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Bevis for virus som årsag inkluderer tilstedeværelsen af [[oligoklonalt bånd|oligoklonale bånd]] i hjernen og [[cerebrospinalvæske]]n hos de fleste patienter, tilknytningen af flere virus med human demyelinerende [[encefalomyelitis]] og induktion af demyelinering i dyr gennem viral infektion.<ref name="pmid15721830">{{cite journal|author=Gilden DH|title=Infectious causes of multiple sclerosis|journal=Lancet Neurol|volume=4|issue=3|pages=195–202|year=2005|month=marts|pmid=15721830|doi=10.1016/S1474-4422(05)01017–3|doi_brokendate=2009-12-24}}</ref> [[Herpesviridae|Human herpesvirus]] er en kandidatgruppe af virus tilknyttet MS;<ref name="pmid17686342">{{cite journal|author=Christensen T|title=Human herpesviruses in MS|journal=Int MS J|volume=14|issue=2|pages=41–7|year=2007|month=juni|pmid=17686342|url=http://www.msforumonline.net/journal/download/default.aspx?pdf=20071441.pdf|format=PDF}}</ref> Personer der aldrig har været inficeret med [[Epstein-Barr]]-virus har mindre risiko for at have sygdommen og blandt inficerede har de der var inficeret som unge voksne større risiko end personer inficeret i en yngre alder.<ref name="pmid17444504"/><ref name="pmid18970977"/> Dette taler mod hygiejnehypotesen, eftersom de ikke-inficerede formentligt har haft en mere hygiejnisk opvækst.<ref name="pmid17444504"/> Andre agenser, der også er blevet forbundet med MS, er humant [[endogent retrovirus]] og ''[[Chlamydia pneumoniae]]''.<ref name="pmid11601494">{{cite journal|author=Johnston JB, Silva C, Holden J, Warren KG, Clark AW, Power C|title=Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases|journal=Ann. Neurol.|volume=50|issue=4|pages=434–42|year=2001|month=oktober|pmid=11601494|doi=10.1002/ana.1131}}</ref><ref name="pmid16635422">{{cite journal|author=Christensen T|title=The role of EBV in MS pathogenesis|journal=Int MS J|volume=13|issue=2|pages=52–7|year=2006|month=maj|pmid=16635422|url=http://www.msforumonline.net/journal/download/default.aspx?pdf=20061352.pdf|format=PDF}}</ref><ref name="pmid11342681">{{cite journal|author=Yao SY, Stratton CW, Mitchell WM, Sriram S|title=CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens|journal=Neurology|volume=56|issue=9|pages=1168–76|year=2001|month=maj|pmid=11342681|url=http://www.neurology.org/cgi/pmidlookup?view=long&pmid=11342681}}</ref>
 
<!-- ==Patofysiologi==
[[Image:MS Demyelinisation KB 10x.jpg|thumb|DemyelinationDemyelinisering ini MS. On (Klüver-Barrera myelin staining,farvning). decolorationOmråder inmed themanglende areafarve ofafslører the lesion can be appreciatedlæsionerne. (Original scaleForstørrelse 1:100).]]▼
{{Hovedartikel|Patofysiologi i multipel sklerose}}
 
===Læsioner===
===Blood-brain barrier breakdown===
Navnet "''multipel sklerose''" henviser til ar-lignenden aflejringerne (bedre kendt som plaques eller læsioner), der dannes i [[centralnervesystem]]et. Læsionerne ses oftest i den [[hvid substans|hvide substans]] omkring [[ventrikelsystemet|ventriklerne]], [[lillehjerne]]n, [[hjernestamme]]n, [[basalganglier]]ne, [[rygmarv]]en og [[synsnerve]]n. Formålet med cellerne i den hvide substans er at formidle signaler fra den [[grå substans]] til resten af kroppen. Det [[perifere nervesystem]] er sjældent involveret i MS.<ref name="pmid11955556">{{cite journal|author=Compston A, Coles A|title=Multiple sclerosis|journal=Lancet|volume=359|issue=9313|pages=1221–31|year=2002|month=April|pmid=11955556|doi=10.1016/S0140-6736(02)08220-X}}</ref>
▲[[Image:MS Demyelinisation KB 10x.jpg|thumb|Demyelination in MS. On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).]]
The [[blood–brain barrier]] is a [[capillary]] system that should prevent entrance of T cells into the nervous system.<ref name="pmid11955556"/> The blood–brain barrier is normally not permeable to these types of cells, unless triggered by infection or a virus, which decreases the integrity of the [[tight junction]]s forming the barrier.<ref name="pmid11955556"/> When the blood–brain barrier regains its integrity, usually after infection or virus has cleared, the T cells are trapped inside the brain.<ref name="pmid11955556"/>
 
Mere specifikt ses der i MS tab af [[oligodendrocyt]]ter, som er involveret i dannelse og vedligeholdelse af [[nervecelle]]rnes [[myelin]]skeder, som effektiviserer videreformidlingen af disses elektriske signaler ([[aktionspotential]]er).<ref name="pmid11955556"/>
===Autoimmunology===
Dette fører til en fortynding eller fuldkomment tab af myelinskederne og yderligere nedbrydning af nervecellernes [[akson]]er som sygdommen skrider frem. Når myelinet tabes er det ikke længere muligt for cellen effektivt at videreformidle elektriske signaler.<ref name="pmid11955556"/> En reparationsprocess kaldet [[remyelinering]] finder sted i sygdommens tidlige stadie, men oligodendrocytterne er ikke tilstrækkelige til at få genopbygget cellernes myelinskeder.<ref name="pmid17531860">{{cite journal |author=Chari DM |title=Remyelination in multiple sclerosis|journal=Int. Rev. Neurobiol. |volume=79 |issue= |pages=589–620 |year=2007 |pmid=17531860|doi=10.1016/S0074-7742(07)79026-8 |url=}}</ref> Gentagne anfald medfører mindre effektiv remyelinering, indtil en arlignende aflejring (plaque eller læsion) dannes omkring det skadede akson.<ref name="pmid17531860"/> Forskellige læsionsmønstrer er blevet observeret i MS.<ref name="pmid17351524">{{cite journal |author=Pittock SJ, Lucchinetti CF |title=The pathology of MS: new insights and potential clinical applications |journal=Neurologist|volume=13 |issue=2 |pages=45–56 |year=2007 |month=March |pmid=17351524|doi=10.1097/01.nrl.0000253065.31662.37 }}</ref>
MS is currently believed to be an immune-mediated disorder with an initial trigger, which may have a viral etiology,<ref name="pmid11955556"/> although this concept has been debated for years and some still oppose it. Damage is believed to be caused by the patient's own immune system. The immune system attacks the nervous system, possibly as a result of exposure to a molecule with a similar structure to one of its own.<ref name="pmid11955556"/>
 
===Autoimmunologi===
;Lesions
MS menes at være en [[autoimmun|immun-medieret lidelse]], som opstår på baggrund af kompleks interaktion med individets genetiske baggrund og uidentificeret miljørelateret årsager.<ref name="pmid11955556"/> Skaderne i CNS menes at være forårsaget af angreb fra individets eget immunforsvar. Nogle af de cellulære komponenter som immunsystemet angriber ([[antigen|autoantigener]]) menes at være "myelin basisk protein" (MBP) og "proteolipid protein" (PLP). Det ofte ordinerede MS-medikament [[glatiramer acetate]] blev designet til at efterligne MBP, og fungere som afledningsmanøvre for autoreaktive immunceller, hvorved angreb på nervecelleaksonerne ville undgås. MBPs rolle i MS-patogenesen er dog omdiskuteret, da proteinet er lokaliseret inde i myelinskeden (frem for på overfladen), hvor immuncellerne ikke er i stand til at erkende det.
The name ''multiple sclerosis'' refers to the scars (scleroses – better known as plaques or lesions) that form in the nervous system. MS lesions most commonly involve [[white matter]] areas close to the [[Ventricular system|ventricles]] of the [[cerebellum]], [[brain stem]], [[basal ganglia]] and [[spinal cord]]; and the [[optic nerve]]. The function of white matter cells is to carry signals between [[grey matter]] areas, where the processing is done, and the rest of the body. The [[peripheral nervous system]] is rarely involved.<ref name="pmid11955556">{{cite journal|author=Compston A, Coles A|title=Multiple sclerosis|journal=Lancet|volume=359|issue=9313|pages=1221–31|year=2002|month=april|pmid=11955556|doi=10.1016/S0140-6736(02)08220-X}}</ref>
More specifically, MS destroys [[oligodendrocyte]]s, the cells responsible for creating and maintaining a fatty layer—known as the [[myelin]] sheath—which helps the neurons carry [[electricity|electrical]] [[Signal (biology)|signal]]s.<ref name="pmid11955556"/> MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron's extensions or [[axons]].<ref name="pmid17606882">{{cite journal|author=Pascual AM, Martínez-Bisbal MC, Boscá I, ''et al''|title=Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis|journal=Neurology|volume=69|issue=1|pages=63–7|year=2007|month=juli|pmid=17606882|doi=10.1212/01.wnl.0000265054.08610.12}}</ref> When the myelin is lost, a neuron can no longer effectively conduct [[Action potential|electrical signals]].<ref name="pmid11955556"/> A repair process, called [[remyelination]], takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cell's myelin sheath.<ref name="pmid17531860">{{cite journal|author=Chari DM|title=Remyelination in multiple sclerosis|journal=Int. Rev. Neurobiol.|volume=79|pages=589–620|year=2007|pmid=17531860|doi=10.1016/S0074-7742(07)79026-8}}</ref> Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons.<ref name="pmid17531860"/> [[pathophysiology of multiple sclerosis#Demyelination patterns|Four different lesion patterns]] have been described.<ref name="pmid10852536">{{cite journal|author=Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H|title=Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination|journal=Ann. Neurol.|volume=47|issue=6|pages=707–17|year=2000|month=juni|pmid=10852536|doi=10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q}}</ref>
 
Nyere studier peger på myelinlipiders involvering i MS.<ref name="pmid22674551">{{cite journal |author=Ho PP, Kanter JL, Johnson AM, ''et al.'' |title=Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation |journal=Sci Transl Med |volume=4 |issue=137 |pages=137ra73 |year=2012 |month=June |pmid=22674551 |doi=10.1126/scitranslmed.3003831 |url=}}</ref> Historisk har det altid været antaget at myelin komponenten som skabte den autoimmune reaktion måtte være et protein, selvom myleinskeden indeholder over 80% lipider. Yderligere argumentation for at lipider kunne være årsag til den autoimmune reaktion, er baseret på en anden autoimmun lidelse kaldet [[Guillain Barre syndrom]].
;Inflammation▼
 
Apart from demyelination, the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by [[T cell]]s, a kind of [[lymphocyte]]. Lymphocytes are cells that play an important role in the body's defenses.<ref name="pmid11955556"/> In MS, T cells gain entry into the brain via the previously described [[blood–brain barrier]]. Recent evidence from animal models also point to a role of [[B cell]]s in addition to T cells in development of the disease.<ref name="pmid19483694">{{cite journal |author=Krishnamoorthy G, Saxena A, Mars LT, Domingues HS, Mentele R, Ben-Nun A, Lassmann H, Dornmair K, Kurschus FC, Liblau RS, Wekerle H |title=Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis |journal=Nat. Med. |volume=15 |issue=6 |pages=626–32 |year=2009 |month=juni |pmid=19483694 |doi=10.1038/nm.1975 |laysource=Max Planck Society |laysummary=http://www.mpg.de/english/illustrationsDocumentation/documentation/pressReleases/2009/pressRelease20090610/ }}</ref><ref name="pmid19487416">{{cite journal |author=Pöllinger B, Krishnamoorthy G, Berer K, Lassmann H, Bösl MR, Dunn R, Domingues HS, Holz A, Kurschus FC, Wekerle H |title=Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells |journal=J. Exp. Med. |volume=206 |issue=6 |pages=1303–16 |year=2009 |month=juni |pmid=19487416 |doi=10.1084/jem.20090299 |pmc=2715069 }}</ref>
Uanset om den cellulære autoantigen er et protein eller et lipid, kan reaktionen opstå som følge af, immuncellerne genkender et fremmed antigen, og efterfølgende krydsreagerer med organismens egne komponenter (kaldet [[antigen|selv antigener]]), da disse minder om det fremmede antigen - et fænomen kaldet [[molekylære mimicry]].<ref name="pmid11955556"/><ref name="pmid7534214">{{cite journal |author=Wucherpfennig KW, Strominger JL |title=Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein |journal=Cell |volume=80 |issue=5 |pages=695–705 |year=1995 |month=March |pmid=7534214 |doi= |url=}}</ref>
 
▲;===Inflammation===
[[Inflammation]] er udover demyelinering det andet hovedsygdomstegn ved MS. Ifølge [[immunologi]]ske teorier vedrørende MS patogenesen er den inflammatoriske reaktion forårsaget af [[T-celle]]r, (en [[lymfocyt|lymfocyt type]] involveret i kroppens immunsystem).<ref name="pmid11955556"/> T-celler opnår adgang til hjernen gennem "sprækker" i [[blod-hjerne-barriere]]n. Undersøgelser af dyremodeller har også vist, at [[B-celle]]r spiller en mulig rolle.<ref name="pmid11596130">{{cite journal |author=Iglesias A, Bauer J, Litzenburger T, Schubart A, Linington C |title=T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis |journal=Glia |volume=36 |issue=2 |pages=220–34 |year=2001|month=November |pmid=11596130 |doi= 10.1002/glia.1111}}</ref>
 
T-cellerne genkender myelinet som fremmed, og angriber dette, som var det en indtrængende virus. Herved igangsættes en inflammatorisk reaktion, der stimulerer andtre immunceller, og opløselige faktorer som [[cytokin]]er og [[antistof]]fer. Processen leder til yderligere lækage af blodhjerne-barrieren, som leder til en række andre skadende effekter såsom [[ødem|opsvulmen]], aktivering af [[makrofag]]er og yderligere aktivering af cytokiner og andre skadelide proteiner.<ref name="pmid11955556"/>
 
Blod-hjerne-barrieren er en del af det [[kapillær]]e system, som hindrer passage af T-celler ind i centralnervesystemet.<ref name="pmid11955556"/> Denne kan dog blive gennemtrængeligt for disse celletyper, som følge af [[virus|viral]] eller [[bakterie]]l infektion.<ref name="pmid11955556"/> Når blod-hjerne barrieren opheles efter destruktion af den infektiøse agens vil T-cellerne være fanget inde i centralnervesystemet.<ref name="pmid11955556"/>
 
The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like [[cytokine]]s and antibodies. Leaks form in the blood–brain barrier, which in turn cause a number of other damaging effects such as [[edema|swelling]], activation of [[macrophages]], and more activation of cytokines and other destructive proteins.<ref name="pmid11955556"/>
-->
== Diagnose ==
 
Hentet fra "https://da.wikipedia.org/wiki/Multipel_sklerose"