Vertebral column: Difference between revisions

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(article outline, headings, note ME/CFS is a disease not a syndrome as per ICD-10, the same may be true of EDS, fix ref error)
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=== Chiari I malformation ===
=== Chiari I malformation ===
{{Main article|page_name=Chiari malformation}}A Chiari malformation (CM) is a structural defect of the base of the skull and the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). This can sometimes lead to non-communicating [[hydrocephalus]] as a result of obstruction of [[cerebrospinal fluid]](CSF) outflow. 
{{Main article|page_name=Chiari malformation}}A Chiari malformation (CM) is a structural defect of the base of the skull and the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). This can sometimes lead to non-communicating [[hydrocephalus]] as a result of obstruction of [[cerebrospinal fluid]] (CSF) outflow. 


While many clinical criteria consider Chiari malformation to be a differential diagnosis, a Swedish study of 234 ME/CFS patients meeting the [[Canadian Consensus Criteria]] found that a substantial proportion of patients had signs on their brain MRIs suggestive of intracranial hypertension: 55% had increased diameter of the optic nerve sheath. In addition 80% had cerebellar tonsillar descent that could potentially cause disruptions to spinal fluid flow, and thus increased intracranial pressure. 13.2% had tonsillar herniations severe enough to be considered a Chiari Malformation.<ref>{{Cite web|url=https://osf.io/qwn5h/|website=Center for Open Science|access-date=2019-12-03|title=Bragee Bertilson et al. - ME CFS and Intracranial Hypertension|date=Nov 27, 2019|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>
While many clinical criteria consider Chiari malformation to be a differential diagnosis, a Swedish study of 234 ME/CFS patients meeting the [[Canadian Consensus Criteria]] found that a substantial proportion of patients had signs on their brain MRIs suggestive of intracranial hypertension: 55% had increased diameter of the optic nerve sheath. In addition 80% had cerebellar tonsillar descent that could potentially cause disruptions to spinal fluid flow, and thus increased intracranial pressure. 13.2% had tonsillar herniations severe enough to be considered a Chiari Malformation.<ref>{{Cite web|url=https://osf.io/qwn5h/|website=Center for Open Science|access-date=2019-12-03|title=Bragee Bertilson et al. - ME CFS and Intracranial Hypertension|date=Nov 27, 2019|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>


=== Craniocervical instability ===
=== Craniocervical instability ===
{{Main article|page_name=Craniocervical instability}}Craniocervical instability (CCI) is a pathological condition of increased mobility at the craniocervical junction, the area where the skull meets the spine. In CCI the ligamentous connections of the craniocervical junction can be stretched, weakened or ruptured.<ref name=":2">{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=2017|title=Neurological and spinal manifestations of the Ehlers–Danlos syndromes|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31549|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876}}</ref><ref name=":11">{{Cite journal|last=Choi|first=Sung Ho|last2=Lee|first2=Sang Gu|last3=Park|first3=Chan Woo|last4=Kim|first4=Woo Kyung|last5=Yoo|first5=Chan Jong|last6=Son|first6=Seong|date=Apr 2013|title=Surgical Outcomes and Complications after Occipito-Cervical Fusion Using the Screw-Rod System in Craniocervical Instability|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698232/|journal=Journal of Korean Neurosurgical Society|volume=53|issue=4|pages=223–227|doi=10.3340/jkns.2013.53.4.223|issn=2005-3711|pmc=3698232|pmid=23826478}}</ref>
{{Main article|page_name=Craniocervical instability}}Craniocervical instability (CCI) is a pathological condition of increased mobility at the craniocervical junction, the area where the skull meets the spine. In CCI the ligamentous connections of the craniocervical junction can be stretched, weakened or ruptured.<ref name=Henderson2017>{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=2017|title=Neurological and spinal manifestations of the Ehlers–Danlos syndromes|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31549|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876}}</ref><ref name=":11">{{Cite journal|last=Choi|first=Sung Ho|last2=Lee|first2=Sang Gu|last3=Park|first3=Chan Woo|last4=Kim|first4=Woo Kyung|last5=Yoo|first5=Chan Jong|last6=Son|first6=Seong|date=Apr 2013|title=Surgical Outcomes and Complications after Occipito-Cervical Fusion Using the Screw-Rod System in Craniocervical Instability|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698232/|journal=Journal of Korean Neurosurgical Society|volume=53|issue=4|pages=223–227|doi=10.3340/jkns.2013.53.4.223|issn=2005-3711|pmc=3698232|pmid=23826478}}</ref>


CCI usually develops as a result of physical trauma such as a car accident, an inflammatory disease such as rheumatoid arthritis or a congenital disorder such as Down's syndrome.<ref name=":10">{{Cite journal|last=Ashafai|first=Nabeel S.|last2=Visocchi|first2=Massimiliano|last3=Wąsik|first3=Norbert|date=2019|title=Occipitocervical Fusion: An Updated Review|url=https://www.ncbi.nlm.nih.gov/pubmed/30610329|journal=Acta Neurochirurgica. Supplement|volume=125|pages=247–252|doi=10.1007/978-3-319-62515-7_35|issn=0065-1419|pmid=30610329}}</ref> More recently, physicians have reported an increased prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS).<ref name=":9">{{Cite journal|last=Henderson|first=Fraser C.|date=2016|title=Cranio-cervical Instability in Patients with Hypermobility Connective Disorders|url=https://www.omicsonline.org/open-access/craniocervical-instability-in-patients-with-hypermobility-connective-disorders-2165-7939-1000299.php?aid=71754|journal=Journal of Spine|language=En|volume=05|issue=02|doi=10.4172/2165-7939.1000299|issn=2165-7939}}</ref> There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with CCI,<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/index.php?threads/have-you-ruled-out-chiari-as-a-cause-of-your-cfs.56908/|title=Have you ruled out Chiari as a cause of your CFS|last=|first=|date=|website=Phoenix Rising|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":1">{{Cite web|url=https://medium.com/@jenbrea/cci-tethered-cord-series-e1e098b5edf|title=CCI + Tethered cord series|last=Brea|first=Jennifer|date=2019-06-06|website=Medium|language=en|access-date=2019-06-06}}</ref><ref name=":4">{{Cite web|url=https://www.mechanicalbasis.org/interviews.html|title=Craniocervical instability, Atlantoaxial Instability, Myalgic Encephalomyelitis, ME, CFS|website=MEchanical Basis|language=en|access-date=2019-06-06}}</ref> although no scientific publication on this subject exists. It frequently co-occurs with [[atlantoaxial instability]] (AAI).{{Citation needed|reason=|date=10 December 2019}}
CCI usually develops as a result of physical trauma such as a car accident, an inflammatory disease such as rheumatoid arthritis or a congenital disorder such as Down's syndrome.<ref name=":10">{{Cite journal|last=Ashafai|first=Nabeel S.|last2=Visocchi|first2=Massimiliano|last3=Wąsik|first3=Norbert|date=2019|title=Occipitocervical Fusion: An Updated Review|url=https://www.ncbi.nlm.nih.gov/pubmed/30610329|journal=Acta Neurochirurgica. Supplement|volume=125|pages=247–252|doi=10.1007/978-3-319-62515-7_35|issn=0065-1419|pmid=30610329}}</ref> More recently, physicians have reported an increased prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS).<ref name="Henderson2016">{{Cite journal|last=Henderson|first=Fraser C.|date=2016|title=Cranio-cervical Instability in Patients with Hypermobility Connective Disorders|url=https://www.omicsonline.org/open-access/craniocervical-instability-in-patients-with-hypermobility-connective-disorders-2165-7939-1000299.php?aid=71754|journal=Journal of Spine|language=En|volume=05|issue=02|doi=10.4172/2165-7939.1000299|issn=2165-7939}}</ref> There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with CCI,<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/index.php?threads/have-you-ruled-out-chiari-as-a-cause-of-your-cfs.56908/|title=Have you ruled out Chiari as a cause of your CFS|last=|first=|date=|website=Phoenix Rising|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":1">{{Cite web|url=https://medium.com/@jenbrea/cci-tethered-cord-series-e1e098b5edf|title=CCI + Tethered cord series|last=Brea|first=Jennifer|date=2019-06-06|website=Medium|language=en|access-date=2019-06-06}}</ref><ref name=":4">{{Cite web|url=https://www.mechanicalbasis.org/interviews.html|title=Craniocervical instability, Atlantoaxial Instability, Myalgic Encephalomyelitis, ME, CFS|website=MEchanical Basis|language=en|access-date=2019-06-06}}</ref> although no scientific publication on this subject exists. It frequently co-occurs with [[atlantoaxial instability]] (AAI).{{Citation needed|reason=|date=10 December 2019}}
=== Atlantoaxial instability ===
=== Atlantoaxial instability ===
{{Main article|page_name=Atlantoaxial instability}}Atlantoaxial instability (AAI) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bone or ligament abnormality.
{{Main article|page_name=Atlantoaxial instability}}Atlantoaxial instability (AAI) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bone or ligament abnormality.


It can be caused by congenital conditions, inflammatory conditions like [[rheumatoid arthritis]], as a result of physical trauma, or infection.<ref>{{Cite journal|date=2019-11-10|title=Atlantoaxial Instability: Background, Pathophysiology, Etiology|url=https://emedicine.medscape.com/article/1265682-overview}}</ref> It has been associated with Down syndrome, Morquio syndrome,<ref>{{Cite journal|last=Li|first=Ming-Feng|last2=Chiu|first2=Pao-Chin|last3=Weng|first3=Mei-Jui|last4=Lai|first4=Ping-Hong|date=2010-12-13|title=Atlantoaxial Instability and Cervical Cord Compression in Morquio Syndrome|url=https://jamanetwork.com/journals/jamaneurology/fullarticle/801729|journal=Archives of Neurology|language=en|volume=67|issue=12|pages=1530–1530|doi=10.1001/archneurol.2010.308|issn=0003-9942}}</ref> [[Marfan syndrome]],<ref>{{Cite journal|last=Herzka|first=Andrea|last2=Sponseller|first2=Paul D.|last3=Pyeritz|first3=Reed E.|date=2000-02-15|title=Atlantoaxial Rotatory Subluxation in Patients With Marfan Syndrome: A Report of Three Cases|url=https://journals.lww.com/spinejournal/Abstract/2000/02150/Atlantoaxial_Rotatory_Subluxation_in_Patients_With.22.aspx|journal=Spine|language=en-US|volume=25|issue=4|pages=524|issn=0362-2436}}</ref><ref name=":3">{{Cite journal|last=MacKenzie|first=James MacKintosh|last2=Rankin|first2=Rosslyn|date=Dec 2003|title=Sudden Death Due to Atlantoaxial Subluxation in Marfan Syndrome|url=https://journals.lww.com/amjforensicmedicine/Abstract/2003/12000/Sudden_Death_Due_to_Atlantoaxial_Subluxation_in.12.aspx|journal=The American Journal of Forensic Medicine and Pathology|language=en-US|volume=24|issue=4|pages=369|doi=10.1097/01.paf.0000097853.26115.bb|issn=0195-7910|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> and [[Ehlers-Danlos syndrome]].<ref>{{Cite web|url=https://europepmc.org/article/med/8596160|title=Europe PMC|website=europepmc.org|access-date=2019-12-10}}</ref><ref>{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=2017|title=Neurological and spinal manifestations of the Ehlers–Danlos syndromes|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31549|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876}}</ref><ref>{{Cite journal|last=Castori|first=Marco|last2=Morlino|first2=Silvia|last3=Ghibellini|first3=Giulia|last4=Celletti|first4=Claudia|last5=Camerota|first5=Filippo|last6=Grammatico|first6=Paola|date=2015|title=Connective tissue, Ehlers–Danlos syndrome(s), and head and cervical pain|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31426|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=169|issue=1|pages=84–96|doi=10.1002/ajmg.c.31426|issn=1552-4876}}</ref><ref>{{Cite journal|last=Lane|first=D.|date=2006-08-01|title=Anaesthetic Implications of Vascular Type Ehlers-Danlos Syndrome|url=https://doi.org/10.1177/0310057X0603400412|journal=Anaesthesia and Intensive Care|language=en|volume=34|issue=4|pages=501–505|doi=10.1177/0310057X0603400412|issn=0310-057X}}</ref><ref>{{Cite journal|last=Dordoni|first=Chiara|last2=Ciaccio|first2=Claudia|last3=Venturini|first3=Marina|last4=Calzavara‐Pinton|first4=Piergiacomo|last5=Ritelli|first5=Marco|last6=Colombi|first6=Marina|date=2016|title=Further delineation of FKBP14-related Ehlers–Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review|url=https://www.onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.37728|journal=American Journal of Medical Genetics Part A|language=en|volume=170|issue=8|pages=2031–2038|doi=10.1002/ajmg.a.37728|issn=1552-4833}}</ref><ref>{{Cite journal|last=Giunta|first=Cecilia|last2=Baumann|first2=Matthias|last3=Fauth|first3=Christine|last4=Lindert|first4=Uschi|last5=Abdalla|first5=Ebtesam M.|last6=Brady|first6=Angela F.|last7=Collins|first7=James|last8=Dastgir|first8=Jahannaz|last9=Donkervoort|first9=Sandra|date=Jan 2018|title=A cohort of 17 patients with kyphoscoliotic Ehlers–Danlos syndrome caused by biallelic mutations in FKBP14 : expansion of the clinical and mutational spectrum and description of the natural history|url=https://www.nature.com/articles/gim201770|journal=Genetics in Medicine|language=en|volume=20|issue=1|pages=42–54|doi=10.1038/gim.2017.70|issn=1530-0366|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref><ref>{{Cite web|url=https://europepmc.org/article/med/2387821|title=Europe PMC|website=europepmc.org|access-date=2019-12-10}}</ref><ref>{{Cite journal|last=Galan|first=Enrique|last2=Kousseff|first2=Boris G.|date=1995-04-01|title=Peripheral neuropathy in Ehlers-Danlos syndrome|url=http://www.sciencedirect.com/science/article/pii/088789949500003X|journal=Pediatric Neurology|volume=12|issue=3|pages=242–245|doi=10.1016/0887-8994(95)00003-X|issn=0887-8994}}</ref><ref>{{Cite journal|last=Wills|first=Brian P. D.|last2=Dormans|first2=John P.|date=Apr 2006|title=Nontraumatic Upper Cervical Spine Instability in Children|url=https://journals.lww.com/jaaos/Citation/2006/04000/Nontraumatic_Upper_Cervical_Spine_Instability_in.5.aspx|journal=JAAOS - Journal of the American Academy of Orthopaedic Surgeons|language=en-US|volume=14|issue=4|pages=233|issn=1067-151X|doi=|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
It can be caused by congenital conditions, inflammatory conditions like [[rheumatoid arthritis]], as a result of physical trauma, or infection.<ref>{{Cite journal|date=2019-11-10|title=Atlantoaxial Instability: Background, Pathophysiology, Etiology|url=https://emedicine.medscape.com/article/1265682-overview}}</ref> It has been associated with Down syndrome, Morquio syndrome,<ref>{{Cite journal|last=Li|first=Ming-Feng|last2=Chiu|first2=Pao-Chin|last3=Weng|first3=Mei-Jui|last4=Lai|first4=Ping-Hong|date=2010-12-13|title=Atlantoaxial Instability and Cervical Cord Compression in Morquio Syndrome|url=https://jamanetwork.com/journals/jamaneurology/fullarticle/801729|journal=Archives of Neurology|language=en|volume=67|issue=12|pages=1530–1530|doi=10.1001/archneurol.2010.308|issn=0003-9942}}</ref> [[Marfan syndrome]],<ref>{{Cite journal|last=Herzka|first=Andrea|last2=Sponseller|first2=Paul D.|last3=Pyeritz|first3=Reed E.|date=2000-02-15|title=Atlantoaxial Rotatory Subluxation in Patients With Marfan Syndrome: A Report of Three Cases|url=https://journals.lww.com/spinejournal/Abstract/2000/02150/Atlantoaxial_Rotatory_Subluxation_in_Patients_With.22.aspx|journal=Spine|language=en-US|volume=25|issue=4|pages=524|issn=0362-2436}}</ref><ref name=":3">{{Cite journal|last=MacKenzie|first=James MacKintosh|last2=Rankin|first2=Rosslyn|date=Dec 2003|title=Sudden Death Due to Atlantoaxial Subluxation in Marfan Syndrome|url=https://journals.lww.com/amjforensicmedicine/Abstract/2003/12000/Sudden_Death_Due_to_Atlantoaxial_Subluxation_in.12.aspx|journal=The American Journal of Forensic Medicine and Pathology|language=en-US|volume=24|issue=4|pages=369|doi=10.1097/01.paf.0000097853.26115.bb|issn=0195-7910|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> and [[Ehlers-Danlos syndrome]].<ref>{{Cite web|url=https://europepmc.org/article/med/8596160|title=Europe PMC|website=europepmc.org|access-date=2019-12-10}}</ref><ref name=Henderson2017 /><ref>{{Cite journal|last=Castori|first=Marco|last2=Morlino|first2=Silvia|last3=Ghibellini|first3=Giulia|last4=Celletti|first4=Claudia|last5=Camerota|first5=Filippo|last6=Grammatico|first6=Paola|date=2015|title=Connective tissue, Ehlers–Danlos syndrome(s), and head and cervical pain|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31426|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=169|issue=1|pages=84–96|doi=10.1002/ajmg.c.31426|issn=1552-4876}}</ref><ref>{{Cite journal|last=Lane|first=D.|date=2006-08-01|title=Anaesthetic Implications of Vascular Type Ehlers-Danlos Syndrome|url=https://doi.org/10.1177/0310057X0603400412|journal=Anaesthesia and Intensive Care|language=en|volume=34|issue=4|pages=501–505|doi=10.1177/0310057X0603400412|issn=0310-057X}}</ref><ref>{{Cite journal|last=Dordoni|first=Chiara|last2=Ciaccio|first2=Claudia|last3=Venturini|first3=Marina|last4=Calzavara‐Pinton|first4=Piergiacomo|last5=Ritelli|first5=Marco|last6=Colombi|first6=Marina|date=2016|title=Further delineation of FKBP14-related Ehlers–Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review|url=https://www.onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.37728|journal=American Journal of Medical Genetics Part A|language=en|volume=170|issue=8|pages=2031–2038|doi=10.1002/ajmg.a.37728|issn=1552-4833}}</ref><ref>{{Cite journal|last=Giunta|first=Cecilia|last2=Baumann|first2=Matthias|last3=Fauth|first3=Christine|last4=Lindert|first4=Uschi|last5=Abdalla|first5=Ebtesam M.|last6=Brady|first6=Angela F.|last7=Collins|first7=James|last8=Dastgir|first8=Jahannaz|last9=Donkervoort|first9=Sandra|date=Jan 2018|title=A cohort of 17 patients with kyphoscoliotic Ehlers–Danlos syndrome caused by biallelic mutations in FKBP14 : expansion of the clinical and mutational spectrum and description of the natural history|url=https://www.nature.com/articles/gim201770|journal=Genetics in Medicine|language=en|volume=20|issue=1|pages=42–54|doi=10.1038/gim.2017.70|issn=1530-0366|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref><ref>{{Cite web|url=https://europepmc.org/article/med/2387821|title=Europe PMC|website=europepmc.org|access-date=2019-12-10}}</ref><ref>{{Cite journal|last=Galan|first=Enrique|last2=Kousseff|first2=Boris G.|date=1995-04-01|title=Peripheral neuropathy in Ehlers-Danlos syndrome|url=http://www.sciencedirect.com/science/article/pii/088789949500003X|journal=Pediatric Neurology|volume=12|issue=3|pages=242–245|doi=10.1016/0887-8994(95)00003-X|issn=0887-8994}}</ref><ref>{{Cite journal|last=Wills|first=Brian P. D.|last2=Dormans|first2=John P.|date=Apr 2006|title=Nontraumatic Upper Cervical Spine Instability in Children|url=https://journals.lww.com/jaaos/Citation/2006/04000/Nontraumatic_Upper_Cervical_Spine_Instability_in.5.aspx|journal=JAAOS - Journal of the American Academy of Orthopaedic Surgeons|language=en-US|volume=14|issue=4|pages=233|issn=1067-151X|doi=|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
=== Cervical stenosis ===
=== Cervical stenosis ===
{{Main|page_name=Cervical spinal stenosis}}
{{Main|page_name=Cervical spinal stenosis}}
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=== Tethered cord syndrome ===
=== Tethered cord syndrome ===
{{Main article|page_name=Tethered cord syndrome}}Tethered cord syndrome is a neurological disorder caused by tissue attachments that limit the movement of the spinal cord within the spinal column. It can be congenital or acquired and appear in childhood or adulthood. It is considered progressive.<ref>{{Cite web|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Tethered-Spinal-Cord-Syndrome-Information-Page|title=Tethered Spinal Cord Syndrome Information Page {{!}} National Institute of Neurological Disorders and Stroke|website=www.ninds.nih.gov|access-date=2019-07-26}}</ref>  It causes spinal cord hypoperfusion, electrophysical changes and metabolic changes, including impaired glucose metabolism.<ref name=":2">{{Cite journal|last=Colohan|first=Austin R. T.|last2=Zouros|first2=Alexander|last3=Siddiqi|first3=Javed|last4=Yamada|first4=Shoko M.|last5=Yamada|first5=Brian S.|last6=Pezeshkpour|first6=Gholam|last7=Won|first7=Daniel J.|last8=Yamada|first8=Shokei|date=2007-08-01|title=Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref><ref>{{Cite journal|last=Colohan|first=Austin R. T.|last2=Yamada|first2=Shokei|date=2009-01-01|title=Tethered Cord Syndrome|url=https://thejns.org/view/journals/j-neurosurg-spine/10/1/article-p79.xml|journal=Journal of Neurosurgery: Spine|language=en-US|volume=10|issue=1|pages=79–80|doi=10.3171/2008.10.SPI15714L}}</ref><ref>{{Cite journal|last=Sullivan|first=Stephen|last2=Park|first2=Paul|last3=Stetler|first3=William R.|date=2010-07-01|title=Pathophysiology of adult tethered cord syndrome: review of the literature|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1080.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1|pages=E2|doi=10.3171/2010.3.FOCUS1080|issn=1092-0684}}</ref> As with [[craniocervical instability]], There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with tethered cord, although no scientific publication on this subject exists.<ref name=":0" /><ref name=":1" /><ref name=":4" /> 
{{Main article|page_name=Tethered cord syndrome}}Tethered cord syndrome is a neurological disorder caused by tissue attachments that limit the movement of the spinal cord within the spinal column. It can be congenital or acquired and appear in childhood or adulthood. It is considered progressive.<ref>{{Cite web|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Tethered-Spinal-Cord-Syndrome-Information-Page|title=Tethered Spinal Cord Syndrome Information Page {{!}} National Institute of Neurological Disorders and Stroke|website=[[National Institute of Neurological Disorders and Stroke]]|access-date=2019-07-26}}</ref>  It causes spinal cord hypoperfusion, electrophysical changes and metabolic changes, including impaired glucose metabolism.<ref name="Colohan2007">{{Cite journal|last=Colohan|first=Austin R. T.|last2=Zouros|first2=Alexander|last3=Siddiqi|first3=Javed|last4=Yamada|first4=Shoko M.|last5=Yamada|first5=Brian S.|last6=Pezeshkpour|first6=Gholam|last7=Won|first7=Daniel J.|last8=Yamada|first8=Shokei|date=2007-08-01|title=Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref><ref>{{Cite journal|last=Colohan|first=Austin R. T.|last2=Yamada|first2=Shokei|date=2009-01-01|title=Tethered Cord Syndrome|url=https://thejns.org/view/journals/j-neurosurg-spine/10/1/article-p79.xml|journal=Journal of Neurosurgery: Spine|language=en-US|volume=10|issue=1|pages=79–80|doi=10.3171/2008.10.SPI15714L}}</ref><ref>{{Cite journal|last=Sullivan|first=Stephen|last2=Park|first2=Paul|last3=Stetler|first3=William R.|date=2010-07-01|title=Pathophysiology of adult tethered cord syndrome: review of the literature|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1080.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1|pages=E2|doi=10.3171/2010.3.FOCUS1080|issn=1092-0684}}</ref> As with [[craniocervical instability]], There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with tethered cord, although no scientific publication on this subject exists.<ref name=":0" /><ref name=":1" /><ref name=":4" /> 


=== Tarlov cysts ===
=== Tarlov cysts ===
{{Main article|page_name=Tarlov cyst}}Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure.  A study of 197 ME/CFS patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%.<ref>{{Cite journal|last=Hulens|first=Mieke|last2=Bruyninckx|first2=Frans|last3=Dankaerts|first3=Wim|last4=Rasschaert|first4=Ricky|last5=De Mulder|first5=Peter|last6=Stalmans|first6=Ingeborg|last7=Vansant|first7=Greet|last8=Bervoets|first8=Chris|date=2020-12-01|title=High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome|url=https://academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaa410/6015822|journal=Pain Medicine|language=en|pages=pnaa410|doi=10.1093/pm/pnaa410|issn=1526-2375}}</ref>
{{Main article|page_name=Tarlov cyst}}Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure.  A study of 197 ME/CFS patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%.<ref>{{Cite journal|last=Hulens|first=Mieke|last2=Bruyninckx|first2=Frans|last3=Dankaerts|first3=Wim|last4=Rasschaert|first4=Ricky|last5=De Mulder|first5=Peter|last6=Stalmans|first6=Ingeborg|last7=Vansant|first7=Greet|last8=Bervoets|first8=Chris|date=2020-12-01|title=High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome|url=https://academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaa410/6015822|journal=Pain Medicine|language=en|pages=pnaa410|doi=10.1093/pm/pnaa410|issn=1526-2375}}</ref>


== Association with syndromes ==
== ME/CFS ==
 
=== ME/CFS ===
{{Main article|page_name=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome}}A 2018 case study published by [[Peter Rowe]] found marked post-operative improvement of symptoms in three patients with severe [[myalgic encephalomyelitis]], [[orthostatic intolerance]] and cervical spinal stenosis.<ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Marden|first2=Colleen L.|last3=Heinlein|first3=Scott|last4=Edwards|first4=Charles C.|date=2018-02-02|title=Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796598/|journal=Journal of Translational Medicine|volume=16|doi=10.1186/s12967-018-1397-7|issn=1479-5876|pmc=5796598|pmid=29391028}}</ref>
{{Main article|page_name=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome}}A 2018 case study published by [[Peter Rowe]] found marked post-operative improvement of symptoms in three patients with severe [[myalgic encephalomyelitis]], [[orthostatic intolerance]] and cervical spinal stenosis.<ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Marden|first2=Colleen L.|last3=Heinlein|first3=Scott|last4=Edwards|first4=Charles C.|date=2018-02-02|title=Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796598/|journal=Journal of Translational Medicine|volume=16|doi=10.1186/s12967-018-1397-7|issn=1479-5876|pmc=5796598|pmid=29391028}}</ref>


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A study of 197 ME/CFS and fibromyalgia patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%, a potential sign of elevated cerebrospinal fluid pressure.<ref>{{Cite journal|last=Hulens|first=Mieke|last2=Bruyninckx|first2=Frans|last3=Dankaerts|first3=Wim|last4=Rasschaert|first4=Ricky|last5=De Mulder|first5=Peter|last6=Stalmans|first6=Ingeborg|last7=Vansant|first7=Greet|last8=Bervoets|first8=Chris|date=2020-12-01|title=High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome|url=https://academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaa410/6015822|journal=Pain Medicine|language=en|pages=pnaa410|doi=10.1093/pm/pnaa410|issn=1526-2375}}</ref>
A study of 197 ME/CFS and fibromyalgia patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%, a potential sign of elevated cerebrospinal fluid pressure.<ref>{{Cite journal|last=Hulens|first=Mieke|last2=Bruyninckx|first2=Frans|last3=Dankaerts|first3=Wim|last4=Rasschaert|first4=Ricky|last5=De Mulder|first5=Peter|last6=Stalmans|first6=Ingeborg|last7=Vansant|first7=Greet|last8=Bervoets|first8=Chris|date=2020-12-01|title=High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome|url=https://academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaa410/6015822|journal=Pain Medicine|language=en|pages=pnaa410|doi=10.1093/pm/pnaa410|issn=1526-2375}}</ref>


=== Fibromyalgia ===
== Fibromyalgia ==
{{Main article|page_name=Fibromyalgia}}
{{Main article|page_name=Fibromyalgia}}


In the 1990s, there was a controversy<ref>{{Cite web|url=https://www.wsj.com/articles/SB942280927444238502|title=Some Doctors Operate on People Diagnosed With Chronic Fatigue|last=Journal|first=Thomas M. BurtonStaff Reporter of The Wall Street|website=WSJ|language=en-US|access-date=2019-07-07}}</ref><ref>{{Cite web|url=https://www.massmecfs.org/more-resources-for-differential-diagnosis/172-cfidsfm-and-chiari-malformation-surgery|title=CFS/FM and Chiari Malformation Surgery|website=www.massmecfs.org|access-date=2019-07-07}}</ref> surrounding whether patients with some patients with Chiari malformation had been misdiagnosed with [[chronic fatigue syndrome]] or [[fibromyalgia]] or whether Chiari malformation could indeed cause the symptoms of each. A 2004 study of 270 patients with [[fibromyalgia]] diagnoses found that 46% had [[cervical spinal stenosis]] and 20% chiari malformation.<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Shah|first5=Sagar|last6=Gottschalk|first6=Robert|last7=Elias|first7=Dean A.|last8=Shepard|first8=Alan|last9=Leurgans|first9=Sue E.|date=2004-04-09|title=Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia|url=https://link.springer.com/article/10.1007/s00586-004-0672-x|journal=European Spine Journal|language=en|volume=13|issue=6|pages=516–523|doi=10.1007/s00586-004-0672-x|issn=0940-6719|pmc=3476600|pmid=15083352}}</ref> However, a 2011 paper failed to find any increased rate of Chiari malformation among people with fibromyalgia.<ref>{{Cite journal|last=Ellenbogen|first=Richard G.|last2=Guan|first2=Qingyan|last3=Noonan|first3=Carolyn|last4=Maravilla|first4=Kenneth R.|last5=Goldberg|first5=Jack|last6=Buchwald|first6=Dedra|last7=Watson|first7=Nathaniel F.|date=2011-02-01|title=Is Chiari I Malformation Associated With Fibromyalgia?|url=https://academic.oup.com/neurosurgery/article/68/2/443/2606332|journal=Neurosurgery|language=en|volume=68|issue=2|pages=443–449|doi=10.1227/NEU.0b013e3182039a31|issn=0148-396X}}</ref> Chiari malformation is associated with [[Ehlers-Danlos syndrome]],<ref>{{Cite journal|last=Castori|first=Marco|last2=Camerota|first2=Filippo|last3=Celletti|first3=Claudia|last4=Danese|first4=Chiara|last5=Santilli|first5=Valter|last6=Saraceni|first6=Vincenzo Maria|last7=Grammatico|first7=Paola|date=2010|title=Natural history and manifestations of the hypermobility type Ehlers–Danlos syndrome: A pilot study on 21 patients|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.33231|journal=American Journal of Medical Genetics Part A|language=en|volume=152A|issue=3|pages=556–564|doi=10.1002/ajmg.a.33231|issn=1552-4833}}</ref><ref>{{Cite journal|last=Francomano|first=Clair A.|last2=McDonnell|first2=Nazli B.|last3=Nishikawa|first3=Misao|last4=Bolognese|first4=Paolo A.|last5=Milhorat|first5=Thomas H.|date=2007-12-01|title=Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue|url=https://thejns.org/view/journals/j-neurosurg-spine/7/6/article-p601.xml|journal=Journal of Neurosurgery: Spine|language=en-US|volume=7|issue=6|pages=601–609|doi=10.3171/SPI-07/12/601}}</ref><ref>{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=2017|title=Neurological and spinal manifestations of the Ehlers–Danlos syndromes|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31549|journal=American Journal of Medical Genetics Part C: Seminars in Medical Genetics|language=en|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876}}</ref> which is sometimes misdiagnosed as fibromyalgia, or with which there may be diagnostic overlap.<ref>{{Cite journal|last=Rombaut|first=Lies|last2=Malfait|first2=Fransiska|last3=Paepe|first3=Anne De|last4=Rimbaut|first4=Steven|last5=Verbruggen|first5=Gust|last6=Wandele|first6=Inge De|last7=Calders|first7=Patrick|date=2011|title=Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: A comparative study with fibromyalgia and rheumatoid arthritis|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/art.30337|journal=Arthritis & Rheumatism|language=en|volume=63|issue=7|pages=1979–1987|doi=10.1002/art.30337|issn=1529-0131}}</ref><ref>{{Cite journal|last=Miller|first=Victor J.|last2=Zeltser|first2=Rephael|last3=Yoeli|first3=Zvi|last4=Bodner|first4=Lipa|date=1997-07-01|title=Ehlers-Danlos Syndrome, Fibromyalgia and Temporomandibular Disorder: Report of an Unusual Combination|url=https://doi.org/10.1080/08869634.1997.11746020|journal=CRANIO®|volume=15|issue=3|pages=267–269|doi=10.1080/08869634.1997.11746020|issn=0886-9634}}</ref>
In the 1990s, there was a controversy<ref>{{Cite web|url=https://www.wsj.com/articles/SB942280927444238502|title=Some Doctors Operate on People Diagnosed With Chronic Fatigue|last=Journal|first=Thomas M. BurtonStaff Reporter of The Wall Street|website=WSJ|language=en-US|access-date=2019-07-07}}</ref><ref>{{Cite web|url=https://www.massmecfs.org/more-resources-for-differential-diagnosis/172-cfidsfm-and-chiari-malformation-surgery|title=CFS/FM and Chiari Malformation Surgery|website=www.massmecfs.org|access-date=2019-07-07}}</ref> surrounding whether patients with some patients with Chiari malformation had been misdiagnosed with [[chronic fatigue syndrome]] or [[fibromyalgia]] or whether Chiari malformation could indeed cause the symptoms of each. A 2004 study of 270 patients with [[fibromyalgia]] diagnoses found that 46% had [[cervical spinal stenosis]] and 20% chiari malformation.<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Shah|first5=Sagar|last6=Gottschalk|first6=Robert|last7=Elias|first7=Dean A.|last8=Shepard|first8=Alan|last9=Leurgans|first9=Sue E.|date=2004-04-09|title=Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia|url=https://link.springer.com/article/10.1007/s00586-004-0672-x|journal=European Spine Journal|language=en|volume=13|issue=6|pages=516–523|doi=10.1007/s00586-004-0672-x|issn=0940-6719|pmc=3476600|pmid=15083352}}</ref> However, a 2011 paper failed to find any increased rate of Chiari malformation among people with fibromyalgia.<ref>{{Cite journal|last=Ellenbogen|first=Richard G.|last2=Guan|first2=Qingyan|last3=Noonan|first3=Carolyn|last4=Maravilla|first4=Kenneth R.|last5=Goldberg|first5=Jack|last6=Buchwald|first6=Dedra|last7=Watson|first7=Nathaniel F.|date=2011-02-01|title=Is Chiari I Malformation Associated With Fibromyalgia?|url=https://academic.oup.com/neurosurgery/article/68/2/443/2606332|journal=Neurosurgery|language=en|volume=68|issue=2|pages=443–449|doi=10.1227/NEU.0b013e3182039a31|issn=0148-396X}}</ref> Chiari malformation is associated with [[Ehlers-Danlos syndrome]],<ref>{{Cite journal|last=Castori|first=Marco|last2=Camerota|first2=Filippo|last3=Celletti|first3=Claudia|last4=Danese|first4=Chiara|last5=Santilli|first5=Valter|last6=Saraceni|first6=Vincenzo Maria|last7=Grammatico|first7=Paola|date=2010|title=Natural history and manifestations of the hypermobility type Ehlers–Danlos syndrome: A pilot study on 21 patients|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.33231|journal=American Journal of Medical Genetics Part A|language=en|volume=152A|issue=3|pages=556–564|doi=10.1002/ajmg.a.33231|issn=1552-4833}}</ref><ref>{{Cite journal|last=Francomano|first=Clair A.|last2=McDonnell|first2=Nazli B.|last3=Nishikawa|first3=Misao|last4=Bolognese|first4=Paolo A.|last5=Milhorat|first5=Thomas H.|date=2007-12-01|title=Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue|url=https://thejns.org/view/journals/j-neurosurg-spine/7/6/article-p601.xml|journal=Journal of Neurosurgery: Spine|language=en-US|volume=7|issue=6|pages=601–609|doi=10.3171/SPI-07/12/601}}</ref><ref name=Henderson2017 /> which is sometimes misdiagnosed as fibromyalgia, or with which there may be diagnostic overlap.<ref>{{Cite journal|last=Rombaut|first=Lies|last2=Malfait|first2=Fransiska|last3=Paepe|first3=Anne De|last4=Rimbaut|first4=Steven|last5=Verbruggen|first5=Gust|last6=Wandele|first6=Inge De|last7=Calders|first7=Patrick|date=2011|title=Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: A comparative study with fibromyalgia and rheumatoid arthritis|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/art.30337|journal=Arthritis & Rheumatism|language=en|volume=63|issue=7|pages=1979–1987|doi=10.1002/art.30337|issn=1529-0131}}</ref><ref>{{Cite journal|last=Miller|first=Victor J.|last2=Zeltser|first2=Rephael|last3=Yoeli|first3=Zvi|last4=Bodner|first4=Lipa|date=1997-07-01|title=Ehlers-Danlos Syndrome, Fibromyalgia and Temporomandibular Disorder: Report of an Unusual Combination|url=https://doi.org/10.1080/08869634.1997.11746020|journal=CRANIO®|volume=15|issue=3|pages=267–269|doi=10.1080/08869634.1997.11746020|issn=0886-9634}}</ref>


A significant improvement in physical and mental well-being was found in fibromyalgia patients with cervical stenosis who received surgery.<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Morrissey|first5=Mary|last6=Elias|first6=Dean A.|last7=Shepard|first7=Alan|date=Sep 2007|title=Treatment of cervical myelopathy in patients with the fibromyalgia syndrome: outcomes and implications|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200733/|journal=European Spine Journal|volume=16|issue=9|pages=1423–1433|doi=10.1007/s00586-007-0366-2|issn=0940-6719|pmc=2200733|pmid=17426987}}</ref> A second study found that 71% had cervical spinal cord compression.<ref name=":02">{{Cite journal|date=2008-07-01|title=Positional Cervical Spinal Cord Compression and Fibromyalgia: A Novel Comorbidity With Important Diagnostic and Treatment Implications|url=https://www.sciencedirect.com/science/article/pii/S1526590008004379|journal=The Journal of Pain|language=en|volume=9|issue=7|pages=613–622|doi=10.1016/j.jpain.2008.01.339|issn=1526-5900}}</ref>
A significant improvement in physical and mental well-being was found in fibromyalgia patients with cervical stenosis who received surgery.<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Morrissey|first5=Mary|last6=Elias|first6=Dean A.|last7=Shepard|first7=Alan|date=Sep 2007|title=Treatment of cervical myelopathy in patients with the fibromyalgia syndrome: outcomes and implications|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200733/|journal=European Spine Journal|volume=16|issue=9|pages=1423–1433|doi=10.1007/s00586-007-0366-2|issn=0940-6719|pmc=2200733|pmid=17426987}}</ref> A second study found that 71% had cervical spinal cord compression.<ref name=":02">{{Cite journal|date=2008-07-01|title=Positional Cervical Spinal Cord Compression and Fibromyalgia: A Novel Comorbidity With Important Diagnostic and Treatment Implications|url=https://www.sciencedirect.com/science/article/pii/S1526590008004379|journal=The Journal of Pain|language=en|volume=9|issue=7|pages=613–622|doi=10.1016/j.jpain.2008.01.339|issn=1526-5900}}</ref>


There are some cases of cervical stenosis that may not be apparent when the neck is in the neutral position, but may be quite severe in extension.<ref>{{Cite journal|last=Zeitoun|first=Delphine|last2=Hajj|first2=Firass El|last3=Sariali|first3=Elhadi|last4=Catonné|first4=Yves|last5=Pascal-Moussellard|first5=Hugues|date=2015-04-01|title=Evaluation of spinal cord compression and hyperintense intramedullary lesions on T2-weighted sequences in patients with cervical spondylotic myelopathy using flexion-extension MRI protocol|url=https://www.thespinejournalonline.com/article/S1529-9430(14)01771-9/abstract|journal=The Spine Journal|language=English|volume=15|issue=4|pages=668–674|doi=10.1016/j.spinee.2014.12.001|issn=1529-9430|pmid=25485484}}</ref> Andrew Holman describes these cases as "positional cervical spinal cord compression." He argues that some symptoms of fibromyalgia may be an inflammatory response to intermittent cord irritation which may not be severe enough to cause more overt symptoms.<ref name=":02" />
There are some cases of cervical stenosis that may not be apparent when the neck is in the neutral position, but may be quite severe in extension.<ref>{{Cite journal|last=Zeitoun|first=Delphine|last2=Hajj|first2=Firass El|last3=Sariali|first3=Elhadi|last4=Catonné|first4=Yves|last5=Pascal-Moussellard|first5=Hugues|date=2015-04-01|title=Evaluation of spinal cord compression and hyperintense intramedullary lesions on T2-weighted sequences in patients with cervical spondylotic myelopathy using flexion-extension MRI protocol|url=https://www.thespinejournalonline.com/article/S1529-9430(14)01771-9/abstract|journal=The Spine Journal|language=English|volume=15|issue=4|pages=668–674|doi=10.1016/j.spinee.2014.12.001|issn=1529-9430|pmid=25485484}}</ref> Andrew Holman describes these cases as "positional cervical spinal cord compression." He argues that some symptoms of fibromyalgia may be an inflammatory response to intermittent cord irritation which may not be severe enough to cause more overt symptoms.<ref name=":02" />
=== Ehlers-Danlos Syndrome ===
 
== Ehlers-Danlos Syndromes ==
{{Main article|page_name=Ehlers-Danlos syndrome}}
{{Main article|page_name=Ehlers-Danlos syndrome}}


Several pathologies of the spine have been associated with [[Ehlers-Danlos Syndrome]], including [[Chiari malformation|Chiari I malformation]], [[Craniocervical instability]], [[Atlantoaxial instability]], [[Tethered cord syndrome]], [[Tarlov cyst]], as well [[intracranial hypertension]].<ref>{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=03 2017|title=Neurological and spinal manifestations of the Ehlers-Danlos syndromes|url=https://pubmed.ncbi.nlm.nih.gov/28220607/|journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876|pmid=28220607}}</ref>
Several pathologies of the spine have been associated with [[Ehlers-Danlos Syndrome]], including [[Chiari malformation|Chiari I malformation]], [[Craniocervical instability]], [[Atlantoaxial instability]], [[Tethered cord syndrome]], [[Tarlov cyst]], as well [[intracranial hypertension]].<ref>{{Cite journal|last=Henderson|first=Fraser C.|last2=Austin|first2=Claudiu|last3=Benzel|first3=Edward|last4=Bolognese|first4=Paolo|last5=Ellenbogen|first5=Richard|last6=Francomano|first6=Clair A.|last7=Ireton|first7=Candace|last8=Klinge|first8=Petra|last9=Koby|first9=Myles|date=03 2017|title=Neurological and spinal manifestations of the Ehlers-Danlos syndromes|url=https://pubmed.ncbi.nlm.nih.gov/28220607/|journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics|volume=175|issue=1|pages=195–211|doi=10.1002/ajmg.c.31549|issn=1552-4876|pmid=28220607}}</ref>


== Related ==
== See also ==
* [[Brain]]
* [[Brain]]
* [[Spinal cord]]
* [[Spinal cord]]


== See also ==
== Learn more ==


== References ==
== References ==
{{reflist}}
{{reflist}}
[[Category:Anatomy]]
[[Category:Anatomy]]

Revision as of 22:59, December 17, 2020

The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates has been replaced by a segmented series of bone: vertebrae separated by intervertebral discs. The vertebral column houses the spinal canal, a cavity that encloses and protects the spinal cord.

Spinal pathologies[edit | edit source]

Chiari I malformation[edit | edit source]

A Chiari malformation (CM) is a structural defect of the base of the skull and the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). This can sometimes lead to non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid (CSF) outflow. 

While many clinical criteria consider Chiari malformation to be a differential diagnosis, a Swedish study of 234 ME/CFS patients meeting the Canadian Consensus Criteria found that a substantial proportion of patients had signs on their brain MRIs suggestive of intracranial hypertension: 55% had increased diameter of the optic nerve sheath. In addition 80% had cerebellar tonsillar descent that could potentially cause disruptions to spinal fluid flow, and thus increased intracranial pressure. 13.2% had tonsillar herniations severe enough to be considered a Chiari Malformation.[1]

Craniocervical instability[edit | edit source]

Craniocervical instability (CCI) is a pathological condition of increased mobility at the craniocervical junction, the area where the skull meets the spine. In CCI the ligamentous connections of the craniocervical junction can be stretched, weakened or ruptured.[2][3]

CCI usually develops as a result of physical trauma such as a car accident, an inflammatory disease such as rheumatoid arthritis or a congenital disorder such as Down's syndrome.[4] More recently, physicians have reported an increased prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS).[5] There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with CCI,[6][7][8] although no scientific publication on this subject exists. It frequently co-occurs with atlantoaxial instability (AAI).[citation needed]

Atlantoaxial instability[edit | edit source]

Atlantoaxial instability (AAI) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bone or ligament abnormality.

It can be caused by congenital conditions, inflammatory conditions like rheumatoid arthritis, as a result of physical trauma, or infection.[9] It has been associated with Down syndrome, Morquio syndrome,[10] Marfan syndrome,[11][12] and Ehlers-Danlos syndrome.[13][2][14][15][16][17][18][19][20]

Cervical stenosis[edit | edit source]

A 2018 case study published by Peter Rowe found marked post-operative improvement of symptoms in three patients with severe myalgic encephalomyelitisorthostatic intolerance and cervical spinal stenosis.[21]

Tethered cord syndrome[edit | edit source]

Tethered cord syndrome is a neurological disorder caused by tissue attachments that limit the movement of the spinal cord within the spinal column. It can be congenital or acquired and appear in childhood or adulthood. It is considered progressive.[22]  It causes spinal cord hypoperfusion, electrophysical changes and metabolic changes, including impaired glucose metabolism.[23][24][25] As with craniocervical instability, There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with tethered cord, although no scientific publication on this subject exists.[6][7][8] 

Tarlov cysts[edit | edit source]

Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure.  A study of 197 ME/CFS patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%.[26]

ME/CFS[edit | edit source]

A 2018 case study published by Peter Rowe found marked post-operative improvement of symptoms in three patients with severe myalgic encephalomyelitisorthostatic intolerance and cervical spinal stenosis.[27]

There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with Craniocervical instability and Tethered cord syndrome,[6][7][8] although no scientific publication on this subject exists.

A study of 197 ME/CFS and fibromyalgia patients found that the prevalence of Tarlov cysts was three times higher in ME/CFS patients than the general population, at 39%, a potential sign of elevated cerebrospinal fluid pressure.[28]

Fibromyalgia[edit | edit source]

In the 1990s, there was a controversy[29][30] surrounding whether patients with some patients with Chiari malformation had been misdiagnosed with chronic fatigue syndrome or fibromyalgia or whether Chiari malformation could indeed cause the symptoms of each. A 2004 study of 270 patients with fibromyalgia diagnoses found that 46% had cervical spinal stenosis and 20% chiari malformation.[31] However, a 2011 paper failed to find any increased rate of Chiari malformation among people with fibromyalgia.[32] Chiari malformation is associated with Ehlers-Danlos syndrome,[33][34][2] which is sometimes misdiagnosed as fibromyalgia, or with which there may be diagnostic overlap.[35][36]

A significant improvement in physical and mental well-being was found in fibromyalgia patients with cervical stenosis who received surgery.[37] A second study found that 71% had cervical spinal cord compression.[38]

There are some cases of cervical stenosis that may not be apparent when the neck is in the neutral position, but may be quite severe in extension.[39] Andrew Holman describes these cases as "positional cervical spinal cord compression." He argues that some symptoms of fibromyalgia may be an inflammatory response to intermittent cord irritation which may not be severe enough to cause more overt symptoms.[38]

Ehlers-Danlos Syndromes[edit | edit source]

Several pathologies of the spine have been associated with Ehlers-Danlos Syndrome, including Chiari I malformation, Craniocervical instability, Atlantoaxial instability, Tethered cord syndrome, Tarlov cyst, as well intracranial hypertension.[40]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. "Bragee Bertilson et al. - ME CFS and Intracranial Hypertension". Center for Open Science. November 27, 2019. Retrieved December 3, 2019. Cite has empty unknown parameter: |dead-url= (help)
  2. 2.0 2.1 2.2 Henderson, Fraser C.; Austin, Claudiu; Benzel, Edward; Bolognese, Paolo; Ellenbogen, Richard; Francomano, Clair A.; Ireton, Candace; Klinge, Petra; Koby, Myles (2017). "Neurological and spinal manifestations of the Ehlers–Danlos syndromes". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 175 (1): 195–211. doi:10.1002/ajmg.c.31549. ISSN 1552-4876.
  3. Choi, Sung Ho; Lee, Sang Gu; Park, Chan Woo; Kim, Woo Kyung; Yoo, Chan Jong; Son, Seong (April 2013). "Surgical Outcomes and Complications after Occipito-Cervical Fusion Using the Screw-Rod System in Craniocervical Instability". Journal of Korean Neurosurgical Society. 53 (4): 223–227. doi:10.3340/jkns.2013.53.4.223. ISSN 2005-3711. PMC 3698232. PMID 23826478.
  4. Ashafai, Nabeel S.; Visocchi, Massimiliano; Wąsik, Norbert (2019). "Occipitocervical Fusion: An Updated Review". Acta Neurochirurgica. Supplement. 125: 247–252. doi:10.1007/978-3-319-62515-7_35. ISSN 0065-1419. PMID 30610329.
  5. Henderson, Fraser C. (2016). "Cranio-cervical Instability in Patients with Hypermobility Connective Disorders". Journal of Spine. 05 (02). doi:10.4172/2165-7939.1000299. ISSN 2165-7939.
  6. 6.0 6.1 6.2 "Have you ruled out Chiari as a cause of your CFS". Phoenix Rising. Cite has empty unknown parameter: |dead-url= (help)
  7. 7.0 7.1 7.2 Brea, Jennifer (June 6, 2019). "CCI + Tethered cord series". Medium. Retrieved June 6, 2019.
  8. 8.0 8.1 8.2 "Craniocervical instability, Atlantoaxial Instability, Myalgic Encephalomyelitis, ME, CFS". MEchanical Basis. Retrieved June 6, 2019.
  9. "Atlantoaxial Instability: Background, Pathophysiology, Etiology". November 10, 2019. Cite journal requires |journal= (help)
  10. Li, Ming-Feng; Chiu, Pao-Chin; Weng, Mei-Jui; Lai, Ping-Hong (December 13, 2010). "Atlantoaxial Instability and Cervical Cord Compression in Morquio Syndrome". Archives of Neurology. 67 (12): 1530–1530. doi:10.1001/archneurol.2010.308. ISSN 0003-9942.
  11. Herzka, Andrea; Sponseller, Paul D.; Pyeritz, Reed E. (February 15, 2000). "Atlantoaxial Rotatory Subluxation in Patients With Marfan Syndrome: A Report of Three Cases". Spine. 25 (4): 524. ISSN 0362-2436.
  12. MacKenzie, James MacKintosh; Rankin, Rosslyn (December 2003). "Sudden Death Due to Atlantoaxial Subluxation in Marfan Syndrome". The American Journal of Forensic Medicine and Pathology. 24 (4): 369. doi:10.1097/01.paf.0000097853.26115.bb. ISSN 0195-7910.
  13. "Europe PMC". europepmc.org. Retrieved December 10, 2019.
  14. Castori, Marco; Morlino, Silvia; Ghibellini, Giulia; Celletti, Claudia; Camerota, Filippo; Grammatico, Paola (2015). "Connective tissue, Ehlers–Danlos syndrome(s), and head and cervical pain". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 169 (1): 84–96. doi:10.1002/ajmg.c.31426. ISSN 1552-4876.
  15. Lane, D. (August 1, 2006). "Anaesthetic Implications of Vascular Type Ehlers-Danlos Syndrome". Anaesthesia and Intensive Care. 34 (4): 501–505. doi:10.1177/0310057X0603400412. ISSN 0310-057X.
  16. Dordoni, Chiara; Ciaccio, Claudia; Venturini, Marina; Calzavara‐Pinton, Piergiacomo; Ritelli, Marco; Colombi, Marina (2016). "Further delineation of FKBP14-related Ehlers–Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review". American Journal of Medical Genetics Part A. 170 (8): 2031–2038. doi:10.1002/ajmg.a.37728. ISSN 1552-4833.
  17. Giunta, Cecilia; Baumann, Matthias; Fauth, Christine; Lindert, Uschi; Abdalla, Ebtesam M.; Brady, Angela F.; Collins, James; Dastgir, Jahannaz; Donkervoort, Sandra (January 2018). "A cohort of 17 patients with kyphoscoliotic Ehlers–Danlos syndrome caused by biallelic mutations in FKBP14 : expansion of the clinical and mutational spectrum and description of the natural history". Genetics in Medicine. 20 (1): 42–54. doi:10.1038/gim.2017.70. ISSN 1530-0366.
  18. "Europe PMC". europepmc.org. Retrieved December 10, 2019.
  19. Galan, Enrique; Kousseff, Boris G. (April 1, 1995). "Peripheral neuropathy in Ehlers-Danlos syndrome". Pediatric Neurology. 12 (3): 242–245. doi:10.1016/0887-8994(95)00003-X. ISSN 0887-8994.
  20. Wills, Brian P. D.; Dormans, John P. (April 2006). "Nontraumatic Upper Cervical Spine Instability in Children". JAAOS - Journal of the American Academy of Orthopaedic Surgeons. 14 (4): 233. ISSN 1067-151X.
  21. Rowe, Peter C.; Marden, Colleen L.; Heinlein, Scott; Edwards, Charles C. (February 2, 2018). "Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis". Journal of Translational Medicine. 16. doi:10.1186/s12967-018-1397-7. ISSN 1479-5876. PMC 5796598. PMID 29391028.
  22. "Tethered Spinal Cord Syndrome Information Page | National Institute of Neurological Disorders and Stroke". National Institute of Neurological Disorders and Stroke. Retrieved July 26, 2019.
  23. Colohan, Austin R. T.; Zouros, Alexander; Siddiqi, Javed; Yamada, Shoko M.; Yamada, Brian S.; Pezeshkpour, Gholam; Won, Daniel J.; Yamada, Shokei (August 1, 2007). "Pathophysiology of tethered cord syndrome and similar complex disorders". Neurosurgical Focus. 23 (2): 1–10. doi:10.3171/FOC-07/08/E6. ISSN 1092-0684.
  24. Colohan, Austin R. T.; Yamada, Shokei (January 1, 2009). "Tethered Cord Syndrome". Journal of Neurosurgery: Spine. 10 (1): 79–80. doi:10.3171/2008.10.SPI15714L.
  25. Sullivan, Stephen; Park, Paul; Stetler, William R. (July 1, 2010). "Pathophysiology of adult tethered cord syndrome: review of the literature". Neurosurgical Focus. 29 (1): E2. doi:10.3171/2010.3.FOCUS1080. ISSN 1092-0684.
  26. Hulens, Mieke; Bruyninckx, Frans; Dankaerts, Wim; Rasschaert, Ricky; De Mulder, Peter; Stalmans, Ingeborg; Vansant, Greet; Bervoets, Chris (December 1, 2020). "High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome". Pain Medicine: pnaa410. doi:10.1093/pm/pnaa410. ISSN 1526-2375.
  27. Rowe, Peter C.; Marden, Colleen L.; Heinlein, Scott; Edwards, Charles C. (February 2, 2018). "Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis". Journal of Translational Medicine. 16. doi:10.1186/s12967-018-1397-7. ISSN 1479-5876. PMC 5796598. PMID 29391028.
  28. Hulens, Mieke; Bruyninckx, Frans; Dankaerts, Wim; Rasschaert, Ricky; De Mulder, Peter; Stalmans, Ingeborg; Vansant, Greet; Bervoets, Chris (December 1, 2020). "High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome". Pain Medicine: pnaa410. doi:10.1093/pm/pnaa410. ISSN 1526-2375.
  29. Journal, Thomas M. BurtonStaff Reporter of The Wall Street. "Some Doctors Operate on People Diagnosed With Chronic Fatigue". WSJ. Retrieved July 7, 2019.
  30. "CFS/FM and Chiari Malformation Surgery". www.massmecfs.org. Retrieved July 7, 2019.
  31. Heffez, Dan S.; Ross, Ruth E.; Shade-Zeldow, Yvonne; Kostas, Konstantinos; Shah, Sagar; Gottschalk, Robert; Elias, Dean A.; Shepard, Alan; Leurgans, Sue E. (April 9, 2004). "Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia". European Spine Journal. 13 (6): 516–523. doi:10.1007/s00586-004-0672-x. ISSN 0940-6719. PMC 3476600. PMID 15083352.
  32. Ellenbogen, Richard G.; Guan, Qingyan; Noonan, Carolyn; Maravilla, Kenneth R.; Goldberg, Jack; Buchwald, Dedra; Watson, Nathaniel F. (February 1, 2011). "Is Chiari I Malformation Associated With Fibromyalgia?". Neurosurgery. 68 (2): 443–449. doi:10.1227/NEU.0b013e3182039a31. ISSN 0148-396X.
  33. Castori, Marco; Camerota, Filippo; Celletti, Claudia; Danese, Chiara; Santilli, Valter; Saraceni, Vincenzo Maria; Grammatico, Paola (2010). "Natural history and manifestations of the hypermobility type Ehlers–Danlos syndrome: A pilot study on 21 patients". American Journal of Medical Genetics Part A. 152A (3): 556–564. doi:10.1002/ajmg.a.33231. ISSN 1552-4833.
  34. Francomano, Clair A.; McDonnell, Nazli B.; Nishikawa, Misao; Bolognese, Paolo A.; Milhorat, Thomas H. (December 1, 2007). "Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue". Journal of Neurosurgery: Spine. 7 (6): 601–609. doi:10.3171/SPI-07/12/601.
  35. Rombaut, Lies; Malfait, Fransiska; Paepe, Anne De; Rimbaut, Steven; Verbruggen, Gust; Wandele, Inge De; Calders, Patrick (2011). "Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: A comparative study with fibromyalgia and rheumatoid arthritis". Arthritis & Rheumatism. 63 (7): 1979–1987. doi:10.1002/art.30337. ISSN 1529-0131.
  36. Miller, Victor J.; Zeltser, Rephael; Yoeli, Zvi; Bodner, Lipa (July 1, 1997). "Ehlers-Danlos Syndrome, Fibromyalgia and Temporomandibular Disorder: Report of an Unusual Combination". CRANIO®. 15 (3): 267–269. doi:10.1080/08869634.1997.11746020. ISSN 0886-9634.
  37. Heffez, Dan S.; Ross, Ruth E.; Shade-Zeldow, Yvonne; Kostas, Konstantinos; Morrissey, Mary; Elias, Dean A.; Shepard, Alan (September 2007). "Treatment of cervical myelopathy in patients with the fibromyalgia syndrome: outcomes and implications". European Spine Journal. 16 (9): 1423–1433. doi:10.1007/s00586-007-0366-2. ISSN 0940-6719. PMC 2200733. PMID 17426987.
  38. 38.0 38.1 "Positional Cervical Spinal Cord Compression and Fibromyalgia: A Novel Comorbidity With Important Diagnostic and Treatment Implications". The Journal of Pain. 9 (7): 613–622. July 1, 2008. doi:10.1016/j.jpain.2008.01.339. ISSN 1526-5900.
  39. Zeitoun, Delphine; Hajj, Firass El; Sariali, Elhadi; Catonné, Yves; Pascal-Moussellard, Hugues (April 1, 2015). "Evaluation of spinal cord compression and hyperintense intramedullary lesions on T2-weighted sequences in patients with cervical spondylotic myelopathy using flexion-extension MRI protocol". The Spine Journal. 15 (4): 668–674. doi:10.1016/j.spinee.2014.12.001. ISSN 1529-9430. PMID 25485484.
  40. Henderson, Fraser C.; Austin, Claudiu; Benzel, Edward; Bolognese, Paolo; Ellenbogen, Richard; Francomano, Clair A.; Ireton, Candace; Klinge, Petra; Koby, Myles (03 2017). "Neurological and spinal manifestations of the Ehlers-Danlos syndromes". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 175 (1): 195–211. doi:10.1002/ajmg.c.31549. ISSN 1552-4876. PMID 28220607. Check date values in: |date= (help)