cleanup]].

===Mark pages as needing cleanup===
If you see a problem with a page, it needs clean-up, and you are not able to resolve it, mark the page as needing cleaning by adding a marker like this including a description of the problem:

''<nowiki>{{Cleanup | reason=the article is full of incorrect capitalization | date=August 2018}}</nowiki>''

For more details see [[Template:Cleanup|Cleanup]].

== Other Resources ==

* [[mw:Help:Editing|Help:Editing]]
* [[mw:Special:MyLanguage/Manual:Configuration_settings|Configuration settings list]]
* [[mw:Special:MyLanguage/Manual:FAQ MediaWiki|FAQ]]
* [https://lists.wikimedia.org/mailman/listinfo/mediawiki-announce MediaWiki release mailing list]
* [[mw:Special:MyLanguage/Localisation#Translation_resources|Localise MediaWiki for your language]]
* [[Power user/editor tips]]
* [[:Category:Fundamental | Categories browser]]

[[Category:MEpedia guidelines]]

MediaWiki:Vector.css

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Bill:date error fix

/* CSS placed here will affect users of the Vector skin */

#p-navigation{
position: absolute;
top: 75px;
}

#p-tb{
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/*Hide error messages when citation in Visual editor*/

.citation-comment{
display:none;
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Welcome to MEpedia

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Bill:Add page views

[[MEpedia]] is a project founded by [[MEAction]], powered by the patient community, and built by volunteers including patients, students, and researchers. We are crowd-sourcing a knowledge base on the history, science and medicine of [[ME]], [[CFS]], and [[related diseases]]. [[How to contribute|Jump in]]!

{| class="wikitable" style="margin: auto; text-align:center; vertical-align:middle; border-width: 20px; border-color: white; caption-side:bottom;"
|+''MEpedia's {{NUMBEROFARTICLES}} articles have been viewed <span class = "totalnumbderofviews"></span> times.''
!'''<inputbox>'''
type=search
break=no
</inputbox>'''
|-
!
<big>[[MEpedia:About|About]] | [[How_to_contribute|Contribute]] | [[Special:PopularPages|Popular]] | [[Special:Random|Random]] | [[Contents]]</big>
|}
----<gallery>
File:UNREST Film Still Whitney.png|link=Portal:Myalgic Encephalomyelitis|[[Portal:Myalgic Encephalomyelitis|What is ME?]]
File:Brain drawing.jpeg|link=Portal:Nervous_system|[[Portal:Nervous_system|Nervous system]]
File:Heart drawing.png|link=Portal:Cardiovascular_system|[[Portal:Cardiovascular system|Cardiovascular system]]
File:Digestive tract.png|link=Portal:Digestive_system|[[Portal:Digestive system|Digestive system]]
File:Mitochondria drawing.jpg|link=Portal:Energy_metabolism|[[Portal:Energy metabolism|Energy metabolism]]
File:Endocrine.jpg|link=Portal:Endocrine_system|[[Portal:Endocrine system|Endocrine system]]
File:Nk cell.jpg|link=Portal:Immune_system|[[Portal:Immune system|Immune system]]
File:BCell EBV.png|link=Portal:Pathogens|[[Portal:Pathogens|Pathogens]]
File:Pills-1885550 960 720.jpg|link=Category:Potential_treatments|Treatments
File:Florence Nightingale by Charles Staal, engraved by G. H. Mote.jpg|link=Portal:History|[[Portal:History|History & People]]
</gallery>

== Primers ==

* [[Primer for doctors and researchers]]
* [[Primer for family, friends and care providers]]
* [[Primer for journalists]]
* [[Primer for patients]]
* [[Primer for the public]]

== Fact sheets & guides ==

* [https://www.meaction.net/resources/reports-and-fact-sheets/ #MEAction fact sheets]: information in PDF form

* [[Best practices for hospitals]]
* [[Advice for patients having surgery|Guide for patients having surgery]]

MediaWiki:Citoid-template-type-map.json

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Bill:citoid map

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