Multiple sclerosis

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Multiple sclerosis (MS) is a chronic, irreversible, autoimmune and neurological disease that affects the central nervous system, including the brain and spinal cord.[1][2] In multiple sclerosis the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, trouble with sensation, or trouble with coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often remain, especially as the disease advances.[citation needed]

Epidemiology[edit | edit source]

MS prevalence.png

Prevalence[edit | edit source]

An estimated 2.3 million people worldwide have multiple sclerosis.

Risk factors[edit | edit source]

Latitude

Vitamin D

Epstein-Barr virus

Gender differences[edit | edit source]

Over the last decades, the ratio of women to men with MS has increased markedly, representing a true increase in MS among women but not men.[3]

Disease mechanisms[edit | edit source]

Immune system[edit | edit source]

In 1997, it was discovered that B cell therapy (eg Rituximab) which reduces the number of B cells, can bring immediate improvement in MS symptoms. This treatment is more effective for the relapsing-remitting variant of MS, and less effective for the primary progressive variant.[4]

Microbiome[edit | edit source]

Specific changes in the gut microbiome might increase the risk of MS[5], and the risk might be reduced using probiotics, antibiotics, a combination, or a change of diet. An 'International Multiple Sclerosis Microbiome Study' commenced in 2015.[4]

Treatments[edit | edit source]

Standard of care[edit | edit source]

Experimental treatments[edit | edit source]

Another discovery was that a commonly available and inexpensive antihistamine, can be used to induce remyelination of the nerve cells.[4]

Dietary tryptophan can help reduce brain inflammation and 'cognitive fog'.[6]

Comparison of Multiple Sclerosis and ME/CFS[edit | edit source]

Multiple Sclerosis patients or samples are sometimes used for comparison with in ME/CFS in research studies, for instance at the UK ME/CFS biobank, and both are female predominant diseases of the central nervous system.[7][8][9]

There are many similar features in multiple sclerosis and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including: severe disabling fatigue that worsens after exercise; debilitating autonomic symptoms, including orthostatic intolerance; illness course may be relapsing-remitting or progressive; infections and psychosocial stress causing exacerbation; auto-immunity and auto-inflammatory processes; mitochondrial dysfunction; and decreased cerebral blood flow, atrophy of some brain structures.[10]

In the United States, the prevalence rate of chronic fatigue syndrome (CFS) is 0.42% of the population versus MS which has a rate of 0.09%.[11] Approximately 14% of MS patients meet the Fukuda criteria for CFS.[12]

In 2017, a study examined whether network analysis of cytokine production differed between patients with CFS, multiple sclerosis, and healthy controls. The study's model, using a select cytokine profile, showed that immunologic activation in CFS was significantly different from that found in the control and multiple sclerosis groups.[13]

A 2015 study found a markedly disturbed immune signature in the cerebrospinal fluid that is consistent with immune activation in the central nervous system (CNS), and autoimmunity. The MS and ME/CFS groups had markedly different immune signatures, and the ME/CFS group had a greater degree of CNS immune activation than the MS group.[14]

In December 2016, Ohanian, et al, published a study identifying two key immune symptoms that physicians could use to differentiate myalgic encephalomyelitis (ME) and CFS from MS: flu-like symptoms and tender lymph nodes. Subjects included 106 people with MS and 354 people with ME or CFS who completed the DePaul Symptom Questionnaire. The data was analyzed using data mining techniques and machine learning that resulted in correctly categorizing MS and ME or CFS 81.2% of the time. The authors conclude that "because ME or CFS and MS have similar presentations recognizing the importance of immune dysfunction for ME or CFS might be important for healthcare providers."[15]

Differences in symptoms between multiple sclerosis and ME/CFS[edit | edit source]

Ohanian et al. (2016) found that the following five symptoms were significantly more common in patients with ME/CFS compared to patients with multiple sclerosis, with mean scores reported as:

  1. Flu-like symptoms: reported in 51 in ME/CFS patients, and 17 inMS patients
  2. Tender lymph nodes: 37 in ME/CFS patients, 8% in MS patients
  3. Alcohol intolerance: 38 in ME/CFS patients, 9 in MS patients
  4. Inability to tolerate upright position: 51 in ME/CFS patients, 16 in MS patients
  5. Next-day soreness after non-strenuous activities: 75 in ME/CFS patients, 46 in MS patients

The presence of just two immune-related symptoms (tender lymph nodes and flu-like symptoms), which are optional symptoms in ME/CFS, was found to correctly classify around 80% of patients with ME/CFS, who did not have MS.[15]

Notable studies comparing ME/CFS and multiple sclerosis[edit | edit source]

  • 2012, 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.[16] - (Full Text)
  • 2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics[10] - (Full Text)
  • 2015, A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[17] - (Full Text)
  • 2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients[18] - (Full Text)
  • 2016, Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis[15] - (Full Text)
  • 2016, Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[19] - (Abstract)
  • 2016, Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison[20] - (Full Text)
  • 2016, Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome[14] - (Abstract)
  • 2017, Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome[21] - (Full Text)
  • 2017, Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis[13] - (Abstract)
  • 2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study[22] - (Full Text)
  • 2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls[23] - (Full Text)

Other studies[edit | edit source]

  • 2015, HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study. - (Abstract)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Javalkar, Vijaykumar; McGee, Jeanie; Minagar, Alireza (2016). "Clinical Manifestations of Multiple Sclerosis". Elsevier: 1–12. doi:10.1016/b978-0-12-800763-1.00001-4. ISBN 9780128007631. 
  2. University College London Hospitals NHS trust. "What is multiple sclerosis?". www.uclh.nhs.uk. Retrieved Apr 17, 2019. 
  3. Harbo, Hanne (July 2013). "Sex and gender issues in multiple sclerosis". Ther Adv Neurol Disord. 
  4. 4.04.14.2 Conway, Claire (Apr 25, 2016), "Wrapping Up Multiple Sclerosis", UCFS News Center 
  5. "Gut bacteria regulate nerve fibre insulation". The Guardian - Science. Apr 5, 2016. 
  6. Rothhammer, Veit; Mascanfroni, Ivan D; Bunse, Lukas; et al. (May 9, 2016). "Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor". Nature Medicine. advance online publication. doi:10.1038/nm.4106. ISSN 1078-8956. Lay summary. 
  7. Lacerda, Eliana M.; Bowman, Erinna W.; Cliff, Jacqueline M.; Kingdon, Caroline C.; King, Elizabeth C.; Lee, Ji-Sook; Clark, Taane G.; Dockrell, Hazel M.; Riley, Eleanor M. (2017). "The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis". Open journal of bioresources. 4. doi:10.5334/ojb.28. ISSN 2056-5542. PMC 5482226Freely accessible. PMID 28649428. 
  8. Morris, Gerwyn; Maes, Michael (Dec 2013). "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics". BMC Medicine. 11 (1). doi:10.1186/1741-7015-11-205. ISSN 1741-7015. PMC 3847236Freely accessible. PMID 24229326. 
  9. White, Andrea T.; Light, Alan R.; Hughen, Ronald W.; VanHaitsma, Timothy A.; Light, Kathleen C. (Jan 2012). "Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls". Psychosomatic Medicine. 74 (1): 46–54. doi:10.1097/PSY.0b013e31824152ed. ISSN 0033-3174. PMC 3256093Freely accessible. PMID 22210239. 
  10. 10.010.1 Morris, Gerwyn; Maes, Michael (2013). "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics". BMC Medicine. 11: 205. doi:10.1186/1741-7015-11-205. ISSN 1741-7015. 
  11. Jason LA, Paavola E, Porter N, Morello M (2010) Frequency and content analysis of CFS in medical textbooks. Aust J Prim Health 16:174-178.
  12. Gaber TAZK, Oo WW, Ringrose H (2014) Multiple sclerosis/chronic fatigue syndrome overlap: When two common disorders collide. Neuro Rehabil 35: 529–534.
  13. 13.013.1 Sorenson, Matthew; Furst, Jacob; Mathews, Herbert; Jason, Leonard A. (2017). "Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis". Fatigue: Biomedicine, Health & Behavior. 5 (3): 145-158. doi:10.1080/21641846.2017.1335237. 
  14. 14.014.1 Hornig, M; Gottschalk, CG; Peterson, DL; et al. (Feb 2016). "Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome". Molecular Psychiatry. 21 (2): 261–269. doi:10.1038/mp.2015.29. ISSN 1359-4184. Lay summary. 
  15. 15.015.115.2 Ohanian, Diana; Brown, Abigail; Sunnquist, Madison; Furst, Jacob; Nicholson, Laura; Klebek, Lauren; Jason, Leonard (2016). "Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis". EC Neurology. 4.1 (2): 41-45. PMID 28066845. 
  16. White, AT; Light, AR; Hughen, RW; Vanhaitsma, TA; Light, KC (2012). "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". Psychosomatic Medicine. 74 (1): 46-54. doi:10.1097/PSY.0b013e31824152ed. 
  17. Brenu, EW; Broadley, S; Nguyen, T; Johnston, S; Ramos, S; Staines, D; Marshall-Gradisnik, S (2016). "A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis" (PDF). Journal of Immunology Research. 2016. doi:10.1155/2016/9064529. 
  18. Wong, Naomi; Nguyen, Thao; Brenu, Ekua Weba; Broadley, Simon; Staines, Donald; Marshall-Gradisnik, Sonya (2015). "A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients". International Journal of Clinical Medicine. 6 (10): 769-783. doi:10.4236/ijcm.2015.610103. 
  19. Huth, TK; Brenu, EW; Ramos, S; Nguyen, T; Broadley, S; Staines, D; Marshall-Gradisnik, S (Jan 2016). "Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis". Scand J Immunol. 83(1): 44-51. doi:10.1111/sji.12388. PMID 26381393. 
  20. Ramos, S; Brenu, E; Broadley, S; Kwiatek, R; Ng, J; Nguyen, T; Freeman, S; Staines, D; Marshall-Gradisnik, S (Mar 20, 2016). "Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison" (PDF). Asian Pac J Allergy Immunol. 2016 (34): 300-305. doi:10.12932/AP0733. 
  21. Jason, LA; Ohanian, D; Brown, A; Sunnquist, M; McManimen, S; Klebek, L; Fox, P; Sorenson, M (2017). "Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome". Insights in Biomedicine. 2 (2). doi:10.21767/2572-5610.100011. 
  22. Polli, Andrea; Willekens, Barbara; Meeus, Mira; Nijs, Jo; Collin, Simon M.; Ickmans, Kelly (2017), "Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study", Pain Physician, 20 (4): E489-E497, PMID 28535557 
  23. Kingdon, Caroline C.; Bowman, Erinna W.; Curran, Hayley; Nacul, Luis; Lacerda, Eliana M. (Dec 1, 2018). "Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls". PharmacoEconomics - Open. 2 (4): 381–392. doi:10.1007/s41669-018-0071-6. ISSN 2509-4254. PMID 29536371. 

B cell - B lymphocyte, or a type of white blood cell, which is involved in the immune response by secreting antibodies to ward off infections. In mammals, they are mostly matured in the bone marrow.

ME/CFS - An acronym that combines myalgic encephalomyelitis with chronic fatigue syndrome. Sometimes they are combined because people have trouble distinguishing one from the other. Sometimes they are combined because people see them as synonyms of each other.

Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

Myalgic encephalomyelitis (ME) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

Endogenous - Growing or originating from within an organism.

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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.