Editing Multiple sclerosis (section)

== Diagnosis ==
{{Main|Multiple sclerosis diagnosis}}
[[File:Monthly multiple sclerosis anim cropped no text.gif|thumb|Animation showing dissemination of brain lesions in time and space as demonstrated by monthly MRI studies along a year]] [[File:MSMRIMark.png|thumb|Multiple sclerosis as seen on MRI]]
Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting [[medical imaging]] and laboratory testing.<ref name="Tsang20112"/> It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.<ref name="pmid1897097722"/><ref name="pmid11794488">{{cite journal | vauthors = Trojano M, Paolicelli D | title = The differential diagnosis of multiple sclerosis: classification and clinical features of relapsing and progressive neurological syndromes | journal = Neurological Sciences | volume = 22 | issue = Suppl 2 | pages = S98-102 | date = November 2001 | pmid = 11794488 | doi = 10.1007/s100720100044| s2cid = 3057096 }}</ref>

===McDonald criteria===
The [[McDonald criteria]], which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis<ref name=Atlas2008>{{cite book |author=World Health Organization |title=Atlas: Multiple Sclerosis Resources in the World 2008 |publisher=World Health Organization |location=Geneva |year=2008 |pages=15–16 |isbn=978-92-4-156375-8 |hdl=10665/43968 |hdl-access=free }}</ref> with the [[Schumacher criteria|Schumacher]] and [[Poser criteria]] being of mostly historical significance.<ref name="pmid15177763">{{cite journal | vauthors = Poser CM, Brinar VV | title = Diagnostic criteria for multiple sclerosis: an historical review | journal = Clinical Neurology and Neurosurgery | volume = 106 | issue = 3 | pages = 147–58 | date = June 2004 | pmid = 15177763 | doi = 10.1016/j.clineuro.2004.02.004 | s2cid = 23452341 }}</ref> The McDonald criteria states that patients with multiple sclerosis should have lesions which are disseminated in time (DIT) and disseminated in space (DIS), i.e. lesions which have appeared in different areas in the brain and at different times.<ref name="Thompson-2018"/> Below is an abbreviated outline of the 2017 McDonald Criteria for diagnosis of MS.
* At least 2 clinical attacks with MRI showing 2 or more lesions characteristic of MS.<ref name="Thompson-2018" />
* At least 2 clinical attacks with MRI showing 1 lesion characteristic of MS with clear historical evidence of a previous attack involving a lesion at a distinct location in the CNS.<ref name="Thompson-2018" />
* At least 2 clinical attacks with MRI showing 1 lesion characteristic of MS, with DIT established by an additional clinical attack at a distinct CNS site or by MRI showing an old MS lesion.<ref name="Thompson-2018" />
* 1 clinical attack with MRI showing at least 2 lesions characteristic of MS, with DIT established by an additional attack, by MRI showing old MS lesion(s), or presence of oligoclonal bands in CSF.<ref name="Thompson-2018" />
* 1 clinical attack with MRI showing 1 lesion characteristic of MS, with DIS established by an additional attack at a different CNS site or by MRI showing old MS lesion(s), and DIT established by an additional attack, by MRI showing old MS lesion(s), or presence of oligoclonal bands in CSF.<ref name="Thompson-2018" />

{{as of|2017}}, no single test (including biopsy) can provide a definitive diagnosis.<ref>{{cite journal | vauthors = Rovira À | title = Diagnosis of Multiple Sclerosis| journal = Journal of the Belgian Society of Radiology | volume = 101 | issue = S1 | pages = 12 | date = November 2017 | doi = 10.5334/jbr-btr.1426| doi-access = free }}</ref>

===MRI===
Magnetic resonance imaging (MRI) of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered [[intravenous]]ly as a [[contrast agent]] to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.<ref name="pmid11456302">{{cite journal | vauthors = McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS | author1-link=W. Ian McDonald | author16-link=Jerry Wolinsky | title = Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis | journal = Annals of Neurology | volume = 50 | issue = 1 | pages = 121–7 | date = July 2001 | pmid = 11456302 | doi = 10.1002/ana.1032 | s2cid=13870943 | doi-access = free }}</ref><ref name="pmid18256986">{{cite journal | vauthors = Rashid W, Miller DH | title = Recent advances in neuroimaging of multiple sclerosis | journal = Seminars in Neurology | volume = 28 | issue = 1 | pages = 46–55 | date = February 2008 | pmid = 18256986 | doi = 10.1055/s-2007-1019127 | s2cid = 260317568 }}</ref>

Central vein signs (CVSs) have been proposed as a good indicator of MS in comparison with other conditions causing white lesions.<ref>{{cite journal | vauthors = Sinnecker T, Clarke MA, Meier D, Enzinger C, Calabrese M, De Stefano N, Pitiot A, Giorgio A, Schoonheim MM, Paul F, Pawlak MA, Schmidt R, Kappos L, Montalban X, Rovira À, Evangelou N, Wuerfel J | title = Evaluation of the Central Vein Sign as a Diagnostic Imaging Biomarker in Multiple Sclerosis | journal = JAMA Neurology | volume = 76 | issue = 12 | pages = 1446–1456 | date = December 2019 | pmid = 31424490 | pmc = 6704746 | doi = 10.1001/jamaneurol.2019.2478 | collaboration = MAGNIMS Study Group }}</ref><ref>{{cite journal |vauthors=Bernitsas E |title=The Central Vein Sign |journal=Practical Neurology |date=February 2020 |url=https://practicalneurology.com/articles/2020-feb/the-central-vein-sign |access-date=5 October 2021 |archive-date=5 October 2021 |archive-url=https://web.archive.org/web/20211005141611/https://practicalneurology.com/articles/2020-feb/the-central-vein-sign |url-status=live }}</ref><ref>{{cite journal | vauthors = Castellaro M, Tamanti A, Pisani AI, Pizzini FB, Crescenzo F, Calabrese M | title = The Use of the Central Vein Sign in the Diagnosis of Multiple Sclerosis: A Systematic Review and Meta-analysis | journal = Diagnostics | volume = 10 | issue = 12 | pages = 1025 | date = November 2020 | pmid = 33260401 | pmc = 7760678 | doi = 10.3390/diagnostics10121025 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Al-Zandi SH, Fayadh NA, Al-Waely NK |title=Central vein sign detected by SWI at 3 T MRI as a discriminator between multiple sclerosis and leukoaraiosis |journal=The Egyptian Journal of Radiology and Nuclear Medicine |date=1 March 2018 |volume=49 |issue=1 |pages=158–164 |doi=10.1016/j.ejrnm.2017.09.003 |doi-access=free }}</ref> One small study found fewer CVSs in older and hypertensive people.<ref>{{cite journal | vauthors = Guisset F, Lolli V, Bugli C, Perrotta G, Absil J, Dachy B, Pot C, Théaudin M, Pasi M, van Pesch V, Maggi P | title = The central vein sign in multiple sclerosis patients with vascular comorbidities | journal = Multiple Sclerosis | volume = 27 | issue = 7 | pages = 1057–1065 | date = June 2021 | pmid = 32749948 | doi = 10.1177/1352458520943785 | hdl-access = free | hdl = 2078.1/239849 }}</ref> Further research on CVS as a biomarker for MS is ongoing.<ref>{{cite news |vauthors=Chapman M |title=$7.2M NIH Grant Supports Study of MS Diagnostic Biomarker |url=https://multiplesclerosisnewstoday.com/news-posts/2020/06/16/cleveland-clinic-given-7-million-nih-grant-study-diagnostic-cvs-biomarker/ |agency=BioNews Services |date=16 June 2020 |access-date=5 October 2021 |archive-date=5 October 2021 |archive-url=https://web.archive.org/web/20211005173348/https://multiplesclerosisnewstoday.com/news-posts/2020/06/16/cleveland-clinic-given-7-million-nih-grant-study-diagnostic-cvs-biomarker/ |url-status=live }}</ref>

====In vivo vs postmortem lesion visibility in MRI scans====
Only postmortem MRI allows visualization of sub-millimetric lesions in cortical layers and in the cerebellar cortex.<ref>{{cite journal | vauthors = Weigel M, Dechent P, Galbusera R, Bahn E, Nair G, Lu PJ, Kappos L, Brück W, Stadelmann C, Granziera C | title = Imaging multiple sclerosis pathology at 160 μm isotropic resolution by human whole-brain ex vivo magnetic resonance imaging at 3 T | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 15491 | date = July 2021 | pmid = 34326420 | pmc = 8322069 | doi = 10.1038/s41598-021-94891-1 }}</ref>

===Cerebrospinal fluid (lumbar puncture)===
Testing of cerebrospinal fluid obtained from a [[lumbar puncture]] can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for [[oligoclonal band]]s of IgG on [[electrophoresis]], which are inflammation markers found in 75–85% of people with MS.<ref name="pmid11456302" /><ref name="pmid16945427">{{cite journal | vauthors = Link H, Huang YM | title = Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness | journal = Journal of Neuroimmunology | volume = 180 | issue = 1–2 | pages = 17–28 | date = November 2006 | pmid = 16945427 | doi = 10.1016/j.jneuroim.2006.07.006 | s2cid = 22724352 }}</ref>

=== Differential diagnosis ===
Several diseases present similarly to MS.<ref name="Loscalzo-2022" /><ref name="Saguil-2022" /> Medical professionals use a patient's specific presentation, history, and exam findings to make an individualized [[Differential diagnosis|differential]]. Red flags are findings that suggest an alternate diagnosis, although they do not rule out MS. Red flags include a patient younger than 15 or older than 60, less than 24 hours of symptoms, involvement of multiple [[cranial nerves]], involvement of organs outside of the [[nervous system]], and atypical lab and exam findings.<ref name="Loscalzo-2022">{{Cite book | vauthors = Hauser SL | chapter = Chapter 442: Diseases of the Spinal Cord | veditors = Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL  |title=Harrison's principles of internal medicine |date=2022 |isbn=978-1-264-26849-8 |edition=21st |location=New York | publisher = McGraw-Hill |oclc=1282172709 | page = 3466 }}</ref><ref name="Saguil-2022">{{cite journal | vauthors = Saguil A, Farnell IV EA, Jordan TS | title = Multiple Sclerosis: A Primary Care Perspective | journal = American Family Physician | volume = 106 | issue = 2 | pages = 173–183 | date = August 2022 | pmid = 35977131 | url = https://www.aafp.org/pubs/afp/issues/2022/0800/multiple-sclerosis.html }}</ref>

In an emergency setting, it is important to rule out a stroke or [[Intracranial hemorrhage|bleeding]] in the brain.<ref name="Saguil-2022" /> Intractable vomiting, severe optic neuritis,<ref name="Petzold_2022" /> or bilateral optic neuritis<ref name="Petzold_2022" /> raises suspicion for [[neuromyelitis optica spectrum disorder]] (NMOSD).<ref name="Solomon2019DiagnosisReview">{{cite journal | vauthors = Solomon AJ | title = Diagnosis, Differential Diagnosis, and Misdiagnosis of Multiple Sclerosis | journal = Continuum | volume = 25 | issue = 3 | pages = 611–635 | date = June 2019 | pmid = 31162308 | doi = 10.1212/CON.0000000000000728 | s2cid = 173991777 }}</ref> Infectious diseases that may look similar to multiple sclerosis include HIV, [[Lyme disease]], and [[Neurosyphilis|syphilis]]. Autoimmune diseases include [[neurosarcoidosis]], [[lupus]], [[Guillain–Barré syndrome|Guillain-Barré syndrome]], [[acute disseminated encephalomyelitis]], and [[Behçet's disease]]. Psychiatric conditions such as [[Generalized anxiety disorder|anxiety]] or [[conversion disorder]] may also present in a similar way. Other rare diseases on the differential include [[Primary central nervous system lymphoma|CNS lymphoma]], [[Leukodystrophy|congenital leukodystrophies]], and [[MOG antibody disease|anti-MOG-associated myelitis]].<ref name="Loscalzo-2022" /><ref name="Saguil-2022" />