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</ul> </li> <li id="toc-Relapses" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Relapses"> <div class="vector-toc-text"> 2.3 Relapses </div> </a> <ul id="toc-Relapses-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Pregnancy" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Pregnancy"> <div class="vector-toc-text"> 2.4 Pregnancy </div> </a> <ul id="toc-Pregnancy-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Causes" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Causes"> <div class="vector-toc-text"> 3 Causes </div> </a> <button aria-controls="toc-Causes-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Causes subsection </button> <ul id="toc-Causes-sublist" class="vector-toc-list"> <li id="toc-Immune_dysregulation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Immune_dysregulation"> <div class="vector-toc-text"> 3.1 Immune dysregulation </div> </a> <ul id="toc-Immune_dysregulation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Infectious_agents" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Infectious_agents"> <div class="vector-toc-text"> 3.2 Infectious agents </div> </a> <ul id="toc-Infectious_agents-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Genetics" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Genetics"> <div class="vector-toc-text"> 3.3 Genetics </div> </a> <ul id="toc-Genetics-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Geography" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Geography"> <div class="vector-toc-text"> 3.4 Geography </div> </a> <ul id="toc-Geography-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Impact_of_temperature" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Impact_of_temperature"> <div class="vector-toc-text"> 3.5 Impact of temperature </div> </a> <ul id="toc-Impact_of_temperature-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Other" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other"> <div class="vector-toc-text"> 3.6 Other </div> </a> <ul id="toc-Other-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Pathophysiology" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Pathophysiology"> <div class="vector-toc-text"> 4 Pathophysiology </div> </a> <button aria-controls="toc-Pathophysiology-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Pathophysiology subsection </button> <ul id="toc-Pathophysiology-sublist" class="vector-toc-list"> <li id="toc-Immune_dysregulation_2" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Immune_dysregulation_2"> <div class="vector-toc-text"> 4.1 Immune dysregulation </div> </a> <ul id="toc-Immune_dysregulation_2-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Lesions" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Lesions"> <div class="vector-toc-text"> 4.2 Lesions </div> </a> <ul id="toc-Lesions-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Inflammation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Inflammation"> <div class="vector-toc-text"> 4.3 Inflammation </div> </a> <ul id="toc-Inflammation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Blood–brain_barrier" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Blood–brain_barrier"> <div class="vector-toc-text"> 4.4 Blood–brain barrier </div> </a> <ul id="toc-Blood–brain_barrier-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-MS_fatigue" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#MS_fatigue"> <div class="vector-toc-text"> 4.5 MS fatigue </div> </a> <ul id="toc-MS_fatigue-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Diagnosis" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Diagnosis"> <div class="vector-toc-text"> 5 Diagnosis </div> </a> <button aria-controls="toc-Diagnosis-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Diagnosis subsection </button> <ul id="toc-Diagnosis-sublist" class="vector-toc-list"> <li id="toc-McDonald_criteria" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#McDonald_criteria"> <div class="vector-toc-text"> 5.1 McDonald criteria </div> </a> <ul id="toc-McDonald_criteria-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-MRI" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#MRI"> <div class="vector-toc-text"> 5.2 MRI </div> </a> <ul id="toc-MRI-sublist" class="vector-toc-list"> <li id="toc-In_vivo_vs_post_portem_lesion_visibility_in_MRI_scans" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#In_vivo_vs_post_portem_lesion_visibility_in_MRI_scans"> <div class="vector-toc-text"> 5.2.1 In vivo vs post portem lesion visibility in MRI scans </div> </a> <ul id="toc-In_vivo_vs_post_portem_lesion_visibility_in_MRI_scans-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Cerebrospinal_fluid_(lumbar_puncture)" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cerebrospinal_fluid_(lumbar_puncture)"> <div class="vector-toc-text"> 5.3 Cerebrospinal fluid (lumbar puncture) </div> </a> <ul id="toc-Cerebrospinal_fluid_(lumbar_puncture)-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Differential_diagnosis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Differential_diagnosis"> <div class="vector-toc-text"> 5.4 Differential diagnosis </div> </a> <ul id="toc-Differential_diagnosis-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Types_and_variants" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Types_and_variants"> <div class="vector-toc-text"> 6 Types and variants </div> </a> <button aria-controls="toc-Types_and_variants-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Types and variants subsection </button> <ul id="toc-Types_and_variants-sublist" class="vector-toc-list"> <li id="toc-Special_courses" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Special_courses"> <div class="vector-toc-text"> 6.1 Special courses </div> </a> <ul id="toc-Special_courses-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Variants" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Variants"> <div class="vector-toc-text"> 6.2 Variants </div> </a> <ul id="toc-Variants-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Management" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Management"> <div class="vector-toc-text"> 7 Management </div> </a> <button aria-controls="toc-Management-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Management subsection </button> <ul id="toc-Management-sublist" class="vector-toc-list"> <li id="toc-Initial_management_of_acute_flare" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Initial_management_of_acute_flare"> <div class="vector-toc-text"> 7.1 Initial management of acute flare </div> </a> <ul id="toc-Initial_management_of_acute_flare-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Chronic_management" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Chronic_management"> <div class="vector-toc-text"> 7.2 Chronic management </div> </a> <ul id="toc-Chronic_management-sublist" class="vector-toc-list"> <li id="toc-Relapsing_remitting_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Relapsing_remitting_multiple_sclerosis"> <div class="vector-toc-text"> 7.2.1 Relapsing remitting multiple sclerosis </div> </a> <ul id="toc-Relapsing_remitting_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Medications" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Medications"> <div class="vector-toc-text"> 7.3 Medications </div> </a> <ul id="toc-Medications-sublist" class="vector-toc-list"> <li id="toc-Progressive_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Progressive_multiple_sclerosis"> <div class="vector-toc-text"> 7.3.1 Progressive multiple sclerosis </div> </a> <ul id="toc-Progressive_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Adverse_effects" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Adverse_effects"> <div class="vector-toc-text"> 7.3.2 Adverse effects </div> </a> <ul id="toc-Adverse_effects-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Associated_symptoms" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Associated_symptoms"> <div class="vector-toc-text"> 7.4 Associated symptoms </div> </a> <ul id="toc-Associated_symptoms-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Non-pharmaceutical" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Non-pharmaceutical"> <div class="vector-toc-text"> 7.5 Non-pharmaceutical </div> </a> <ul id="toc-Non-pharmaceutical-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Alternative_treatments" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Alternative_treatments"> <div class="vector-toc-text"> 7.6 Alternative treatments </div> </a> <ul id="toc-Alternative_treatments-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Prognosis" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Prognosis"> <div class="vector-toc-text"> 8 Prognosis </div> </a> <ul id="toc-Prognosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Epidemiology" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Epidemiology"> <div class="vector-toc-text"> 9 Epidemiology </div> </a> <ul id="toc-Epidemiology-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-History" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#History"> <div class="vector-toc-text"> 10 History </div> </a> <button aria-controls="toc-History-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle History subsection </button> <ul id="toc-History-sublist" class="vector-toc-list"> <li id="toc-Medical_discovery" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Medical_discovery"> <div class="vector-toc-text"> 10.1 Medical discovery </div> </a> <ul id="toc-Medical_discovery-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Diagnosis_history" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Diagnosis_history"> <div class="vector-toc-text"> 10.2 Diagnosis history </div> </a> <ul id="toc-Diagnosis_history-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Historical_cases" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Historical_cases"> <div class="vector-toc-text"> 10.3 Historical cases </div> </a> <ul id="toc-Historical_cases-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Research" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Research"> <div class="vector-toc-text"> 11 Research </div> </a> <button aria-controls="toc-Research-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Research subsection </button> <ul id="toc-Research-sublist" class="vector-toc-list"> <li id="toc-Epstein-Barr_virus" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Epstein-Barr_virus"> <div class="vector-toc-text"> 11.1 Epstein-Barr virus </div> </a> <ul id="toc-Epstein-Barr_virus-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Human_endogenous_retroviruses" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Human_endogenous_retroviruses"> <div class="vector-toc-text"> 11.2 Human endogenous retroviruses </div> </a> <ul id="toc-Human_endogenous_retroviruses-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Medications_2" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Medications_2"> <div class="vector-toc-text"> 11.3 Medications </div> </a> <ul id="toc-Medications_2-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Pathogenesis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Pathogenesis"> <div class="vector-toc-text"> 11.4 Pathogenesis </div> </a> <ul id="toc-Pathogenesis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Biomarkers" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Biomarkers"> <div class="vector-toc-text"> 11.5 Biomarkers </div> </a> <ul id="toc-Biomarkers-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-COVID-19" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#COVID-19"> <div class="vector-toc-text"> 11.6 COVID-19 </div> </a> <ul id="toc-COVID-19-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Metformin" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Metformin"> <div class="vector-toc-text"> 11.7 Metformin </div> </a> <ul id="toc-Metformin-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Other_emerging_theories" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other_emerging_theories"> <div class="vector-toc-text"> 11.8 Other emerging theories </div> </a> <ul id="toc-Other_emerging_theories-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> 12 See also </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> 13 References </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> 14 External links </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label id="vector-page-titlebar-toc-label" for="vector-page-titlebar-toc-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" > Toggle the table of contents </label> <div class="vector-dropdown-content"> <div id="vector-page-titlebar-toc-unpinned-container" class="vector-unpinned-container"> </div> </div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading">Multiple sclerosis</h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 74 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-74" aria-hidden="true" > 74 languages </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-af mw-list-item"><a href="https://af.wikipedia.org/wiki/Veelvuldige_sklerose" title="Veelvuldige sklerose – Afrikaans" lang="af" hreflang="af" data-title="Veelvuldige sklerose" data-language-autonym="Afrikaans" data-language-local-name="Afrikaans" class="interlanguage-link-target">Afrikaans</a></li><li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%AA%D8%B5%D9%84%D8%A8_%D9%85%D8%AA%D8%B9%D8%AF%D8%AF" title="تصلب متعدد – Arabic" lang="ar" hreflang="ar" data-title="تصلب متعدد" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target">العربية</a></li><li class="interlanguage-link interwiki-an mw-list-item"><a href="https://an.wikipedia.org/wiki/Esclerosi_multiple" title="Esclerosi multiple – Aragonese" lang="an" hreflang="an" data-title="Esclerosi multiple" data-language-autonym="Aragonés" data-language-local-name="Aragonese" class="interlanguage-link-target">Aragonés</a></li><li class="interlanguage-link interwiki-ast mw-list-item"><a href="https://ast.wikipedia.org/wiki/Esclerosis_m%C3%BAltiple" title="Esclerosis múltiple – Asturian" lang="ast" hreflang="ast" data-title="Esclerosis múltiple" data-language-autonym="Asturianu" data-language-local-name="Asturian" class="interlanguage-link-target">Asturianu</a></li><li class="interlanguage-link interwiki-az mw-list-item"><a href="https://az.wikipedia.org/wiki/Da%C4%9F%C4%B1n%C4%B1q_skleroz" title="Dağınıq skleroz – Azerbaijani" lang="az" hreflang="az" data-title="Dağınıq skleroz" data-language-autonym="Azərbaycanca" data-language-local-name="Azerbaijani" class="interlanguage-link-target">Azərbaycanca</a></li><li class="interlanguage-link interwiki-azb mw-list-item"><a href="https://azb.wikipedia.org/wiki/%D9%85%D9%88%D9%84%D8%AA%DB%8C%D9%BE%D9%84_%D8%A7%DB%8C%D8%B3%DA%A9%D9%84%D8%B1%D9%88%D8%B2%DB%8C%D8%B3" title="مولتیپل ایسکلروزیس – South Azerbaijani" lang="azb" hreflang="azb" data-title="مولتیپل ایسکلروزیس" data-language-autonym="تۆرکجه" data-language-local-name="South Azerbaijani" class="interlanguage-link-target">تۆرکجه</a></li><li class="interlanguage-link interwiki-bn mw-list-item"><a href="https://bn.wikipedia.org/wiki/%E0%A6%AE%E0%A6%BE%E0%A6%B2%E0%A7%8D%E0%A6%9F%E0%A6%BF%E0%A6%AA%E0%A6%B2_%E0%A6%B8%E0%A7%8D%E0%A6%95%E0%A7%8D%E0%A6%B2%E0%A7%87%E0%A6%B0%E0%A7%8B%E0%A6%B8%E0%A6%BF%E0%A6%B8" title="মাল্টিপল স্ক্লেরোসিস – Bangla" lang="bn" hreflang="bn" data-title="মাল্টিপল স্ক্লেরোসিস" data-language-autonym="বাংলা" data-language-local-name="Bangla" class="interlanguage-link-target">বাংলা</a></li><li class="interlanguage-link interwiki-bg badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://bg.wikipedia.org/wiki/%D0%9C%D0%BD%D0%BE%D0%B6%D0%B5%D1%81%D1%82%D0%B2%D0%B5%D0%BD%D0%B0_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7%D0%B0" title="Множествена склероза – Bulgarian" lang="bg" hreflang="bg" data-title="Множествена склероза" data-language-autonym="Български" data-language-local-name="Bulgarian" class="interlanguage-link-target">Български</a></li><li class="interlanguage-link interwiki-bs badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://bs.wikipedia.org/wiki/Multipla_skleroza" title="Multipla skleroza – Bosnian" lang="bs" hreflang="bs" data-title="Multipla skleroza" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target">Bosanski</a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Esclerosi_m%C3%BAltiple" title="Esclerosi múltiple – Catalan" lang="ca" hreflang="ca" data-title="Esclerosi múltiple" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target">Català</a></li><li class="interlanguage-link interwiki-cs badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://cs.wikipedia.org/wiki/Roztrou%C5%A1en%C3%A1_skler%C3%B3za" title="Roztroušená skleróza – Czech" lang="cs" hreflang="cs" data-title="Roztroušená skleróza" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target">Čeština</a></li><li class="interlanguage-link interwiki-cy mw-list-item"><a href="https://cy.wikipedia.org/wiki/Sglerosis_ymledol" title="Sglerosis ymledol – Welsh" lang="cy" hreflang="cy" data-title="Sglerosis ymledol" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target">Cymraeg</a></li><li class="interlanguage-link interwiki-da badge-Q17559452 badge-recommendedarticle mw-list-item" title="recommended article"><a href="https://da.wikipedia.org/wiki/Multipel_sklerose" title="Multipel sklerose – Danish" lang="da" hreflang="da" data-title="Multipel sklerose" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target">Dansk</a></li><li class="interlanguage-link interwiki-de badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://de.wikipedia.org/wiki/Multiple_Sklerose" title="Multiple Sklerose – German" lang="de" hreflang="de" data-title="Multiple Sklerose" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target">Deutsch</a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Pol%C3%BCskleroos" title="Polüskleroos – Estonian" lang="et" hreflang="et" data-title="Polüskleroos" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target">Eesti</a></li><li class="interlanguage-link interwiki-el mw-list-item"><a href="https://el.wikipedia.org/wiki/%CE%A0%CE%BF%CE%BB%CE%BB%CE%B1%CF%80%CE%BB%CE%AE_%CF%83%CE%BA%CE%BB%CE%AE%CF%81%CF%85%CE%BD%CF%83%CE%B7" title="Πολλαπλή σκλήρυνση – Greek" lang="el" hreflang="el" data-title="Πολλαπλή σκλήρυνση" data-language-autonym="Ελληνικά" data-language-local-name="Greek" class="interlanguage-link-target">Ελληνικά</a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Esclerosis_m%C3%BAltiple" title="Esclerosis múltiple – Spanish" lang="es" hreflang="es" data-title="Esclerosis múltiple" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target">Español</a></li><li class="interlanguage-link interwiki-eo mw-list-item"><a href="https://eo.wikipedia.org/wiki/Multloka_sklerozo" title="Multloka sklerozo – Esperanto" lang="eo" hreflang="eo" data-title="Multloka sklerozo" data-language-autonym="Esperanto" data-language-local-name="Esperanto" class="interlanguage-link-target">Esperanto</a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/Esklerosi_anizkoitz" title="Esklerosi anizkoitz – Basque" lang="eu" hreflang="eu" data-title="Esklerosi anizkoitz" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target">Euskara</a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%A7%D9%85%E2%80%8C%D8%A7%D8%B3" title="ام‌اس – Persian" lang="fa" hreflang="fa" data-title="ام‌اس" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target">فارسی</a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Scl%C3%A9rose_en_plaques" title="Sclérose en plaques – French" lang="fr" hreflang="fr" data-title="Sclérose en plaques" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target">Français</a></li><li class="interlanguage-link interwiki-ga mw-list-item"><a href="https://ga.wikipedia.org/wiki/Scl%C3%A9ar%C3%B3is_iolrach" title="Scléaróis iolrach – Irish" lang="ga" hreflang="ga" data-title="Scléaróis iolrach" data-language-autonym="Gaeilge" data-language-local-name="Irish" class="interlanguage-link-target">Gaeilge</a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Esclerose_m%C3%BAltiple" title="Esclerose múltiple – Galician" lang="gl" hreflang="gl" data-title="Esclerose múltiple" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target">Galego</a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EB%8B%A4%EB%B0%9C%EC%84%B1_%EA%B2%BD%ED%99%94%EC%A6%9D" title="다발성 경화증 – Korean" lang="ko" hreflang="ko" data-title="다발성 경화증" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target">한국어</a></li><li class="interlanguage-link interwiki-ha mw-list-item"><a href="https://ha.wikipedia.org/wiki/Sclerosis_da_yawa" title="Sclerosis da yawa – Hausa" lang="ha" hreflang="ha" data-title="Sclerosis da yawa" data-language-autonym="Hausa" data-language-local-name="Hausa" class="interlanguage-link-target">Hausa</a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D5%91%D6%80%D5%BE%D5%A1%D5%AE_%D5%BD%D5%AF%D5%AC%D5%A5%D6%80%D5%B8%D5%A6" title="Ցրված սկլերոզ – Armenian" lang="hy" hreflang="hy" data-title="Ցրված սկլերոզ" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target">Հայերեն</a></li><li class="interlanguage-link interwiki-hi mw-list-item"><a href="https://hi.wikipedia.org/wiki/%E0%A4%AC%E0%A4%B9%E0%A5%81%E0%A4%B8%E0%A5%83%E0%A4%A4_%E0%A4%95%E0%A4%BE%E0%A4%A0%E0%A4%BF%E0%A4%A8%E0%A5%8D%E0%A4%AF" title="बहुसृत काठिन्य – Hindi" lang="hi" hreflang="hi" data-title="बहुसृत काठिन्य" data-language-autonym="हिन्दी" data-language-local-name="Hindi" class="interlanguage-link-target">हिन्दी</a></li><li class="interlanguage-link interwiki-hr badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://hr.wikipedia.org/wiki/Multipla_skleroza" title="Multipla skleroza – Croatian" lang="hr" hreflang="hr" data-title="Multipla skleroza" data-language-autonym="Hrvatski" data-language-local-name="Croatian" class="interlanguage-link-target">Hrvatski</a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Sklerosis_multipel" title="Sklerosis multipel – Indonesian" lang="id" hreflang="id" data-title="Sklerosis multipel" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target">Bahasa Indonesia</a></li><li class="interlanguage-link interwiki-ia mw-list-item"><a href="https://ia.wikipedia.org/wiki/Multiple_sclerose" title="Multiple sclerose – Interlingua" lang="ia" hreflang="ia" data-title="Multiple sclerose" data-language-autonym="Interlingua" data-language-local-name="Interlingua" class="interlanguage-link-target">Interlingua</a></li><li class="interlanguage-link interwiki-is mw-list-item"><a href="https://is.wikipedia.org/wiki/MS_(sj%C3%BAkd%C3%B3mur)" title="MS (sjúkdómur) – Icelandic" lang="is" hreflang="is" data-title="MS (sjúkdómur)" data-language-autonym="Íslenska" data-language-local-name="Icelandic" class="interlanguage-link-target">Íslenska</a></li><li class="interlanguage-link interwiki-it badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://it.wikipedia.org/wiki/Sclerosi_multipla" title="Sclerosi multipla – Italian" lang="it" hreflang="it" data-title="Sclerosi multipla" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target">Italiano</a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%98%D7%A8%D7%A9%D7%AA_%D7%A0%D7%A4%D7%95%D7%A6%D7%94" title="טרשת נפוצה – Hebrew" lang="he" hreflang="he" data-title="טרשת נפוצה" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target">עברית</a></li><li class="interlanguage-link interwiki-sw mw-list-item"><a href="https://sw.wikipedia.org/wiki/Sklerosisi_ya_sehemu_nyingi" title="Sklerosisi ya sehemu nyingi – Swahili" lang="sw" hreflang="sw" data-title="Sklerosisi ya sehemu nyingi" data-language-autonym="Kiswahili" data-language-local-name="Swahili" class="interlanguage-link-target">Kiswahili</a></li><li class="interlanguage-link interwiki-ku mw-list-item"><a href="https://ku.wikipedia.org/wiki/Skleroza_en%C3%AEfireh" title="Skleroza enîfireh – Kurdish" lang="ku" hreflang="ku" data-title="Skleroza enîfireh" data-language-autonym="Kurdî" data-language-local-name="Kurdish" class="interlanguage-link-target">Kurdî</a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Encephalomyelitis_disseminata" title="Encephalomyelitis disseminata – Latin" lang="la" hreflang="la" data-title="Encephalomyelitis disseminata" data-language-autonym="Latina" data-language-local-name="Latin" class="interlanguage-link-target">Latina</a></li><li class="interlanguage-link interwiki-lv mw-list-item"><a href="https://lv.wikipedia.org/wiki/Izkais%C4%ABt%C4%81_skleroze" title="Izkaisītā skleroze – Latvian" lang="lv" hreflang="lv" data-title="Izkaisītā skleroze" data-language-autonym="Latviešu" data-language-local-name="Latvian" class="interlanguage-link-target">Latviešu</a></li><li class="interlanguage-link interwiki-lt mw-list-item"><a href="https://lt.wikipedia.org/wiki/I%C5%A1s%C4%97tin%C4%97_skleroz%C4%97" title="Išsėtinė sklerozė – Lithuanian" lang="lt" hreflang="lt" data-title="Išsėtinė sklerozė" data-language-autonym="Lietuvių" data-language-local-name="Lithuanian" class="interlanguage-link-target">Lietuvių</a></li><li class="interlanguage-link interwiki-lfn mw-list-item"><a href="https://lfn.wikipedia.org/wiki/Sclerose_multiple" title="Sclerose multiple – Lingua Franca Nova" lang="lfn" hreflang="lfn" data-title="Sclerose multiple" data-language-autonym="Lingua Franca Nova" data-language-local-name="Lingua Franca Nova" class="interlanguage-link-target">Lingua Franca Nova</a></li><li class="interlanguage-link interwiki-hu badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://hu.wikipedia.org/wiki/Sclerosis_multiplex" title="Sclerosis multiplex – Hungarian" lang="hu" hreflang="hu" data-title="Sclerosis multiplex" data-language-autonym="Magyar" data-language-local-name="Hungarian" class="interlanguage-link-target">Magyar</a></li><li class="interlanguage-link interwiki-mk mw-list-item"><a href="https://mk.wikipedia.org/wiki/%D0%9C%D1%83%D0%BB%D1%82%D0%B8%D0%BF%D0%BB%D0%B0_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7%D0%B0" title="Мултипла склероза – Macedonian" lang="mk" hreflang="mk" data-title="Мултипла склероза" data-language-autonym="Македонски" data-language-local-name="Macedonian" class="interlanguage-link-target">Македонски</a></li><li class="interlanguage-link interwiki-ml mw-list-item"><a href="https://ml.wikipedia.org/wiki/%E0%B4%AE%E0%B5%BE%E0%B4%9F%E0%B5%8D%E0%B4%9F%E0%B4%BF%E0%B4%AA%E0%B5%8D%E0%B4%AA%E0%B4%BF%E0%B5%BE_%E0%B4%B8%E0%B5%8D%E0%B4%95%E0%B5%8D%E0%B4%B2%E0%B5%80%E0%B4%B1%E0%B5%8B%E0%B4%B8%E0%B4%BF%E0%B4%B8%E0%B5%8D" title="മൾട്ടിപ്പിൾ സ്ക്ലീറോസിസ് – Malayalam" lang="ml" hreflang="ml" data-title="മൾട്ടിപ്പിൾ സ്ക്ലീറോസിസ്" data-language-autonym="മലയാളം" data-language-local-name="Malayalam" class="interlanguage-link-target">മലയാളം</a></li><li class="interlanguage-link interwiki-mr mw-list-item"><a href="https://mr.wikipedia.org/wiki/%E0%A4%AE%E0%A4%B2%E0%A5%8D%E0%A4%9F%E0%A4%BF%E0%A4%AA%E0%A4%B2_%E0%A4%B8%E0%A5%8D%E0%A4%95%E0%A5%8D%E0%A4%B2%E0%A5%87%E0%A4%B0%E0%A5%89%E0%A4%B8%E0%A4%BF%E0%A4%B8" title="मल्टिपल स्क्लेरॉसिस – Marathi" lang="mr" hreflang="mr" data-title="मल्टिपल स्क्लेरॉसिस" data-language-autonym="मराठी" data-language-local-name="Marathi" class="interlanguage-link-target">मराठी</a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Sklerosis_berbilang" title="Sklerosis berbilang – Malay" lang="ms" hreflang="ms" data-title="Sklerosis berbilang" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target">Bahasa Melayu</a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Multiple_sclerose" title="Multiple sclerose – Dutch" lang="nl" hreflang="nl" data-title="Multiple sclerose" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target">Nederlands</a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E5%A4%9A%E7%99%BA%E6%80%A7%E7%A1%AC%E5%8C%96%E7%97%87" title="多発性硬化症 – Japanese" lang="ja" hreflang="ja" data-title="多発性硬化症" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target">日本語</a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/Multippel_sklerose" title="Multippel sklerose – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Multippel sklerose" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target">Norsk bokmål</a></li><li class="interlanguage-link interwiki-nn mw-list-item"><a href="https://nn.wikipedia.org/wiki/Multippel_sklerose" title="Multippel sklerose – Norwegian Nynorsk" lang="nn" hreflang="nn" data-title="Multippel sklerose" data-language-autonym="Norsk nynorsk" data-language-local-name="Norwegian Nynorsk" class="interlanguage-link-target">Norsk nynorsk</a></li><li class="interlanguage-link interwiki-oc mw-list-item"><a href="https://oc.wikipedia.org/wiki/Escler%C3%B2si_multipla" title="Escleròsi multipla – Occitan" lang="oc" hreflang="oc" data-title="Escleròsi multipla" data-language-autonym="Occitan" data-language-local-name="Occitan" class="interlanguage-link-target">Occitan</a></li><li class="interlanguage-link interwiki-or mw-list-item"><a href="https://or.wikipedia.org/wiki/%E0%AC%AE%E0%AC%B2%E0%AD%8D%E0%AC%9F%E0%AC%BF%E0%AC%AA%E0%AD%8D%E0%AC%B2_%E0%AC%B8%E0%AD%8D%E0%AC%95%E0%AD%8D%E0%AC%B2%E0%AD%87%E0%AC%B0%E0%AD%8B%E0%AC%B8%E0%AC%BF%E0%AC%B8" title="ମଲ୍ଟିପ୍ଲ ସ୍କ୍ଲେରୋସିସ – Odia" lang="or" hreflang="or" data-title="ମଲ୍ଟିପ୍ଲ ସ୍କ୍ଲେରୋସିସ" data-language-autonym="ଓଡ଼ିଆ" data-language-local-name="Odia" class="interlanguage-link-target">ଓଡ଼ିଆ</a></li><li class="interlanguage-link interwiki-pl badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://pl.wikipedia.org/wiki/Stwardnienie_rozsiane" title="Stwardnienie rozsiane – Polish" lang="pl" hreflang="pl" data-title="Stwardnienie rozsiane" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target">Polski</a></li><li class="interlanguage-link interwiki-pt badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://pt.wikipedia.org/wiki/Esclerose_m%C3%BAltipla" title="Esclerose múltipla – Portuguese" lang="pt" hreflang="pt" data-title="Esclerose múltipla" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target">Português</a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Scleroz%C4%83_multipl%C4%83" title="Scleroză multiplă – Romanian" lang="ro" hreflang="ro" data-title="Scleroză multiplă" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target">Română</a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%A0%D0%B0%D1%81%D1%81%D0%B5%D1%8F%D0%BD%D0%BD%D1%8B%D0%B9_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7" title="Рассеянный склероз – Russian" lang="ru" hreflang="ru" data-title="Рассеянный склероз" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target">Русский</a></li><li class="interlanguage-link interwiki-sq mw-list-item"><a href="https://sq.wikipedia.org/wiki/Multiple_skleroza" title="Multiple skleroza – Albanian" lang="sq" hreflang="sq" data-title="Multiple skleroza" data-language-autonym="Shqip" data-language-local-name="Albanian" class="interlanguage-link-target">Shqip</a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Multiple_sclerosis" title="Multiple sclerosis – Simple English" lang="en-simple" hreflang="en-simple" data-title="Multiple sclerosis" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target">Simple English</a></li><li class="interlanguage-link interwiki-sk mw-list-item"><a href="https://sk.wikipedia.org/wiki/Skler%C3%B3za_multiplex" title="Skleróza multiplex – Slovak" lang="sk" hreflang="sk" data-title="Skleróza multiplex" data-language-autonym="Slovenčina" data-language-local-name="Slovak" class="interlanguage-link-target">Slovenčina</a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Multipla_skleroza" title="Multipla skleroza – Slovenian" lang="sl" hreflang="sl" data-title="Multipla skleroza" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target">Slovenščina</a></li><li class="interlanguage-link interwiki-ckb mw-list-item"><a href="https://ckb.wikipedia.org/wiki/%D9%81%D8%B1%DB%95_%DA%95%DB%95%D9%82%D8%A8%D9%88%D9%88%D9%86" title="فرە ڕەقبوون – Central Kurdish" lang="ckb" hreflang="ckb" data-title="فرە ڕەقبوون" data-language-autonym="کوردی" data-language-local-name="Central Kurdish" class="interlanguage-link-target">کوردی</a></li><li class="interlanguage-link interwiki-sr badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://sr.wikipedia.org/wiki/Multipla_skleroza" title="Multipla skleroza – Serbian" lang="sr" hreflang="sr" data-title="Multipla skleroza" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target">Српски / srpski</a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Multipla_skleroza" title="Multipla skleroza – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Multipla skleroza" 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id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Disease that damages the myelin sheaths around nerves</div> <style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+link+.ambox{margin-top:-1px}html body.mediawiki .mw-parser-output .ambox.mbox-small-left{margin:4px 1em 4px 0;overflow:hidden;width:238px;border-collapse:collapse;font-size:88%;line-height:1.25em}.mw-parser-output .ambox-speedy{border-left:10px solid #b32424;background-color:#fee7e6}.mw-parser-output .ambox-delete{border-left:10px solid #b32424}.mw-parser-output .ambox-content{border-left:10px solid #f28500}.mw-parser-output .ambox-style{border-left:10px solid #fc3}.mw-parser-output .ambox-move{border-left:10px solid #9932cc}.mw-parser-output .ambox-protection{border-left:10px solid #a2a9b1}.mw-parser-output .ambox .mbox-text{border:none;padding:0.25em 0.5em;width:100%}.mw-parser-output .ambox .mbox-image{border:none;padding:2px 0 2px 0.5em;text-align:center}.mw-parser-output .ambox .mbox-imageright{border:none;padding:2px 0.5em 2px 0;text-align:center}.mw-parser-output .ambox .mbox-empty-cell{border:none;padding:0;width:1px}.mw-parser-output .ambox .mbox-image-div{width:52px}@media(min-width:720px){.mw-parser-output .ambox{margin:0 10%}}@media print{body.ns-0 .mw-parser-output .ambox{display:none!important}}</style><table class="box-Medical_citations_needed plainlinks metadata ambox ambox-content" role="presentation"><tbody><tr><td class="mbox-image"><div class="mbox-image-div"><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/b/b4/Ambox_important.svg/40px-Ambox_important.svg.png" decoding="async" width="40" height="40" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/b/b4/Ambox_important.svg/60px-Ambox_important.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/b/b4/Ambox_important.svg/80px-Ambox_important.svg.png 2x" data-file-width="40" data-file-height="40" /></div></td><td class="mbox-text"><div class="mbox-text-span">This article needs more <a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">reliable medical references</a> for <a href="/wiki/Wikipedia:Verifiability" title="Wikipedia:Verifiability">verification</a> or relies too heavily on <a 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Please review the contents of the article and <a class="external text" href="https://en.wikipedia.org/w/index.php?title=Multiple_sclerosis&action=edit">add the appropriate references</a> if you can. Unsourced or poorly sourced material may be challenged and <a href="/wiki/Wikipedia:Verifiability#Burden_of_evidence" title="Wikipedia:Verifiability">removed</a>. Find sources: <a rel="nofollow" class="external text" href="https://www.google.com/search?as_eq=wikipedia&q=%22Multiple+sclerosis%22">"Multiple sclerosis"</a> – <a rel="nofollow" class="external text" href="https://www.google.com/search?tbm=nws&q=%22Multiple+sclerosis%22+-wikipedia&tbs=ar:1">news</a> · <a rel="nofollow" class="external text" href="https://www.google.com/search?&q=%22Multiple+sclerosis%22&tbs=bkt:s&tbm=bks">newspapers</a> · <a rel="nofollow" class="external text" href="https://www.google.com/search?tbs=bks:1&q=%22Multiple+sclerosis%22+-wikipedia">books</a> · <a rel="nofollow" class="external text" href="https://scholar.google.com/scholar?q=%22Multiple+sclerosis%22">scholar</a> · <a rel="nofollow" class="external text" href="https://www.jstor.org/action/doBasicSearch?Query=%22Multiple+sclerosis%22&acc=on&wc=on">JSTOR</a> (July 2022)</div></td><td class="mbox-imageright"><div class="mbox-image-div"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/52px-Star_of_life.svg.png" decoding="async" width="52" height="50" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/77px-Star_of_life.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/103px-Star_of_life.svg.png 2x" data-file-width="198" data-file-height="192" /></div></td></tr></tbody></table> <div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Medical condition</div><style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox ib-medical-condition"><tbody><tr><th colspan="2" class="infobox-above" style="background:#ccc">Multiple sclerosis</th></tr><tr><th scope="row" class="infobox-label">Other names</th><td class="infobox-data">Multiple cerebral sclerosis, multiple cerebro-spinal sclerosis, disseminated sclerosis, encephalomyelitis disseminata</td></tr><tr style="background-color: #f8f9fa;"><td colspan="2" class="infobox-full-data"><a href="/wiki/File:MS_Demyelinisation_CD68_10xv2.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/59/MS_Demyelinisation_CD68_10xv2.jpg/220px-MS_Demyelinisation_CD68_10xv2.jpg" decoding="async" width="220" height="163" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/59/MS_Demyelinisation_CD68_10xv2.jpg/330px-MS_Demyelinisation_CD68_10xv2.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/59/MS_Demyelinisation_CD68_10xv2.jpg/440px-MS_Demyelinisation_CD68_10xv2.jpg 2x" data-file-width="2080" data-file-height="1544" /></a></td></tr><tr><td colspan="2" class="infobox-full-data"><a href="/wiki/CD68" title="CD68">CD68</a>-stained tissue shows several <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a> in the area of a demyelinated lesion caused by MS.</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_specialty" title="Medical specialty">Specialty</a></th><td class="infobox-data"><a href="/wiki/Neurology" title="Neurology">Neurology</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Signs_and_symptoms" title="Signs and symptoms">Symptoms</a></th><td class="infobox-data">Involving <a href="/wiki/Autonomic_nervous_system" title="Autonomic nervous system">autonomic</a>, visual, motor, and sensory systems, almost any central or <a href="/wiki/Peripheral_neuropathy" title="Peripheral neuropathy">peripheral neurological symptom</a>.<a href="#cite_note-pmid1897097722-1">[1]</a></td></tr><tr><th scope="row" class="infobox-label">Usual onset</th><td class="infobox-data">Age 20–50<a href="#cite_note-Milo2010-2">[2]</a></td></tr><tr><th scope="row" class="infobox-label">Duration</th><td class="infobox-data">Long term<a href="#cite_note-NIH2015-3">[3]</a></td></tr><tr><th scope="row" class="infobox-label">Causes</th><td class="infobox-data">Unknown<a href="#cite_note-Nak20122-4">[4]</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_diagnosis" title="Medical diagnosis">Diagnostic method</a></th><td class="infobox-data">Based on symptoms and medical tests<a href="#cite_note-Tsang20112-5">[5]</a></td></tr><tr><th scope="row" class="infobox-label">Treatment</th><td class="infobox-data"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style><div class="plainlist"> <ul><li>Disease-modifying therapies<a href="#cite_note-Liu_2021-6">[6]</a></li> <li>Physiotherapy<a href="#cite_note-Alphonsus_20192-7">[7]</a></li> <li>Occupational therapy<a href="#cite_note-Alphonsus_20192-7">[7]</a></li></ul> </div></td></tr><tr><th scope="row" class="infobox-label">Frequency</th><td class="infobox-data">0.032% (<a href="/wiki/World" title="World">world</a>)</td></tr></tbody></table> Multiple sclerosis (MS) is an <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune disease</a> in which the <a href="/wiki/Myelin" title="Myelin">insulating covers</a> of <a href="/wiki/Nerve_cells" class="mw-redirect" title="Nerve cells">nerve cells</a> in the brain and <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a> are damaged.<a href="#cite_note-NIH2015-3">[3]</a> Being a <a href="/wiki/Demyelinating_disease" title="Demyelinating disease">demyelinating disease</a>, MS disrupts the ability of parts of the nervous system to <a href="/wiki/Action_potential" title="Action potential">transmit signals</a>, resulting in a range of <a href="/wiki/Signs_and_symptoms" title="Signs and symptoms">signs and symptoms</a>, including physical, <a href="/wiki/Cognitive_disability" class="mw-redirect" title="Cognitive disability">mental</a>, and sometimes psychiatric problems.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid119555563-8">[8]</a><a href="#cite_note-9">[9]</a> Symptoms include <a href="/wiki/Double_vision" class="mw-redirect" title="Double vision">double vision</a>, vision loss, eye pain, muscle weakness, and loss of <a href="/wiki/Sensation_(psychology)" class="mw-redirect" title="Sensation (psychology)">sensation</a> or coordination.<a href="#cite_note-NIH2015-3">[3]</a><a href="#cite_note-Piryonesi-2021-10">[10]</a><a href="#cite_note-11">[11]</a> MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms).<a href="#cite_note-12">[12]</a><a href="#cite_note-pmid8780061-13">[13]</a> In relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances.<a href="#cite_note-pmid8780061-13">[13]</a> In progressive forms of MS, bodily function slowly deteriorates once symptoms manifest and will steadily worsen if left untreated.<a href="#cite_note-14">[14]</a> While its cause is unclear, the underlying mechanism is thought to be either <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">destruction by the immune system</a> or failure of the myelin-producing cells.<a href="#cite_note-Nak20122-4">[4]</a> Proposed causes for this include immune dysregulation, <a href="/wiki/Genetics" title="Genetics">genetics</a>, and environmental factors, such as <a href="/wiki/Viral_infection" class="mw-redirect" title="Viral infection">viral infections</a>.<a href="#cite_note-Ward_988–1005-15">[15]</a><a href="#cite_note-Aloisi20222-16">[16]</a><a href="#cite_note-pmid119555563-8">[8]</a><a href="#cite_note-Ascherio_2007-17">[17]</a> MS is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests.<a href="#cite_note-Tsang20112-5">[5]</a> No cure for multiple sclerosis is known.<a href="#cite_note-NIH20152-18">[18]</a> Current treatments are aimed at mitigating inflammation and resulting symptoms from acute flares and prevention of further attacks with disease-modifying medications.<a href="#cite_note-pmid119555563-8">[8]</a><a href="#cite_note-McGinley_2021-19">[19]</a> <a href="/wiki/Physical_therapy" title="Physical therapy">Physical therapy</a><a href="#cite_note-Alphonsus_20192-7">[7]</a> and <a href="/wiki/Occupational_therapy" title="Occupational therapy">occupational therapy</a>,<a href="#cite_note-20">[20]</a> along with patient-centered symptom management, can help with people's ability to function. The long-term outcome is difficult to predict; better outcomes are more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks.<a href="#cite_note-pmid80178902-21">[21]</a> Multiple sclerosis is the most common <a href="/wiki/Immune_disorder" title="Immune disorder">immune-mediated disorder</a> affecting the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a>.<a href="#cite_note-pmid24746689-22">[22]</a> Nearly one million people in the United States had MS in 2022,<a href="#cite_note-McGinley2021-23">[23]</a> and in 2020, about 2.8 million people were affected globally, with rates varying widely in different regions and among different populations.<a href="#cite_note-Lane2022-24">[24]</a> The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men.<a href="#cite_note-Milo2010-2">[2]</a> MS was first described in 1868 by French neurologist <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a>.<a href="#cite_note-Charcot1-25">[25]</a> The name "multiple <a href="/wiki/Sclerosis_(medicine)" title="Sclerosis (medicine)">sclerosis</a>" is short for multiple cerebro-spinal sclerosis, which refers to the numerous <a href="/wiki/Glial_scar" title="Glial scar">glial scars</a> (or sclerae – essentially plaques or lesions) that develop on the <a href="/wiki/White_matter" title="White matter">white matter</a> of the brain and spinal cord.<a href="#cite_note-Charcot1-25">[25]</a> <style data-mw-deduplicate="TemplateStyles:r886046785">.mw-parser-output .toclimit-2 .toclevel-1 ul,.mw-parser-output .toclimit-3 .toclevel-2 ul,.mw-parser-output .toclimit-4 .toclevel-3 ul,.mw-parser-output .toclimit-5 .toclevel-4 ul,.mw-parser-output .toclimit-6 .toclevel-5 ul,.mw-parser-output .toclimit-7 .toclevel-6 ul{display:none}</style><div class="toclimit-3"><meta property="mw:PageProp/toc" /></div> <div class="mw-heading mw-heading2"><h2 id="Signs_and_symptoms">Signs and symptoms</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=1" title="Edit section: Signs and symptoms">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Multiple_sclerosis_signs_and_symptoms" class="mw-redirect" title="Multiple sclerosis signs and symptoms">Multiple sclerosis signs and symptoms</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Symptoms_of_multiple_sclerosis.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/bf/Symptoms_of_multiple_sclerosis.svg/290px-Symptoms_of_multiple_sclerosis.svg.png" decoding="async" width="290" height="441" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/bf/Symptoms_of_multiple_sclerosis.svg/435px-Symptoms_of_multiple_sclerosis.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/bf/Symptoms_of_multiple_sclerosis.svg/580px-Symptoms_of_multiple_sclerosis.svg.png 2x" data-file-width="828" data-file-height="1260" /></a><figcaption>Main symptoms of multiple sclerosis</figcaption></figure> As multiple sclerosis (MS) lesions can affect any part of the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a>, a person with MS can have almost any <a href="/wiki/Neurological" class="mw-redirect" title="Neurological">neurological</a> symptom or sign referable to the central nervous system. <a href="/wiki/Fatigue" title="Fatigue">Fatigue</a> is one of the most common symptoms of MS.<a href="#cite_note-26">[26]</a><a href="#cite_note-27">[27]</a> Some 65% of people with MS experience fatigue symptomatology, and of these, some 15–40% report fatigue as their most disabling MS symptom.<a href="#cite_note-pmid37602098-28">[28]</a> <a href="/wiki/Autonomic_nervous_system" title="Autonomic nervous system">Autonomic</a>, visual, motor, and sensory problems are also among the most common symptoms.<a href="#cite_note-pmid1897097722-1">[1]</a> The specific symptoms are determined by the locations of the lesions within the nervous system, and may include focal <a href="/wiki/Hypoesthesia" title="Hypoesthesia">loss of sensitivity</a> or <a href="/wiki/Paresthesia" title="Paresthesia">changes in sensation</a> in the limbs, such as feeling tingling, pins and needles, or numbness; limb motor weakness/pain, <a href="/wiki/Blurred_vision" title="Blurred vision">blurred vision</a>,<a href="#cite_note-29">[29]</a> <a href="/wiki/Clonus" title="Clonus">pronounced reflexes</a>, <a href="/wiki/Muscle_spasms" class="mw-redirect" title="Muscle spasms">muscle spasms</a>, difficulty with ambulation (walking), difficulties with coordination and balance (<a href="/wiki/Ataxia" title="Ataxia">ataxia</a>); <a href="/wiki/Dysarthria" title="Dysarthria">problems with speech</a><a href="#cite_note-30">[30]</a> or <a href="/wiki/Dysphagia" title="Dysphagia">swallowing</a>, visual problems (<a href="/wiki/Optic_neuritis" title="Optic neuritis">optic neuritis</a> manifesting as eye pain & vision loss,<a href="#cite_note-Petzold_2022-31">[31]</a> or <a href="/wiki/Nystagmus" title="Nystagmus">nystagmus</a> manifesting as <a href="/wiki/Diplopia" title="Diplopia">double vision</a>), fatigue, and bladder and bowel difficulties (such as urinary or fecal incontinence or retention), among others.<a href="#cite_note-pmid1897097722-1">[1]</a> When multiple sclerosis is more advanced, walking difficulties can occur and the risk of falling increases.<a href="#cite_note-32">[32]</a><a href="#cite_note-McGinley_2021-19">[19]</a><a href="#cite_note-33">[33]</a> Difficulties thinking and emotional problems such as depression or <a href="/wiki/Labile_affect" class="mw-redirect" title="Labile affect">unstable mood</a> are also common.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-34">[34]</a> The primary deficit in cognitive function that people with MS experience is slowed information-processing speed, with memory also commonly affected, and <a href="/wiki/Executive_functions" title="Executive functions">executive function</a> less commonly. Intelligence, language, and <a href="/wiki/Semantic_memory" title="Semantic memory">semantic memory</a> are usually preserved, and the level of cognitive impairment varies considerably between people with MS.<a href="#cite_note-35">[35]</a><a href="#cite_note-36">[36]</a><a href="#cite_note-37">[37]</a> <a href="/wiki/Uhthoff%27s_phenomenon" title="Uhthoff's phenomenon">Uhthoff's phenomenon</a>, a worsening of symptoms due to exposure to higher-than-usual temperatures, and <a href="/wiki/Lhermitte%27s_sign" title="Lhermitte's sign">Lhermitte's sign</a>, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS, although may not always be present.<a href="#cite_note-pmid1897097722-1">[1]</a> Another presenting manifestation that is rare but highly suggestive of a demyelinating process such as MS is bilateral internuclear ophthalmoplegia, where the patient experiences double vision when attempting to move their gaze to the right & left.<a href="#cite_note-38">[38]</a> Some 60% or more of MS patients find their symptoms, particularly including fatigue,<a href="#cite_note-Multiple_Sclerosis_Trust-39">[39]</a> are affected by changes in body temperature.<a href="#cite_note-Christogianni-2018-40">[40]</a><a href="#cite_note-Heat_Sensitivity-41">[41]</a><a href="#cite_note-Multiple_Sclerosis_Trust-2-42">[42]</a> <div class="mw-heading mw-heading3"><h3 id="Measures_of_disability">Measures of disability</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=2" title="Edit section: Measures of disability">edit</a>]</div> The main measure of disability and severity is the <a href="/wiki/Expanded_disability_status_scale" class="mw-redirect" title="Expanded disability status scale">expanded disability status scale</a> (EDSS), with other measures such as the <a href="/wiki/Multiple_sclerosis_functional_composite" title="Multiple sclerosis functional composite">multiple sclerosis functional composite</a> being increasingly used in research.<a href="#cite_note-43">[43]</a><a href="#cite_note-pmid10467378-44">[44]</a><a href="#cite_note-pmid12356200-45">[45]</a> EDSS is also correlated with falls in people with MS.<a href="#cite_note-Piryonesi-2021-10">[10]</a> While it is a popular measure, EDSS has been criticized for some of its limitations, such as relying too much on walking.<a href="#cite_note-46">[46]</a><a href="#cite_note-Piryonesi-2021-10">[10]</a> <div class="mw-heading mw-heading2"><h2 id="Disease_course">Disease course</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=3" title="Edit section: Disease course">edit</a>]</div> <div class="mw-heading mw-heading3"><h3 id="Prodromal_phase">Prodromal phase</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=4" title="Edit section: Prodromal phase">edit</a>]</div> MS may have a <a href="/wiki/Prodromal" class="mw-redirect" title="Prodromal">prodromal</a> phase in the years leading up to its manifestation, characterized by psychiatric issues, cognitive impairment, and increased use of healthcare.<a href="#cite_note-Makhani2021Prodrome-47">[47]</a><a href="#cite_note-Marrie2019_Prodrome-48">[48]</a> <div class="mw-heading mw-heading3"><h3 id="Onset">Onset</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=5" title="Edit section: Onset">edit</a>]</div> The condition begins in 85% of cases as a <a href="/wiki/Clinically_isolated_syndrome" title="Clinically isolated syndrome">clinically isolated syndrome</a> (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis,<a href="#cite_note-Petzold_2022-31">[31]</a> and 10% having symptoms related to <a href="/wiki/Brainstem" title="Brainstem">brainstem</a> dysfunction, while the remaining 25% have more than one of the previous difficulties.<a href="#cite_note-Tsang20112-5">[5]</a> Regarding optic neuritis as the most common presenting symptom, people with MS notice sub-acute loss of vision, often associated with pain worsening on eye movement, and reduced colour vision. Early diagnosis of MS-associated <a href="/wiki/Optic_neuritis" title="Optic neuritis">optic neuritis</a> helps timely initiation of targeted treatments. However, it is crucial to adhere to established diagnostic criteria when treating optic neuritis due to the broad range of alternative causes, such as <a href="/wiki/Neuromyelitis_optica" class="mw-redirect" title="Neuromyelitis optica">neuromyelitis optica</a> spectrum disorder (NMOSD), and other autoimmune or infectious conditions. The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called <a href="/wiki/Relapse" title="Relapse">relapses</a>, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10–15% of cases).<a href="#cite_note-Milo2010-2">[2]</a> A combination of these two patterns may also occur<a href="#cite_note-pmid8780061-13">[13]</a> or people may start in a relapsing and remitting course that then becomes progressive later on.<a href="#cite_note-Milo2010-2">[2]</a> <div class="mw-heading mw-heading3"><h3 id="Relapses">Relapses</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=6" title="Edit section: Relapses">edit</a>]</div> Relapses are usually unpredictable, occurring without warning.<a href="#cite_note-pmid1897097722-1">[1]</a> Exacerbations rarely occur more frequently than twice per year.<a href="#cite_note-pmid1897097722-1">[1]</a> Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer.<a href="#cite_note-pmid168043312-49">[49]</a> Similarly, viral infections such as the <a href="/wiki/Common_cold" title="Common cold">common cold</a>, <a href="/wiki/Influenza" title="Influenza">influenza</a>, or <a href="/wiki/Gastroenteritis" title="Gastroenteritis">gastroenteritis</a> increase their risk.<a href="#cite_note-pmid1897097722-1">[1]</a> <a href="/wiki/Stress_(medicine)" class="mw-redirect" title="Stress (medicine)">Stress</a> may also trigger an attack.<a href="#cite_note-pmid17439878-50">[50]</a> Many events have been found not to affect rates of relapse requiring hospitalization including <a href="/wiki/Vaccination" title="Vaccination">vaccination</a>,<a href="#cite_note-51">[51]</a><a href="#cite_note-52">[52]</a> <a href="/wiki/Breast_feeding" class="mw-redirect" title="Breast feeding">breast feeding</a>,<a href="#cite_note-pmid1897097722-1">[1]</a> physical trauma,<a href="#cite_note-pmid112053612-53">[53]</a> and <a href="/wiki/Uhthoff%27s_phenomenon" title="Uhthoff's phenomenon">Uhthoff's phenomenon</a>.<a href="#cite_note-pmid168043312-49">[49]</a> <div class="mw-heading mw-heading3"><h3 id="Pregnancy">Pregnancy</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=7" title="Edit section: Pregnancy">edit</a>]</div> Many people with MS <a href="/wiki/Pre-existing_disease_in_pregnancy" title="Pre-existing disease in pregnancy">who become pregnant</a> experience lower symptoms<a href="#cite_note-54">[54]</a><a href="#cite_note-Varytė-2020-55">[55]</a><a href="#cite_note-56">[56]</a> During the first months after delivery, the risk increases.<a href="#cite_note-pmid1897097722-1">[1]</a> Overall, pregnancy does not seem to influence long-term disability.<a href="#cite_note-pmid1897097722-1">[1]</a> <div class="mw-heading mw-heading2"><h2 id="Causes">Causes</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=8" title="Edit section: Causes">edit</a>]</div> Multiple sclerosis is an autoimmune disease with a combination of genetic and environmental causes underlying it. Both T-cells and B-cells are involved, although T-cells are often considered to be the driving force of the disease. The causes of the disease are not fully understood. The <a href="/wiki/Epstein%E2%80%93Barr_virus" title="Epstein–Barr virus">Epstein-Barr Virus</a> (EBV) has been shown to be directly present in the brain of most cases of MS and the virus is transcriptionally active in infected cells.<a href="#cite_note-57">[57]</a><a href="#cite_note-Hassani-2018-58">[58]</a> EBV nuclear antigens are believed to be involved in the pathogenesis of multiple sclerosis, but not all people with MS have signs of EBV infection.<a href="#cite_note-Ward_988–1005-15">[15]</a> Dozens of human <a href="/wiki/Peptide" title="Peptide">peptides</a> have been identified in different cases of the disease, and while some have plausible links to infectious organisms or known environmental factors, others do not.<a href="#cite_note-59">[59]</a> <div class="mw-heading mw-heading3"><h3 id="Immune_dysregulation">Immune dysregulation</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=9" title="Edit section: Immune dysregulation">edit</a>]</div> Failure of both central and peripheral nervous system clearance of autoreactive immune cells is implicated in the development of MS.<a href="#cite_note-Ward_988–1005-15">[15]</a> The thymus is responsible for the immune system's central tolerance, where autoreactive T-cells are killed without being released into circulation. Via a similar mechanism, autoreactive B-cells in the bone marrow are killed. Some autoreactive T-cells & B-cells may escape these defense mechanisms, which is where peripheral immune tolerance defenses take action by preventing them from causing disease. However, these additional lines of defense can still fail.<a href="#cite_note-Ward_988–1005-15">[15]</a><a href="#cite_note-McGinley_2021-19">[19]</a> Further detail on immune dysregulation's contribution to MS risk is provided in the <a class="mw-selflink-fragment" href="#Pathophysiology">pathophysiology</a> section of this article as well as the standalone article on the <a href="/wiki/Pathophysiology_of_multiple_sclerosis" title="Pathophysiology of multiple sclerosis">pathophysiology of MS</a>. <div class="mw-heading mw-heading3"><h3 id="Infectious_agents">Infectious agents</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=10" title="Edit section: Infectious agents">edit</a>]</div> Early evidence suggested the association between several viruses with human demyelinating <a href="/wiki/Encephalomyelitis" title="Encephalomyelitis">encephalomyelitis</a>, and the occurrence of demyelination in animals caused by some viral infections.<a href="#cite_note-pmid15721830-60">[60]</a> One such virus, <a href="/wiki/Epstein%E2%80%93Barr_virus" title="Epstein–Barr virus">Epstein-Barr</a> <a href="/wiki/Herpesviridae#Human_herpesvirus_types" title="Herpesviridae">virus</a> (EBV), can cause <a href="/wiki/Infectious_mononucleosis" title="Infectious mononucleosis">infectious mononucleosis</a> and infects about 95% of adults, though only a small proportion of those infected later develop MS.<a href="#cite_note-61">[61]</a><a href="#cite_note-Aloisi20222-16">[16]</a><a href="#cite_note-Bjornevik2022-62">[62]</a><a href="#cite_note-Hassani-2018-58">[58]</a> A study of more than 10 million US military members compared 801 people who developed MS to 1,566 matched controls who did not develop MS. The study found a 32-fold increased risk of developing MS after infection with EBV. It did not find an increased risk after infection with other viruses, including the similar <a href="/wiki/Cytomegalovirus" title="Cytomegalovirus">cytomegalovirus</a>. These findings strongly suggest that EBV plays a role in MS onset, although EBV alone may be insufficient to cause it.<a href="#cite_note-Aloisi20222-16">[16]</a><a href="#cite_note-Bjornevik2022-62">[62]</a> The <a href="/wiki/Epstein%E2%80%93Barr_virus_nuclear_antigen_1" title="Epstein–Barr virus nuclear antigen 1">nuclear antigen of EBV</a>, which is the most consistent marker of EBV infection across all strains,<a href="#cite_note-63">[63]</a> has been identified as a direct source of autoreactivity in the human body. These antigens appear to be more likely to promote autoimmune responses in a person who also has a vitamin D deficiency. The exact nature of this relationship is poorly understood.<a href="#cite_note-64">[64]</a><a href="#cite_note-Ward_988–1005-15">[15]</a> <div class="mw-heading mw-heading3"><h3 id="Genetics">Genetics</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=11" title="Edit section: Genetics">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:HLA.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/77/HLA.svg/220px-HLA.svg.png" decoding="async" width="220" height="416" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/77/HLA.svg/330px-HLA.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/77/HLA.svg/440px-HLA.svg.png 2x" data-file-width="230" data-file-height="435" /></a><figcaption>HLA region of chromosome 6: Changes in this area increase the probability of getting MS.</figcaption></figure> MS is not considered a <a href="/wiki/Hereditary_disease" class="mw-redirect" title="Hereditary disease">hereditary disease</a>, but several <a href="/wiki/Genetics" title="Genetics">genetic variations</a> have been shown to increase its risk.<a href="#cite_note-pmid14747002-65">[65]</a> Some of these genes appear to have higher expression levels in <a href="/wiki/Microglia" title="Microglia">microglial cells</a> than expected by chance.<a href="#cite_note-SkeneGrant2016-66">[66]</a> The probability of developing MS is higher in relatives of an affected person, with a greater risk among those more closely related.<a href="#cite_note-pmid119555563-8">[8]</a> An <a href="/wiki/Identical_twin" class="mw-redirect" title="Identical twin">identical twin</a> of an affected individual has a 30% chance of developing MS, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half sibling.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid119555563-8">[8]</a><a href="#cite_note-67">[67]</a> If both parents are affected, the risk in their children is 10 times that of the general population.<a href="#cite_note-Milo2010-2">[2]</a> MS is also more common in some ethnic groups than others.<a href="#cite_note-pmid11603614-68">[68]</a> Specific <a href="/wiki/Gene" title="Gene">genes</a> that have been linked with MS include differences in the <a href="/wiki/Human_leukocyte_antigen" title="Human leukocyte antigen">human leukocyte antigen</a> (HLA) system—a group of genes on <a href="/wiki/Chromosome_6_(human)" class="mw-redirect" title="Chromosome 6 (human)">chromosome 6</a> that serves as the <a href="/wiki/Major_histocompatibility_complex" title="Major histocompatibility complex">major histocompatibility complex</a> (MHC).<a href="#cite_note-pmid1897097722-1">[1]</a> The contribution of HLA variants to MS susceptibility has been known since the 1980s,<a href="#cite_note-pmid21247752-69">[69]</a> and this same region has also been implicated in the development of other autoimmune diseases, such as <a href="/wiki/Diabetes_type_I" class="mw-redirect" title="Diabetes type I">type 1 diabetes</a> and <a href="/wiki/Systemic_lupus_erythematosus" class="mw-redirect" title="Systemic lupus erythematosus">systemic lupus erythematosus</a>.<a href="#cite_note-pmid21247752-69">[69]</a> The most consistent finding is the association between higher risk of developing multiple sclerosis and the MHC <a href="/wiki/Allele" title="Allele">allele</a> <a href="/wiki/HLA-DR15" title="HLA-DR15">DR15</a>, which is present in 30% of the U.S. and Northern European population.<a href="#cite_note-Ward_988–1005-15">[15]</a><a href="#cite_note-pmid1897097722-1">[1]</a> Other loci exhibit a protective effect, such as <a href="/wiki/HLA-C554" class="mw-redirect" title="HLA-C554">HLA-C554</a> and <a href="/wiki/HLA-DRB1" title="HLA-DRB1">HLA-DRB1</a>*11.<a href="#cite_note-pmid1897097722-1">[1]</a> HLA differences account for an estimated 20 to 60% of the <a href="/wiki/Genetic_predisposition" title="Genetic predisposition">genetic predisposition</a>.<a href="#cite_note-pmid21247752-69">[69]</a> <a href="/wiki/Genome-wide_association_study" title="Genome-wide association study">Genome-wide association studies</a> have revealed at least 200 variants outside the HLA <a href="/wiki/Locus_(genetics)" title="Locus (genetics)">locus</a> that affect the risk of MS.<a href="#cite_note-pmid31604244-70">[70]</a> <div class="mw-heading mw-heading3"><h3 id="Geography">Geography</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=12" title="Edit section: Geography">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:MS_Risk.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/90/MS_Risk.svg/220px-MS_Risk.svg.png" decoding="async" width="220" height="134" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/90/MS_Risk.svg/330px-MS_Risk.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/90/MS_Risk.svg/440px-MS_Risk.svg.png 2x" data-file-width="1200" data-file-height="732" /></a><figcaption>Geographic risk distribution of MS</figcaption></figure> The prevalence of MS from a geographic standpoint resembles a gradient, with MS being more common in people who live farther from the <a href="/wiki/Equator" title="Equator">equator</a> (e.g. those who live in northern regions of the world), although exceptions exist. The cause of this geographical pattern is not clear, although exposure to <a href="/wiki/Ultraviolet" title="Ultraviolet">ultraviolet B</a> (UVB) radiation and <a href="/wiki/Vitamin_D" title="Vitamin D">vitamin D</a> levels have been proposed as potential explanations.<a href="#cite_note-Milo20102-71">[71]</a><a href="#cite_note-Ward_988–1005-15">[15]</a> As such, those who live in northern regions of the world are thought to have less exposure to UVB radiation and subsequently lower levels of vitamin D, which is a known risk factor for developing MS.<a href="#cite_note-Ward_988–1005-15">[15]</a> Inversely, those who live in areas of relatively higher sun exposure and subsequently increased UVB radiation have a decreased risk of developing MS.<a href="#cite_note-Ward_988–1005-15">[15]</a> As of 2019, the north–south gradient of incidence is still present and is increasing.<a href="#cite_note-pmid31217172-72">[72]</a> MS is more common in regions with northern European populations,<a href="#cite_note-pmid1897097722-1">[1]</a> so the geographic variation may simply reflect the global distribution of these high-risk populations.<a href="#cite_note-Milo2010-2">[2]</a> A relationship between season of birth and MS lends support to this idea, with fewer people born in the Northern Hemisphere in November compared to May being affected later in life.<a href="#cite_note-pmid19897699-73">[73]</a> Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region's risk of MS. If migration takes place after age 15, the persons retain the risk of their home country.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid15556803-74">[74]</a> Some evidence indicates that the effect of moving may still apply to people older than 15.<a href="#cite_note-pmid1897097722-1">[1]</a> There are some exceptions to the above mentioned geographic pattern. These include ethnic groups that are at low risk and that live far from the equator such as the <a href="/wiki/Sami_people" class="mw-redirect" title="Sami people">Sami</a>, <a href="/wiki/Indigenous_peoples_of_the_Americas" title="Indigenous peoples of the Americas">Amerindians</a>, Canadian <a href="/wiki/Hutterite" class="mw-redirect" title="Hutterite">Hutterites</a>, New Zealand <a href="/wiki/M%C4%81ori_people" title="Māori people">Māori</a>,<a href="#cite_note-pmid121276522-75">[75]</a> and Canada's <a href="/wiki/Inuit" title="Inuit">Inuit</a>,<a href="#cite_note-Milo20102-71">[71]</a> as well as groups that have a relatively high risk and that live closer to the equator such as <a href="/wiki/Sardinian_people" title="Sardinian people">Sardinians</a>,<a href="#cite_note-Milo20102-71">[71]</a> inland <a href="/wiki/Sicily" title="Sicily">Sicilians</a>,<a href="#cite_note-76">[76]</a> <a href="/wiki/Palestinians" title="Palestinians">Palestinians</a>, and <a href="/wiki/Parsi" class="mw-redirect" title="Parsi">Parsi</a>.<a href="#cite_note-pmid121276522-75">[75]</a> <div class="mw-heading mw-heading3"><h3 id="Impact_of_temperature">Impact of temperature</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=13" title="Edit section: Impact of temperature">edit</a>]</div> MS symptoms may increase if body temperature is dysregulated.<a href="#cite_note-Heat_and_cold_sensitivity_in_multiple_sclerosis-77">[77]</a><a href="#cite_note-Davis-2010-78">[78]</a><a href="#cite_note-Davis-2018-79">[79]</a> Fatigue is particularly affected.<a href="#cite_note-Multiple_Sclerosis_Trust-39">[39]</a><a href="#cite_note-Christogianni-2018-40">[40]</a><a href="#cite_note-Heat_Sensitivity-41">[41]</a><a href="#cite_note-Multiple_Sclerosis_Trust-2-42">[42]</a><a href="#cite_note-Staff-2014-80">[80]</a><a href="#cite_note-Sumowski-2014-81">[81]</a><a href="#cite_note-82">[82]</a><a href="#cite_note-Christogianni-2022-83">[83]</a> <div class="mw-heading mw-heading3"><h3 id="Other">Other</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=14" title="Edit section: Other">edit</a>]</div> <a href="/wiki/Tobacco_smoking" title="Tobacco smoking">Smoking</a> may be an independent risk factor for MS.<a href="#cite_note-pmid17492755-84">[84]</a> <a href="/wiki/Stress_(biological)" class="mw-redirect" title="Stress (biological)">Stress</a> may also be a risk factor, although the evidence to support this is weak.<a href="#cite_note-pmid15556803-74">[74]</a> Association with occupational exposures and <a href="/wiki/Toxin" title="Toxin">toxins</a>—mainly organic <a href="/wiki/Solvent" title="Solvent">solvents</a><a href="#cite_note-85">[85]</a>—has been evaluated, but no clear conclusions have been reached.<a href="#cite_note-pmid15556803-74">[74]</a> <a href="/wiki/Vaccine" title="Vaccine">Vaccinations</a> were studied as causal factors; most studies, though, show no association.<a href="#cite_note-pmid15556803-74">[74]</a><a href="#cite_note-86">[86]</a> Several other possible risk factors, such as <a href="/wiki/Diet_(nutrition)" title="Diet (nutrition)">diet</a> and <a href="/wiki/Hormone" title="Hormone">hormone</a> intake, have been evaluated, but evidence on their relation with the disease is "sparse and unpersuasive".<a href="#cite_note-pmid17492755-84">[84]</a> <a href="/wiki/Gout" title="Gout">Gout</a> occurs less than would be expected and lower levels of <a href="/wiki/Uric_acid" title="Uric acid">uric acid</a> have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown.<a href="#cite_note-pmid18219824-87">[87]</a> Obesity during adolescence and young adulthood is a risk factor for MS.<a href="#cite_note-Nourbakhsh2019RisksPathogenesis-88">[88]</a> <div class="mw-heading mw-heading2"><h2 id="Pathophysiology">Pathophysiology</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=15" title="Edit section: Pathophysiology">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Pathophysiology_of_multiple_sclerosis" title="Pathophysiology of multiple sclerosis">Pathophysiology of multiple sclerosis</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Multiple_Sclerosis.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/2/2a/Multiple_Sclerosis.png/220px-Multiple_Sclerosis.png" decoding="async" width="220" height="183" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/2a/Multiple_Sclerosis.png/330px-Multiple_Sclerosis.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/2a/Multiple_Sclerosis.png/440px-Multiple_Sclerosis.png 2x" data-file-width="1200" data-file-height="1000" /></a><figcaption>Multiple sclerosis</figcaption></figure> Multiple sclerosis is an autoimmune disease, primarily mediated by T-cells.<a href="#cite_note-Ward_988–1005-15">[15]</a> The three main characteristics of MS are the formation of lesions in the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a> (also called plaques), inflammation, and the destruction of <a href="/wiki/Myelin_sheath" class="mw-redirect" title="Myelin sheath">myelin sheaths</a> of <a href="/wiki/Neuron" title="Neuron">neurons</a>. These features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue, and in turn, the signs and symptoms of the disease.<a href="#cite_note-pmid1897097722-1">[1]</a> Damage is believed to be caused, at least in part, by attack on the nervous system by a person's own immune system.<a href="#cite_note-pmid1897097722-1">[1]</a> <div class="mw-heading mw-heading3"><h3 id="Immune_dysregulation_2">Immune dysregulation</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=16" title="Edit section: Immune dysregulation">edit</a>]</div> As briefly detailed in the <a class="mw-selflink-fragment" href="#Immune_dysregulation">causes section</a> of this article, MS is currently thought to stem from a failure of the body's immune system to kill off autoreactive T-cells & B-cells.<a href="#cite_note-Ward_988–1005-15">[15]</a> Currently, the T-cell subpopulations that are thought to drive the development of MS are autoreactive CD8+ T-cells, CD4+ helper T-cells, and TH17 cells. These autoreactive T-cells produce substances called <a href="/wiki/Cytokine" title="Cytokine">cytokines</a> that induce an inflammatory immune response in the CNS, leading to the development of the disease.<a href="#cite_note-Ward_988–1005-15">[15]</a> More recently, however, the role of autoreactive B-cells has been elucidated. Evidence of their contribution to the development of MS is implicated through the presence of oligoclonal IgG bands (antibodies produced by B-cells) in the CSF of patients with MS.<a href="#cite_note-Ward_988–1005-15">[15]</a><a href="#cite_note-McGinley_2021-19">[19]</a> The presence of these oligoclonal bands has been used as supportive evidence in clinching a diagnosis of MS.<a href="#cite_note-Thompson-2018-89">[89]</a> As similarly described before, B-cells can also produce cytokines that induce an inflammatory immune response via activation of autoreactive T-cells.<a href="#cite_note-Ward_988–1005-15">[15]</a><a href="#cite_note-90">[90]</a> As such, higher levels of these autoreactive B-cells is associated with increased number of lesions & neurodegeneration as well as worse disability.<a href="#cite_note-Ward_988–1005-15">[15]</a> Another cell population that is becoming increasingly implicated in MS are <a href="/wiki/Microglia" title="Microglia">microglia</a>. These cells are resident to & keep watch over the CNS, responding to pathogens by shifting between pro- & anti-inflammatory states. Microglia have been shown to be involved in the formation of MS lesions and have been shown to be involved in other diseases that primarily affect the CNS white matter. Although, because of their ability to switch between pro- & anti-inflammatory states, microglia have also been shown to be able to assist in remyelination & subsequent neuron repair.<a href="#cite_note-Ward_988–1005-15">[15]</a> As such, microglia are thought to be participating in both acute & chronic MS lesions, with 40% of phagocytic cells in early active MS lesions being proinflammatory microglia.<a href="#cite_note-Ward_988–1005-15">[15]</a> <div class="mw-heading mw-heading3"><h3 id="Lesions">Lesions</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=17" title="Edit section: Lesions">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:MS_Demyelinisation_KB_10x.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/MS_Demyelinisation_KB_10x.jpg/220px-MS_Demyelinisation_KB_10x.jpg" decoding="async" width="220" height="163" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/MS_Demyelinisation_KB_10x.jpg/330px-MS_Demyelinisation_KB_10x.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e4/MS_Demyelinisation_KB_10x.jpg/440px-MS_Demyelinisation_KB_10x.jpg 2x" data-file-width="2080" data-file-height="1544" /></a><figcaption>Demyelination in MS: On <a href="/wiki/Kl%C3%BCver-Barrera" class="mw-redirect" title="Klüver-Barrera">Klüver-Barrera</a> myelin staining, decoloration in the area of the lesion can be appreciated.</figcaption></figure> The name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. These lesions most commonly affect the <a href="/wiki/White_matter" title="White matter">white matter</a> in the <a href="/wiki/Optic_nerve" title="Optic nerve">optic nerve</a>, <a href="/wiki/Brain_stem" class="mw-redirect" title="Brain stem">brain stem</a>, <a href="/wiki/Basal_ganglia" title="Basal ganglia">basal ganglia</a>, and <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a>, or white matter tracts close to the lateral <a href="/wiki/Ventricular_system" title="Ventricular system">ventricles</a>.<a href="#cite_note-pmid1897097722-1">[1]</a> The function of white matter cells is to carry signals between <a href="/wiki/Grey_matter" title="Grey matter">grey matter</a> areas, where the processing is done, and the rest of the body. The <a href="/wiki/Peripheral_nervous_system" title="Peripheral nervous system">peripheral nervous system</a> is rarely involved.<a href="#cite_note-pmid119555563-8">[8]</a> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:MRI_machine_with_patient_(23423505123).jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f7/MRI_machine_with_patient_%2823423505123%29.jpg/220px-MRI_machine_with_patient_%2823423505123%29.jpg" decoding="async" width="220" height="146" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f7/MRI_machine_with_patient_%2823423505123%29.jpg/330px-MRI_machine_with_patient_%2823423505123%29.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f7/MRI_machine_with_patient_%2823423505123%29.jpg/440px-MRI_machine_with_patient_%2823423505123%29.jpg 2x" data-file-width="4288" data-file-height="2848" /></a><figcaption>MRI machine used as a tool for MS diagnosis</figcaption></figure> To be specific, MS involves the loss of <a href="/wiki/Oligodendrocyte" title="Oligodendrocyte">oligodendrocytes</a>, the cells responsible for creating and maintaining a fatty layer—known as the <a href="/wiki/Myelin" title="Myelin">myelin</a> sheath—which helps the neurons carry <a href="/wiki/Action_potential" title="Action potential">electrical signals</a> (action potentials).<a href="#cite_note-pmid1897097722-1">[1]</a> This results in a thinning or complete loss of myelin, and as the disease advances, the breakdown of the <a href="/wiki/Axons" class="mw-redirect" title="Axons">axons</a> of neurons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.<a href="#cite_note-pmid119555563-8">[8]</a> A repair process, called <a href="/wiki/Remyelination" title="Remyelination">remyelination</a>, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath.<a href="#cite_note-pmid17531860-91">[91]</a> Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.<a href="#cite_note-pmid17531860-91">[91]</a> These scars are the origin of the symptoms and during an attack <a href="/wiki/Magnetic_resonance_imaging" title="Magnetic resonance imaging">magnetic resonance imaging</a> (MRI) often shows more than 10 new plaques.<a href="#cite_note-pmid1897097722-1">[1]</a> This could indicate that some number of lesions exist, below which the brain is capable of repairing itself without producing noticeable consequences.<a href="#cite_note-pmid1897097722-1">[1]</a> Another process involved in the creation of lesions is an abnormal <a href="/wiki/Astrocytosis" class="mw-redirect" title="Astrocytosis">increase in the number of astrocytes</a> due to the destruction of nearby neurons.<a href="#cite_note-pmid1897097722-1">[1]</a> A number of <a href="/wiki/Pathophysiology_of_multiple_sclerosis#Demyelination_patterns" title="Pathophysiology of multiple sclerosis">lesion patterns</a> have been described.<a href="#cite_note-pmid17351524-92">[92]</a> <div class="mw-heading mw-heading3"><h3 id="Inflammation">Inflammation</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=18" title="Edit section: Inflammation">edit</a>]</div> Apart from demyelination, the other sign of the disease is <a href="/wiki/Inflammation" title="Inflammation">inflammation</a>. Fitting with an <a href="/wiki/Immunological" class="mw-redirect" title="Immunological">immunological</a> explanation, the inflammatory process is caused by <a href="/wiki/T_cell" title="T cell">T cells</a>, a kind of <a href="/wiki/Lymphocyte" title="Lymphocyte">lymphocytes</a> that plays an important role in the body's defenses.<a href="#cite_note-pmid119555563-8">[8]</a> T cells gain entry into the brain as a result of disruptions in the <a href="/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier">blood–brain barrier</a>. The T cells recognize myelin as foreign and attack it, explaining why these cells are also called "autoreactive lymphocytes".<a href="#cite_note-pmid1897097722-1">[1]</a> The attack on myelin starts inflammatory processes, which trigger other immune cells and the release of soluble factors like <a href="/wiki/Cytokine" title="Cytokine">cytokines</a> and <a href="/wiki/Antibodies" class="mw-redirect" title="Antibodies">antibodies</a>. A further breakdown of the blood-brain barrier, in turn, causes a number of other damaging effects, such as <a href="/wiki/Oedema" class="mw-redirect" title="Oedema">swelling</a>, activation of <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>, and more activation of cytokines and other destructive proteins.<a href="#cite_note-pmid119555563-8">[8]</a> Inflammation can potentially reduce transmission of information between neurons in at least three ways.<a href="#cite_note-pmid1897097722-1">[1]</a> The soluble factors released might stop neurotransmission by intact neurons. These factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.<a href="#cite_note-pmid1897097722-1">[1]</a> <div class="mw-heading mw-heading3"><h3 id="Blood–brain_barrier">Blood–brain barrier</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=19" title="Edit section: Blood–brain barrier">edit</a>]</div> The blood–brain barrier (BBB) is a part of the <a href="/wiki/Capillary" title="Capillary">capillary</a> system that prevents the entry of T cells into the central nervous system. It may become permeable to these types of cells secondary to an infection by a virus or bacteria. After it repairs itself, typically once the infection has cleared, T cells may remain trapped inside the brain.<a href="#cite_note-pmid119555563-8">[8]</a><a href="#cite_note-93">[93]</a> <a href="/wiki/Gadolinium" title="Gadolinium">Gadolinium</a> cannot cross a normal BBB, so gadolinium-enhanced MRI is used to show BBB breakdowns.<a href="#cite_note-pmid23088946-94">[94]</a> <div class="mw-heading mw-heading3"><h3 id="MS_fatigue">MS fatigue</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=20" title="Edit section: MS fatigue">edit</a>]</div> The pathophysiology and mechanisms causing MS <a href="/wiki/Fatigue" title="Fatigue">fatigue</a> are not well understood.<a href="#cite_note-95">[95]</a><a href="#cite_note-96">[96]</a><a href="#cite_note-97">[97]</a> MS fatigue can be affected by body heat,<a href="#cite_note-Heat_and_cold_sensitivity_in_multiple_sclerosis-77">[77]</a><a href="#cite_note-Davis-2018-79">[79]</a> and this may differentiate MS fatigue from other primary fatigue.<a href="#cite_note-Multiple_Sclerosis_Trust-39">[39]</a><a href="#cite_note-Christogianni-2018-40">[40]</a><a href="#cite_note-Christogianni-2022-83">[83]</a> Fatigability (loss of strength) may increase perception of fatigue, but the two measures warrant independent assessment in clinical studies.<a href="#cite_note-loy-98">[98]</a> <div class="mw-heading mw-heading2"><h2 id="Diagnosis">Diagnosis</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=21" title="Edit section: Diagnosis">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Multiple_sclerosis_diagnosis" class="mw-redirect" title="Multiple sclerosis diagnosis">Multiple sclerosis diagnosis</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Monthly_multiple_sclerosis_anim_cropped_no_text.gif" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/6c/Monthly_multiple_sclerosis_anim_cropped_no_text.gif/220px-Monthly_multiple_sclerosis_anim_cropped_no_text.gif" decoding="async" width="220" height="243" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/6/6c/Monthly_multiple_sclerosis_anim_cropped_no_text.gif 1.5x" data-file-width="240" data-file-height="265" /></a><figcaption>Animation showing dissemination of brain lesions in time and space as demonstrated by monthly MRI studies along a year</figcaption></figure> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:MSMRIMark.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/2/28/MSMRIMark.png/220px-MSMRIMark.png" decoding="async" width="220" height="274" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/28/MSMRIMark.png/330px-MSMRIMark.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/28/MSMRIMark.png/440px-MSMRIMark.png 2x" data-file-width="756" data-file-height="942" /></a><figcaption>Multiple sclerosis as seen on MRI</figcaption></figure> Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting <a href="/wiki/Medical_imaging" title="Medical imaging">medical imaging</a> and laboratory testing.<a href="#cite_note-Tsang20112-5">[5]</a> It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid11794488-99">[99]</a> <div class="mw-heading mw-heading3"><h3 id="McDonald_criteria">McDonald criteria</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=22" title="Edit section: McDonald criteria">edit</a>]</div> The <a href="/wiki/McDonald_criteria" title="McDonald criteria">McDonald criteria</a>, 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<a href="#cite_note-Atlas2008-100">[100]</a> with the <a href="/wiki/Schumacher_criteria" title="Schumacher criteria">Schumacher</a> and <a href="/wiki/Poser_criteria" title="Poser criteria">Poser criteria</a> being of mostly historical significance.<a href="#cite_note-pmid15177763-101">[101]</a> 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.<a href="#cite_note-Thompson-2018-89">[89]</a> Below is an abbreviated outline of the 2017 McDonald Criteria for diagnosis of MS. <ul><li>At least 2 clinical attacks with MRI showing 2 or more lesions characteristic of MS.<a href="#cite_note-Thompson-2018-89">[89]</a></li> <li>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.<a href="#cite_note-Thompson-2018-89">[89]</a></li> <li>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.<a href="#cite_note-Thompson-2018-89">[89]</a></li> <li>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.<a href="#cite_note-Thompson-2018-89">[89]</a></li> <li>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.<a href="#cite_note-Thompson-2018-89">[89]</a></li></ul> As of 2017<a class="external text" href="https://en.wikipedia.org/w/index.php?title=Multiple_sclerosis&action=edit">[update]</a>, no single test (including biopsy) can provide a definitive diagnosis.<a href="#cite_note-102">[102]</a> <div class="mw-heading mw-heading3"><h3 id="MRI">MRI</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=23" title="Edit section: MRI">edit</a>]</div> Magnetic resonance imaging (MRI) of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered <a href="/wiki/Intravenous" class="mw-redirect" title="Intravenous">intravenously</a> as a <a href="/wiki/Contrast_agent" title="Contrast agent">contrast agent</a> to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.<a href="#cite_note-pmid11456302-103">[103]</a><a href="#cite_note-pmid18256986-104">[104]</a> Central vein signs (CVSs) have been proposed as a good indicator of MS in comparison with other conditions causing white lesions.<a href="#cite_note-105">[105]</a><a href="#cite_note-106">[106]</a><a href="#cite_note-107">[107]</a><a href="#cite_note-108">[108]</a> One small study found fewer CVSs in older and hypertensive people.<a href="#cite_note-109">[109]</a> Further research on CVS as a biomarker for MS is ongoing.<a href="#cite_note-110">[110]</a> <div class="mw-heading mw-heading4"><h4 id="In_vivo_vs_post_portem_lesion_visibility_in_MRI_scans">In vivo vs post portem lesion visibility in MRI scans</h4>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=24" title="Edit section: In vivo vs post portem lesion visibility in MRI scans">edit</a>]</div> Only postmortem MRI allows visualization of sub-millimetric lesions in cortical layers and in the cerebellar cortex.<a href="#cite_note-111">[111]</a> <div class="mw-heading mw-heading3"><h3 id="Cerebrospinal_fluid_(lumbar_puncture)">Cerebrospinal fluid (lumbar puncture)</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=25" title="Edit section: Cerebrospinal fluid (lumbar puncture)">edit</a>]</div> Testing of cerebrospinal fluid obtained from a <a href="/wiki/Lumbar_puncture" title="Lumbar puncture">lumbar puncture</a> can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for <a href="/wiki/Oligoclonal_band" title="Oligoclonal band">oligoclonal bands</a> of IgG on <a href="/wiki/Electrophoresis" title="Electrophoresis">electrophoresis</a>, which are inflammation markers found in 75–85% of people with MS.<a href="#cite_note-pmid11456302-103">[103]</a><a href="#cite_note-pmid16945427-112">[112]</a> <div class="mw-heading mw-heading3"><h3 id="Differential_diagnosis">Differential diagnosis</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=26" title="Edit section: Differential diagnosis">edit</a>]</div> Several diseases present similarly to MS.<a href="#cite_note-Loscalzo-2022-113">[113]</a><a href="#cite_note-Saguil-2022-114">[114]</a> Medical professionals use a patient's specific presentation, history, and exam findings to make an individualized <a href="/wiki/Differential_diagnosis" title="Differential diagnosis">differential</a>. 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 <a href="/wiki/Cranial_nerves" title="Cranial nerves">cranial nerves</a>, involvement of organs outside of the <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a>, and atypical lab and exam findings.<a href="#cite_note-Loscalzo-2022-113">[113]</a><a href="#cite_note-Saguil-2022-114">[114]</a> In an emergency setting, it is important to rule out a stroke or <a href="/wiki/Intracranial_hemorrhage" title="Intracranial hemorrhage">bleeding</a> in the brain.<a href="#cite_note-Saguil-2022-114">[114]</a> Intractable vomiting, severe optic neuritis,<a href="#cite_note-Petzold_2022-31">[31]</a> or bilateral optic neuritis<a href="#cite_note-Petzold_2022-31">[31]</a> raises suspicion for <a href="/wiki/Neuromyelitis_optica_spectrum_disorder" title="Neuromyelitis optica spectrum disorder">neuromyelitis optica spectrum disorder</a> (NMOSD).<a href="#cite_note-Solomon2019DiagnosisReview-115">[115]</a> Infectious diseases that may look similar to multiple sclerosis include HIV, <a href="/wiki/Lyme_disease" title="Lyme disease">Lyme disease</a>, and <a href="/wiki/Neurosyphilis" title="Neurosyphilis">syphilis</a>. Autoimmune diseases include <a href="/wiki/Neurosarcoidosis" title="Neurosarcoidosis">neurosarcoidosis</a>, <a href="/wiki/Lupus" title="Lupus">lupus</a>, <a href="/wiki/Guillain%E2%80%93Barr%C3%A9_syndrome" title="Guillain–Barré syndrome">Guillain-Barré syndrome</a>, <a href="/wiki/Acute_disseminated_encephalomyelitis" title="Acute disseminated encephalomyelitis">acute disseminated encephalomyelitis</a>, and <a href="/wiki/Beh%C3%A7et%27s_disease" title="Behçet's disease">Behçet's disease</a>. Psychiatric conditions such as <a href="/wiki/Generalized_anxiety_disorder" title="Generalized anxiety disorder">anxiety</a> or <a href="/wiki/Conversion_disorder" title="Conversion disorder">conversion disorder</a> may also present in a similar way. Other rare diseases on the differential include <a href="/wiki/Primary_central_nervous_system_lymphoma" title="Primary central nervous system lymphoma">CNS lymphoma</a>, <a href="/wiki/Leukodystrophy" title="Leukodystrophy">congenital leukodystrophies</a>, and <a href="/wiki/MOG_antibody_disease" title="MOG antibody disease">anti-MOG-associated myelitis</a>.<a href="#cite_note-Loscalzo-2022-113">[113]</a><a href="#cite_note-Saguil-2022-114">[114]</a> <div class="mw-heading mw-heading2"><h2 id="Types_and_variants">Types and variants</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=27" title="Edit section: Types and variants">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Ms_progression_types.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/220px-Ms_progression_types.svg.png" decoding="async" width="220" height="236" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/330px-Ms_progression_types.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/440px-Ms_progression_types.svg.png 2x" data-file-width="736" data-file-height="790" /></a><figcaption>MS progression types. From bottom to top: RRMS, PPMS, SPMS.</figcaption></figure> Several <a href="/wiki/Phenotype_(clinical_medicine)" title="Phenotype (clinical medicine)">phenotypes</a> (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 <a href="/wiki/Multiple_sclerosis_research#Lublin_classification" class="mw-redirect" title="Multiple sclerosis research">Lublin classification</a>:<a href="#cite_note-Lublin-116">[116]</a><a href="#cite_note-117">[117]</a> <ol><li><a href="/wiki/Clinically_isolated_syndrome" title="Clinically isolated syndrome">Clinically isolated syndrome</a> (CIS)</li> <li><a href="/wiki/Relapsing%E2%80%93remitting" title="Relapsing–remitting">Relapsing-remitting</a> MS (RRMS)</li> <li>Primary progressive MS (PPMS)</li> <li>Secondary progressive MS (SPMS)</li></ol> 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 <a href="/wiki/Inflammation" title="Inflammation">inflammation</a> or <a href="/wiki/Demyelinating_disease" title="Demyelinating disease">demyelination</a> of the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a>.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-118">[118]</a> 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.<a href="#cite_note-pmid15847841-119">[119]</a> RRMS is characterized by unpredictable relapses followed by periods of months to years of relative quiet (<a href="/wiki/Remission_(medicine)" title="Remission (medicine)">remission</a>) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave <a href="/wiki/Sequelae" class="mw-redirect" title="Sequelae">problems</a>, the latter in about 40% of attacks and being more common the longer a person has had the disease.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-Tsang20112-5">[5]</a> This describes the initial course of 80% of individuals with MS.<a href="#cite_note-pmid1897097722-1">[1]</a> PPMS occurs in roughly 10–20% of individuals with the disease, with no remission after the initial symptoms.<a href="#cite_note-Tsang20112-5">[5]</a><a href="#cite_note-pmid17884680-120">[120]</a> It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.<a href="#cite_note-pmid8780061-13">[13]</a> The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in RRMS, around 40 years of age.<a href="#cite_note-pmid1897097722-1">[1]</a> 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.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid8780061-13">[13]</a> Occasional relapses and minor remissions may appear.<a href="#cite_note-pmid8780061-13">[13]</a> The most common length of time between disease onset and conversion from RRMS to SPMS is 19 years.<a href="#cite_note-pmid16545751-121">[121]</a> <div class="mw-heading mw-heading3"><h3 id="Special_courses">Special courses</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=28" title="Edit section: Special courses">edit</a>]</div> Independently of the types published by the MS associations, regulatory agencies such as the FDA often consider special courses, trying to reflect some clinical trials results on their approval documents. Some examples could be "highly active MS" (HAMS),<a href="#cite_note-sorensen-122">[122]</a> "active secondary MS" (similar to the old progressive-relapsing)<a href="#cite_note-novartis.com-123">[123]</a> and "rapidly progressing PPMS".<a href="#cite_note-124">[124]</a> Also, deficits always resolving between attacks is sometimes referred to as "benign" MS,<a href="#cite_note-pmid18219812-125">[125]</a> although people still build up some degree of disability in the long term.<a href="#cite_note-pmid1897097722-1">[1]</a> On the other hand, the term <a href="/wiki/Malignant_multiple_sclerosis" title="Malignant multiple sclerosis">malignant multiple sclerosis</a> is used to describe people with MS having reached significant level of disability in a short period.<a href="#cite_note-126">[126]</a> An international panel has published a standardized definition for the course HAMS.<a href="#cite_note-sorensen-122">[122]</a> <div class="mw-heading mw-heading3"><h3 id="Variants">Variants</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=29" title="Edit section: Variants">edit</a>]</div> Atypical <a href="/wiki/Idiopathic_inflammatory_demyelinating_diseases" class="mw-redirect" title="Idiopathic inflammatory demyelinating diseases">variants</a> of MS have been described; these include <a href="/wiki/Tumefactive_multiple_sclerosis" title="Tumefactive multiple sclerosis">tumefactive multiple sclerosis</a>, <a href="/wiki/Balo_concentric_sclerosis" title="Balo concentric sclerosis">Balo concentric sclerosis</a>, <a href="/wiki/Diffuse_myelinoclastic_sclerosis" title="Diffuse myelinoclastic sclerosis">Schilder's diffuse sclerosis</a>, and <a href="/wiki/Marburg_multiple_sclerosis" class="mw-redirect" title="Marburg multiple sclerosis">Marburg multiple sclerosis</a>. Debate remains on whether they are MS variants or different diseases.<a href="#cite_note-pmid15727225-127">[127]</a> Some diseases previously considered MS variants, such as <a href="/wiki/Devic%27s_disease" class="mw-redirect" title="Devic's disease">Devic's disease</a>, are now considered outside the MS spectrum.<a href="#cite_note-128">[128]</a> <div class="mw-heading mw-heading2"><h2 id="Management">Management</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=30" title="Edit section: Management">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Management_of_multiple_sclerosis" title="Management of multiple sclerosis">Management of multiple sclerosis</a></div> Although no cure for multiple sclerosis has been found, several therapies have proven helpful. Several effective treatments can decrease the number of attacks and the rate of progression.<a href="#cite_note-McGinley2021-23">[23]</a> The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. Starting medications is generally recommended in people after the first attack when more than two lesions are seen on MRI.<a href="#cite_note-Neurology2018-129">[129]</a> The first approved medications used to treat MS were modestly effective, though were poorly tolerated and had many adverse effects.<a href="#cite_note-NIH2015-3">[3]</a> Several treatment options with better safety and tolerability profiles have been introduced,<a href="#cite_note-McGinley2021-23">[23]</a> improving the prognosis of MS. As with any medical treatment, medications used in the management of MS have several <a href="/wiki/Adverse_effect_(medicine)" class="mw-redirect" title="Adverse effect (medicine)">adverse effects</a>. <a href="/wiki/Alternative_medicine" title="Alternative medicine">Alternative treatments</a> are pursued by some people, despite the shortage of supporting evidence of efficacy. <div class="mw-heading mw-heading3"><h3 id="Initial_management_of_acute_flare">Initial management of acute flare</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=31" title="Edit section: Initial management of acute flare">edit</a>]</div> During symptomatic attacks, administration of high doses of <a href="/wiki/Intravenous_therapy" title="Intravenous therapy">intravenous</a> <a href="/wiki/Corticosteroid" title="Corticosteroid">corticosteroids</a>, such as <a href="/wiki/Methylprednisolone" title="Methylprednisolone">methylprednisolone</a>, is the usual therapy,<a href="#cite_note-pmid1897097722-1">[1]</a> with oral corticosteroids seeming to have a similar efficacy and safety profile.<a href="#cite_note-130">[130]</a> Although effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.<a href="#cite_note-131">[131]</a><a href="#cite_note-RCOP_acute-132">[132]</a> The long-term benefit is unclear in optic neuritis as of 2020.<a href="#cite_note-133">[133]</a><a href="#cite_note-Petzold_2022-31">[31]</a> The consequences of severe attacks that do not respond to corticosteroids might be treatable by <a href="/wiki/Plasmapheresis" title="Plasmapheresis">plasmapheresis</a>.<a href="#cite_note-pmid1897097722-1">[1]</a> <div class="mw-heading mw-heading3"><h3 id="Chronic_management">Chronic management</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=32" title="Edit section: Chronic management">edit</a>]</div> <div class="mw-heading mw-heading4"><h4 id="Relapsing_remitting_multiple_sclerosis">Relapsing remitting multiple sclerosis</h4>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=33" title="Edit section: Relapsing remitting multiple sclerosis">edit</a>]</div> Multiple <a href="/wiki/Management_of_multiple_sclerosis#Disease-modifying_treatments" title="Management of multiple sclerosis">disease-modifying</a> medications were approved by regulatory agencies for RRMS; they are modestly effective at decreasing the number of attacks.<a href="#cite_note-He2016-134">[134]</a> <a href="/wiki/Interferons" class="mw-redirect" title="Interferons">Interferons</a><a href="#cite_note-Rice2001-135">[135]</a> and <a href="/wiki/Glatiramer_acetate" title="Glatiramer acetate">glatiramer acetate</a> are first-line treatments<a href="#cite_note-Tsang20112-5">[5]</a> and are roughly equivalent, reducing relapses by approximately 30%.<a href="#cite_note-Hassan2011-136">[136]</a> Early-initiated long-term therapy is safe and improves outcomes.<a href="#cite_note-pmid21205679-137">[137]</a><a href="#cite_note-pmid22284996-138">[138]</a> Treatment of CIS with interferons decreases the chance of progressing to clinical MS.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid21205678-139">[139]</a><a href="#cite_note-140">[140]</a> Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults.<a href="#cite_note-pmid22642799-141">[141]</a> The role of some newer agents such as <a href="/wiki/Fingolimod" title="Fingolimod">fingolimod</a>,<a href="#cite_note-LaMantia2016-142">[142]</a> <a href="/wiki/Teriflunomide" title="Teriflunomide">teriflunomide</a>, and <a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">dimethyl fumarate</a>,<a href="#cite_note-Xu2015-143">[143]</a> is not yet entirely clear.<a href="#cite_note-pmid22014437-144">[144]</a> Making firm conclusions about the best treatment is difficult, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease-modifying therapies or long-term monitoring of patient outcomes.<a href="#cite_note-145">[145]</a> The relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies.<a href="#cite_note-Filippini2013-146">[146]</a> Direct comparisons of interferons and glatiramer acetate indicate similar effects or only small differences in effects on relapse rate, disease progression, and MRI measures.<a href="#cite_note-147">[147]</a> There is high confidence that natalizumab, cladribine, or alemtuzumab are decreasing relapses over a period of two years for people with RRMS.<a href="#cite_note-Tramacere2015-148">[148]</a> <a href="/wiki/Natalizumab" title="Natalizumab">Natalizumab</a> and <a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">interferon beta-1a</a> (<a href="/wiki/Interferon_beta-1a#Brand_names" title="Interferon beta-1a">Rebif</a>) may reduce relapses compared to both placebo and interferon beta-1a (Avonex) while <a href="/wiki/Interferon_beta-1b" title="Interferon beta-1b">Interferon beta-1b</a> (<a href="/wiki/Interferon_beta-1b#Commercial_formulations" title="Interferon beta-1b">Betaseron</a>), <a href="/wiki/Glatiramer_acetate" title="Glatiramer acetate">glatiramer acetate</a>, and <a href="/wiki/Mitoxantrone" title="Mitoxantrone">mitoxantrone</a> may also prevent relapses.<a href="#cite_note-Filippini2013-146">[146]</a> Evidence on relative effectiveness in reducing disability progression is unclear.<a href="#cite_note-Filippini2013-146">[146]</a> There is moderate confidence that a two-year treatment with natalizumab slows disability progression for people with RRMS.<a href="#cite_note-Tramacere2015-148">[148]</a> All medications are associated with adverse effects that may influence their risk to benefit profiles.<a href="#cite_note-Filippini2013-146">[146]</a><a href="#cite_note-Tramacere2015-148">[148]</a> <a href="/wiki/Ublituximab" title="Ublituximab">Ublituximab</a> was approved for medical use in the United States in December 2022.<a href="#cite_note-149">[149]</a> <div class="mw-heading mw-heading3"><h3 id="Medications">Medications</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=34" title="Edit section: Medications">edit</a>]</div> Overview of medications available for MS.<a href="#cite_note-MSTrust-150">[150]</a> <table class="wikitable"> <tbody><tr> <th>Medication </th> <th>Compound </th> <th>Producer </th> <th>Use </th> <th>Efficacy (annualized relapse reduction rate) </th> <th>Annualized relapse rate (ARR) </th></tr> <tr> <td>Avonex </td> <td><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a> </td> <td><a href="/wiki/Biogen" title="Biogen">Biogen</a> </td> <td><a href="/wiki/Intramuscular_injection" title="Intramuscular injection">Intramuscular</a> </td> <td>30% </td> <td>0.25 </td></tr> <tr> <td>Rebif </td> <td><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a> </td> <td><a href="/wiki/Merck_Serono" title="Merck Serono">Merck Serono</a> </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td>30% </td> <td>0.256 </td></tr> <tr> <td>Extavia </td> <td><a href="/wiki/Interferon_beta-1b" title="Interferon beta-1b">Interferon beta-1b</a> </td> <td><a href="/wiki/Bayer_Schering" class="mw-redirect" title="Bayer Schering">Bayer Schering</a> </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td>30% </td> <td>0.256 </td></tr> <tr> <td>Copaxone </td> <td><a href="/wiki/Glatiramer_acetate" title="Glatiramer acetate">Glatiramer acetate</a> </td> <td><a href="/wiki/Teva_Pharmaceuticals" title="Teva Pharmaceuticals">Teva Pharmaceuticals</a> </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td>30% </td> <td>0.3 </td></tr> <tr> <td>Aubagio </td> <td><a href="/wiki/Teriflunomide" title="Teriflunomide">Teriflunomide</a> </td> <td><a href="/wiki/Genzyme" title="Genzyme">Genzyme</a> </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td>30% </td> <td>0.35 </td></tr> <tr> <td>Plegridy </td> <td><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a> </td> <td>Biogen </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td>30% </td> <td>0.12 </td></tr> <tr> <td>Tecfidera </td> <td><a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">Dimethyl fumarate</a> </td> <td>Biogen </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td>50% </td> <td>0.15 </td></tr> <tr> <td>Vumerity </td> <td><a href="/wiki/Diroximel_fumarate" title="Diroximel fumarate">Diroximel fumarate</a> </td> <td>Biogen </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td>50% </td> <td>0.11-0.15 </td></tr> <tr> <td>Gilenya </td> <td><a href="/wiki/Fingolimod" title="Fingolimod">Fingolimod</a> </td> <td> </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td>50% </td> <td>0.22-0.25 </td></tr> <tr> <td>Zeposia </td> <td><a href="/wiki/Ozanimod" title="Ozanimod">Ozanimod</a> </td> <td>[<a href="/wiki/Wikipedia:NOTRS" class="mw-redirect" title="Wikipedia:NOTRS">better source needed</a>] </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td> </td> <td>0.18-0.24 </td></tr> <tr> <td>Kesimpta </td> <td><a href="/wiki/Ofatumumab" title="Ofatumumab">Ofatumumab</a> </td> <td> </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td>70% </td> <td>0.09-0.14 </td></tr> <tr> <td>Mavenclad </td> <td><a href="/wiki/Cladribine" title="Cladribine">Cladribine</a> </td> <td> </td> <td><a href="/wiki/Oral_administration" title="Oral administration">Oral</a> </td> <td>70% </td> <td>0.1-0.14 </td></tr> <tr> <td>Lemtrada </td> <td><a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a> </td> <td> </td> <td><a href="/wiki/Intravenous_therapy" title="Intravenous therapy">Intravenous</a> </td> <td>70% </td> <td>0.08 </td></tr> <tr> <td>Ocrevus </td> <td><a href="/wiki/Ocrelizumab" title="Ocrelizumab">Ocrelizumab</a> </td> <td> </td> <td><a href="/wiki/Intravenous_therapy" title="Intravenous therapy">Intravenous</a> </td> <td>70% </td> <td>0.09 </td></tr> <tr> <td>Ocrevus Zunovo </td> <td><a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">Ocrelizumab/hyaluronidase</a> </td> <td> </td> <td><a href="/wiki/Subcutaneous_administration" title="Subcutaneous administration">Subcutaneous</a> </td> <td> </td> <td> </td></tr> </tbody></table> <div class="mw-heading mw-heading4"><h4 id="Progressive_multiple_sclerosis">Progressive multiple sclerosis</h4>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=35" title="Edit section: Progressive multiple sclerosis">edit</a>]</div> In 2011, mitoxantrone was the first medication approved for secondary progressive MS.<a href="#cite_note-BopeKellerman2011-151">[151]</a> In this population, tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years.<a href="#cite_note-CochMit2013-152">[152]</a><a href="#cite_note-153">[153]</a> New approved medications continue to emerge. In March 2017, the FDA approved ocrelizumab as a treatment for primary progressive MS in adults, the first drug to gain that approval,<a href="#cite_note-pmid31598138-154">[154]</a><a href="#cite_note-STATapproval-155">[155]</a><a href="#cite_note-Ocrevus_FDA_label-156">[156]</a> with requirements for several <a href="/wiki/Phases_of_clinical_research#Phase_IV" title="Phases of clinical research">Phase IV</a> clinical trials.<a href="#cite_note-FDABLAapproval-157">[157]</a> It is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.<a href="#cite_note-Ocrevus_FDA_label-156">[156]</a> According to a 2021 <a href="/wiki/Cochrane_review" class="mw-redirect" title="Cochrane review">Cochrane review</a>, ocrelizumab may reduce worsening of symptoms for primary progressive MS and probably increases unwanted effects but makes little or no difference to the number of serious unwanted effects.<a href="#cite_note-158">[158]</a> In 2019, <a href="/wiki/Siponimod" title="Siponimod">siponimod</a> and <a href="/wiki/Cladribine" title="Cladribine">cladribine</a> were approved in the United States for the treatment of secondary progressive multiple sclerosis (SPMS).<a href="#cite_note-pmid31598138-154">[154]</a> Subsequently, <a href="/wiki/Ozanimod" title="Ozanimod">ozanimod</a> was approved in 2020, and <a href="/wiki/Ponesimod" title="Ponesimod">ponesimod</a> was approved in 2021, which were both approved for management of CIS, relapsing MS, and SPMS in the U.S., and RRMS in Europe.<a href="#cite_note-159">[159]</a> <a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">Ocrelizumab/hyaluronidase</a> was approved for medical use in the United States in September 2024.<a href="#cite_note-160">[160]</a><a href="#cite_note-161">[161]</a> <div class="mw-heading mw-heading4"><h4 id="Adverse_effects">Adverse effects</h4>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=36" title="Edit section: Adverse effects">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Copaxone_Injection_Site_Reaction.JPG" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Copaxone_Injection_Site_Reaction.JPG/220px-Copaxone_Injection_Site_Reaction.JPG" decoding="async" width="220" height="318" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/a/a0/Copaxone_Injection_Site_Reaction.JPG 1.5x" data-file-width="315" data-file-height="456" /></a><figcaption>Irritation zone after injection of glatiramer acetate</figcaption></figure> The <a href="/wiki/Disease-modifying_treatment" title="Disease-modifying treatment">disease-modifying treatments</a> have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections).<a href="#cite_note-Rice2001-135">[135]</a><a href="#cite_note-Balak2012-162">[162]</a> Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as <a href="/wiki/Lipoatrophy" title="Lipoatrophy">lipoatrophy</a>, may develop.<a href="#cite_note-Balak2012-162">[162]</a> Interferons may produce <a href="/wiki/Flu-like_symptoms" class="mw-redirect" title="Flu-like symptoms">flu-like symptoms</a>;<a href="#cite_note-pmid17131933-163">[163]</a> some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes.<a href="#cite_note-164">[164]</a> More dangerous but much less common are <a href="/wiki/Hepatotoxicity" title="Hepatotoxicity">liver damage</a> from interferons,<a href="#cite_note-pmid15592724-165">[165]</a> <a href="/wiki/Systolic_dysfunction" class="mw-redirect" title="Systolic dysfunction">systolic dysfunction</a> (12%), <a href="/wiki/Infertility" title="Infertility">infertility</a>, and <a href="/wiki/Acute_myeloid_leukemia" title="Acute myeloid leukemia">acute myeloid leukemia</a> (0.8%) from mitoxantrone,<a href="#cite_note-CochMit2013-152">[152]</a><a href="#cite_note-pmid19882365-166">[166]</a> and <a href="/wiki/Progressive_multifocal_leukoencephalopathy" title="Progressive multifocal leukoencephalopathy">progressive multifocal leukoencephalopathy</a> occurring with natalizumab (occurring in 1 in 600 people treated).<a href="#cite_note-Tsang20112-5">[5]</a><a href="#cite_note-167">[167]</a> Fingolimod may give rise to <a href="/wiki/Hypertension" title="Hypertension">hypertension</a> and <a href="/wiki/Bradycardia" title="Bradycardia">slowed heart rate</a>, <a href="/wiki/Macular_edema" title="Macular edema">macular edema</a>, elevated liver enzymes, or a <a href="/wiki/Lymphopenia" class="mw-redirect" title="Lymphopenia">reduction in lymphocyte levels</a>.<a href="#cite_note-LaMantia2016-142">[142]</a><a href="#cite_note-pmid22014437-144">[144]</a> Tentative evidence supports the short-term safety of teriflunomide, with common side effects including: headaches, fatigue, nausea, hair loss, and limb pain.<a href="#cite_note-He2016-134">[134]</a> There have also been reports of liver failure and PML with its use and it is <a href="/wiki/Teratology" title="Teratology">dangerous for fetal development</a>.<a href="#cite_note-pmid22014437-144">[144]</a> Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems.<a href="#cite_note-Xu2015-143">[143]</a><a href="#cite_note-fumarate-168">[168]</a><a href="#cite_note-pmid22014437-144">[144]</a> While dimethyl fumarate may lead to a <a href="/wiki/Neutropenia" title="Neutropenia">reduction in the white blood cell count</a> there were no reported cases of opportunistic infections during trials.<a href="#cite_note-fumarateNDA-169">[169]</a> <div class="mw-heading mw-heading3"><h3 id="Associated_symptoms">Associated symptoms</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=37" title="Edit section: Associated symptoms">edit</a>]</div> Both medications and <a href="/wiki/Neurorehabilitation" title="Neurorehabilitation">neurorehabilitation</a> have been shown to improve some symptoms, though neither changes the course of the disease.<a href="#cite_note-pmid16168933-170">[170]</a> Some symptoms have a good response to medication, such as bladder <a href="/wiki/Spasticity" title="Spasticity">spasticity</a>, while others are little changed.<a href="#cite_note-pmid1897097722-1">[1]</a> Equipment such as <a href="/wiki/Catheter" title="Catheter">catheters</a> for neurogenic bladder dysfunction or mobility aids can be helpful in improving functional status. A <a href="/wiki/Multidisciplinary" class="mw-redirect" title="Multidisciplinary">multidisciplinary</a> approach is important for improving quality of life; however, it is difficult to specify a 'core team' as many health services may be needed at different points in time.<a href="#cite_note-pmid1897097722-1">[1]</a> Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.<a href="#cite_note-pmid17443610-171">[171]</a> Studies investigating information provision in support of patient understanding and participation suggest that while interventions (written information, decision aids, coaching, educational programmes) may increase knowledge, the evidence of an effect on decision making and quality of life is mixed and low certainty.<a href="#cite_note-172">[172]</a> There is limited evidence for the overall efficacy of individual therapeutic disciplines,<a href="#cite_note-pmid15859525-173">[173]</a><a href="#cite_note-pmid12917976-174">[174]</a> though there is good evidence that specific approaches, such as exercise,<a href="#cite_note-175">[175]</a><a href="#cite_note-176">[176]</a><a href="#cite_note-pmid17482708-177">[177]</a><a href="#cite_note-178">[178]</a> and psychological therapies are effective.<a href="#cite_note-179">[179]</a> Cognitive training, alone or combined with other neuropsychological interventions, may show positive effects for memory and attention though firm conclusions are not possible given small sample numbers, variable methodology, interventions and outcome measures.<a href="#cite_note-180">[180]</a> The effectiveness of <a href="/wiki/Palliative_care" title="Palliative care">palliative approaches</a> in addition to standard care is uncertain, due to lack of evidence.<a href="#cite_note-181">[181]</a> The effectiveness of interventions, including exercise, specifically for the prevention of falls in people with MS is uncertain, while there is some evidence of an effect on balance function and mobility.<a href="#cite_note-182">[182]</a> <a href="/wiki/Cognitive_behavioral_therapy" title="Cognitive behavioral therapy">Cognitive behavioral therapy</a> has shown to be moderately effective for reducing MS fatigue.<a href="#cite_note-183">[183]</a> The evidence for the effectiveness of non-pharmacological interventions for chronic pain is insufficient to recommend such interventions alone, however their use in combination with medications may be reasonable.<a href="#cite_note-184">[184]</a> <div class="mw-heading mw-heading3"><h3 id="Non-pharmaceutical">Non-pharmaceutical</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=38" title="Edit section: Non-pharmaceutical">edit</a>]</div> There is some evidence that <a href="/wiki/Aquatic_therapy" title="Aquatic therapy">aquatic therapy</a> is a beneficial intervention.<a href="#cite_note-185">[185]</a> The spasticity associated with MS can be difficult to manage because of the progressive and fluctuating course of the disease.<a href="#cite_note-186">[186]</a> Although there is no firm conclusion on the efficacy in reducing spasticity, PT interventions can be a safe and beneficial option for patients with multiple sclerosis. Physical therapy including vibration interventions, electrical stimulation, exercise therapy, standing therapy, and radial shock wave therapy (RSWT), were beneficial for limiting spasticity, helping limit excitability, or increasing range of motion.<a href="#cite_note-187">[187]</a> <div class="mw-heading mw-heading3"><h3 id="Alternative_treatments">Alternative treatments</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=39" title="Edit section: Alternative treatments">edit</a>]</div> Over 50% of people with MS may use <a href="/wiki/Complementary_and_alternative_medicine" class="mw-redirect" title="Complementary and alternative medicine">complementary and alternative medicine</a>, although percentages vary depending on how alternative medicine is defined.<a href="#cite_note-pmid16420779-188">[188]</a> Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.<a href="#cite_note-pmid16420779-188">[188]</a> The evidence for the effectiveness for such treatments in most cases is weak or absent.<a href="#cite_note-pmid16420779-188">[188]</a><a href="#cite_note-pmid19222053-189">[189]</a> Treatments of unproven benefit used by people with MS include dietary supplementation and regimens,<a href="#cite_note-pmid16420779-188">[188]</a><a href="#cite_note-190">[190]</a><a href="#cite_note-pmid21965673-191">[191]</a> <a href="/wiki/Vitamin_D" title="Vitamin D">vitamin D</a>,<a href="#cite_note-192">[192]</a> <a href="/wiki/Relaxation_technique" title="Relaxation technique">relaxation techniques</a> such as <a href="/wiki/Yoga_as_exercise" title="Yoga as exercise">yoga</a>,<a href="#cite_note-pmid16420779-188">[188]</a> <a href="/wiki/Herbal_medicine" title="Herbal medicine">herbal medicine</a> (including <a href="/wiki/Medical_cannabis" title="Medical cannabis">medical cannabis</a>),<a href="#cite_note-pmid16420779-188">[188]</a><a href="#cite_note-193">[193]</a><a href="#cite_note-194">[194]</a> <a href="/wiki/Hyperbaric_oxygen_therapy" class="mw-redirect" title="Hyperbaric oxygen therapy">hyperbaric oxygen therapy</a>,<a href="#cite_note-pmid14974004-195">[195]</a> <a href="/wiki/Helminthic_therapy" title="Helminthic therapy">self-infection with hookworms</a>, <a href="/wiki/Reflexology" title="Reflexology">reflexology</a>, <a href="/wiki/Acupuncture" title="Acupuncture">acupuncture</a>,<a href="#cite_note-pmid16420779-188">[188]</a><a href="#cite_note-196">[196]</a> and <a href="/wiki/Mindfulness" title="Mindfulness">mindfulness</a>.<a href="#cite_note-197">[197]</a> Evidence suggests vitamin D supplementation, irrespective of the form and dose, provides no benefit for people with MS; this includes for measures such as relapse recurrence, disability, and MRI lesions while effects on health‐related quality of life and fatigue are unclear.<a href="#cite_note-198">[198]</a> There is insufficient evidence supporting high-dose <a href="/wiki/Biotin" title="Biotin">biotin</a><a href="#cite_note-Motte2020-199">[199]</a><a href="#cite_note-200">[200]</a><a href="#cite_note-201">[201]</a> and some evidence for increased disease activity and higher risk of relapse with its use.<a href="#cite_note-Goldschmidt2020-202">[202]</a> A recent review of the effectiveness of <a href="/wiki/Cannabis_(drug)" title="Cannabis (drug)">Cannabis</a> and <a href="/wiki/Cannabinoid" title="Cannabinoid">Cannabinoids</a> (2022) found that compared with placebo <a href="/wiki/Nabiximols" title="Nabiximols">nabiximols</a> probably reduce the severity of spasticity in the short term.<a href="#cite_note-203">[203]</a> <div class="mw-heading mw-heading2"><h2 id="Prognosis">Prognosis</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=40" title="Edit section: Prognosis">edit</a>]</div> The availability of treatments that modify the course of multiple sclerosis beginning in the 1990s, known as disease-modifying therapies (DMTs), has improved prognosis. These treatments can reduce relapses and slow progression, but there is no cure.<a href="#cite_note-McGinley2021-23">[23]</a><a href="#cite_note-Cree2022-204">[204]</a> The prognosis of MS depends on the subtype of the disease, and there is considerable individual variation in the progression of the disease.<a href="#cite_note-Oh2018-205">[205]</a> In relapsing MS, the most common subtype, a 2016 cohort study found that after a median of 16.8 years from onset, one in ten needed a walking aid, and almost two in ten transitioned to secondary progressive MS, a form characterized by more progressive decline.<a href="#cite_note-McGinley2021-23">[23]</a> With treatments available in the 2020s, relapses can be eliminated or substantially reduced. However, "silent progression" of the disease still occurs.<a href="#cite_note-Cree2022-204">[204]</a><a href="#cite_note-206">[206]</a> In addition to secondary progressive MS (SPMS), a small proportion of people with MS (10–15%) experience progressive decline from the onset, known as primary progressive MS (PPMS). Most treatments have been approved for use in relapsing MS; there are fewer treatments with lower efficacy for progressive forms of MS.<a href="#cite_note-Continuum-207">[207]</a><a href="#cite_note-Cree2022-204">[204]</a><a href="#cite_note-McGinley2021-23">[23]</a> The prognosis for progressive MS is worse, with faster accumulation of disability, though with considerable individual variation.<a href="#cite_note-Continuum-207">[207]</a> In untreated PPMS, the median time from onset to requiring a walking aid is estimated as seven years.<a href="#cite_note-McGinley2021-23">[23]</a> In SPMS, a 2014 cohort study reported that people required a walking aid after an average of five years from onset of SPMS, and were chair or bed-bound after an average of fifteen years.<a href="#cite_note-208">[208]</a> After diagnosis of MS, characteristics that predict a worse course are male sex, older age, and greater disability at the time of diagnosis; female sex is associated with a higher relapse rate.<a href="#cite_note-lancet2018-209">[209]</a> Currently, no biomarker can accurately predict disease progression in every patient.<a href="#cite_note-Oh2018-205">[205]</a> Spinal cord lesions, abnormalities on MRI, and more <a href="/wiki/Cerebral_atrophy" title="Cerebral atrophy">brain atrophy</a> are predictive of a worse course, though brain atrophy as a predictor of disease course is experimental and not used in clinical practice.<a href="#cite_note-lancet2018-209">[209]</a> Early treatment leads to a better prognosis, but a higher relapse frequency when treated with DMTs is associated with a poorer prognosis.<a href="#cite_note-Oh2018-205">[205]</a><a href="#cite_note-lancet2018-209">[209]</a> A 60-year longitudinal population study conducted in Norway found that those with MS had a <a href="/wiki/Life_expectancy" title="Life expectancy">life expectancy</a> seven years shorter than the general population. Median life expectancy for RRMS patients was 77.8 years and 71.4 years for PPMS, compared to 81.8 years for the general population. Life expectancy for men was five years shorter than for women.<a href="#cite_note-210">[210]</a> <div class="mw-heading mw-heading2"><h2 id="Epidemiology">Epidemiology</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=41" title="Edit section: Epidemiology">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1251242444"><table class="box-Update plainlinks metadata ambox ambox-content ambox-Update" role="presentation"><tbody><tr><td class="mbox-image"><div class="mbox-image-div"><img alt="" src="//upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Ambox_current_red_Asia_Australia.svg/42px-Ambox_current_red_Asia_Australia.svg.png" decoding="async" width="42" height="34" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Ambox_current_red_Asia_Australia.svg/63px-Ambox_current_red_Asia_Australia.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Ambox_current_red_Asia_Australia.svg/84px-Ambox_current_red_Asia_Australia.svg.png 2x" data-file-width="360" data-file-height="290" /></div></td><td class="mbox-text"><div class="mbox-text-span">This section needs to be updated. Please help update this article to reflect recent events or newly available information. (July 2022)</div></td></tr></tbody></table> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/1f/Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg/290px-Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg.png" decoding="async" width="290" height="128" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/1f/Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg/435px-Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/1f/Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg/580px-Multiple_sclerosis_world_map-Deaths_per_million_persons-WHO2012.svg.png 2x" data-file-width="940" data-file-height="415" /></a><figcaption>Deaths from multiple sclerosis per million persons in 2012 <style data-mw-deduplicate="TemplateStyles:r1184024115">.mw-parser-output .div-col{margin-top:0.3em;column-width:30em}.mw-parser-output .div-col-small{font-size:90%}.mw-parser-output .div-col-rules{column-rule:1px solid #aaa}.mw-parser-output .div-col dl,.mw-parser-output .div-col ol,.mw-parser-output .div-col ul{margin-top:0}.mw-parser-output .div-col li,.mw-parser-output .div-col dd{page-break-inside:avoid;break-inside:avoid-column}</style><div class="div-col div-col-small" style="column-width: 10em;"><style data-mw-deduplicate="TemplateStyles:r981673959">.mw-parser-output .legend{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .legend-color{display:inline-block;min-width:1.25em;height:1.25em;line-height:1.25;margin:1px 0;text-align:center;border:1px solid black;background-color:transparent;color:black}.mw-parser-output .legend-text{}</style><div class="legend">  0</div><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r981673959"><div class="legend">  1</div><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r981673959"><div class="legend">  2</div><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r981673959"><div class="legend">  3–5</div><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r981673959"><div class="legend">  6–12</div><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r981673959"><div class="legend">  13–25</div></div></figcaption></figure> MS is the most common autoimmune disorder of the central nervous system.<a href="#cite_note-pmid24746689-22">[22]</a> The latest estimation of the total number of people with MS was 2.8 million globally, with a <a href="/wiki/Prevalence" title="Prevalence">prevalence</a> of 36 per 100,000 people. Moreover, prevalence varies widely in different regions around the world.<a href="#cite_note-Lane2022-24">[24]</a> In Africa, there are five people per 100,000 diagnosed with MS, compared to South East Asia where the prevalence is nine per 100,000, 112 per 100,000 in the Americas, and 133 per 100,000 in Europe.<a href="#cite_note-211">[211]</a> Increasing rates of MS may be explained simply by better diagnosis.<a href="#cite_note-Milo2010-2">[2]</a> Studies on populational and <a href="#Geography">geographical patterns</a> have been common<a href="#cite_note-pmid8269393-212">[212]</a> and have led to a number of theories about the cause.<a href="#cite_note-Ascherio_2007-17">[17]</a><a href="#cite_note-pmid15556803-74">[74]</a><a href="#cite_note-pmid17492755-84">[84]</a> MS usually appears in adults in their late twenties or early thirties but it can rarely start in childhood and after 50 years of age.<a href="#cite_note-Milo2010-2">[2]</a><a href="#cite_note-Atlas2008-100">[100]</a> The primary progressive subtype is more common in people in their fifties.<a href="#cite_note-pmid17884680-120">[120]</a> Similarly to many autoimmune disorders, the disease is more common in women, and the trend may be increasing.<a href="#cite_note-pmid1897097722-1">[1]</a><a href="#cite_note-pmid18606967-213">[213]</a> As of 2020, globally it is about two times more common in women than in men, and the ratio of women to men with MS is as high as 4:1 in some countries.<a href="#cite_note-214">[214]</a>[<a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">medical citation needed</a>] In children, it is even more common in females than males,<a href="#cite_note-pmid1897097722-1">[1]</a> while in people over fifty, it affects males and females almost equally.<a href="#cite_note-pmid17884680-120">[120]</a> <div class="mw-heading mw-heading2"><h2 id="History">History</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=42" title="Edit section: History">edit</a>]</div> <div class="mw-heading mw-heading3"><h3 id="Medical_discovery">Medical discovery</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=43" title="Edit section: Medical discovery">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Carswell-Multiple_Sclerosis2.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e5/Carswell-Multiple_Sclerosis2.jpg/220px-Carswell-Multiple_Sclerosis2.jpg" decoding="async" width="220" height="309" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/e/e5/Carswell-Multiple_Sclerosis2.jpg 1.5x" data-file-width="299" data-file-height="420" /></a><figcaption>Detail of Carswell's drawing of MS lesions in the <a href="/wiki/Brain_stem" class="mw-redirect" title="Brain stem">brain stem</a> and <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a> (1838)</figcaption></figure> <a href="/wiki/Robert_Carswell_(pathologist)" title="Robert Carswell (pathologist)">Robert Carswell</a> (1793–1857), a British professor of <a href="/wiki/Pathology" title="Pathology">pathology</a>, and <a href="/wiki/Jean_Cruveilhier" title="Jean Cruveilhier">Jean Cruveilhier</a> (1791–1873), a French professor of pathologic anatomy, described and illustrated many of the disease's clinical details, but did not identify it as a separate disease.<a href="#cite_note-pmid3066846-215">[215]</a> Specifically, Carswell described the injuries he found as "a remarkable lesion of the spinal cord accompanied with atrophy".<a href="#cite_note-pmid1897097722-1">[1]</a> Under the microscope, Swiss pathologist <a href="/wiki/Georg_Eduard_Rindfleisch" class="mw-redirect" title="Georg Eduard Rindfleisch">Georg Eduard Rindfleisch</a> (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.<a href="#cite_note-pmid10603616-216">[216]</a><a href="#cite_note-217">[217]</a> The French <a href="/wiki/Neurologist" class="mw-redirect" title="Neurologist">neurologist</a> <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a> (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.<a href="#cite_note-pmid3066846-215">[215]</a> Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. <div class="mw-heading mw-heading3"><h3 id="Diagnosis_history">Diagnosis history</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=44" title="Edit section: Diagnosis history">edit</a>]</div> The first attempt to establish a set of diagnostic criteria was also due to Charcot in 1868. He published what now is known as the "<a href="/wiki/Charcot%27s_neurologic_triad" title="Charcot's neurologic triad">Charcot triad</a>", consisting in nystagmus, <a href="/wiki/Intention_tremor" title="Intention tremor">intention tremor</a>, and <a href="/wiki/Telegraphic_speech" title="Telegraphic speech">telegraphic speech</a> (scanning speech).<a href="#cite_note-Milo-218">[218]</a> Charcot also observed cognition changes, describing his patients as having a "marked enfeeblement of the memory" and "conceptions that formed slowly".<a href="#cite_note-Charcot1-25">[25]</a> Diagnosis was based on Charcot triad and clinical observation until Schumacher made the first attempt to standardize criteria in 1965 by introducing some fundamental requirements: Dissemination of the lesions in time (DIT) and space (DIS), and that "signs and symptoms cannot be explained better by another disease process".<a href="#cite_note-Milo-218">[218]</a> The DIT and DIS requirement was later inherited by the Poser and McDonald criteria, whose 2017 revision is in use.<a href="#cite_note-Milo-218">[218]</a><a href="#cite_note-Oh2018-205">[205]</a> During the 20th century, theories about the cause and pathogenesis were developed and effective treatments began to appear in the 1990s.<a href="#cite_note-pmid1897097722-1">[1]</a> Since the beginning of the 21st century, refinements of the concepts have taken place. The 2010 revision of the McDonald criteria allowed for the diagnosis of MS with only one proved lesion (CIS).<a href="#cite_note-mcdonald2010-219">[219]</a> In 1996, the US National Multiple Sclerosis Society (NMSS) (Advisory Committee on Clinical Trials) defined the first version of the clinical phenotypes that is in use. In this first version they provided standardized definitions for four MS clinical courses: relapsing-remitting (RR), secondary progressive (SP), primary progressive (PP), and progressive relapsing (PR). In 2010, PR was dropped and CIS was incorporated.<a href="#cite_note-mcdonald2010-219">[219]</a> Three years later, the 2013 revision of the "phenotypes for the disease course" were forced to consider CIS as one of the phenotypes of MS, making obsolete some expressions like "conversion from CIS to MS".<a href="#cite_note-220">[220]</a> Other organizations have proposed later new clinical phenotypes, like HAMS (Highly Active MS).<a href="#cite_note-221">[221]</a> <div class="mw-heading mw-heading3"><h3 id="Historical_cases">Historical cases</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=45" title="Edit section: Historical cases">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Animal_locomotion._Plate_541_(Boston_Public_Library).jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/8/85/Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg/220px-Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg" decoding="async" width="220" height="129" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/85/Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg/330px-Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/85/Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg/440px-Animal_locomotion._Plate_541_%28Boston_Public_Library%29.jpg 2x" data-file-width="4256" data-file-height="2492" /></a><figcaption>Photographic study of locomotion of a woman with MS with walking difficulties created in 1887 by <a href="/wiki/Muybridge" class="mw-redirect" title="Muybridge">Muybridge</a></figcaption></figure> There are several historical accounts of people who probably had MS and lived before or shortly after the disease was described by Charcot. A young woman called Halldora who lived in <a href="/wiki/Iceland" title="Iceland">Iceland</a> around 1200 suddenly lost her vision and mobility but recovered them seven days after. <a href="/wiki/Saint_Lidwina" class="mw-redirect" title="Saint Lidwina">Saint Lidwina</a> of <a href="/wiki/Schiedam" title="Schiedam">Schiedam</a> (1380–1433), a Dutch <a href="/wiki/Nun" title="Nun">nun</a>, may be one of the first clearly identifiable people with MS. From the age of 16 until her death at 53, she had intermittent pain, weakness of the legs and vision loss: symptoms typical of MS.<a href="#cite_note-pmid390966-222">[222]</a> Both cases have led to the proposal of a "Viking gene" hypothesis for the dissemination of the disease.<a href="#cite_note-pmid16479124-223">[223]</a> <a href="/wiki/Augustus_d%27Este" title="Augustus d'Este">Augustus Frederick d'Este</a> (1794–1848), son of <a href="/wiki/Prince_Augustus_Frederick,_Duke_of_Sussex" title="Prince Augustus Frederick, Duke of Sussex">Prince Augustus Frederick, Duke of Sussex</a> and <a href="/wiki/Lady_Augusta_Murray" title="Lady Augusta Murray">Lady Augusta Murray</a> and a grandson of <a href="/wiki/George_III_of_the_United_Kingdom" class="mw-redirect" title="George III of the United Kingdom">George III of the United Kingdom</a>, almost certainly had MS. D'Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (<a href="/wiki/Amaurosis_fugax" title="Amaurosis fugax">amaurosis fugax</a>) after the funeral of a friend. During his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbance and <a href="/wiki/Erectile_dysfunction" title="Erectile dysfunction">erectile dysfunction</a>. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.<a href="#cite_note-224">[224]</a><a href="#cite_note-pmid16103678-225">[225]</a> Another early account of MS was kept by the British diarist <a href="/wiki/W._N._P._Barbellion" title="W. N. P. Barbellion">W. N. P. Barbellion</a>, pen name of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle.<a href="#cite_note-pmid16103678-225">[225]</a> His diary was published in 1919 as <a href="/wiki/The_Journal_of_a_Disappointed_Man" title="The Journal of a Disappointed Man">The Journal of a Disappointed Man</a>.<a href="#cite_note-226">[226]</a> <a href="/wiki/Charles_Dickens" title="Charles Dickens">Charles Dickens</a>, a keen observer, described possible bilateral <a href="/wiki/Optic_neuritis" title="Optic neuritis">optic neuritis</a> with reduced contrast vision and <a href="/wiki/Uhthoff%27s_phenomenon" title="Uhthoff's phenomenon">Uhthoff's phenomenon</a> in the main female character of Bleak House (1852–1853), Esther Summerville.<a href="#cite_note-227">[227]</a> <div class="mw-heading mw-heading2"><h2 id="Research">Research</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=46" title="Edit section: Research">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Research_in_multiple_sclerosis" title="Research in multiple sclerosis">Research in multiple sclerosis</a></div> <div class="mw-heading mw-heading3"><h3 id="Epstein-Barr_virus">Epstein-Barr virus</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=47" title="Edit section: Epstein-Barr virus">edit</a>]</div> As of 2022, the pathogenesis of MS as it relates to <a href="/wiki/Epstein%E2%80%93Barr_virus" title="Epstein–Barr virus">Epstein-Barr virus (EBV)</a> is actively investigated, as are disease-modifying therapies; understanding of how risk factors combine with EBV to initiate MS is sought. Whether EBV is the only cause of MS might be better understood if an <a href="/wiki/Epstein%E2%80%93Barr_virus_vaccine" title="Epstein–Barr virus vaccine">EBV vaccine</a> is developed and shown to prevent MS as well.<a href="#cite_note-Aloisi20222-16">[16]</a> Even though a variety of studies showed the connection between an EBV infection and a later development of multiple sclerosis, the mechanisms behind this correlation are not completely clear, and several theories have been proposed to explain the relationship between the two diseases. It is thought that the involvement of EBV-infected <a href="/wiki/B_cell" title="B cell">B-cells</a> (B lymphocytes)<a href="#cite_note-228">[228]</a> and the involvement of anti-<a href="/wiki/EBNA" class="mw-redirect" title="EBNA">EBNA</a> antibodies, which appear to be significantly higher in multiple sclerosis patients, play a crucial role in the development of the disease.<a href="#cite_note-229">[229]</a> This is supported by the fact that treatment against B-cells, e.g. <a href="/wiki/Ocrelizumab" title="Ocrelizumab">ocrelizumab</a>, reduces the symptoms of multiple sclerosis: annual relapses appear less frequently and the disability progression is slower.<a href="#cite_note-230">[230]</a> A 2022 <a href="/wiki/Stanford_University" title="Stanford University">Stanford University</a> study has shown that during an EBV infection, molecular mimicry can occur, where the immune system will produce antibodies against the <a href="/wiki/EBNA" class="mw-redirect" title="EBNA">EBNA</a>1 protein, which at the same time is able to bind to GlialCAM in the myelin. Additionally, they observed a phenomenon which is uncommon in healthy individuals but often detected in multiple sclerosis patients – B-cells are trafficking to the brain and spinal cord, where they are producing oligoclonal antibody bands. A majority of these oligoclonal bands do have an affinity to the viral protein EBNA1, which is cross-reactive to GlialCAM. These antibodies are abundant in approximately 20–25% of multiple sclerosis patients and worsen the autoimmune demyelination which leads consequently to an pathophysiological exacerbation of the disease. Furthermore, the intrathecal oligoclonal expansion with a constant somatic hypermutation is unique in multiple sclerosis when compared to other neuroinflammatory diseases. In the study there was also the abundance of antibodies with IGHV 3–7 genes measured, which appears to be connected to the disease progress. Antibodies which are IGHV3–7-based are binding with a high affinity to EBNA1 and GlialCAM. This process is actively thriving the demyelination. It is probable that B-cells, expressing IGHV 3–7 genes entered the CSF and underwent affinity maturation after facing GlialCAM, which led consequently to the production of high affinity anti-GlialCAM antibodies. This was additionally shown in the EAE mouse model where immunization with EBNA1 lead to a strong B-cell response against GlialCAM, which worsened the EAE.<a href="#cite_note-231">[231]</a> <div class="mw-heading mw-heading3"><h3 id="Human_endogenous_retroviruses">Human endogenous retroviruses</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=48" title="Edit section: Human endogenous retroviruses">edit</a>]</div> Two members of the human endogenous retroviruses-W (<a href="/wiki/HERV" class="mw-redirect" title="HERV">HERV</a>-W) family, namely, ERVWE1 and MS-associated retrovirus (MSRV), may be co-factors in MS immunopathogenesis. HERVs constitute up to 8% of the human genome; most are epigenetically silent, but can be reactivated by exogenous viruses, proinflammatory conditions or oxidative stress.<a href="#cite_note-232">[232]</a><a href="#cite_note-233">[233]</a><a href="#cite_note-234">[234]</a> <div class="mw-heading mw-heading3"><h3 id="Medications_2">Medications</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=49" title="Edit section: Medications">edit</a>]</div> Medications that influence voltage-gated sodium ion channels are under investigation as a potential neuroprotective strategy because of hypothesized role of sodium in the pathological process leading to axonal injury and accumulating disability. There is insufficient evidence of an effect of sodium channel blockers for people with MS.<a href="#cite_note-235">[235]</a> <div class="mw-heading mw-heading3"><h3 id="Pathogenesis">Pathogenesis</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=50" title="Edit section: Pathogenesis">edit</a>]</div> MS is a clinically defined entity with several atypical presentations. Some auto-antibodies have been found in atypical MS cases, giving birth to separate disease families and restricting the previously wider concept of MS. <a href="/wiki/Aquaporin_4" class="mw-redirect" title="Aquaporin 4">Anti-AQP4 autoantibodies</a> were found in <a href="/wiki/Neuromyelitis_optica" class="mw-redirect" title="Neuromyelitis optica">neuromyelitis optica</a> (NMO), which was previously considered a MS variant. A spectrum of diseases named NMOSD (NMO spectrum diseases) or anti-AQP4 diseases has been accepted.<a href="#cite_note-Misu-236">[236]</a> Some cases of MS were presenting <a href="/wiki/Myelin_oligodendrocyte_glycoprotein" title="Myelin oligodendrocyte glycoprotein">anti-MOG autoantibodies</a>, mainly overlapping with the Marburg variant. Anti-MOG autoantibodies were found to be also present in ADEM, and a second spectrum of separated diseases is being considered. This spectrum is named inconsistently across different authors, but it is normally something similar to <a href="/wiki/Anti-MOG_associated_encephalomyelitis" class="mw-redirect" title="Anti-MOG associated encephalomyelitis">anti-MOG demyelinating diseases</a>.<a href="#cite_note-Misu-236">[236]</a> A third kind of auto-antibodies is accepted. They are several <a href="/wiki/Neurofascin" class="mw-redirect" title="Neurofascin">anti-neurofascin</a> auto-antibodies which damage the Ranvier nodes of the neurons. These antibodies are more related to the peripheral nervous demyelination, but they were also found in chronic progressive PPMS and <a href="/wiki/Combined_central_and_peripheral_demyelination" class="mw-redirect" title="Combined central and peripheral demyelination">combined central and peripheral demyelination</a> (CCPD, which is considered another atypical MS presentation).<a href="#cite_note-Kira-237">[237]</a> In addition to the significance of auto-antibodies in MS, four different patterns of demyelination have been reported, opening the door to consider MS as a <a href="/wiki/Heterogeneous_disease" class="mw-redirect" title="Heterogeneous disease">heterogeneous disease</a>.<a href="#cite_note-pmid23917093-238">[238]</a> <div class="mw-heading mw-heading3"><h3 id="Biomarkers">Biomarkers</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=51" title="Edit section: Biomarkers">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Biomarkers_of_multiple_sclerosis" title="Biomarkers of multiple sclerosis">Biomarkers of multiple sclerosis</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Journal.pone.0057573.g005_cropped.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/af/Journal.pone.0057573.g005_cropped.png/170px-Journal.pone.0057573.g005_cropped.png" decoding="async" width="170" height="203" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/af/Journal.pone.0057573.g005_cropped.png/255px-Journal.pone.0057573.g005_cropped.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/af/Journal.pone.0057573.g005_cropped.png/340px-Journal.pone.0057573.g005_cropped.png 2x" data-file-width="437" data-file-height="521" /></a><figcaption><a href="/wiki/Magnetic_resonance_imaging" title="Magnetic resonance imaging">MRI</a> brain scan produced using a Gradient-echo phase sequence showing an iron deposit in a white matter lesion (inside green box in the middle of the image; enhanced and marked by red arrow top-left corner)<a href="#cite_note-pmid23516409-239">[239]</a></figcaption></figure> Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as <a href="/wiki/Neurofilament" title="Neurofilament">neurofilaments</a>, <a href="/wiki/Tau_protein" title="Tau protein">tau</a>, and <a href="/wiki/N-acetylaspartate" class="mw-redirect" title="N-acetylaspartate">N-acetylaspartate</a> are under investigation.<a href="#cite_note-240">[240]</a><a href="#cite_note-241">[241]</a> Improvement in neuroimaging techniques such as <a href="/wiki/Positron_emission_tomography" title="Positron emission tomography">positron emission tomography</a> (PET) or MRI carry a promise for better diagnosis and prognosis predictions. Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, <a href="/wiki/Magnetization_transfer" title="Magnetization transfer">magnetization transfer</a>, <a href="/wiki/Diffusion_MRI#Diffusion_tensor_imaging" class="mw-redirect" title="Diffusion MRI">diffusion tensor</a>, and <a href="/wiki/Functional_magnetic_resonance_imaging" title="Functional magnetic resonance imaging">functional magnetic resonance imaging</a>.<a href="#cite_note-pmid22159052-242">[242]</a> These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values.<a href="#cite_note-pmid22159052-242">[242]</a> This is particularly the case for <a href="/wiki/Proton_magnetic_resonance_spectroscopy" class="mw-redirect" title="Proton magnetic resonance spectroscopy">proton magnetic resonance spectroscopy</a>, for which a number of methodological variations observed in the literature may underlie continued inconsistencies in central nervous system metabolic abnormalities, particularly in <a href="/wiki/N-acetyl_aspartate" class="mw-redirect" title="N-acetyl aspartate">N-acetyl aspartate</a>, <a href="/wiki/Myoinositol" class="mw-redirect" title="Myoinositol">myoinositol</a>, <a href="/wiki/Choline" title="Choline">choline</a>, <a href="/wiki/Glutamate_(neurotransmitter)" title="Glutamate (neurotransmitter)">glutamate</a>, <a href="/wiki/GABA" title="GABA">GABA</a>, and <a href="/wiki/Glutathione" title="Glutathione">GSH</a>, observed for multiple sclerosis and its subtypes.<a href="#cite_note-243">[243]</a> There are other techniques under development that include contrast agents capable of measuring levels of peripheral <a href="/wiki/Macrophage" title="Macrophage">macrophages</a>, inflammation, or neuronal dysfunction,<a href="#cite_note-pmid22159052-242">[242]</a> and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion.<a href="#cite_note-pmid22159052-242">[242]</a> <div class="mw-heading mw-heading3"><h3 id="COVID-19">COVID-19</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=52" title="Edit section: COVID-19">edit</a>]</div> The hospitalization rate was found to be higher among individuals with MS and COVID-19 infection, at 10%, while the pooled infection rate is estimated at 4%. The pooled prevalence of death in hospitalized individuals with MS is estimated as 4%.<a href="#cite_note-244">[244]</a> <div class="mw-heading mw-heading3"><h3 id="Metformin">Metformin</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=53" title="Edit section: Metformin">edit</a>]</div> A 2019 study on rats and a 2024 study on mice showed that a first-line medication for the treatment of <a href="/wiki/Type_2_diabetes" title="Type 2 diabetes">type 2 diabetes</a>, <a href="/wiki/Metformin" title="Metformin">metformin</a>, could promote <a href="/wiki/Remyelination" title="Remyelination">remyelination</a>.<a href="#cite_note-245">[245]</a><a href="#cite_note-246">[246]</a> The promising drug is currently being researched on humans in the Octopus trials, a multi-arm, multi-stage trial, focussed on testing existing drugs for other conditions on patients with MS.<a href="#cite_note-247">[247]</a> Currently, clinical trials on humans are ongoing in <a href="/wiki/Belgium" title="Belgium">Belgium</a>, for patients with non-active progressive MS,<a href="#cite_note-248">[248]</a> in the <a href="/wiki/United_Kingdom" title="United Kingdom">U.K.</a>, in combination with <a href="/wiki/Clemastine" title="Clemastine">clemastine</a> for the treatment of relapsing remitting MS,<a href="#cite_note-249">[249]</a> and <a href="/wiki/Canada" title="Canada">Canada</a>, for MS patients up to 25 years old.<a href="#cite_note-250">[250]</a><a href="#cite_note-251">[251]</a> <div class="mw-heading mw-heading3"><h3 id="Other_emerging_theories">Other emerging theories</h3>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=54" title="Edit section: Other emerging theories">edit</a>]</div> One emerging hypothesis, referred to as the hygiene hypothesis, suggests that early-life exposure to infectious agents helps to develop the immune system and reduces susceptibility to allergies and autoimmune disorders. The hygiene hypothesis has been linked with MS and <a href="/wiki/Microbiome" title="Microbiome">microbiome</a> hypotheses.<a href="#cite_note-252">[252]</a> It has also been proposed that certain bacteria found in the gut use molecular mimicry to infiltrate the brain via the <a href="/wiki/Gut%E2%80%93brain_axis" title="Gut–brain axis">gut–brain axis</a>, initiating an inflammatory response and increasing blood-brain barrier permeability. <a href="/wiki/Vitamin_D" title="Vitamin D">Vitamin D</a> levels have also been correlated with MS; lower levels of vitamin D correspond to an increased risk of MS, suggesting a reduced prevalence in the tropics – an area with more Vitamin D-rich sunlight – strengthening the impact of geographical location on MS development.<a href="#cite_note-253">[253]</a> MS mechanisms begin when peripheral <a href="/wiki/Autoreactive_lymphocyte" class="mw-redirect" title="Autoreactive lymphocyte">autoreactive</a> effector <a href="/wiki/CD4%2B_T_cells" class="mw-redirect" title="CD4+ T cells">CD4+ T cells</a> get activated and move into the CNS. <a href="/wiki/Antigen-presenting_cell" title="Antigen-presenting cell">Antigen-presenting cells</a> localize the reactivation of autoreactive effector CD4-T cells once they have entered the CNS, attracting more T cells and macrophages to form the inflammatory lesion.<a href="#cite_note-254">[254]</a>[<a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">medical citation needed</a>] In MS patients, macrophages and microglia assemble at locations where demyelination and neurodegeneration are actively occurring, and microglial activation is more apparent in the normal-appearing white matter of MS patients.<a href="#cite_note-255">[255]</a> <a href="/wiki/Astrocyte" title="Astrocyte">Astrocytes</a> generate neurotoxic chemicals like <a href="/wiki/Nitric_oxide" title="Nitric oxide">nitric oxide</a> and <a href="/wiki/TNF%CE%B1" class="mw-redirect" title="TNFα">TNFα</a>, attract neurotoxic inflammatory <a href="/wiki/Monocyte" title="Monocyte">monocytes</a> to the CNS, and are responsible for <a href="/wiki/Astrogliosis" title="Astrogliosis">astrogliosis</a>, the scarring that prevents the spread of neuroinflammation and kills neurons inside the scarred area.<a href="#cite_note-256">[256]</a>[<a href="/wiki/Wikipedia:NOTRS" class="mw-redirect" title="Wikipedia:NOTRS">better source needed</a>] In 2024, scientists shared research on their findings of ancient migration to northern Europe from the <a href="/wiki/Yamnaya_culture" title="Yamnaya culture">Yamnaya area of culture</a>,<a href="#cite_note-257">[257]</a> tracing MS-risk gene variants dating back around 5,000 years.<a href="#cite_note-258">[258]</a><a href="#cite_note-259">[259]</a> The MS-risk gene variants protected ancient cattle herders from animal diseases,<a href="#cite_note-260">[260]</a> but modern lifestyles, diets and better hygiene, have allowed the gene to develop, resulting in the higher risk of MS today.<a href="#cite_note-261">[261]</a> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=55" title="Edit section: See also">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1239009302">.mw-parser-output .portalbox{padding:0;margin:0.5em 0;display:table;box-sizing:border-box;max-width:175px;list-style:none}.mw-parser-output .portalborder{border:1px solid var(--border-color-base,#a2a9b1);padding:0.1em;background:var(--background-color-neutral-subtle,#f8f9fa)}.mw-parser-output .portalbox-entry{display:table-row;font-size:85%;line-height:110%;height:1.9em;font-style:italic;font-weight:bold}.mw-parser-output .portalbox-image{display:table-cell;padding:0.2em;vertical-align:middle;text-align:center}.mw-parser-output .portalbox-link{display:table-cell;padding:0.2em 0.2em 0.2em 0.3em;vertical-align:middle}@media(min-width:720px){.mw-parser-output .portalleft{clear:left;float:left;margin:0.5em 1em 0.5em 0}.mw-parser-output .portalright{clear:right;float:right;margin:0.5em 0 0.5em 1em}}</style><ul role="navigation" aria-label="Portals" class="noprint portalbox portalborder portalright"> <li class="portalbox-entry"><img alt="icon" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/12px-WHO_Rod.svg.png" decoding="async" width="12" height="28" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/18px-WHO_Rod.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/24px-WHO_Rod.svg.png 2x" data-file-width="107" data-file-height="250" /><a href="/wiki/Portal:Medicine" title="Portal:Medicine">Medicine portal</a></li></ul> <ul><li><a href="/wiki/List_of_multiple_sclerosis_organizations" title="List of multiple sclerosis organizations">List of multiple sclerosis organizations</a></li> <li><a href="/wiki/List_of_people_with_multiple_sclerosis" title="List of people with multiple sclerosis">List of people with multiple sclerosis</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2>[<a href="/w/index.php?title=Multiple_sclerosis&action=edit&section=56" title="Edit section: References">edit</a>]</div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output 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"Elevated genetic risk for multiple sclerosis originated in Steppe Pastoralist populations". <a href="/wiki/BioRxiv_(identifier)" class="mw-redirect" title="BioRxiv (identifier)">bioRxiv</a> <a rel="nofollow" class="external text" href="https://doi.org/10.1101%2F2023.10.06.561165">10.1101/2023.10.06.561165</a>. <q>Our findings also support the interpretation of increased pathogen pressure as a driver of positive selection on immunogenetic variants associated with risk of the autoimmune disease multiple sclerosis in Steppe populations around 5,000 years ago<a href="//doi.org/10.1101/2022.09.23.509097" class="extiw" title="doi:10.1101/2022.09.23.509097">[59]</a></q></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=preprint&rft.jtitle=bioRxiv&rft.atitle=Elevated+genetic+risk+for+multiple+sclerosis+originated+in+Steppe+Pastoralist+populations.&rft.date=2023-10-06&rft_id=https%3A%2F%2Fdoi.org%2F10.1101%2F2023.10.06.561165%23id-name%3DbioRxiv&rft.aulast=Barrie&rft.aufirst=W&rft.au=Yang%2C+Y&rft.au=Irving-Pease%2C+E&rft.au=Attfield%2C+KE&rft.au=Scorrano%2C+G&rft.au=Jensen%2C+LT&rft.au=Armen%2C+AP&rft.au=Dimopoulos%2C+EA&rft.au=Stern%2C+A&rft.au=Refoyo-Martinez%2C+A&rft.au=Pearson%2C+A&rfr_id=info%3Asid%2Fen.wikipedia.org%3AMultiple+sclerosis" class="Z3988"> </li> <li id="cite_note-261"><a href="#cite_ref-261">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.nationalmssociety.org/About-the-Society/News/Novel-Study-Suggests-that-MS-was-Brought-to-Northe">"Novel Study Suggests that MS was Brought to Northern Europe 5,000 Years Ago"</a>. 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dd:last-child::after,.mw-parser-output .hlist li dt:last-child::after,.mw-parser-output .hlist li li:last-child::after{content:")";font-weight:normal}.mw-parser-output .hlist ol{counter-reset:listitem}.mw-parser-output .hlist ol>li{counter-increment:listitem}.mw-parser-output .hlist ol>li::before{content:" "counter(listitem)"\a0 "}.mw-parser-output .hlist dd ol>li:first-child::before,.mw-parser-output .hlist dt ol>li:first-child::before,.mw-parser-output .hlist li ol>li:first-child::before{content:" ("counter(listitem)"\a0 "}</style><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"></div><div role="navigation" class="navbox" aria-label="Navbox" style="width:100%; margin:0.5em 0 0.5em 0;;padding:3px"><table class="nowraplinks navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;background: #EAECF0;color:black;">Classification</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><div style="position:relative; float:right; font-size:0.8em;"><a href="https://www.wikidata.org/wiki/Q8277" class="extiw" title="d:Q8277">D</a></div><div class="hlist" style="text-align:left;"><ul><li><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/ICD-11" title="ICD-11">11</a>: <a rel="nofollow" class="external text" href="https://icd.who.int/browse/latest-release/mms/en#1298865187">8A40</a></li><li><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/ICD-10" title="ICD-10">10</a>: <a rel="nofollow" class="external text" href="https://icd.who.int/browse10/2019/en#/G35">G35</a></li><li><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/List_of_ICD-9_codes" title="List of ICD-9 codes">9-CM</a>: <a rel="nofollow" class="external text" href="http://www.icd9data.com/getICD9Code.ashx?icd9=340">340</a></li><li><a href="/wiki/Online_Mendelian_Inheritance_in_Man" title="Online Mendelian Inheritance in Man">OMIM</a>: <a rel="nofollow" class="external text" href="https://omim.org/entry/126200">126200</a></li><li><a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">MeSH</a>: <a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?ui=D009103">D009103</a></li><li><a href="/wiki/Diseases_Database" title="Diseases Database">DiseasesDB</a>: <a rel="nofollow" class="external text" href="http://www.diseasesdatabase.com/ddb8412.htm">8412</a></li></ul></div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background: #EAECF0;color:black;">External resources</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"><div class="hlist" style="text-align:left;"><ul><li><a href="/wiki/MedlinePlus" title="MedlinePlus">MedlinePlus</a>: <a rel="nofollow" class="external text" href="https://www.nlm.nih.gov/medlineplus/ency/article/000737.htm">000737</a></li><li><a href="/wiki/EMedicine" title="EMedicine">eMedicine</a>: <a rel="nofollow" class="external text" href="https://emedicine.medscape.com/neuro/228-overview">neuro/228</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/oph/topic179.htm#">oph/179</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/emerg/topic321.htm#">emerg/321</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/pmr/topic82.htm#">pmr/82</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/radio/topic461.htm#">radio/461</a></li><li><a href="/wiki/Patient_UK" title="Patient UK">Patient UK</a>: <a rel="nofollow" class="external text" href="https://patient.info/doctor/multiple-sclerosis-pro">Multiple sclerosis</a></li><li><a href="/wiki/GeneReviews" title="GeneReviews">GeneReviews</a>: <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/books/NBK1316/">Overview</a></li></ul></div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Demyelinating_diseases_of_the_central_nervous_system" style="padding:3px"><table class="nowraplinks hlist mw-collapsible expanded navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Demyelinating_diseases_of_CNS" title="Template:Demyelinating diseases of CNS"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Demyelinating_diseases_of_CNS" title="Template talk:Demyelinating diseases of CNS"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Demyelinating_diseases_of_CNS" title="Special:EditPage/Template:Demyelinating diseases of CNS"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Demyelinating_diseases_of_the_central_nervous_system" style="font-size:114%;margin:0 4em">Demyelinating diseases of the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Signs_and_symptoms_of_multiple_sclerosis" title="Signs and symptoms of multiple sclerosis">Signs and symptoms</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ataxia" title="Ataxia">Ataxia</a></li> <li><a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">Depression</a></li> <li><a href="/wiki/Diplopia" title="Diplopia">Diplopia</a></li> <li><a href="/wiki/Dysarthria" title="Dysarthria">Dysarthria</a></li> <li><a href="/wiki/Dysphagia" title="Dysphagia">Dysphagia</a></li> <li><a href="/wiki/Fatigue" title="Fatigue">Fatigue</a></li> <li><a href="/wiki/Urinary_incontinence" title="Urinary incontinence">Incontinence</a></li> <li><a href="/wiki/Nystagmus" title="Nystagmus">Nystagmus</a></li> <li><a href="/wiki/Optic_neuritis" title="Optic neuritis">Optic neuritis</a></li> <li><a href="/wiki/Pain" title="Pain">Pain</a></li> <li><a href="/wiki/Uhthoff%27s_phenomenon" title="Uhthoff's phenomenon">Uhthoff's phenomenon</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Investigations and diagnosis</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Diagnosis_of_multiple_sclerosis" title="Diagnosis of multiple sclerosis">Diagnosis of multiple sclerosis</a> <ul><li><a href="/wiki/McDonald_criteria" title="McDonald criteria">McDonald criteria</a></li></ul></li> <li><a href="/wiki/Poser_criteria" title="Poser criteria">Poser criteria</a></li></ul> <ul><li>Clinical <ul><li><a href="/wiki/Clinically_isolated_syndrome" title="Clinically isolated syndrome">Clinically isolated syndrome</a></li> <li><a href="/wiki/Expanded_Disability_Status_Scale" title="Expanded Disability Status Scale">Expanded Disability Status Scale</a></li></ul></li> <li>Serological and CSF <ul><li><a href="/wiki/Oligoclonal_band" title="Oligoclonal band">Oligoclonal bands</a></li></ul></li> <li>Radiological <ul><li><a href="/wiki/Radiologically_isolated_syndrome" title="Radiologically isolated syndrome">Radiologically isolated syndrome</a></li> <li><a href="/wiki/Lesional_demyelinations_of_the_central_nervous_system" title="Lesional demyelinations of the central nervous system">Lesional demyelinations of the central nervous system</a></li> <li><a href="/wiki/Dawson%27s_fingers" class="mw-redirect" title="Dawson's fingers">Dawson's fingers</a></li></ul></li> <li><a href="/wiki/Frexalimab" title="Frexalimab">Frexalimab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Approved treatment</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Management_of_multiple_sclerosis" title="Management of multiple sclerosis">Management of multiple sclerosis</a></li> <li><a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a></li> <li><a href="/wiki/Cladribine" title="Cladribine">Cladribine</a></li> <li><a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">Dimethyl fumarate</a></li> <li><a href="/wiki/Diroximel_fumarate" title="Diroximel fumarate">Diroximel fumarate</a></li> <li><a href="/wiki/Fingolimod" title="Fingolimod">Fingolimod</a></li> <li><a href="/wiki/Glatiramer_acetate" title="Glatiramer acetate">Glatiramer acetate</a></li> <li><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a></li> <li><a href="/wiki/Interferon_beta-1b" title="Interferon beta-1b">Interferon beta-1b</a></li> <li><a href="/wiki/Laquinimod" title="Laquinimod">Laquinimod</a></li> <li><a href="/wiki/Mitoxantrone" title="Mitoxantrone">Mitoxantrone</a></li> <li><a href="/wiki/Monomethyl_fumarate" title="Monomethyl fumarate">Monomethyl fumarate</a></li> <li><a href="/wiki/Natalizumab" title="Natalizumab">Natalizumab</a></li> <li><a href="/wiki/Ocrelizumab" title="Ocrelizumab">Ocrelizumab</a> (<a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Ozanimod" title="Ozanimod">Ozanimod</a></li> <li><a href="/wiki/Ponesimod" title="Ponesimod">Ponesimod</a></li> <li><a href="/wiki/Siponimod" title="Siponimod">Siponimod</a></li> <li><a href="/wiki/Teriflunomide" title="Teriflunomide">Teriflunomide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other treatments</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Former <ul><li><a href="/wiki/Daclizumab" title="Daclizumab">Daclizumab</a></li></ul></li> <li><a href="/wiki/Research_in_multiple_sclerosis" title="Research in multiple sclerosis">Research in multiple sclerosis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Demyelinating diseases</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/CNS_demyelinating_autoimmune_diseases" title="CNS demyelinating autoimmune diseases">Autoimmune</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Neuromyelitis_optica_spectrum_disorder" title="Neuromyelitis optica spectrum disorder">Neuromyelitis optica spectrum disorder</a></li> <li><a href="/wiki/Diffuse_myelinoclastic_sclerosis" title="Diffuse myelinoclastic sclerosis">Diffuse myelinoclastic sclerosis</a></li> <li><a href="/wiki/MOG_antibody_disease" title="MOG antibody disease">MOG antibody disease</a></li> <li><a class="mw-selflink selflink">Multiple sclerosis</a></li> <li><a href="/wiki/Chronic_inflammatory_demyelinating_polyneuropathy" title="Chronic inflammatory demyelinating polyneuropathy">Chronic inflammatory demyelinating polyneuropathy</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Inflammatory_demyelinating_diseases_of_the_central_nervous_system" title="Inflammatory demyelinating diseases of the central nervous system">Inflammatory</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Acute_disseminated_encephalomyelitis" title="Acute disseminated encephalomyelitis">Acute disseminated encephalomyelitis</a></li> <li><a href="/wiki/Balo_concentric_sclerosis" title="Balo concentric sclerosis">Balo concentric sclerosis</a></li> <li><a href="/wiki/Marburg_acute_multiple_sclerosis" title="Marburg acute multiple sclerosis">Marburg acute multiple sclerosis</a></li> <li><a href="/wiki/Neuromyelitis_optica_spectrum_disorder" title="Neuromyelitis optica spectrum disorder">Neuromyelitis optica spectrum disorder</a></li> <li><a href="/wiki/Diffuse_myelinoclastic_sclerosis" title="Diffuse myelinoclastic sclerosis">Diffuse myelinoclastic sclerosis</a></li> <li><a href="/wiki/Tumefactive_multiple_sclerosis" title="Tumefactive multiple sclerosis">Tumefactive multiple sclerosis</a></li> <li><a href="/wiki/Experimental_autoimmune_encephalomyelitis" title="Experimental autoimmune encephalomyelitis">Experimental autoimmune encephalomyelitis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Hereditary_CNS_demyelinating_disease" title="Hereditary CNS demyelinating disease">Hereditary</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adrenoleukodystrophy" title="Adrenoleukodystrophy">Adrenoleukodystrophy</a></li> <li><a href="/wiki/Alexander_disease" title="Alexander disease">Alexander disease</a></li> <li><a href="/wiki/Canavan_disease" title="Canavan disease">Canavan disease</a></li> <li><a href="/wiki/Krabbe_disease" title="Krabbe disease">Krabbe disease</a></li> <li><a href="/wiki/Metachromatic_leukodystrophy" title="Metachromatic leukodystrophy">Metachromatic leukodystrophy</a></li> <li><a href="/wiki/Pelizaeus%E2%80%93Merzbacher_disease" title="Pelizaeus–Merzbacher disease">Pelizaeus–Merzbacher disease</a></li> <li><a href="/wiki/Leukoencephalopathy_with_vanishing_white_matter" title="Leukoencephalopathy with vanishing white matter">Leukoencephalopathy with vanishing white matter</a></li> <li><a href="/wiki/Megalencephalic_leukoencephalopathy_with_subcortical_cysts" title="Megalencephalic leukoencephalopathy with subcortical cysts">Megalencephalic leukoencephalopathy with subcortical cysts</a></li> <li><a href="/wiki/CAMFAK_syndrome" title="CAMFAK syndrome">CAMFAK syndrome</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Central_pontine_myelinolysis" title="Central pontine myelinolysis">Central pontine myelinolysis</a></li> <li><a href="/wiki/Marchiafava%E2%80%93Bignami_disease" title="Marchiafava–Bignami disease">Marchiafava–Bignami disease</a></li> <li><a href="/wiki/Mitochondrial_DNA_depletion_syndrome" title="Mitochondrial DNA depletion syndrome">Mitochondrial DNA depletion syndrome</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/List_of_multiple_sclerosis_organizations" title="List of multiple sclerosis organizations">List of multiple sclerosis organizations</a></li> <li><a href="/wiki/List_of_people_with_multiple_sclerosis" title="List of people with multiple sclerosis">List of people with multiple sclerosis</a></li> <li><a href="/wiki/Multiple_sclerosis_drug_pipeline" title="Multiple sclerosis drug pipeline">Multiple sclerosis drug pipeline</a></li> <li><a href="/wiki/Pathophysiology_of_multiple_sclerosis" title="Pathophysiology of multiple sclerosis">Pathophysiology</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Diseases_of_the_nervous_system,_primarily_CNS" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Central_nervous_system_disease" title="Template:Central nervous system disease"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Central_nervous_system_disease" title="Template talk:Central nervous system disease"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Central_nervous_system_disease" title="Special:EditPage/Template:Central nervous system disease"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Diseases_of_the_nervous_system,_primarily_CNS" style="font-size:114%;margin:0 4em">Diseases of the <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a>, primarily <a href="/wiki/Central_nervous_system_disease" title="Central nervous system disease">CNS</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Inflammation" title="Inflammation">Inflammation</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Brain" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Human_brain" title="Human brain">Brain</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Encephalitis" title="Encephalitis">Encephalitis</a> <ul><li><a href="/wiki/Viral_encephalitis" title="Viral encephalitis">Viral encephalitis</a></li> <li><a href="/wiki/Herpesviral_encephalitis" class="mw-redirect" title="Herpesviral encephalitis">Herpesviral encephalitis</a></li> <li><a href="/wiki/Limbic_encephalitis" title="Limbic encephalitis">Limbic encephalitis</a></li> <li><a href="/wiki/Encephalitis_lethargica" title="Encephalitis lethargica">Encephalitis lethargica</a></li></ul></li> <li><a href="/wiki/Cavernous_sinus_thrombosis" title="Cavernous sinus thrombosis">Cavernous sinus thrombosis</a></li> <li><a href="/wiki/Brain_abscess" title="Brain abscess">Brain abscess</a> <ul><li><a href="/wiki/Amoebic_brain_abscess" title="Amoebic brain abscess">Amoebic</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Brain and <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Encephalomyelitis" title="Encephalomyelitis">Encephalomyelitis</a> <ul><li><a href="/wiki/Acute_disseminated_encephalomyelitis" title="Acute disseminated encephalomyelitis">Acute disseminated</a></li></ul></li> <li><a href="/wiki/Meningitis" title="Meningitis">Meningitis</a></li> <li><a href="/wiki/Meningoencephalitis" title="Meningoencephalitis">Meningoencephalitis</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Human_brain" title="Human brain">Brain</a>/ <a href="/wiki/Encephalopathy" title="Encephalopathy">encephalopathy</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Neurodegenerative_disease" title="Neurodegenerative disease">Degenerative</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Extrapyramidal_system" title="Extrapyramidal system">Extrapyramidal</a> and <a href="/wiki/Movement_disorders" class="mw-redirect" title="Movement disorders">movement disorders</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Basal_ganglia_disease" title="Basal ganglia disease">Basal ganglia disease</a> <ul><li><a href="/wiki/Parkinsonism" title="Parkinsonism">Parkinsonism</a> <ul><li><a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">PD</a></li> <li><a href="/wiki/Postencephalitic_parkinsonism" class="mw-redirect" title="Postencephalitic parkinsonism">Postencephalitic</a></li> <li><a href="/wiki/Neuroleptic_malignant_syndrome" title="Neuroleptic malignant syndrome">NMS</a></li></ul></li> <li><a href="/wiki/Neurodegeneration_with_brain_iron_accumulation" title="Neurodegeneration with brain iron accumulation">NBIA</a> <ul><li><a href="/wiki/Pantothenate_kinase-associated_neurodegeneration" title="Pantothenate kinase-associated neurodegeneration">PKAN</a></li></ul></li> <li><a href="/wiki/Tauopathy" title="Tauopathy">Tauopathy</a> <ul><li><a href="/wiki/Progressive_supranuclear_palsy" title="Progressive supranuclear palsy">PSP</a></li></ul></li> <li><a href="/wiki/Multiple_system_atrophy" title="Multiple system atrophy">Striatonigral degeneration</a></li> <li><a href="/wiki/Hemiballismus" title="Hemiballismus">Hemiballismus</a></li> <li><a href="/wiki/Huntington%27s_disease" title="Huntington's disease">HD</a></li> <li><a href="/wiki/Olivopontocerebellar_atrophy" class="mw-redirect" title="Olivopontocerebellar atrophy">OA</a></li></ul></li></ul> <ul><li><a href="/wiki/Dyskinesia" title="Dyskinesia">Dyskinesia</a> <ul><li><a href="/wiki/Dystonia" title="Dystonia">Dystonia</a> <ul><li><a href="/wiki/Status_dystonicus" title="Status dystonicus">Status dystonicus</a></li> <li><a href="/wiki/Spasmodic_torticollis" title="Spasmodic torticollis">Spasmodic torticollis</a></li> <li><a href="/wiki/Meige%27s_syndrome" title="Meige's syndrome">Meige's</a></li> <li><a href="/wiki/Blepharospasm" title="Blepharospasm">Blepharospasm</a></li></ul></li> <li><a href="/wiki/Athetosis" title="Athetosis">Athetosis</a></li> <li><a href="/wiki/Chorea" title="Chorea">Chorea</a> <ul><li><a href="/wiki/Choreoathetosis" title="Choreoathetosis">Choreoathetosis</a></li></ul></li> <li><a href="/wiki/Myoclonus" title="Myoclonus">Myoclonus</a> <ul><li><a href="/wiki/Myoclonic_epilepsy" title="Myoclonic epilepsy">Myoclonic epilepsy</a></li></ul></li> <li><a href="/wiki/Akathisia" title="Akathisia">Akathisia</a></li></ul></li></ul> <ul><li><a href="/wiki/Tremor" title="Tremor">Tremor</a> <ul><li><a href="/wiki/Essential_tremor" title="Essential tremor">Essential tremor</a></li> <li><a href="/wiki/Intention_tremor" title="Intention tremor">Intention tremor</a></li></ul></li> <li><a href="/wiki/Restless_legs_syndrome" title="Restless legs syndrome">Restless legs</a></li> <li><a href="/wiki/Stiff-person_syndrome" title="Stiff-person syndrome">Stiff-person</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Dementia" title="Dementia">Dementia</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Tauopathy" title="Tauopathy">Tauopathy</a> <ul><li><a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's</a> <ul><li><a href="/wiki/Early-onset_Alzheimer%27s_disease" title="Early-onset Alzheimer's disease">Early-onset</a></li></ul></li> <li><a href="/wiki/Primary_progressive_aphasia" title="Primary progressive aphasia">Primary progressive aphasia</a></li></ul></li> <li><a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">Frontotemporal dementia</a>/<a href="/wiki/Frontotemporal_lobar_degeneration" title="Frontotemporal lobar degeneration">Frontotemporal lobar degeneration</a> <ul><li><a href="/wiki/Pick%27s_disease" class="mw-redirect" title="Pick's disease">Pick's</a></li></ul></li> <li><a href="/wiki/Lewy_bodies_dementia" class="mw-redirect" title="Lewy bodies dementia">Lewy bodies dementia</a></li> <li><a href="/wiki/Posterior_cortical_atrophy" title="Posterior cortical atrophy">Posterior cortical atrophy</a></li></ul> <a href="/wiki/Creutzfeldt%E2%80%93Jakob_disease" title="Creutzfeldt–Jakob disease">Creutzfeldt–Jakob disease</a> <ul><li><a href="/wiki/Vascular_dementia" title="Vascular dementia">Vascular dementia</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Mitochondrial_disease" title="Mitochondrial disease">Mitochondrial disease</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Leigh_syndrome" title="Leigh syndrome">Leigh syndrome</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Demyelinating_disease" title="Demyelinating disease">Demyelinating</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CNS_demyelinating_autoimmune_diseases" title="CNS demyelinating autoimmune diseases">Autoimmune</a></li> <li><a href="/wiki/Inflammatory_demyelinating_diseases_of_the_central_nervous_system" title="Inflammatory demyelinating diseases of the central nervous system">Inflammatory</a></li> <li><a class="mw-selflink selflink">Multiple sclerosis</a></li> <li>For more detailed coverage, see <a href="/wiki/Template:Demyelinating_diseases_of_CNS" title="Template:Demyelinating diseases of CNS">Template:Demyelinating diseases of CNS</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Episodic/ <a href="/wiki/Paroxysmal_attack" title="Paroxysmal attack">paroxysmal</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Epileptic_seizure" class="mw-redirect" title="Epileptic seizure">Seizures</a> and <a href="/wiki/Epilepsy" title="Epilepsy">epilepsy</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Focal_seizure" title="Focal seizure">Focal</a></li> <li><a href="/wiki/Generalized_epilepsy" title="Generalized epilepsy">Generalised</a></li> <li><a href="/wiki/Status_epilepticus" title="Status epilepticus">Status epilepticus</a></li> <li>For more detailed coverage, see <a href="/wiki/Template:Epilepsy" class="mw-redirect" title="Template:Epilepsy">Template:Epilepsy</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Headache" title="Headache">Headache</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Migraine" title="Migraine">Migraine</a></li> <li><a href="/wiki/Cluster_headache" title="Cluster headache">Cluster</a></li> <li><a href="/wiki/Tension_headache" title="Tension headache">Tension</a></li> <li>For more detailed coverage, see <a href="/wiki/Template:Headache" title="Template:Headache">Template:Headache</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cerebrovascular_disease" title="Cerebrovascular disease">Cerebrovascular</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Transient_ischemic_attack" title="Transient ischemic attack">TIA</a></li> <li><a href="/wiki/Stroke" title="Stroke">Stroke</a></li> <li>For more detailed coverage, see <a href="/wiki/Template:Cerebrovascular_diseases" title="Template:Cerebrovascular diseases">Template:Cerebrovascular diseases</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Sleep_disorders" class="mw-redirect" title="Sleep disorders">Sleep disorders</a> <ul><li>For more detailed coverage, see <a href="/wiki/Template:Sleep" title="Template:Sleep">Template:Sleep</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cerebrospinal_fluid" title="Cerebrospinal fluid">CSF</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Intracranial_pressure" title="Intracranial pressure">Intracranial hypertension</a> <ul><li><a href="/wiki/Hydrocephalus" title="Hydrocephalus">Hydrocephalus</a></li> <li><a href="/wiki/Normal_pressure_hydrocephalus" title="Normal pressure hydrocephalus">Normal pressure hydrocephalus</a></li> <li><a href="/wiki/Choroid_plexus_papilloma" title="Choroid plexus papilloma">Choroid plexus papilloma</a></li> <li><a href="/wiki/Idiopathic_intracranial_hypertension" title="Idiopathic intracranial hypertension">Idiopathic intracranial hypertension</a></li></ul></li> <li><a href="/wiki/Cerebral_edema" title="Cerebral edema">Cerebral edema</a></li> <li><a href="/wiki/Spontaneous_cerebrospinal_fluid_leak" class="mw-redirect" title="Spontaneous cerebrospinal fluid leak">Intracranial hypotension</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Brain_herniation" title="Brain herniation">Brain herniation</a></li> <li><a href="/wiki/Reye_syndrome" title="Reye syndrome">Reye syndrome</a></li> <li><a href="/wiki/Hepatic_encephalopathy" title="Hepatic encephalopathy">Hepatic encephalopathy</a></li> <li><a href="/wiki/Toxic_encephalopathy" title="Toxic encephalopathy">Toxic encephalopathy</a></li> <li><a href="/wiki/Hashimoto%27s_encephalopathy" title="Hashimoto's encephalopathy">Hashimoto's encephalopathy</a></li> <li><a href="/wiki/Fetal_alcohol_spectrum_disorder" title="Fetal alcohol spectrum disorder">Static encephalopathy</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Both/either</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Degenerative" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Neurodegenerative_disease" title="Neurodegenerative disease">Degenerative</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Spinocerebellar_ataxia" title="Spinocerebellar ataxia">SA</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Friedreich%27s_ataxia" title="Friedreich's ataxia">Friedreich's ataxia</a></li> <li><a href="/wiki/Ataxia%E2%80%93telangiectasia" title="Ataxia–telangiectasia">Ataxia–telangiectasia</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">MND</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Upper_motor_neuron" title="Upper motor neuron">UMN</a> only: <ul><li><a href="/wiki/Primary_lateral_sclerosis" title="Primary lateral sclerosis">Primary lateral sclerosis</a></li> <li><a href="/wiki/Pseudobulbar_palsy" title="Pseudobulbar palsy">Pseudobulbar palsy</a></li> <li><a href="/wiki/Hereditary_spastic_paraplegia" title="Hereditary spastic paraplegia">Hereditary spastic paraplegia</a></li></ul></li></ul> <ul><li><a href="/wiki/Lower_motor_neuron" title="Lower motor neuron">LMN</a> only: <ul><li><a href="/wiki/Distal_hereditary_motor_neuronopathies" title="Distal hereditary motor neuronopathies">Distal hereditary motor neuronopathies</a></li> <li><a href="/wiki/Spinal_muscular_atrophies" title="Spinal muscular atrophies">Spinal muscular atrophies</a> <ul><li><a href="/wiki/Spinal_muscular_atrophy" title="Spinal muscular atrophy">SMA</a></li> <li><a href="/wiki/Spinal_and_bulbar_muscular_atrophy" title="Spinal and bulbar muscular atrophy">SMAX1</a></li> <li><a href="/wiki/X-linked_spinal_muscular_atrophy_type_2" title="X-linked spinal muscular atrophy type 2">SMAX2</a></li> <li><a href="/wiki/Distal_spinal_muscular_atrophy_type_1" title="Distal spinal muscular atrophy type 1">DSMA1</a></li> <li><a href="/wiki/Congenital_distal_spinal_muscular_atrophy" title="Congenital distal spinal muscular atrophy">Congenital DSMA</a></li> <li>Spinal muscular atrophy with lower extremity predominance (SMALED) <ul><li><a href="/wiki/Spinal_muscular_atrophy_with_lower_extremity_predominance_1" title="Spinal muscular atrophy with lower extremity predominance 1">SMALED1</a></li> <li><a href="/wiki/Spinal_muscular_atrophy_with_lower_extremity_predominance_2A" title="Spinal muscular atrophy with lower extremity predominance 2A">SMALED2A</a></li> <li><a href="/wiki/Spinal_muscular_atrophy_with_lower_extremity_predominance_2B" title="Spinal muscular atrophy with lower extremity predominance 2B">SMALED2B</a></li></ul></li> <li><a href="/wiki/Pontocerebellar_hypoplasia" title="Pontocerebellar hypoplasia">SMA-PCH</a></li> <li><a href="/wiki/Spinal_muscular_atrophy_with_progressive_myoclonic_epilepsy" title="Spinal muscular atrophy with progressive myoclonic epilepsy">SMA-PME</a></li></ul></li> <li><a href="/wiki/Progressive_muscular_atrophy" title="Progressive muscular atrophy">Progressive muscular atrophy</a></li> <li><a href="/wiki/Progressive_bulbar_palsy" title="Progressive bulbar palsy">Progressive bulbar palsy</a> <ul><li><a href="/wiki/Fazio%E2%80%93Londe_disease" title="Fazio–Londe disease">Fazio–Londe</a></li> <li><a href="/wiki/Infantile_progressive_bulbar_palsy" title="Infantile progressive bulbar palsy">Infantile progressive bulbar palsy</a></li></ul></li></ul></li></ul> <ul><li>both: <ul><li><a href="/wiki/Amyotrophic_lateral_sclerosis" class="mw-redirect" title="Amyotrophic lateral sclerosis">Amyotrophic lateral sclerosis</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Hypersensitivity_and_autoimmune_diseases" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Hypersensitivity_disease_by_cause" title="Template:Hypersensitivity disease by cause"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Hypersensitivity_disease_by_cause" title="Template talk:Hypersensitivity disease by cause"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Hypersensitivity_disease_by_cause" title="Special:EditPage/Template:Hypersensitivity disease by cause"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Hypersensitivity_and_autoimmune_diseases" style="font-size:114%;margin:0 4em"><a href="/wiki/Hypersensitivity" title="Hypersensitivity">Hypersensitivity</a> and <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune diseases</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_I_hypersensitivity" title="Type I hypersensitivity">Type I</a>/<a href="/wiki/Allergy" title="Allergy">allergy</a>/<a href="/wiki/Atopy" title="Atopy">atopy</a> (<a href="/wiki/Immunoglobulin_E" title="Immunoglobulin E">IgE</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Allergic_asthma" class="mw-redirect" title="Allergic asthma">Allergic asthma</a></li> <li><a href="/wiki/Allergic_urticaria" class="mw-redirect" title="Allergic urticaria">Allergic urticaria</a></li> <li><a href="/wiki/Allergic_rhinitis" title="Allergic rhinitis">Allergic rhinitis</a> (Hay fever)</li> <li><a href="/wiki/Anaphylaxis" title="Anaphylaxis">Anaphylaxis</a></li> <li><a href="/wiki/Atopic_dermatitis" title="Atopic dermatitis">Atopic dermatitis</a></li> <li><a href="/wiki/Food_allergy" title="Food allergy">Food allergy</a> <ul><li>common allergies include: <a href="/wiki/Egg_allergy" title="Egg allergy">Egg</a></li> <li><a href="/wiki/Milk_allergy" title="Milk allergy">Milk</a></li> <li><a href="/wiki/Peanut_allergy" title="Peanut allergy">Peanut</a></li> <li><a href="/wiki/Seafood_allergy" class="mw-redirect" title="Seafood allergy">Seafood</a></li> <li><a href="/wiki/Soy_allergy" title="Soy allergy">Soy</a></li> <li><a href="/wiki/Tree_nut_allergy" title="Tree nut allergy">Tree nut</a></li> <li><a href="/wiki/Wheat_allergy" title="Wheat allergy">Wheat</a></li></ul></li> <li><a href="/wiki/Side_effects_of_penicillin" title="Side effects of penicillin">Penicillin allergy</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Autoimmune_urticaria" title="Autoimmune urticaria">Autoimmune urticaria</a></li> <li><a href="/wiki/Eosinophilic_esophagitis" title="Eosinophilic esophagitis">Eosinophilic esophagitis</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_II_hypersensitivity" title="Type II hypersensitivity">Type II</a>/<a href="/wiki/Antibody-dependent_cellular_cytotoxicity" title="Antibody-dependent cellular cytotoxicity">ADCC</a> <ul><li><ul><li><a href="/wiki/Immunoglobulin_G" title="Immunoglobulin G">IgG</a></li> <li><a href="/wiki/Immunoglobulin_M" title="Immunoglobulin M">IgM</a></li></ul></li></ul></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <li><a href="/wiki/Hemolytic_disease_of_the_newborn" title="Hemolytic disease of the newborn">Hemolytic disease of the newborn</a></li> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cytotoxicity" title="Cytotoxicity">Cytotoxic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Autoimmune_hemolytic_anemia" title="Autoimmune hemolytic anemia">Autoimmune hemolytic anemia</a></li> <li><a href="/wiki/Bullous_pemphigoid" title="Bullous pemphigoid">Bullous pemphigoid</a></li> <li><a href="/wiki/Goodpasture_syndrome" title="Goodpasture syndrome">Goodpasture syndrome</a></li> <li><a href="/wiki/Guillain%E2%80%93Barr%C3%A9_syndrome" title="Guillain–Barré syndrome">Guillain–Barré syndrome</a></li> <li><a href="/wiki/Immune_thrombocytopenic_purpura" title="Immune thrombocytopenic purpura">Immune thrombocytopenic purpura</a></li> <li><a href="/wiki/Pemphigus_vulgaris" title="Pemphigus vulgaris">Pemphigus vulgaris</a></li> <li><a href="/wiki/Rheumatic_fever" title="Rheumatic fever">Rheumatic fever</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">"<a href="/wiki/Hypersensitivity#Type_V" title="Hypersensitivity">Type V</a>"/<a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Graves%27_disease" title="Graves' disease">Graves' disease</a></li> <li><a href="/wiki/Myasthenia_gravis" title="Myasthenia gravis">Myasthenia gravis</a></li> <li><a href="/wiki/Pernicious_anemia" title="Pernicious anemia">Pernicious anemia</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_III_hypersensitivity" title="Type III hypersensitivity">Type III</a> (<a href="/wiki/Immune_complex" title="Immune complex">Immune complex</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Arthus_reaction" title="Arthus reaction">Arthus reaction</a></li> <li><a href="/wiki/Farmer%27s_lung" title="Farmer's lung">Farmer's lung</a></li> <li><a href="/wiki/Henoch%E2%80%93Sch%C3%B6nlein_purpura" title="Henoch–Schönlein purpura">Henoch–Schönlein purpura</a></li> <li><a href="/wiki/Cutaneous_small-vessel_vasculitis" title="Cutaneous small-vessel vasculitis">Hypersensitivity vasculitis</a></li> <li><a href="/wiki/Acute_proliferative_glomerulonephritis" title="Acute proliferative glomerulonephritis">Post-streptococcal glomerulonephritis</a></li> <li><a href="/wiki/Reactive_arthritis" title="Reactive arthritis">Reactive arthritis</a></li> <li><a href="/wiki/Serum_sickness" title="Serum sickness">Serum sickness</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Lupus" title="Lupus">Lupus</a></li> <li><a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">Rheumatoid arthritis</a></li> <li><a href="/wiki/Subacute_bacterial_endocarditis" title="Subacute bacterial endocarditis">Subacute bacterial endocarditis</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_IV_hypersensitivity" title="Type IV hypersensitivity">Type IV</a>/<a href="/wiki/Cell-mediated_immunity" title="Cell-mediated immunity">cell-mediated</a> (<a href="/wiki/T_cell" title="T cell">T cells</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Allergic_contact_dermatitis" title="Allergic contact dermatitis">Allergic contact dermatitis</a></li> <li><a href="/wiki/Mantoux_test" title="Mantoux test">Mantoux test</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Coeliac_disease" title="Coeliac disease">Coeliac disease</a></li> <li><a href="/wiki/Giant_cell_arteritis" title="Giant cell arteritis">Giant cell arteritis</a></li> <li><a href="/wiki/Hashimoto%27s_thyroiditis" title="Hashimoto's thyroiditis">Hashimoto's thyroiditis</a></li> <li><a class="mw-selflink selflink">Multiple sclerosis</a></li> <li><a href="/wiki/Postorgasmic_illness_syndrome" title="Postorgasmic illness syndrome">Postorgasmic illness syndrome</a></li> <li><a href="/wiki/Reactive_arthritis" title="Reactive arthritis">Reactive arthritis</a></li> <li><a href="/wiki/Type_1_diabetes" title="Type 1 diabetes">Type 1 diabetes</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Graft-versus-host_disease" title="Graft-versus-host disease">GVHD</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Transfusion-associated_graft-versus-host_disease" title="Transfusion-associated graft-versus-host disease">Transfusion-associated graft-versus-host disease</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Unknown/ multiple</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hypersensitivity_pneumonitis" title="Hypersensitivity pneumonitis">Hypersensitivity pneumonitis</a> <ul><li><a href="/wiki/Allergic_bronchopulmonary_aspergillosis" title="Allergic bronchopulmonary aspergillosis">Allergic bronchopulmonary aspergillosis</a></li></ul></li> <li><a href="/wiki/Latex_allergy" title="Latex allergy">Latex allergy</a> (I+IV)</li> <li><a href="/wiki/Transplant_rejection" title="Transplant rejection">Transplant rejection</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Addison%27s_disease" title="Addison's disease">Autoimmune adrenalitis</a></li> <li><a href="/wiki/Autoimmune_hepatitis" title="Autoimmune hepatitis">Autoimmune hepatitis</a></li> <li><a href="/wiki/Autoimmune_polyendocrine_syndrome" title="Autoimmune polyendocrine syndrome">Autoimmune polyendocrine syndrome</a> <ul><li><a href="/wiki/Autoimmune_polyendocrine_syndrome_type_1" title="Autoimmune polyendocrine syndrome type 1">APS1</a></li> <li><a href="/wiki/Autoimmune_polyendocrine_syndrome_type_2" title="Autoimmune polyendocrine syndrome type 2">APS2</a></li></ul></li> <li><a href="/wiki/Sj%C3%B6gren_syndrome" title="Sjögren syndrome">Sjögren syndrome</a></li> <li><a href="/wiki/Autoimmune_disease" title="Autoimmune disease">Systemic autoimmune disease</a></li></ul> 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