Editing Multiple sclerosis (section)

== Types and variants ==
[[File:Ms progression types.svg|thumb|MS progression types. From bottom to top: RRMS, PPMS, SPMS.]]
Several [[Phenotype (clinical medicine)|phenotypes]] (commonly termed "types"), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions.

The International Advisory Committee on Clinical Trials of MS describes four types of MS (revised in 2013) in what is known as the [[Multiple sclerosis research#Lublin classification|Lublin classification]]:<ref name=Lublin>{{cite journal| title = Defining the clinical course of multiple sclerosis, The 2013 revisions | journal = Neurology | volume = 83 | issue = 3 | pages = 278–286 |vauthors=Lublin FD, etal | date = 15 July 2014| doi = 10.1212/WNL.0000000000000560 | pmid = 24871874 | pmc = 4117366}}</ref><ref>{{cite journal |vauthors=Lublin FD, Coetzee T, Cohen JA, Marrie RA, Thompson AJ |title=The 2013 clinical course descriptors for multiple sclerosis: A clarification |journal=Neurology |volume=94 |issue=24 |pages=1088–1092 |date=June 2020 |pmid=32471886 |pmc=7455332 |doi=10.1212/WNL.0000000000009636}}</ref>

# [[Clinically isolated syndrome]] (CIS)
# [[Relapsing–remitting|Relapsing-remitting]] MS (RRMS)
# Primary progressive MS (PPMS)
# Secondary progressive MS (SPMS)
CIS can be characterised as a single lesion seen on MRI which is associated with signs or symptoms found in MS. Due to the McDonald criteria, it does not completely fit the criteria to be diagnosed as MS, hence being named "clinically isolated syndrome". CIS can be seen as the first episode of demyelination in the central nervous system. To be classified as CIS, the attack must last at least 24 hours and be caused by [[inflammation]] or [[Demyelinating disease|demyelination]] of the [[central nervous system]].<ref name="pmid1897097722"/><ref>{{Cite web |title=Clinically Isolated Syndrome (CIS) |url=https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Clinically-Isolated-Syndrome-(CIS) |access-date=4 October 2023 |website=National MS Society |archive-date=30 September 2023 |archive-url=https://web.archive.org/web/20230930160029/https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Clinically-Isolated-Syndrome-(CIS) |url-status=dead }}</ref> Patients who suffer from CIS may or may not go on to develop MS, but 30 to 70% of persons who experience CIS will later develop MS.<ref name="pmid15847841">{{cite journal |vauthors=Miller D, Barkhof F, Montalban X, Thompson A, Filippi M |date=May 2005 |title=Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis |journal=The Lancet. Neurology |volume=4 |issue=5 |pages=281–8 |doi=10.1016/S1474-4422(05)70071-5 |pmid=15847841 |s2cid=36401666}}</ref>

RRMS is characterized by unpredictable relapses followed by periods of months to years of relative quiet ([[remission (medicine)|remission]]) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave [[sequelae|problems]], the latter in about 40% of attacks and being more common the longer a person has had the disease.<ref name="pmid1897097722"/><ref name="Tsang20112"/> This describes the initial course of 80% of individuals with MS.<ref name="pmid1897097722"/>

PPMS occurs in roughly 10–20% of individuals with the disease, with no remission after the initial symptoms.<ref name="Tsang20112"/><ref name="pmid17884680">{{cite journal | vauthors = Miller DH, Leary SM | title = Primary-progressive multiple sclerosis | journal = The Lancet. Neurology | volume = 6 | issue = 10 | pages = 903–12 | date = October 2007 | pmid = 17884680 | doi = 10.1016/S1474-4422(07)70243-0 | s2cid = 31389841 | hdl = 1871/24666 | hdl-access = free }}</ref> It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.<ref name="pmid8780061" /> The usual age of onset for the primary progressive subtype is later than that of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in RRMS, around 40 years of age.<ref name="pmid1897097722"/>

SPMS occurs in around 65% of those with initial RRMS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission.<ref name="pmid1897097722"/><ref name="pmid8780061" /> Occasional relapses and minor remissions may appear.<ref name="pmid8780061" /> The most common length of time between disease onset and conversion from RRMS to SPMS is 19 years.<ref name="pmid16545751">{{cite journal | vauthors = Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M | title = Secondary progressive multiple sclerosis: current knowledge and future challenges | journal = The Lancet. Neurology | volume = 5 | issue = 4 | pages = 343–54 | date = April 2006 | pmid = 16545751 | doi = 10.1016/S1474-4422(06)70410-0 | s2cid = 39503553 }}</ref>

=== Special courses ===
Independently of the types published by the MS associations, regulatory agencies such as the FDA often consider special courses, trying to reflect some clinical trial results on their approval documents. Some examples could be "highly active MS" (HAMS),<ref name="sorensen">{{cite journal |vauthors=Sørensen PS, Centonze D, Giovannoni G, et al. |title=Expert opinion on the use of cladribine tablets in clinical practice |journal=Ther Adv Neurol Disord |volume=13 |pages=1756286420935019 |year=2020 |pmid=32636933 |pmc=7318823 |doi=10.1177/1756286420935019 |type= Review}}</ref> "active secondary MS" (similar to the old progressive-relapsing)<ref name="novartis.com">{{Cite web|url=https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-mayzent-siponimod-first-oral-drug-treat-secondary-progressive-ms-active-disease|title=Novartis receives FDA approval for Mayzent® (siponimod), the first oral drug to treat secondary progressive MS with active disease|website=Novartis.com|access-date=12 November 2021|archive-date=20 November 2020|archive-url=https://web.archive.org/web/20201120002815/https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-mayzent-siponimod-first-oral-drug-treat-secondary-progressive-ms-active-disease|url-status=live}}</ref> and "rapidly progressing PPMS".<ref>{{cite journal |vauthors=Saida T |title=多発性硬化症: 再燃時の治療と再発予防 |trans-title=Multiple sclerosis: treatment and prevention of relapses and progression in multiple sclerosis |language=ja |journal=臨床神経学 |trans-journal=Rinsho Shinkeigaku |volume=44 |issue=11 |pages=796–8 |date=November 2004 |pmid=15651294 |type= Review}}</ref>

Also, deficits always resolving between attacks is sometimes referred to as "benign" MS,<ref name="pmid18219812">{{cite book | vauthors = Pittock SJ, Rodriguez M | chapter = Benign Multiple Sclerosis: A Distinct Clinical Entity with Therapeutic Implications | veditors = Rodriguez M | title = Advances in multiple Sclerosis and Experimental Demyelinating Diseases | series = Current Topics in Microbiology and Immunology | volume = 318 | pages = 1–17 | year = 2008 | pmid = 18219812 | doi = 10.1007/978-3-540-73677-6_1 | isbn = 978-3-540-73676-9 }}</ref> although people still build up some degree of disability in the long term.<ref name="pmid1897097722"/> On the other hand, the term [[malignant multiple sclerosis]] is used to describe people with MS having reached a significant level of disability in a short period.<ref>{{cite book | vauthors = Feinstein A | chapter = Chapter 1 - Multiple sclerosis: diagnosis and definitions |title=The Clinical Neuropsychiatry of Multiple Sclerosis |date=2007 |isbn=978-0-521-85234-0 | pages = 1–27 |doi=10.1017/CBO9780511543760 }}</ref>

An international panel has published a standardized definition for the course HAMS.<ref name="sorensen" />

=== Variants ===
Atypical [[Idiopathic inflammatory demyelinating diseases|variants]] of MS have been described; these include [[tumefactive multiple sclerosis]], [[Balo concentric sclerosis]], [[Diffuse myelinoclastic sclerosis|Schilder's diffuse sclerosis]], and [[Marburg multiple sclerosis]]. Debate remains on whether they are MS variants or different diseases.<ref name="pmid15727225">{{cite journal | vauthors = Stadelmann C, Brück W | title = Lessons from the neuropathology of atypical forms of multiple sclerosis | journal = Neurological Sciences | volume = 25 | issue = Suppl 4 | pages = S319–S322 | date = November 2004 | pmid = 15727225 | doi = 10.1007/s10072-004-0333-1 | s2cid = 21212935 }}</ref> Some diseases previously considered MS variants, such as [[Devic's disease]], are now considered outside the MS spectrum.<ref>{{cite journal | vauthors = Fujihara K | title = Neuromyelitis optica spectrum disorders: still evolving and broadening | journal = Current Opinion in Neurology | volume = 32 | issue = 3 | pages = 385–394 | date = June 2019 | pmid = 30893099 | pmc = 6522202 | doi = 10.1097/WCO.0000000000000694 | type = Review }}</ref>