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</a> <ul id="toc-Subtypes_of_motor_neuron_disease-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Rare_isolated_variants_of_ALS" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Rare_isolated_variants_of_ALS"> <div class="vector-toc-text"> 1.2 Rare isolated variants of ALS </div> </a> <ul id="toc-Rare_isolated_variants_of_ALS-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Age_of_onset" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Age_of_onset"> <div class="vector-toc-text"> 1.3 Age of onset </div> </a> <ul id="toc-Age_of_onset-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Signs_and_symptoms" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Signs_and_symptoms"> <div class="vector-toc-text"> 2 Signs and symptoms </div> </a> <button aria-controls="toc-Signs_and_symptoms-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Signs and symptoms subsection </button> <ul id="toc-Signs_and_symptoms-sublist" class="vector-toc-list"> <li id="toc-Initial_symptoms" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Initial_symptoms"> <div class="vector-toc-text"> 2.1 Initial symptoms </div> </a> <ul id="toc-Initial_symptoms-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Progression" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Progression"> <div class="vector-toc-text"> 2.2 Progression </div> </a> <ul id="toc-Progression-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Late_stage_disease_management" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Late_stage_disease_management"> <div class="vector-toc-text"> 2.3 Late stage disease management </div> </a> <ul id="toc-Late_stage_disease_management-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Prognosis,_staging,_and_survival" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Prognosis,_staging,_and_survival"> <div class="vector-toc-text"> 2.4 Prognosis, staging, and survival </div> </a> <ul id="toc-Prognosis,_staging,_and_survival-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Cognitive,_emotional,_and_behavioral_symptoms" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cognitive,_emotional,_and_behavioral_symptoms"> <div class="vector-toc-text"> 2.5 Cognitive, emotional, and behavioral symptoms </div> </a> <ul id="toc-Cognitive,_emotional,_and_behavioral_symptoms-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Cause" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Cause"> <div class="vector-toc-text"> 3 Cause </div> </a> <button aria-controls="toc-Cause-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> Toggle Cause subsection </button> <ul id="toc-Cause-sublist" class="vector-toc-list"> <li id="toc-Genetics_and_genetic_testing" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Genetics_and_genetic_testing"> <div class="vector-toc-text"> 3.1 Genetics and genetic testing </div> </a> <ul id="toc-Genetics_and_genetic_testing-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Environmental_and_other_factors" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Environmental_and_other_factors"> <div class="vector-toc-text"> 3.2 Environmental and other factors </div> </a> <ul id="toc-Environmental_and_other_factors-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-Neuropathology" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Neuropathology"> <div class="vector-toc-text"> 4.1 Neuropathology </div> </a> <ul id="toc-Neuropathology-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Biochemistry" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Biochemistry"> <div class="vector-toc-text"> 4.2 Biochemistry </div> </a> <ul id="toc-Biochemistry-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-Differential_diagnosis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Differential_diagnosis"> <div class="vector-toc-text"> 5.1 Differential diagnosis </div> </a> <ul id="toc-Differential_diagnosis-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"> 6 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-Medications" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Medications"> <div class="vector-toc-text"> 6.1 Medications </div> </a> <ul id="toc-Medications-sublist" class="vector-toc-list"> <li id="toc-Disease-slowing_treatments" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Disease-slowing_treatments"> <div class="vector-toc-text"> 6.1.1 Disease-slowing treatments </div> </a> <ul id="toc-Disease-slowing_treatments-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Symptomatic_treatments" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Symptomatic_treatments"> <div class="vector-toc-text"> 6.1.2 Symptomatic treatments </div> </a> <ul id="toc-Symptomatic_treatments-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Breathing_support" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Breathing_support"> <div class="vector-toc-text"> 6.2 Breathing support </div> </a> <ul id="toc-Breathing_support-sublist" class="vector-toc-list"> <li id="toc-Non-invasive_ventilation" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Non-invasive_ventilation"> <div class="vector-toc-text"> 6.2.1 Non-invasive ventilation </div> </a> <ul id="toc-Non-invasive_ventilation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Invasive_ventilation" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Invasive_ventilation"> <div class="vector-toc-text"> 6.2.2 Invasive ventilation </div> </a> <ul id="toc-Invasive_ventilation-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Therapy" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Therapy"> <div class="vector-toc-text"> 6.3 Therapy </div> </a> <ul id="toc-Therapy-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Nutrition" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Nutrition"> <div class="vector-toc-text"> 6.4 Nutrition </div> </a> <ul id="toc-Nutrition-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-End-of-life_care" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#End-of-life_care"> <div class="vector-toc-text"> 6.5 End-of-life care </div> </a> <ul id="toc-End-of-life_care-sublist" class="vector-toc-list"> </ul> </li> </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"> 7 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"> 8 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-Diagnostic_criteria" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Diagnostic_criteria"> <div class="vector-toc-text"> 8.1 Diagnostic criteria </div> </a> <ul id="toc-Diagnostic_criteria-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Name" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Name"> <div class="vector-toc-text"> 8.2 Name </div> </a> <ul id="toc-Name-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Society_and_culture" class="vector-toc-list-item vector-toc-level-1"> <a class="vector-toc-link" href="#Society_and_culture"> <div class="vector-toc-text"> 9 Society and culture </div> </a> <ul id="toc-Society_and_culture-sublist" class="vector-toc-list"> </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"> 10 Research </div> </a> <ul id="toc-Research-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"> 11 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"> 12 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">ALS</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 68 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-68" aria-hidden="true" > 68 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/Motorneuronsiekte" title="Motorneuronsiekte – Afrikaans" lang="af" hreflang="af" data-title="Motorneuronsiekte" 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_%D8%AC%D8%A7%D9%86%D8%A8%D9%8A_%D8%B6%D9%85%D9%88%D8%B1%D9%8A" title="تصلب جانبي ضموري – Arabic" lang="ar" hreflang="ar" data-title="تصلب جانبي ضموري" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target">العربية</a></li><li class="interlanguage-link interwiki-ast mw-list-item"><a href="https://ast.wikipedia.org/wiki/Esclerosis_llateral_amiotr%C3%B3fica" title="Esclerosis llateral amiotrófica – Asturian" lang="ast" hreflang="ast" data-title="Esclerosis llateral amiotrófica" 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/Yan_amiotrofik_skleroz" title="Yan amiotrofik skleroz – Azerbaijani" lang="az" hreflang="az" data-title="Yan amiotrofik 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/%D8%A2%D9%85%D9%88%D8%AA%D8%B1%D9%88%D9%81%DB%8C%DA%A9_%D9%84%DB%8C%D8%AA%D8%B1%D8%A7%D9%84" title="آموتروفیک لیترال – South Azerbaijani" lang="azb" hreflang="azb" data-title="آموتروفیک لیترال" data-language-autonym="تۆرکجه" data-language-local-name="South Azerbaijani" class="interlanguage-link-target">تۆرکجه</a></li><li class="interlanguage-link interwiki-bg mw-list-item"><a href="https://bg.wikipedia.org/wiki/%D0%90%D0%BC%D0%B8%D0%BE%D1%82%D1%80%D0%BE%D1%84%D0%B8%D1%87%D0%BD%D0%B0_%D0%BB%D0%B0%D1%82%D0%B5%D1%80%D0%B0%D0%BB%D0%BD%D0%B0_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7%D0%B0" title="Амиотрофична латерална склероза – Bulgarian" lang="bg" hreflang="bg" data-title="Амиотрофична латерална склероза" data-language-autonym="Български" data-language-local-name="Bulgarian" class="interlanguage-link-target">Български</a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/ALS4" title="ALS4 – Bosnian" lang="bs" hreflang="bs" data-title="ALS4" 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_lateral_amiotr%C3%B2fica" title="Esclerosi lateral amiotròfica – Catalan" lang="ca" hreflang="ca" data-title="Esclerosi lateral amiotròfica" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target">Català</a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Amyotrofick%C3%A1_later%C3%A1ln%C3%AD_skler%C3%B3za" title="Amyotrofická laterální skleróza – Czech" lang="cs" hreflang="cs" data-title="Amyotrofická laterální skleróza" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target">Čeština</a></li><li class="interlanguage-link interwiki-da mw-list-item"><a href="https://da.wikipedia.org/wiki/Amyotrofisk_lateral_sklerose" title="Amyotrofisk lateral sklerose – Danish" lang="da" hreflang="da" data-title="Amyotrofisk lateral sklerose" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target">Dansk</a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Amyotrophe_Lateralsklerose" title="Amyotrophe Lateralsklerose – German" lang="de" hreflang="de" data-title="Amyotrophe Lateralsklerose" 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/Am%C3%BCotroofne_lateraalskleroos" title="Amüotroofne lateraalskleroos – Estonian" lang="et" hreflang="et" data-title="Amüotroofne lateraalskleroos" 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%91%CE%BC%CF%85%CE%BF%CF%84%CF%81%CE%BF%CF%86%CE%B9%CE%BA%CE%AE_%CF%80%CE%BB%CE%B5%CF%85%CF%81%CE%B9%CE%BA%CE%AE_%CF%83%CE%BA%CE%BB%CE%AE%CF%81%CF%85%CE%BD%CF%83%CE%B7" title="Αμυοτροφική πλευρική σκλήρυνση – Greek" lang="el" hreflang="el" data-title="Αμυοτροφική πλευρική 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_lateral_amiotr%C3%B3fica" title="Esclerosis lateral amiotrófica – Spanish" lang="es" hreflang="es" data-title="Esclerosis lateral amiotrófica" 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/Amiotrofa_lateralsklerozo" title="Amiotrofa lateralsklerozo – Esperanto" lang="eo" hreflang="eo" data-title="Amiotrofa lateralsklerozo" 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/Alboko_esklerosi_amiotrofiko" title="Alboko esklerosi amiotrofiko – Basque" lang="eu" hreflang="eu" data-title="Alboko esklerosi amiotrofiko" 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%D8%B3%DA%A9%D9%84%D8%B1%D9%88%D8%B2_%D8%AC%D8%A7%D9%86%D8%A8%DB%8C_%D8%A2%D9%85%DB%8C%D9%88%D8%AA%D8%B1%D9%88%D9%81%DB%8C%DA%A9" title="اسکلروز جانبی آمیوتروفیک – Persian" lang="fa" hreflang="fa" data-title="اسکلروز جانبی آمیوتروفیک" 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_lat%C3%A9rale_amyotrophique" title="Sclérose latérale amyotrophique – French" lang="fr" hreflang="fr" data-title="Sclérose latérale amyotrophique" 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_chliath%C3%A1nach_amatr%C3%B3fach" title="Scléaróis chliathánach amatrófach – Irish" lang="ga" hreflang="ga" data-title="Scléaróis chliathánach amatrófach" 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_lateral_amiotr%C3%B3fica" title="Esclerose lateral amiotrófica – Galician" lang="gl" hreflang="gl" data-title="Esclerose lateral amiotrófica" 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/%EA%B7%BC%EC%9C%84%EC%B6%95%EC%84%B1_%EC%B8%A1%EC%82%AD%EA%B2%BD%ED%99%94%EC%A6%9D" title="근위축성 측삭경화증 – Korean" lang="ko" hreflang="ko" data-title="근위축성 측삭경화증" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target">한국어</a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D4%BF%D5%B8%D5%B2%D5%B4%D5%B6%D5%A1%D5%B5%D5%AB%D5%B6_%D5%A1%D5%B4%D5%AB%D5%B8%D5%BF%D6%80%D5%B8%D6%86%D5%AB%D5%AF_%D5%BD%D5%AF%D5%AC%D5%A5%D6%80%D5%B8%D5%A6" title="Կողմնային ամիոտրոֆիկ սկլերոզ – Armenian" lang="hy" hreflang="hy" data-title="Կողմնային ամիոտրոֆիկ 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%AA%E0%A5%87%E0%A4%B6%E0%A5%80%E0%A4%B6%E0%A5%8B%E0%A4%B7%E0%A5%80_%E0%A4%AA%E0%A4%BE%E0%A4%B0%E0%A5%8D%E0%A4%B6%E0%A5%8D%E0%A4%B5_%E0%A4%95%E0%A4%BE%E0%A4%A0%E0%A4%BF%E0%A4%A8%E0%A5%8D%E0%A4%AF_(%E0%A4%8F%E0%A4%AE%E0%A4%BF%E0%A4%AF%E0%A5%8B%E0%A4%9F%E0%A5%8D%E0%A4%B0%E0%A5%89%E0%A4%AB%E0%A4%BC%E0%A4%BF%E0%A4%95_%E0%A4%B2%E0%A5%88%E0%A4%9F%E0%A4%B0%E0%A4%B2_%E0%A4%B8%E0%A5%8D%E0%A4%95%E0%A4%B2%E0%A4%BF%E0%A4%B0%E0%A5%89%E0%A4%B8%E0%A4%BF%E0%A4%B8)" title="पेशीशोषी पार्श्व काठिन्य (एमियोट्रॉफ़िक लैटरल स्कलिरॉसिस) – Hindi" lang="hi" hreflang="hi" data-title="पेशीशोषी पार्श्व काठिन्य (एमियोट्रॉफ़िक लैटरल स्कलिरॉसिस)" data-language-autonym="हिन्दी" data-language-local-name="Hindi" class="interlanguage-link-target">हिन्दी</a></li><li class="interlanguage-link interwiki-hr mw-list-item"><a href="https://hr.wikipedia.org/wiki/Amiotrofi%C4%8Dna_lateralna_skleroza" title="Amiotrofična lateralna skleroza – Croatian" lang="hr" hreflang="hr" data-title="Amiotrofična lateralna 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_lateral_amiotrofik" title="Sklerosis lateral amiotrofik – Indonesian" lang="id" hreflang="id" data-title="Sklerosis lateral amiotrofik" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target">Bahasa Indonesia</a></li><li class="interlanguage-link interwiki-is mw-list-item"><a href="https://is.wikipedia.org/wiki/Lou_Gehrig-sj%C3%BAkd%C3%B3mur" title="Lou Gehrig-sjúkdómur – Icelandic" lang="is" hreflang="is" data-title="Lou Gehrig-sjúkdómur" data-language-autonym="Íslenska" data-language-local-name="Icelandic" class="interlanguage-link-target">Íslenska</a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Sclerosi_laterale_amiotrofica" title="Sclerosi laterale amiotrofica – Italian" lang="it" hreflang="it" data-title="Sclerosi laterale amiotrofica" 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%90%D7%9E%D7%99%D7%95%D7%98%D7%A8%D7%95%D7%A4%D7%99%D7%AA_%D7%A6%D7%99%D7%93%D7%99%D7%AA" title="טרשת אמיוטרופית צידית – Hebrew" lang="he" hreflang="he" data-title="טרשת אמיוטרופית צידית" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target">עברית</a></li><li class="interlanguage-link interwiki-ka mw-list-item"><a href="https://ka.wikipedia.org/wiki/%E1%83%90%E1%83%9B%E1%83%98%E1%83%9D%E1%83%A2%E1%83%A0%E1%83%9D%E1%83%A4%E1%83%A3%E1%83%9A%E1%83%98_%E1%83%92%E1%83%95%E1%83%94%E1%83%A0%E1%83%93%E1%83%98%E1%83%97%E1%83%98_%E1%83%A1%E1%83%99%E1%83%9A%E1%83%94%E1%83%A0%E1%83%9D%E1%83%96%E1%83%98" title="ამიოტროფული გვერდითი სკლეროზი – Georgian" lang="ka" hreflang="ka" data-title="ამიოტროფული გვერდითი სკლეროზი" data-language-autonym="ქართული" data-language-local-name="Georgian" class="interlanguage-link-target">ქართული</a></li><li class="interlanguage-link interwiki-sw mw-list-item"><a href="https://sw.wikipedia.org/wiki/Sklerosisi_ya_kimiotrofia_ya_pembezoni" title="Sklerosisi ya kimiotrofia ya pembezoni – Swahili" lang="sw" hreflang="sw" data-title="Sklerosisi ya kimiotrofia ya pembezoni" data-language-autonym="Kiswahili" data-language-local-name="Swahili" class="interlanguage-link-target">Kiswahili</a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Sclerosis_lateralis_amyotrophica" title="Sclerosis lateralis amyotrophica – Latin" lang="la" hreflang="la" data-title="Sclerosis lateralis amyotrophica" 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/Amiotrof%C4%81_later%C4%81l%C4%81_skleroze" title="Amiotrofā laterālā skleroze – Latvian" lang="lv" hreflang="lv" data-title="Amiotrofā laterālā skleroze" data-language-autonym="Latviešu" data-language-local-name="Latvian" class="interlanguage-link-target">Latviešu</a></li><li class="interlanguage-link interwiki-lb mw-list-item"><a href="https://lb.wikipedia.org/wiki/Amyotroph_Lateral_Skleros" title="Amyotroph Lateral Skleros – Luxembourgish" lang="lb" hreflang="lb" data-title="Amyotroph Lateral Skleros" data-language-autonym="Lëtzebuergesch" data-language-local-name="Luxembourgish" class="interlanguage-link-target">Lëtzebuergesch</a></li><li class="interlanguage-link interwiki-li mw-list-item"><a href="https://li.wikipedia.org/wiki/ALS" title="ALS – Limburgish" lang="li" hreflang="li" data-title="ALS" data-language-autonym="Limburgs" data-language-local-name="Limburgish" class="interlanguage-link-target">Limburgs</a></li><li class="interlanguage-link interwiki-hu mw-list-item"><a href="https://hu.wikipedia.org/wiki/Amiotr%C3%B3fi%C3%A1s_later%C3%A1lszkler%C3%B3zis" title="Amiotrófiás laterálszklerózis – Hungarian" lang="hu" hreflang="hu" data-title="Amiotrófiás laterálszklerózis" 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%90%D0%BC%D0%B8%D0%BE%D1%82%D1%80%D0%BE%D1%84%D0%B8%D1%87%D0%BD%D0%B0_%D0%BB%D0%B0%D1%82%D0%B5%D1%80%D0%B0%D0%BB%D0%BD%D0%B0_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7%D0%B0" title="Амиотрофична латерална склероза – Macedonian" lang="mk" hreflang="mk" data-title="Амиотрофична латерална 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%85%E0%B4%AE%E0%B4%BF%E0%B4%9F%E0%B5%8D%E0%B4%B0%E0%B5%8B%E0%B4%AB%E0%B4%BF%E0%B4%95%E0%B5%8D_%E0%B4%B2%E0%B4%BE%E0%B4%B1%E0%B5%8D%E0%B4%B1%E0%B4%B1%E0%B5%BD_%E0%B4%B8%E0%B5%8D%E2%80%8C%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="അമിട്രോഫിക് ലാറ്ററൽ സ്‌ക്ലീറോസിസ് – Malayalam" lang="ml" hreflang="ml" data-title="അമിട്രോഫിക് ലാറ്ററൽ സ്‌ക്ലീറോസിസ്" data-language-autonym="മലയാളം" data-language-local-name="Malayalam" class="interlanguage-link-target">മലയാളം</a></li><li class="interlanguage-link interwiki-xmf mw-list-item"><a href="https://xmf.wikipedia.org/wiki/%E1%83%90%E1%83%9B%E1%83%98%E1%83%9D%E1%83%A2%E1%83%A0%E1%83%9D%E1%83%A4%E1%83%A3%E1%83%9A%E1%83%98_%E1%83%A1%E1%83%99%E1%83%9A%E1%83%94%E1%83%A0%E1%83%9D%E1%83%96%E1%83%98" title="ამიოტროფული სკლეროზი – Mingrelian" lang="xmf" hreflang="xmf" data-title="ამიოტროფული სკლეროზი" data-language-autonym="მარგალური" data-language-local-name="Mingrelian" class="interlanguage-link-target">მარგალური</a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Sklerosis_lateral_amiotrofik" title="Sklerosis lateral amiotrofik – Malay" lang="ms" hreflang="ms" data-title="Sklerosis lateral amiotrofik" 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/Amyotrofe_laterale_sclerose" title="Amyotrofe laterale sclerose – Dutch" lang="nl" hreflang="nl" data-title="Amyotrofe laterale 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/%E7%AD%8B%E8%90%8E%E7%B8%AE%E6%80%A7%E5%81%B4%E7%B4%A2%E7%A1%AC%E5%8C%96%E7%97%87" title="筋萎縮性側索硬化症 – Japanese" lang="ja" hreflang="ja" data-title="筋萎縮性側索硬化症" 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/Amyotrofisk_lateralsklerose" title="Amyotrofisk lateralsklerose – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Amyotrofisk lateralsklerose" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target">Norsk bokmål</a></li><li class="interlanguage-link interwiki-or mw-list-item"><a href="https://or.wikipedia.org/wiki/%E0%AC%86%E0%AC%AE%E0%AC%BE%E0%AD%9F%E0%AD%8B%E0%AC%9F%E0%AD%8D%E0%AC%B0%E0%AD%8B%E0%AC%AB%E0%AC%BF%E0%AC%95%E0%AD%8D_%E0%AC%B2%E0%AC%BE%E0%AC%9F%E0%AD%87%E0%AC%B0%E0%AC%BE%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%E0%AD%8D" title="ଆମାୟୋଟ୍ରୋଫିକ୍ ଲାଟେରାଲ ସ୍କ୍ଲେରୋସିସ୍ – Odia" lang="or" hreflang="or" data-title="ଆମାୟୋଟ୍ରୋଫିକ୍ ଲାଟେରାଲ ସ୍କ୍ଲେରୋସିସ୍" data-language-autonym="ଓଡ଼ିଆ" data-language-local-name="Odia" class="interlanguage-link-target">ଓଡ଼ିଆ</a></li><li class="interlanguage-link interwiki-uz mw-list-item"><a href="https://uz.wikipedia.org/wiki/Amiotrofik_lateral_skleroz" title="Amiotrofik lateral skleroz – Uzbek" lang="uz" hreflang="uz" data-title="Amiotrofik lateral skleroz" data-language-autonym="Oʻzbekcha / ўзбекча" data-language-local-name="Uzbek" class="interlanguage-link-target">Oʻzbekcha / ўзбекча</a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Stwardnienie_zanikowe_boczne" title="Stwardnienie zanikowe boczne – Polish" lang="pl" hreflang="pl" data-title="Stwardnienie zanikowe boczne" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target">Polski</a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Esclerose_lateral_amiotr%C3%B3fica" title="Esclerose lateral amiotrófica – Portuguese" lang="pt" hreflang="pt" data-title="Esclerose lateral amiotrófica" 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_lateral%C4%83_amiotrofic%C4%83" title="Scleroză laterală amiotrofică – Romanian" lang="ro" hreflang="ro" data-title="Scleroză laterală amiotrofică" 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%91%D0%BE%D0%BA%D0%BE%D0%B2%D0%BE%D0%B9_%D0%B0%D0%BC%D0%B8%D0%BE%D1%82%D1%80%D0%BE%D1%84%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B8%D0%B9_%D1%81%D0%BA%D0%BB%D0%B5%D1%80%D0%BE%D0%B7" title="Боковой амиотрофический склероз – Russian" lang="ru" hreflang="ru" data-title="Боковой амиотрофический склероз" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target">Русский</a></li><li class="interlanguage-link interwiki-sco mw-list-item"><a href="https://sco.wikipedia.org/wiki/Motor_neurone_tribbles" title="Motor neurone tribbles – Scots" lang="sco" hreflang="sco" data-title="Motor neurone tribbles" data-language-autonym="Scots" data-language-local-name="Scots" class="interlanguage-link-target">Scots</a></li><li class="interlanguage-link interwiki-si mw-list-item"><a href="https://si.wikipedia.org/wiki/%E0%B6%B4%E0%B7%9A%E0%B7%82%E0%B7%93%E0%B6%B4%E0%B7%9D%E0%B7%82%E0%B6%AB_%E0%B6%B4%E0%B7%8F%E0%B6%BB%E0%B7%8A%E0%B7%81%E0%B7%8A%E0%B7%80%E0%B7%93%E0%B6%BA_%E0%B6%A2%E0%B7%8F%E0%B6%BB%E0%B6%A8%E0%B7%8A%E2%80%8D%E0%B6%BA%E0%B6%BA" title="පේෂීපෝෂණ පාර්ශ්වීය ජාරඨ්‍යය – Sinhala" lang="si" hreflang="si" data-title="පේෂීපෝෂණ පාර්ශ්වීය ජාරඨ්‍යය" data-language-autonym="සිංහල" data-language-local-name="Sinhala" class="interlanguage-link-target">සිංහල</a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Motor_neurone_disease" title="Motor neurone disease – Simple English" lang="en-simple" hreflang="en-simple" data-title="Motor neurone disease" 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/Amyotrofick%C3%A1_later%C3%A1lna_skler%C3%B3za" title="Amyotrofická laterálna skleróza – Slovak" lang="sk" hreflang="sk" data-title="Amyotrofická laterálna skleróza" 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/Amiotrofi%C4%8Dna_lateralna_skleroza" title="Amiotrofična lateralna skleroza – Slovenian" lang="sl" hreflang="sl" data-title="Amiotrofična lateralna 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/%D8%A6%D8%A7%D9%85%DB%8C%DB%86%D8%AA%D8%B1%DB%86%D9%81%DB%8C%DA%A9_%D9%84%D8%A7%D8%AA%DB%8E%D8%B1%D8%A7%D9%84_%D8%B3%DA%A9%D9%84%DB%8E%D8%B1%DB%86%D8%B2%DB%8C%D8%B3" title="ئامیۆترۆفیک لاتێرال سکلێرۆزیس – Central Kurdish" lang="ckb" hreflang="ckb" data-title="ئامیۆترۆفیک لاتێرال سکلێرۆزیس" data-language-autonym="کوردی" data-language-local-name="Central Kurdish" class="interlanguage-link-target">کوردی</a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/Amiotrofi%C4%8Dna_lateralna_skleroza" title="Amiotrofična lateralna skleroza – Serbian" lang="sr" hreflang="sr" data-title="Amiotrofična lateralna 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/Amiotrofi%C4%8Dna_lateralna_skleroza" title="Amiotrofična lateralna skleroza – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Amiotrofična lateralna skleroza" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target">Srpskohrvatski / српскохрватски</a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/ALS-tauti" title="ALS-tauti – Finnish" lang="fi" hreflang="fi" data-title="ALS-tauti" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target">Suomi</a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/Amyotrofisk_lateralskleros" title="Amyotrofisk lateralskleros – Swedish" lang="sv" hreflang="sv" data-title="Amyotrofisk lateralskleros" data-language-autonym="Svenska" data-language-local-name="Swedish" class="interlanguage-link-target">Svenska</a></li><li class="interlanguage-link interwiki-tl mw-list-item"><a href="https://tl.wikipedia.org/wiki/Amyotrophic_lateral_sclerosis" title="Amyotrophic lateral sclerosis – Tagalog" lang="tl" hreflang="tl" data-title="Amyotrophic lateral sclerosis" data-language-autonym="Tagalog" data-language-local-name="Tagalog" class="interlanguage-link-target">Tagalog</a></li><li class="interlanguage-link interwiki-ta mw-list-item"><a href="https://ta.wikipedia.org/wiki/%E0%AE%A4%E0%AE%9A%E0%AF%88%E0%AE%AF%E0%AF%82%E0%AE%9F%E0%AF%8D%E0%AE%9F%E0%AE%AE%E0%AE%B1%E0%AF%8D%E0%AE%B1_%E0%AE%AA%E0%AE%95%E0%AF%8D%E0%AE%95_%E0%AE%AE%E0%AE%B0%E0%AE%AA%E0%AF%8D%E0%AE%AA%E0%AF%81_%E0%AE%A8%E0%AF%8B%E0%AE%AF%E0%AF%8D" title="தசையூட்டமற்ற பக்க மரப்பு நோய் – Tamil" lang="ta" hreflang="ta" data-title="தசையூட்டமற்ற பக்க மரப்பு நோய்" data-language-autonym="தமிழ்" data-language-local-name="Tamil" class="interlanguage-link-target">தமிழ்</a></li><li class="interlanguage-link interwiki-th mw-list-item"><a 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Click here for more information."><img alt="This is a good article. Click here for more information." src="//upload.wikimedia.org/wikipedia/en/thumb/9/94/Symbol_support_vote.svg/19px-Symbol_support_vote.svg.png" decoding="async" width="19" height="20" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/9/94/Symbol_support_vote.svg/29px-Symbol_support_vote.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/9/94/Symbol_support_vote.svg/39px-Symbol_support_vote.svg.png 2x" data-file-width="180" data-file-height="185" /></a></div></div> </div> <div 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">Rare neurodegenerative disease</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">This article is about the neurodegenerative disease. For other uses, see <a href="/wiki/ALS_(disambiguation)" class="mw-disambig" title="ALS (disambiguation)">ALS (disambiguation)</a>.</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">"Motor neuron disease" and "Motor neurone disease" redirect here. For a group of muscle-wasting disorders, see <a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">Motor neuron diseases</a>.</div> <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">Amyotrophic lateral sclerosis</th></tr><tr><th scope="row" class="infobox-label">Other names</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>Motor neurone disease (MND)</li><li><a href="/wiki/Lou_Gehrig" title="Lou Gehrig">Lou Gehrig</a>'s disease</li><li><a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Charcot's disease</a><a href="#cite_note-Orphanet2009-1">[1]</a></li></ul></div></td></tr><tr style="background-color: #f8f9fa;"><td colspan="2" class="infobox-full-data"><a href="/wiki/File:ALS_Affected_neurons_and_muscles.png" class="mw-file-description"><img alt="Diagram of a human nervous system highlighting the brain, spinal cord, motor neurons, and muscles of the body affected by ALS" src="//upload.wikimedia.org/wikipedia/commons/thumb/1/16/ALS_Affected_neurons_and_muscles.png/220px-ALS_Affected_neurons_and_muscles.png" decoding="async" width="220" height="195" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/16/ALS_Affected_neurons_and_muscles.png/330px-ALS_Affected_neurons_and_muscles.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/16/ALS_Affected_neurons_and_muscles.png/440px-ALS_Affected_neurons_and_muscles.png 2x" data-file-width="4520" data-file-height="4011" /></a></td></tr><tr><td colspan="2" class="infobox-full-data">Parts of the <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a> affected by ALS, causing progressive symptoms in <a href="/wiki/Skeletal_muscles" class="mw-redirect" title="Skeletal muscles">skeletal muscles</a> throughout the body<a href="#cite_note-Masrori-2020-2">[2]</a></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">Early: <a href="/wiki/Spasticity" title="Spasticity">Stiff muscles</a>, <a href="/wiki/Fasciculation" title="Fasciculation">muscle twitches</a>, gradual increasing weakness<a href="#cite_note-NINDS2020-3">[3]</a> Later: Difficulty in <a href="/wiki/Dysarthria" title="Dysarthria">speaking</a>, <a href="/wiki/Dysphagia" title="Dysphagia">swallowing</a>, and <a href="/wiki/Shortness_of_breath" title="Shortness of breath">breathing</a>; <a href="/wiki/Respiratory_failure" title="Respiratory failure">respiratory failure</a>;<a href="#cite_note-NINDS2020-3">[3]</a> 10–15% experience <a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">frontotemporal dementia</a><a href="#cite_note-Masrori-2020-2">[2]</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Complication_(medicine)" title="Complication (medicine)">Complications</a></th><td class="infobox-data"><a href="/wiki/Falling_(accident)" title="Falling (accident)">Falling (accident)</a>; <a href="/wiki/Respiratory_failure" title="Respiratory failure">Respiratory failure</a>; <a href="/wiki/Pneumonia" title="Pneumonia">Pneumonia</a>; <a href="/wiki/Malnutrition" title="Malnutrition">Malnutrition</a></td></tr><tr><th scope="row" class="infobox-label">Usual onset</th><td class="infobox-data">45–75 years<a href="#cite_note-Masrori-2020-2">[2]</a></td></tr><tr><th scope="row" class="infobox-label">Causes</th><td class="infobox-data">Unknown (about 85%), genetic (about 15%)</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Risk_factor" title="Risk factor">Risk factors</a></th><td class="infobox-data">Genetic risk factors; age; <a href="/wiki/Male" title="Male">male sex</a>; heavy metals; organic chemicals; smoking; electric shock; physical exercise; head injury<a href="#cite_note-Masrori-2020-2">[2]</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">Clinical diagnosis of exclusion based on progressive symptoms of upper and lower motor neuron degeneration in which no other explanation can be found. Supportive evidence from <a href="/wiki/Electromyography" title="Electromyography">electromyography</a>, <a href="/wiki/Genetic_testing" title="Genetic testing">genetic testing</a>, and <a href="/wiki/Neuroimaging" title="Neuroimaging">neuroimaging</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Differential_diagnosis" title="Differential diagnosis">Differential diagnosis</a></th><td class="infobox-data"><a href="/wiki/Multifocal_motor_neuropathy" title="Multifocal motor neuropathy">Multifocal motor neuropathy</a>, <a href="/wiki/Kennedy%27s_disease" class="mw-redirect" title="Kennedy's disease">Kennedy's disease</a>, <a href="/wiki/Hereditary_spastic_paraplegia" title="Hereditary spastic paraplegia">Hereditary spastic paraplegia</a>, <a href="/wiki/Nerve_compression_syndrome" title="Nerve compression syndrome">Nerve compression syndrome</a>, <a href="/wiki/Diabetic_neuropathy" title="Diabetic neuropathy">Diabetic neuropathy</a>, <a href="/wiki/Post-polio_syndrome" title="Post-polio syndrome">Post-polio syndrome</a>, <a href="/wiki/Myasthenia_gravis" title="Myasthenia gravis">Myasthenia gravis</a>, <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">Multiple sclerosis</a><a href="#cite_note-4">[4]</a></td></tr><tr><th scope="row" class="infobox-label">Treatment</th><td class="infobox-data"><a href="/wiki/Walker_(mobility)" title="Walker (mobility)">Walker (mobility)</a>; <a href="/wiki/Wheelchair" title="Wheelchair">Wheelchair</a>; <a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">Non-invasive ventilation</a>;<a href="#cite_note-Support2016-5">[5]</a> <a href="/wiki/Feeding_tube" title="Feeding tube">Feeding tube</a>; <a href="/wiki/Augmentative_and_alternative_communication" title="Augmentative and alternative communication">Augmentative and alternative communication</a>; symptomatic management</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medication" title="Medication">Medication</a></th><td class="infobox-data"><a href="/wiki/Riluzole" title="Riluzole">Riluzole</a>, <a href="/wiki/Edaravone" title="Edaravone">Edaravone</a>, <a href="/wiki/Sodium_phenylbutyrate/ursodoxicoltaurine" title="Sodium phenylbutyrate/ursodoxicoltaurine">Sodium phenylbutyrate/ursodoxicoltaurine</a>, <a href="/wiki/Tofersen" title="Tofersen">Tofersen</a>, <a href="/wiki/Dextromethorphan/quinidine" title="Dextromethorphan/quinidine">Dextromethorphan/quinidine</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Prognosis" title="Prognosis">Prognosis</a></th><td class="infobox-data">Life expectancy highly variable but typically 2–4 years after diagnosis<a href="#cite_note-Goutman_480–493-6">[6]</a></td></tr><tr><th scope="row" class="infobox-label">Frequency</th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li>Incidence: 1.6/100,000 individuals per year<a href="#cite_note-Goutman_480–493-6">[6]</a></li> <li>Prevalence: 4.4/100,000 living individuals<a href="#cite_note-Goutman_480–493-6">[6]</a></li> <li>Lifetime risk: 1 in 400 individuals<a href="#cite_note-7">[7]</a></li></ul> </div></td></tr></tbody></table> Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease (LGD) in the United States, is a rare, terminal <a href="/wiki/Neurodegenerative_disease" title="Neurodegenerative disease">neurodegenerative disorder</a> that results in the progressive loss of both upper and lower <a href="/wiki/Motor_neuron" title="Motor neuron">motor neurons</a> that normally control <a href="/wiki/Skeletal_muscle" title="Skeletal muscle">voluntary muscle</a> contraction.<a href="#cite_note-NINDS2020-3">[3]</a> ALS is the most common form of the <a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">motor neuron diseases</a>.<a href="#cite_note-8">[8]</a> ALS often presents in its early stages with gradual muscle <a href="/wiki/Spasticity" title="Spasticity">stiffness</a>, <a href="/wiki/Fasciculation" title="Fasciculation">twitches</a>, <a href="/wiki/Muscle_weakness" title="Muscle weakness">weakness</a>, and <a href="/wiki/Muscle_atrophy" title="Muscle atrophy">wasting</a>.<a href="#cite_note-NINDS2020-3">[3]</a> Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost.<a href="#cite_note-NINDS2020-3">[3]</a> While only 15% of people with ALS also fully develop <a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">frontotemporal dementia</a>, an estimated 50% face at least some minor difficulties with <a href="/wiki/Cognitive_disorder" title="Cognitive disorder">thinking</a> and <a href="/wiki/Behavior" title="Behavior">behavior</a>.<a href="#cite_note-Lancet2017-9">[9]</a> Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in <a href="/wiki/Dysarthria" title="Dysarthria">speaking</a> or <a href="/wiki/Dysphagia" title="Dysphagia">swallowing</a>).<a href="#cite_note-Nature2017-10">[10]</a> Most cases of ALS (about 90–95%) have <a href="/wiki/Idiopathic" class="mw-redirect" title="Idiopathic">no known cause</a>, and are known as sporadic ALS.<a href="#cite_note-NINDS2020-3">[3]</a><a href="#cite_note-11">[11]</a> However, both <a href="/wiki/Genetics" title="Genetics">genetic</a> and <a href="/wiki/Environmental_factors" class="mw-redirect" title="Environmental factors">environmental factors</a> are believed to be involved.<a href="#cite_note-Wingo2011-12">[12]</a> The remaining 5–10% of cases have a genetic cause, often linked to a <a href="/wiki/Family_history_(medicine)" title="Family history (medicine)">family history of the disease</a>, and these are known as familial ALS (hereditary).<a href="#cite_note-Goutman_480–493-6">[6]</a><a href="#cite_note-13">[13]</a> About half of these genetic cases are due to disease-causing variants in one of four specific <a href="/wiki/Gene" title="Gene">genes</a>.<a href="#cite_note-Goutman-2022-14">[14]</a> The <a href="/wiki/Diagnosis" title="Diagnosis">diagnosis</a> is based on a person's <a href="/wiki/Signs_and_symptoms" title="Signs and symptoms">signs and symptoms</a>, with testing conducted to rule out other potential causes.<a href="#cite_note-NINDS2020-3">[3]</a> There is no known cure for ALS.<a href="#cite_note-NINDS2020-3">[3]</a> The goal of treatment is to slow the disease progression, and improve symptoms.<a href="#cite_note-Lancet2017-9">[9]</a> FDA approved treatments that slow the progression of ALS include <a href="/wiki/Riluzole" title="Riluzole">riluzole</a> and edaravone.<a href="#cite_note-alsa1-15">[15]</a> <a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">Non-invasive ventilation</a> may result in both improved quality, and length of life.<a href="#cite_note-Support2016-5">[5]</a> <a href="/wiki/Mechanical_ventilation" title="Mechanical ventilation">Mechanical ventilation</a> can prolong survival but does not stop disease progression.<a href="#cite_note-Care2017-16">[16]</a> A <a href="/wiki/Feeding_tube" title="Feeding tube">feeding tube</a> may help maintain weight and nutrition.<a href="#cite_note-Conn2015-17">[17]</a> Death is usually caused by respiratory failure.<a href="#cite_note-Lancet2011-18">[18]</a> The disease can affect people of any age, but usually starts around the age of 60.<a href="#cite_note-Lancet2011-18">[18]</a> The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years.<a href="#cite_note-Pupillo-2014-19">[19]</a> Descriptions of the disease date back to at least 1824 by <a href="/wiki/Charles_Bell" title="Charles Bell">Charles Bell</a>.<a href="#cite_note-Rowland2001-20">[20]</a> In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a>, who in 1874 began using the term amyotrophic lateral sclerosis.<a href="#cite_note-Rowland2001-20">[20]</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="Classification">Classification</h2>[<a href="/w/index.php?title=ALS&action=edit&section=1" title="Edit section: Classification">edit</a>]</div> ALS is a <a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">motor neuron disease</a>, which is a group of <a href="/wiki/Neurological_disorder" title="Neurological disorder">neurological disorders</a> that selectively affect <a href="/wiki/Motor_neuron" title="Motor neuron">motor neurons</a>, the cells that control <a href="/wiki/Skeletal_muscle" title="Skeletal muscle">voluntary muscles</a> of the body.<a href="#cite_note-NINDS2020-3">[3]</a> Other motor neuron diseases include <a href="/wiki/Primary_lateral_sclerosis" title="Primary lateral sclerosis">primary lateral sclerosis</a> (PLS), <a href="/wiki/Progressive_muscular_atrophy" title="Progressive muscular atrophy">progressive muscular atrophy</a> (PMA), <a href="/wiki/Progressive_bulbar_palsy" title="Progressive bulbar palsy">progressive bulbar palsy</a>, <a href="/wiki/Pseudobulbar_palsy" title="Pseudobulbar palsy">pseudobulbar palsy</a>, and <a href="/wiki/Monomelic_amyotrophy" class="mw-redirect" title="Monomelic amyotrophy">monomelic amyotrophy</a> (MMA).<a href="#cite_note-21">[21]</a> As a disease, ALS itself can be classified in a few different ways: by which part of the motor neurons are affected; by the parts of the body first affected; whether it is genetic; and the age at which it started. Each individual diagnosed with the condition will sit at a unique place at the intersection of these complex and overlapping subtypes, which presents a challenge to diagnosis, understanding, and prognosis.<a href="#cite_note-22">[22]</a> <div class="mw-heading mw-heading3"><h3 id="Subtypes_of_motor_neuron_disease">Subtypes of motor neuron disease</h3>[<a href="/w/index.php?title=ALS&action=edit&section=2" title="Edit section: Subtypes of motor neuron disease">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex,_via_spinal_cord,_to_skeletal_muscle.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg/220px-Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg" decoding="async" width="220" height="124" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg/330px-Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg/440px-Illustration_of_the_motor_neuron_tract_descending_from_primary_motor_cortex%2C_via_spinal_cord%2C_to_skeletal_muscle.jpg 2x" data-file-width="8000" data-file-height="4500" /></a><figcaption>Classic ALS involves neurons in the brain and spinal cord (<a href="/wiki/Upper_motor_neuron" title="Upper motor neuron">upper motor neurons</a>, highlighted red), as well as the <a href="/wiki/Lower_motor_neuron" title="Lower motor neuron">lower motor neurons</a>, which go from the spinal cord to the muscles, highlighted teal.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> </figcaption></figure> ALS can be classified by the types of motor neurons that are affected.<a href="#cite_note-Masrori-2020-2">[2]</a> To successfully control any voluntary muscle in the body, a signal must be sent from the <a href="/wiki/Motor_cortex" title="Motor cortex">motor cortex</a> in the brain down the <a href="/wiki/Upper_motor_neuron" title="Upper motor neuron">upper motor neuron</a> as it travels down the spinal cord. There, it connects via a <a href="/wiki/Synapse" title="Synapse">synapse</a> to the <a href="/wiki/Lower_motor_neuron" title="Lower motor neuron">lower motor neuron</a> which connects to the muscle itself. Damage to either the upper or lower motor neuron, as it makes its way from the brain to muscle, causes different types of symptoms.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> Damage to the upper motor neuron typically causes <a href="/wiki/Spasticity" title="Spasticity">spasticity</a> including stiffness and increased <a href="/wiki/Tendon_reflex" title="Tendon reflex">tendon reflexes</a>, and/or <a href="/wiki/Clonus" title="Clonus">clonus</a>, while damage to the lower motor neuron typically causes <a href="/wiki/Muscle_weakness" title="Muscle weakness">weakness</a>, <a href="/wiki/Muscular_atrophy#Pathophysiology" class="mw-redirect" title="Muscular atrophy">muscle atrophy</a>, and <a href="/wiki/Fasciculation" title="Fasciculation">fasciculations</a>.<a href="#cite_note-arora-2023-24">[24]</a> Classical, or classic ALS, involves degeneration to both the <a href="/wiki/Upper_motor_neuron" title="Upper motor neuron">upper motor neurons</a> in the brain and the <a href="/wiki/Lower_motor_neuron" title="Lower motor neuron">lower motor neurons</a> in the spinal cord.<a href="#cite_note-Goutman_480–493-6">[6]</a><a href="#cite_note-Masrori-2020-2">[2]</a> <a href="/wiki/Primary_lateral_sclerosis" title="Primary lateral sclerosis">Primary lateral sclerosis</a> (PLS) involves degeneration of only the upper motor neurons, and <a href="/wiki/Progressive_muscular_atrophy" title="Progressive muscular atrophy">progressive muscular atrophy</a> (PMA) involves only the lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS.<a href="#cite_note-Lancet2017-9">[9]</a> <table class="wikitable"> <caption> </caption> <tbody><tr> <th>Main ALS subtypes </th> <th><a href="/wiki/Upper_motor_neuron" title="Upper motor neuron">Upper motor neuron</a> degeneration </th> <th><a href="/wiki/Lower_motor_neuron" title="Lower motor neuron">Lower motor neuron</a> degeneration </th></tr> <tr> <td>Classical ALS </td> <td>Yes </td> <td>Yes </td></tr> <tr> <td>Primary lateral sclerosis (PLS) </td> <td>Yes </td> <td>No </td></tr> <tr> <td>Progressive muscular atrophy (PMA) </td> <td>No </td> <td>Yes </td></tr></tbody></table> Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into where symptoms first appear as these are usually focussed to one region of the body at initial presentation before later spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS.<a href="#cite_note-Lancet2017-9">[9]</a> Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs<a href="#cite_note-Nature2017-10">[10]</a> and accounts for about two-thirds of all classical ALS cases.<a href="#cite_note-Lancet2017-9">[9]</a> Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> and accounts for about 25% of classical ALS cases.<a href="#cite_note-Goutman_480–493-6">[6]</a> A rarer type of classical ALS affecting around 3% of patients is respiratory-onset,<a href="#cite_note-Lancet2017-9">[9]</a> in which the initial symptoms are difficulty breathing (<a href="/wiki/Dyspnea" class="mw-redirect" title="Dyspnea">dyspnea</a>) upon exertion, at rest, or while lying flat (<a href="/wiki/Orthopnea" title="Orthopnea">orthopnea</a>).<a href="#cite_note-25">[25]</a> <a href="/wiki/Primary_lateral_sclerosis" title="Primary lateral sclerosis">Primary lateral sclerosis</a> (PLS) is a subtype of the overall ALS category which accounts for about 5% of all cases and only affects the upper motor neurons in the arms, legs, and bulbar region.<a href="#cite_note-Nature2014-26">[26]</a> However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that a definitive diagnosis of PLS cannot be made until several years have passed.<a href="#cite_note-Classification2016-27">[27]</a> PLS has a better prognosis than classical ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS.<a href="#cite_note-Nature2014-26">[26]</a> <a href="/wiki/Progressive_muscular_atrophy" title="Progressive muscular atrophy">Progressive muscular atrophy</a> (PMA) is another subtype that accounts for about 5% of the overall ALS category and affects lower motor neurons in the arms, legs, and bulbar region.<a href="#cite_note-Nature2014-26">[26]</a> While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death.<a href="#cite_note-Lancet2017-9">[9]</a> As with PLS developing into classical ALS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS.<a href="#cite_note-Classification2016-27">[27]</a> <div class="mw-heading mw-heading3"><h3 id="Rare_isolated_variants_of_ALS">Rare isolated variants of ALS</h3>[<a href="/w/index.php?title=ALS&action=edit&section=3" title="Edit section: Rare isolated variants of ALS">edit</a>]</div> Isolated variants of ALS have symptoms that are limited to a single region for at least a year; they progress more slowly than classical ALS and are associated with longer survival.<a href="#cite_note-Masrori-2020-2">[2]</a> These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to other spinal cord regions for an extended period of time (at least 12 months).<a href="#cite_note-28">[28]</a> <a href="/wiki/Vulpian-Bernhardt_Syndrome" class="mw-redirect" title="Vulpian-Bernhardt Syndrome">Flail arm syndrome</a> is characterized by lower motor neuron damage affecting the arm muscles, typically starting with the upper arms symmetrically and progressing downwards to the hands.<a href="#cite_note-Masrori-2020-2">[2]</a> Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting around the feet.<a href="#cite_note-Masrori-2020-2">[2]</a> Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months),<a href="#cite_note-29">[29]</a> leading to gradual onset of difficulty with speech (<a href="/wiki/Dysarthria" title="Dysarthria">dysarthria</a>) and swallowing (<a href="/wiki/Dysphagia" title="Dysphagia">dysphagia</a>). <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:ALS_subtypes_UMN_LMN_distribution.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/9c/ALS_subtypes_UMN_LMN_distribution.png/220px-ALS_subtypes_UMN_LMN_distribution.png" decoding="async" width="220" height="220" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/9c/ALS_subtypes_UMN_LMN_distribution.png/330px-ALS_subtypes_UMN_LMN_distribution.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/9c/ALS_subtypes_UMN_LMN_distribution.png/440px-ALS_subtypes_UMN_LMN_distribution.png 2x" data-file-width="8000" data-file-height="8000" /></a><figcaption>Illustration showing the range of upper and lower motor neuron involvement in the two most common types of ALS (top row) and three of the most common rare subtypes of ALS (bottom row)</figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="Age_of_onset">Age of onset</h3>[<a href="/w/index.php?title=ALS&action=edit&section=4" title="Edit section: Age of onset">edit</a>]</div> ALS can also be classified based on the age of onset. While the peak age of onset is 58 to 63 for sporadic ALS and 47 to 52 for genetic ALS,<a href="#cite_note-Lancet2011-18">[18]</a> about 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS).<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease.<a href="#cite_note-Classification2016-27">[27]</a> Juvenile ALS is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are <a href="/wiki/FUS_(gene)" class="mw-redirect" title="FUS (gene)">FUS</a>, <a href="/wiki/ALS2" title="ALS2">ALS2</a>, and <a href="/wiki/SETX" title="SETX">SETX</a>.<a href="#cite_note-30">[30]</a> Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in <a href="/wiki/FUS_(gene)" class="mw-redirect" title="FUS (gene)">FUS</a> and <a href="/wiki/SOD1" title="SOD1">SOD1</a> that are associated with a poor prognosis.<a href="#cite_note-31">[31]</a> Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.<a href="#cite_note-Clinical_Features_of_ALS-32">[32]</a> <div class="mw-heading mw-heading2"><h2 id="Signs_and_symptoms">Signs and symptoms</h2>[<a href="/w/index.php?title=ALS&action=edit&section=5" title="Edit section: Signs and symptoms">edit</a>]</div> The disorder causes muscle weakness, <a href="/wiki/Atrophy" title="Atrophy">atrophy</a>, and <a href="/wiki/Spasticity" title="Spasticity">muscle spasms</a> throughout the body due to the degeneration of the upper motor and lower motor neurons. <a href="/wiki/Sensory_neuron" title="Sensory neuron">Sensory nerves</a> and the <a href="/wiki/Autonomic_nervous_system" title="Autonomic nervous system">autonomic nervous system</a> are generally unaffected, meaning the majority of people with ALS maintain <a href="/wiki/Hearing" title="Hearing">hearing</a>, <a href="/wiki/Visual_perception" title="Visual perception">sight</a>, <a href="/wiki/Somatosensory_system" title="Somatosensory system">touch</a>, <a href="/wiki/Olfaction" class="mw-redirect" title="Olfaction">smell</a>, and <a href="/wiki/Taste" title="Taste">taste</a>.<a href="#cite_note-NINDS2020-3">[3]</a> <div class="mw-heading mw-heading3"><h3 id="Initial_symptoms">Initial symptoms</h3>[<a href="/w/index.php?title=ALS&action=edit&section=6" title="Edit section: Initial symptoms">edit</a>]</div> The start of ALS may be so subtle that the symptoms are overlooked.<a href="#cite_note-NINDS2020-3">[3]</a> The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of the body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.<a href="#cite_note-33">[33]</a> In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a "<a href="/wiki/Foot_drop" title="Foot drop">dropped foot</a>" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock.<a href="#cite_note-34">[34]</a> In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the <a href="/wiki/Intercostal_muscle" class="mw-redirect" title="Intercostal muscle">intercostal muscles</a> that support breathing are affected first.<a href="#cite_note-Lancet2011-18">[18]</a> Over time, people experience increasing difficulty moving, swallowing (<a href="/wiki/Dysphagia" title="Dysphagia">dysphagia</a>), and speaking or forming words (<a href="/wiki/Dysarthria" title="Dysarthria">dysarthria</a>). Symptoms of upper motor neuron involvement include tight and stiff muscles (<a href="/wiki/Spasticity" title="Spasticity">spasticity</a>) and exaggerated reflexes (<a href="/wiki/Hyperreflexia" title="Hyperreflexia">hyperreflexia</a>), including an overactive gag reflex.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> While the disease does not cause pain directly, pain is a symptom experienced by most people with ALS caused by reduced mobility.<a href="#cite_note-Pain2017-35">[35]</a> Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (<a href="/wiki/Fasciculation" title="Fasciculation">fasciculations</a>).<a href="#cite_note-arora-2023-24">[24]</a> <div class="mw-heading mw-heading3"><h3 id="Progression">Progression</h3>[<a href="/w/index.php?title=ALS&action=edit&section=7" title="Edit section: Progression">edit</a>]</div> Although the initial site of symptoms and subsequent rate of disability progression vary from person to person, the initially affected body region is usually the most affected over time, and symptoms usually spread to a neighbouring body region. For example, symptoms starting in one arm usually spread next to either the opposite arm or to the leg on the same side.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> Bulbar-onset patients most typically get their next symptoms in their arms rather than legs, arm-onset patients typically spreads to the legs before the bulbar region, and leg-onset patients typically spread to the arms rather than the bulbar region.<a href="#cite_note-36">[36]</a> Over time, regardless of where symptoms began, most people eventually lose the ability to walk or use their hands and arms independently. Less consistently, they may lose the ability to speak and to swallow food. It is the eventual development of weakness of the respiratory muscles, with the loss of ability to cough and to breathe without support, that is ultimately life-shortening in ALS.<a href="#cite_note-Support2016-5">[5]</a> The rate of progression can be measured using the <a href="/wiki/ALS_Functional_Rating_Scale_-_Revised" title="ALS Functional Rating Scale - Revised">ALS Functional Rating Scale - Revised</a> (ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability).<a href="#cite_note-37">[37]</a> The ALSFRS-R is the most frequently used outcome measure in clinical trials<a href="#cite_note-38">[38]</a> and is used by doctors to track disease progression.<a href="#cite_note-39">[39]</a> Though the degree of variability is high and a small percentage of people have a much slower progression, on average people with ALS lose about 1 ALSFRS-R point per month.<a href="#cite_note-40">[40]</a> Brief periods of stabilization ("plateaus") and even small reversals in ALSFRS-R score are not uncommon, due to the fact the tool is subjective, can be affected by medication, and different forms of compensation for changes in function.<a href="#cite_note-Bedlack-2016-41">[41]</a> However, it is rare (<1%) for these improvements to be large (i.e. greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12 months).<a href="#cite_note-Bedlack-2016-41">[41]</a> A survey-based study among clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful, which is the most common threshold used to determine whether a new treatment is working in clinical trials.<a href="#cite_note-42">[42]</a> <div class="mw-heading mw-heading3"><h3 id="Late_stage_disease_management">Late stage disease management</h3>[<a href="/w/index.php?title=ALS&action=edit&section=8" title="Edit section: Late stage disease management">edit</a>]</div> Difficulties with chewing and swallowing make eating very difficult (<a href="/wiki/Dysphagia" title="Dysphagia">dysphagia</a>) and increase the risk of choking or of <a href="/wiki/Pulmonary_aspiration" title="Pulmonary aspiration">aspirating</a> food into the lungs.<a href="#cite_note-Yunusova-2019-43">[43]</a> In later stages of the disorder, <a href="/wiki/Aspiration_pneumonia" title="Aspiration pneumonia">aspiration pneumonia</a> can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube.<a href="#cite_note-Yunusova-2019-43">[43]</a> As the diaphragm and <a href="/wiki/Intercostal_muscle" class="mw-redirect" title="Intercostal muscle">intercostal muscles</a> of the <a href="/wiki/Rib_cage" title="Rib cage">rib cage</a> that support breathing weaken, measures of <a href="/wiki/Spirometry" title="Spirometry">lung function</a> such as <a href="/wiki/Vital_capacity" title="Vital capacity">vital capacity</a> and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement,<a href="#cite_note-Support2016-5">[5]</a> known as <a href="/wiki/Locked-in_syndrome" title="Locked-in syndrome">locked-in syndrome</a>. Bladder and bowel function are usually spared, meaning <a href="/wiki/Urinary_incontinence" title="Urinary incontinence">urinary</a> and <a href="/wiki/Fecal_incontinence" title="Fecal incontinence">fecal incontinence</a> are uncommon, although trouble getting to a toilet can lead to difficulties. The <a href="/wiki/Extraocular_muscles" title="Extraocular muscles">extraocular muscles</a> responsible for eye movement are usually spared,<a href="#cite_note-44">[44]</a> meaning the use of <a href="/wiki/Eye_tracking" title="Eye tracking">eye tracking</a> technology to support <a href="/wiki/Augmentative_and_alternative_communication" title="Augmentative and alternative communication">augmentative communication</a> is often feasible, albeit slow, and needs may change over time.<a href="#cite_note-45">[45]</a> Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life.<a href="#cite_note-46">[46]</a> <div class="mw-heading mw-heading3"><h3 id="Prognosis,_staging,_and_survival">Prognosis, staging, and survival</h3>[<a href="/w/index.php?title=ALS&action=edit&section=9" title="Edit section: Prognosis, staging, and survival">edit</a>]</div> Although respiratory support using <a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">non-invasive ventilation</a> can ease problems with breathing and prolong survival,<a href="#cite_note-47">[47]</a> it does not affect the progression rate of ALS. Most people with ALS die between two and four years after the diagnosis.<a href="#cite_note-Support2016-5">[5]</a> Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years,<a href="#cite_note-Lancet2011-18">[18]</a> and about 10% survive for 10 years or longer.<a href="#cite_note-Pupillo-2014-19">[19]</a> The most common cause of death among people with ALS is <a href="/wiki/Respiratory_failure" title="Respiratory failure">respiratory failure</a>, often accelerated by <a href="/wiki/Pneumonia" title="Pneumonia">pneumonia</a>.<a href="#cite_note-Lancet2011-18">[18]</a> Most ALS patients die at home after a period of worsening difficulty breathing, a decline in their nutritional status, or a rapid worsening of symptoms.<a href="#cite_note-Bede-2011-48">[48]</a> Sudden death or acute respiratory distress are uncommon.<a href="#cite_note-49">[49]</a> Access to <a href="/wiki/Palliative_care" title="Palliative care">palliative care</a> is recommended from an early stage to explore options, ensure psychosocial support for the patient and caregivers, and to discuss <a href="/wiki/Advance_healthcare_directive" title="Advance healthcare directive">advance healthcare directives</a>.<a href="#cite_note-Bede-2011-48">[48]</a> As with <a href="/wiki/Cancer_staging" title="Cancer staging">cancer staging</a>, ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials.<a href="#cite_note-Goutman_480–493-6">[6]</a> Two very similar staging systems emerged around a similar time, the King's staging system and Milano-Torino (MiToS) functional staging.<a href="#cite_note-50">[50]</a> <table class="wikitable"> <caption style="text-align: left;">Kings ALS staging system and prognosis at each stage </caption> <tbody><tr> <th> </th> <th>Stage 1 </th> <th>Stage 2 </th> <th>Stage 3 </th> <th>Stage 4 </th></tr> <tr> <td>Stage description </td> <td>Symptom onset, involvement of the first region </td> <td>2A: Diagnosis 2B: Involvement of the second region </td> <td>Involvement of the third region </td> <td>4A: Need for a feeding tube 4B: Need for non-invasive ventilation </td></tr> <tr> <td>Median time to stage </td> <td>13.5 months </td> <td>17.7 months </td> <td>23.3 months </td> <td>4A: 17.7 months 4B: 30.3 months </td></tr></tbody></table> <table class="wikitable"> <caption style="text-align: left;">MiToS ALS staging system and prognosis at each stage </caption> <tbody><tr> <th> </th> <th>Stage 0 </th> <th>Stage 1 </th> <th>Stage 2 </th> <th>Stage 3 </th> <th>Stage 4 </th> <th>Stage 5 </th></tr> <tr> <td>Stage description </td> <td>No loss of a functional domain </td> <td>Loss of 1 domain </td> <td>Loss of 2 domains </td> <td>Loss of 3 domains </td> <td>Loss of 4 domains </td> <td>Death </td></tr> <tr> <td>Probability of death at each stage </td> <td>7% </td> <td>26% </td> <td>33% </td> <td>33% </td> <td>86% </td> <td> </td></tr></tbody></table> Providing individual patients with a precise prognosis is not currently possible, though research is underway to provide statistical models on the basis of prognostic factors including age at onset, progression rate, site of onset, and presence of <a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">frontotemporal dementia</a>.<a href="#cite_note-Goutman_480–493-6">[6]</a> Those with a bulbar onset have a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS patients had a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS patients had a median survival of 2.6 years and a 10-year survival rate of 13%.<a href="#cite_note-JNNP_July_2011-51">[51]</a> Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years.<a href="#cite_note-JNNP_July_2011-51">[51]</a> While <a href="/wiki/Astrophysics" title="Astrophysics">astrophysicist</a> <a href="/wiki/Stephen_Hawking" title="Stephen Hawking">Stephen Hawking</a> lived for 55 more years following his diagnosis, his was an unusual case.<a href="#cite_note-52">[52]</a> <div class="mw-heading mw-heading3"><h3 id="Cognitive,_emotional,_and_behavioral_symptoms">Cognitive, emotional, and behavioral symptoms</h3>[<a href="/w/index.php?title=ALS&action=edit&section=10" title="Edit section: Cognitive, emotional, and behavioral symptoms">edit</a>]</div> <a href="/wiki/Cognitive_disorder" title="Cognitive disorder">Cognitive impairment</a> or behavioral dysfunction is present in 30–50% of individuals with ALS,<a href="#cite_note-Martin2017-53">[53]</a> and can appear more frequently in later stages of the disease.<a href="#cite_note-Crockford-2018-54">[54]</a> <a href="/wiki/Language_disorder" title="Language disorder">Language dysfunction</a>, <a href="/wiki/Executive_dysfunction" title="Executive dysfunction">executive dysfunction</a>, and troubles with <a href="/wiki/Social_cognition" title="Social cognition">social cognition</a> and <a href="/wiki/Verbal_memory" title="Verbal memory">verbal memory</a> are the most commonly reported cognitive symptoms in ALS.<a href="#cite_note-Crockford-2018-54">[54]</a> Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms, <a href="/wiki/Family_history_(medicine)" title="Family history (medicine)">family history</a> of ALS, and/or a predominantly upper motor neuron phenotype.<a href="#cite_note-55">[55]</a> <a href="/wiki/Pseudobulbar_affect" title="Pseudobulbar affect">Emotional lability</a> is a symptom in which patients cry, smile, yawn, or laugh, either in the absence of emotional stimuli, or when they are feeling the opposite emotion to that being expressed;<a href="#cite_note-56">[56]</a> it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS.<a href="#cite_note-Support2016-5">[5]</a> While relatively benign relative to other symptoms, it can cause increased stigma and social isolation as people around the patient struggle to react appropriately to what can be frequent and inappropriate outbursts in public.<a href="#cite_note-57">[57]</a> In addition to mild changes in cognition that may only emerge during neuropsychological testing, around 10–15% of individuals have signs of <a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">frontotemporal dementia</a> (FTD).<a href="#cite_note-Support2016-5">[5]</a> <a href="/wiki/Perseveration" title="Perseveration">Repeating phrases or gestures</a>, apathy, and <a href="/wiki/Disinhibition" title="Disinhibition">loss of inhibition</a> are the most frequently reported behavioral features of ALS.<a href="#cite_note-58">[58]</a> ALS and FTD are now considered to be part of a common disease spectrum (ALS–FTD) because of genetic, clinical, and pathological similarities.<a href="#cite_note-59">[59]</a> Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of genetic FTD.<a href="#cite_note-Neuroscience2014-60">[60]</a> Cognitive and behavioral issues are associated with poorer prognosis as they may reduce adherence to medical advice, and deficits in empathy and social cognition which may increase caregiver burden.<a href="#cite_note-61">[61]</a> <div class="mw-heading mw-heading2"><h2 id="Cause">Cause</h2>[<a href="/w/index.php?title=ALS&action=edit&section=11" title="Edit section: Cause">edit</a>]</div> It is not known what causes sporadic ALS, hence it is described as an <a href="/wiki/Idiopathic_disease" title="Idiopathic disease">idiopathic disease</a>.<a href="#cite_note-Lancet2011-18">[18]</a> Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance.<a href="#cite_note-Wingo2011-12">[12]</a> The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A multi-step <a href="/wiki/Liability_threshold_model" class="mw-redirect" title="Liability threshold model">liability threshold model</a> for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life.<a href="#cite_note-Conspiracy-62">[62]</a> ALS can strike at any age, but its likelihood increases with age.<a href="#cite_note-Mayo_Clinic-63">[63]</a> Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis.<a href="#cite_note-auto-64">[64]</a> ALS is 20% more common in men than women,<a href="#cite_note-auto-64">[64]</a> but this difference in sex distribution is no longer present in patients with onset after age 70.<a href="#cite_note-Mayo_Clinic-63">[63]</a> <div class="mw-heading mw-heading3"><h3 id="Genetics_and_genetic_testing">Genetics and genetic testing</h3>[<a href="/w/index.php?title=ALS&action=edit&section=12" title="Edit section: Genetics and genetic testing">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/Genetics_of_amyotrophic_lateral_sclerosis" title="Genetics of amyotrophic lateral sclerosis">Genetics of amyotrophic lateral sclerosis</a></div> While they appear identical clinically and pathologically,<a href="#cite_note-65">[65]</a> ALS can be classified as being either familial or sporadic, depending on whether there is a known family history of the disease and/or whether an ALS-associated genetic mutation has been identified via genetic testing.<a href="#cite_note-66">[66]</a> Familial ALS is thought to account for 10–15% of cases overall and can include <a href="/wiki/Monogenic_(genetics)" class="mw-redirect" title="Monogenic (genetics)">monogenic</a>, <a href="/wiki/Oligogenic_inheritance" title="Oligogenic inheritance">oligogenic</a>, and <a href="/wiki/Polygenic_inheritance" class="mw-redirect" title="Polygenic inheritance">polygenic</a> modes of inheritance.<a href="#cite_note-Goutman-2022-14">[14]</a> There is considerable variation among clinicians on how to approach genetic testing in ALS, and only about half discuss the possibility of genetic inheritance with their patients, particularly if there is no discernible family history of the disease.<a href="#cite_note-67">[67]</a> In the past, genetic counseling and testing was only offered to those with obviously familial ALS.<a href="#cite_note-Goutman-2022-14">[14]</a> But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing <a href="/wiki/De_novo_mutation" title="De novo mutation">de novo mutations</a> in <a href="/wiki/SOD1" title="SOD1">SOD1</a>, or <a href="/wiki/C9orf72" title="C9orf72">C9orf72</a>,<a href="#cite_note-68">[68]</a> an incomplete family history, or incomplete <a href="/wiki/Penetrance" title="Penetrance">penetrance</a>, meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes.<a href="#cite_note-Goutman-2022-14">[14]</a> The lack of positive family history may be caused by lack of historical records, having a smaller family, older generations dying earlier of causes other than ALS, genetic <a href="/wiki/Non-paternity_event" title="Non-paternity event">non-paternity</a>, and uncertainty over whether certain neuropsychiatric conditions (e.g. <a href="/wiki/Frontotemporal_dementia" title="Frontotemporal dementia">frontotemporal dementia</a>, other forms of <a href="/wiki/Dementia" title="Dementia">dementia</a>, suicide, psychosis, <a href="/wiki/Schizophrenia" title="Schizophrenia">schizophrenia</a>) should be considered significant when determining a family history.<a href="#cite_note-Goutman-2022-14">[14]</a> There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS,<a href="#cite_note-69">[69]</a> particularly as there is now a licensed gene therapy (<a href="/wiki/Tofersen" title="Tofersen">tofersen</a>) specifically targeted to carriers of SOD-1 ALS. A shortage of genetic counselors and limited clinical capacity to see such at-risk individuals makes this challenging in practice, as does the unequal access to genetic testing around the world.<a href="#cite_note-70">[70]</a> More than 40 genes have been associated with ALS, of which four account for nearly half of familial cases, and around 5% of sporadic cases:<a href="#cite_note-Goutman-2022-14">[14]</a> <a href="/wiki/C9orf72" title="C9orf72">C9orf72</a> (40% of familial cases, 7% sporadic), <a href="/wiki/SOD1" title="SOD1">SOD1</a> (12% of familial cases, 1–2% sporadic), <a href="/wiki/FUS_(gene)" class="mw-redirect" title="FUS (gene)">FUS</a> (4% of familial cases, 1% sporadic), and <a href="/wiki/TARDBP" class="mw-redirect" title="TARDBP">TARDBP</a> (4% of familial cases, 1% sporadic), with the remaining genes mostly accounting for fewer than 1% of either familial or sporadic cases.<a href="#cite_note-Goutman-2022-14">[14]</a> ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS.<a href="#cite_note-Goutman-2022-14">[14]</a> Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves.<a href="#cite_note-Goutman-2022-14">[14]</a> <div class="mw-heading mw-heading3"><h3 id="Environmental_and_other_factors">Environmental and other factors</h3>[<a href="/w/index.php?title=ALS&action=edit&section=13" title="Edit section: Environmental and other factors">edit</a>]</div> The multi-step hypothesis suggests the disease is caused by some interaction between an individual's genetic risk factors and their cumulative lifetime of exposures to environmental factors, termed their <a href="/wiki/Exposome" title="Exposome">exposome</a>.<a href="#cite_note-Goutman-2022-14">[14]</a> The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. <a href="/wiki/Lead" title="Lead">lead</a> and <a href="/wiki/Mercury_(element)" title="Mercury (element)">mercury</a>), chemicals (e.g. <a href="/wiki/Pesticide" title="Pesticide">pesticides</a> and <a href="/wiki/Solvent" title="Solvent">solvents</a>), <a href="/wiki/Electrical_injury" title="Electrical injury">electric shock</a>, <a href="/wiki/Injury" title="Injury">physical injury</a> (including <a href="/wiki/Head_injury" title="Head injury">head injury</a>), and <a href="/wiki/Smoking" title="Smoking">smoking</a> (in men more than women).<a href="#cite_note-Wang_2017-71">[71]</a> Overall these effects are small, with each exposure in isolation only increasing the likelihood of a very rare condition by a small amount. For instance an individual's lifetime risk of developing ALS might go from "1 in 400" without an exposure to between "1 in 300" and "1 in 200" if they were exposed to heavy metals.<a href="#cite_note-Wang_2017-71">[71]</a> A range of other exposures have weaker evidence supporting them and include participation in <a href="/wiki/Professional_sports" title="Professional sports">professional sports</a>, having a lower <a href="/wiki/Body_mass_index" title="Body mass index">body mass index</a>, lower <a href="/wiki/Educational_attainment" title="Educational attainment">educational attainment</a>, manual occupations, military service, exposure to <a href="/wiki/Beta-Methylamino-L-alanine" class="mw-redirect" title="Beta-Methylamino-L-alanine">Beta-N-methylamino-L-alanin</a> (BMAA), and viral infections.<a href="#cite_note-Wang_2017-71">[71]</a> Although some personality traits, such as <a href="/wiki/Openness_to_experience" title="Openness to experience">openness</a>,<a href="#cite_note-Grossman2006-72">[72]</a> <a href="/wiki/Agreeableness" title="Agreeableness">agreeableness</a><a href="#cite_note-PK2018-73">[73]</a> and <a href="/wiki/Conscientiousness" title="Conscientiousness">conscientiousness</a><a href="#cite_note-PK2018-73">[73]</a> appear remarkably common among patients with ALS, it remains open whether personality can increase susceptibility to ALS directly.<a href="#cite_note-74">[74]</a> Instead, genetic factors giving rise to personality might simultaneously predispose people to developing ALS,<a href="#cite_note-Grossman2006-72">[72]</a> or the above personality traits might underlie lifestyle choices which are in turn risk factors for ALS.<a href="#cite_note-PK2018-73">[73]</a> <div class="mw-heading mw-heading2"><h2 id="Pathophysiology">Pathophysiology</h2>[<a href="/w/index.php?title=ALS&action=edit&section=14" title="Edit section: Pathophysiology">edit</a>]</div> <div class="mw-heading mw-heading3"><h3 id="Neuropathology">Neuropathology</h3>[<a href="/w/index.php?title=ALS&action=edit&section=15" title="Edit section: Neuropathology">edit</a>]</div> Upon examination at autopsy, features of the disease that can be <a href="/wiki/Gross_pathology" title="Gross pathology">seen with the naked eye</a> include skeletal <a href="/wiki/Muscle_atrophy" title="Muscle atrophy">muscle atrophy</a>, motor cortex atrophy, <a href="/wiki/Sclerosis_(medicine)" title="Sclerosis (medicine)">sclerosis</a> of the <a href="/wiki/Corticospinal_tract" title="Corticospinal tract">corticospinal</a> and <a href="/wiki/Corticobulbar_tract" title="Corticobulbar tract">corticobulbar tracts</a>, thinning of the <a href="/wiki/Hypoglossal_nerve" title="Hypoglossal nerve">hypoglossal nerves</a> (which control the tongue), and thinning of the <a href="/wiki/Anterior_roots" class="mw-redirect" title="Anterior roots">anterior roots</a> of the spinal cord.<a href="#cite_note-Nature2017-10">[10]</a> The defining feature of ALS is the death of both upper motor neurons (located in the <a href="/wiki/Motor_cortex" title="Motor cortex">motor cortex</a> of the brain) and lower motor neurons (located in the brainstem and spinal cord).<a href="#cite_note-75">[75]</a> In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well.<a href="#cite_note-NEJM_2017-76">[76]</a> The pathological hallmark of ALS is the presence of <a href="/wiki/Inclusion_bodies" title="Inclusion bodies">inclusion bodies</a> (abnormal aggregations of protein) known as Bunina bodies in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is <a href="/wiki/TDP-43" class="mw-redirect" title="TDP-43">TDP-43</a> protein;<a href="#cite_note-Nature2017-10">[10]</a> however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies<a href="#cite_note-77">[77]</a><a href="#cite_note-78">[78]</a> is SOD1 protein or FUS protein, respectively.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> <a href="/wiki/Prion" title="Prion">Prion</a>-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others.<a href="#cite_note-Cold_Spring_Harbor_2017-23">[23]</a> The <a href="/wiki/Glymphatic_system" title="Glymphatic system">glymphatic system</a> may also be involved in the <a href="/wiki/Pathogenesis" title="Pathogenesis">pathogenesis</a> of ALS.<a href="#cite_note-79">[79]</a> <div class="mw-heading mw-heading3"><h3 id="Biochemistry">Biochemistry</h3>[<a href="/w/index.php?title=ALS&action=edit&section=16" title="Edit section: Biochemistry">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/76/ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg/260px-ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg" decoding="async" width="260" height="316" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/76/ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg/390px-ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/76/ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg/520px-ALS_Disease_Pathology_and_Proposed_Disease_Mechanisms.jpg 2x" data-file-width="1052" data-file-height="1280" /></a><figcaption>This figure shows ten proposed disease mechanisms for ALS and the genes associated with them.<a href="#cite_note-80">[80]</a></figcaption></figure> It is still not fully understood why neurons die in ALS, but this <a href="/wiki/Neurodegeneration" class="mw-redirect" title="Neurodegeneration">neurodegeneration</a> is thought to involve many different cellular and molecular processes.<a href="#cite_note-Lancet2017-9">[9]</a> The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the <a href="/wiki/Cytoskeleton" title="Cytoskeleton">cytoskeleton</a>, and RNA processing.<a href="#cite_note-81">[81]</a> Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of <a href="/wiki/Wild-type" class="mw-redirect" title="Wild-type">wild-type</a> (normal) SOD1 protein are common in sporadic ALS.<a href="#cite_note-NEJM_2017-76">[76]</a> It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner.<a href="#cite_note-Nature2017-10">[10]</a> Other protein degradation genes that can cause ALS when mutated include <a href="/wiki/Valosin-containing_protein" title="Valosin-containing protein">VCP</a>, <a href="/wiki/Optineurin" title="Optineurin">OPTN</a>, <a href="/wiki/TBK1_(gene)" class="mw-redirect" title="TBK1 (gene)">TBK1</a>, and <a href="/wiki/SQSTM1" class="mw-redirect" title="SQSTM1">SQSTM1</a>. Three genes implicated in ALS that are important for maintaining the cytoskeleton<a href="#cite_note-NEJM_2017-76">[76]</a> and for axonal transport<a href="#cite_note-Nature2017-10">[10]</a> include <a href="/wiki/DCTN1" title="DCTN1">DCTN1</a>, <a href="/wiki/PFN1" class="mw-redirect" title="PFN1">PFN1</a>, and <a href="/wiki/TUBA4A" title="TUBA4A">TUBA4A</a>.<a href="#cite_note-NEJM_2017-76">[76]</a> There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein,<a href="#cite_note-NEJM_2017-76">[76]</a> a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS.<a href="#cite_note-Nature2017-10">[10]</a> FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated.<a href="#cite_note-Neuroscience2014-60">[60]</a> It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm.<a href="#cite_note-82">[82]</a> Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal proteins both within and between cells in a prion-like manner.<a href="#cite_note-NEJM_2017-76">[76]</a> This also leads to decreased levels of RNA-binding protein in the nucleus, which may mean that their target RNA transcripts do not undergo normal processing. Other RNA metabolism genes associated with ALS include <a href="/wiki/Angiogenin" title="Angiogenin">ANG</a>, <a href="/wiki/SETX" title="SETX">SETX</a>, and <a href="/wiki/MATR3" title="MATR3">MATR3</a>.<a href="#cite_note-Nature2017-10">[10]</a> C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms.<a href="#cite_note-NEJM_2017-76">[76]</a> The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over);<a href="#cite_note-83">[83]</a> people with up to 30 repeats are considered normal, while people with hundreds or thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS.<a href="#cite_note-84">[84]</a> The three mechanisms of disease associated with these C9orf72 repeats are deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein.<a href="#cite_note-NEJM_2017-76">[76]</a> Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal length and fast axonal transport of mitochondrial cargo) has been shown to occur in C9orf72-ALS using human <a href="/wiki/Induced_pluripotent_stem_cells" class="mw-redirect" title="Induced pluripotent stem cells">induced pluripotent stem cell</a> (iPSC) technologies coupled with <a href="/wiki/CRISPR/Cas9-mediated_genome_editing" class="mw-redirect" title="CRISPR/Cas9-mediated genome editing">CRISPR/Cas9</a> gene-editing, and human post-mortem spinal cord tissue examination.<a href="#cite_note-85">[85]</a> <a href="/wiki/Excitotoxicity" title="Excitotoxicity">Excitotoxicity</a>, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> <a href="/wiki/Glutamate" class="mw-redirect" title="Glutamate">glutamate</a>, is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the <a href="/wiki/AMPA_receptor" title="AMPA receptor">AMPA receptor</a>) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (<a href="/wiki/EAAT2" class="mw-redirect" title="EAAT2">EAAT2</a>), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. <a href="/wiki/Riluzole" title="Riluzole">Riluzole</a>, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect.<a href="#cite_note-Nature2017-10">[10]</a> <div class="mw-heading mw-heading2"><h2 id="Diagnosis">Diagnosis</h2>[<a href="/w/index.php?title=ALS&action=edit&section=17" title="Edit section: Diagnosis">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:ALS_cross.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/6d/ALS_cross.jpg/260px-ALS_cross.jpg" decoding="async" width="260" height="342" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/6d/ALS_cross.jpg/390px-ALS_cross.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/6d/ALS_cross.jpg/520px-ALS_cross.jpg 2x" data-file-width="713" data-file-height="938" /></a><figcaption>An <a href="/wiki/MRI_of_the_brain" class="mw-redirect" title="MRI of the brain">MRI of the brain</a> (axial <a href="/wiki/Fluid-attenuated_inversion_recovery" title="Fluid-attenuated inversion recovery">FLAIR</a>) looking at a person as if from above that shows increased <a href="/wiki/Spin-spin_relaxation" class="mw-redirect" title="Spin-spin relaxation">T2</a> signal as a small white region within the <a href="/wiki/Internal_capsule#Posterior_limb" title="Internal capsule">posterior part of the internal capsule</a> around the center of the image, consistent with the diagnosis of ALS</figcaption></figure> No single test can provide a definite diagnosis of ALS.<a href="#cite_note-NINDS2020-3">[3]</a> Instead, the diagnosis of ALS is primarily made based on a physician's clinical assessment after ruling out other diseases.<a href="#cite_note-NINDS2020-3">[3]</a> Physicians often obtain the person's full <a href="/wiki/Medical_history" title="Medical history">medical history</a> and conduct neurologic examinations at regular intervals to assess whether signs and symptoms such as muscle weakness, <a href="/wiki/Muscle_atrophy" title="Muscle atrophy">muscle atrophy</a>, <a href="/wiki/Hyperreflexia" title="Hyperreflexia">hyperreflexia</a>, <a href="/wiki/Plantar_reflex" title="Plantar reflex">Babinski's sign</a>, and spasticity are worsening.<a href="#cite_note-NINDS2020-3">[3]</a> A number of biomarkers are being studied for the condition, but as of 2023 are not in general medical use.<a href="#cite_note-86">[86]</a><figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:ALS_Coronal.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/75/ALS_Coronal.jpg/220px-ALS_Coronal.jpg" decoding="async" width="220" height="224" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/75/ALS_Coronal.jpg/330px-ALS_Coronal.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/75/ALS_Coronal.jpg/440px-ALS_Coronal.jpg 2x" data-file-width="920" data-file-height="938" /></a><figcaption>An <a href="/wiki/MRI_of_the_brain" class="mw-redirect" title="MRI of the brain">MRI of the brain</a> looking at a person from side-on that shows <a href="/wiki/T2-weighted" class="mw-redirect" title="T2-weighted">increased T2 signal</a> as a white region in the posterior part of the <a href="/wiki/Internal_capsule" title="Internal capsule">internal capsule</a> that can be tracked to the <a href="/wiki/Motor_cortex" title="Motor cortex">motor cortex</a>, consistent with the diagnosis of ALS </figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="Differential_diagnosis">Differential diagnosis</h3>[<a href="/w/index.php?title=ALS&action=edit&section=18" title="Edit section: Differential diagnosis">edit</a>]</div> Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is <a href="/wiki/Electromyography" title="Electromyography">electromyography</a> (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures <a href="/wiki/Nerve_conduction_velocity" title="Nerve conduction velocity">nerve conduction velocity</a> (NCV).<a href="#cite_note-87">[87]</a> Specific abnormalities in the NCV results may suggest, for example, that the person has a form of <a href="/wiki/Peripheral_neuropathy" title="Peripheral neuropathy">peripheral neuropathy</a> (damage to peripheral nerves) or <a href="/wiki/Myopathy" title="Myopathy">myopathy</a> (muscle disease) rather than ALS. While a <a href="/wiki/Magnetic_resonance_imaging" title="Magnetic resonance imaging">magnetic resonance imaging</a> (MRI) is often normal in people with early-stage ALS, it can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>, a <a href="/wiki/Herniated_disc" class="mw-redirect" title="Herniated disc">herniated disc</a> in the neck, <a href="/wiki/Syringomyelia" title="Syringomyelia">syringomyelia</a>, or cervical <a href="/wiki/Spondylosis" title="Spondylosis">spondylosis</a>.<a href="#cite_note-NINDS2020-3">[3]</a> Based on the person's symptoms and findings from the examination and from these tests, the physician may order tests on blood and <a href="/wiki/Urine" title="Urine">urine</a> samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.<a href="#cite_note-NINDS2020-3">[3]</a> A number of infectious diseases can sometimes cause ALS-like symptoms,<a href="#cite_note-NINDS2020-3">[3]</a> including human immunodeficiency virus (<a href="/wiki/HIV" title="HIV">HIV</a>), <a href="/wiki/Human_T-lymphotropic_virus" class="mw-redirect" title="Human T-lymphotropic virus">human T-lymphotropic virus</a> (HTLV), <a href="/wiki/Lyme_disease" title="Lyme disease">Lyme disease</a>, and <a href="/wiki/Syphilis" title="Syphilis">syphilis</a>.<a href="#cite_note-Lancet2017-9">[9]</a> Neurological disorders such as multiple sclerosis, <a href="/wiki/Post-polio_syndrome" title="Post-polio syndrome">post-polio syndrome</a>, <a href="/wiki/Multifocal_motor_neuropathy" title="Multifocal motor neuropathy">multifocal motor neuropathy</a>, <a href="/wiki/Chronic_inflammatory_demyelinating_polyneuropathy" title="Chronic inflammatory demyelinating polyneuropathy">CIDP</a>, <a href="/wiki/Spinal_muscular_atrophy" title="Spinal muscular atrophy">spinal muscular atrophy</a>, and <a href="/wiki/Spinal_and_bulbar_muscular_atrophy" title="Spinal and bulbar muscular atrophy">spinal and bulbar muscular atrophy</a> can also mimic certain aspects of the disease and should be considered.<a href="#cite_note-NINDS2020-3">[3]</a> ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants.<a href="#cite_note-88">[88]</a> Because the prognosis of ALS and closely related subtypes of motor neuron disease are generally poor, neurologists may carry out investigations to evaluate and exclude other diagnostic possibilities. Disorders of the <a href="/wiki/Neuromuscular_junction" title="Neuromuscular junction">neuromuscular junction</a>, such as <a href="/wiki/Myasthenia_gravis" title="Myasthenia gravis">myasthenia gravis</a> (MG) and <a href="/wiki/Lambert%E2%80%93Eaton_myasthenic_syndrome" title="Lambert–Eaton myasthenic syndrome">Lambert–Eaton myasthenic syndrome</a>, may also mimic ALS, although this rarely presents diagnostic difficulty over time.<a href="#cite_note-89">[89]</a><a href="#cite_note-90">[90]</a> <a href="/wiki/Benign_fasciculation_syndrome" title="Benign fasciculation syndrome">Benign fasciculation syndrome</a> and <a href="/wiki/Cramp_fasciculation_syndrome" title="Cramp fasciculation syndrome">cramp fasciculation syndrome</a> may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time, the distinction will not present any difficulty to the experienced neurologist; where doubt remains, EMG may be helpful.<a href="#cite_note-91">[91]</a> <div class="mw-heading mw-heading2"><h2 id="Management">Management</h2>[<a href="/w/index.php?title=ALS&action=edit&section=19" title="Edit section: Management">edit</a>]</div> There is no cure for ALS.<a href="#cite_note-Lancet2017-9">[9]</a> Management focuses on treating symptoms and providing supportive care, with the goal of improving quality of life and prolonging survival.<a href="#cite_note-Lancet2017-9">[9]</a> This care is best provided by multidisciplinary teams of healthcare professionals; attending a multidisciplinary ALS clinic is associated with longer survival, fewer hospitalizations, and improved quality of life.<a href="#cite_note-Support2016-5">[5]</a> <a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">Non-invasive ventilation</a> (NIV) is the main treatment for respiratory failure in ALS.<a href="#cite_note-Nature2017-10">[10]</a> In people with normal bulbar function, it prolongs survival by about seven months and improves quality of life. One study found that NIV is ineffective for people with poor bulbar function<a href="#cite_note-Cochrane_NIV-92">[92]</a> while another suggested that it may provide a modest survival benefit.<a href="#cite_note-Lancet2017-9">[9]</a> Many people with ALS have difficulty tolerating NIV.<a href="#cite_note-Sleep_Disorders_and_Respiratory_Function-93">[93]</a> Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms.<a href="#cite_note-Support2016-5">[5]</a> While invasive ventilation prolongs survival, disease progression and functional decline continue.<a href="#cite_note-Care2017-16">[16]</a> It may decrease the quality of life of people with ALS or their caregivers.<a href="#cite_note-Conn2015-17">[17]</a><a href="#cite_note-Care2017-16">[16]</a> Invasive ventilation is more commonly used in Japan than in North America or Europe.<a href="#cite_note-ALS_Ethics-94">[94]</a> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Per_Villand.jpg" class="mw-file-description"><img alt="Person with ALS and their assistive technologies" src="//upload.wikimedia.org/wikipedia/commons/thumb/3/3d/Per_Villand.jpg/220px-Per_Villand.jpg" decoding="async" width="220" height="123" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/3d/Per_Villand.jpg/330px-Per_Villand.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/3d/Per_Villand.jpg/440px-Per_Villand.jpg 2x" data-file-width="980" data-file-height="550" /></a><figcaption>A person with late-stage ALS with a range of assistive technologies to support movement (power wheelchair), breathing (invasive ventilation), and communication (eye tracker and computer)</figcaption></figure> Physical therapy can promote functional independence<a href="#cite_note-Lewis_&_Rushanan-95">[95]</a><a href="#cite_note-asha-96">[96]</a> through aerobic, range of motion, and stretching exercises.<a href="#cite_note-British_Medical_Bulletin-97">[97]</a> Occupational therapy can assist with activities of daily living through adaptive equipment.<a href="#cite_note-ajop-98">[98]</a> Speech therapy can assist people with ALS who have difficulty speaking.<a href="#cite_note-asha-96">[96]</a> Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life.<a href="#cite_note-Lancet2017-9">[9]</a> Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A <a href="/wiki/Feeding_tube" title="Feeding tube">feeding tube</a> should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water.<a href="#cite_note-Nature2017-10">[10]</a> The feeding tube is usually inserted by <a href="/wiki/Percutaneous_endoscopic_gastrostomy" title="Percutaneous endoscopic gastrostomy">percutaneous endoscopic gastrostomy</a> (PEG). There is weak evidence that PEG tubes improve survival.<a href="#cite_note-:0-99">[99]</a> PEG insertion is usually performed with the intent of improving quality of life.<a href="#cite_note-Conn2015-17">[17]</a> <a href="/wiki/Palliative_care" title="Palliative care">Palliative care</a> should begin shortly after someone is diagnosed with ALS.<a href="#cite_note-EFNS_2012-100">[100]</a> Discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Hospice care can improve symptom management at the end of life and increases the likelihood of a peaceful death.<a href="#cite_note-Conn2015-17">[17]</a> In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.<a href="#cite_note-Care2017-16">[16]</a> <div class="mw-heading mw-heading3"><h3 id="Medications">Medications</h3>[<a href="/w/index.php?title=ALS&action=edit&section=20" title="Edit section: Medications">edit</a>]</div> <div class="mw-heading mw-heading4"><h4 id="Disease-slowing_treatments">Disease-slowing treatments</h4>[<a href="/w/index.php?title=ALS&action=edit&section=21" title="Edit section: Disease-slowing treatments">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Riluzole2DACS.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Riluzole2DACS.svg/260px-Riluzole2DACS.svg.png" decoding="async" width="260" height="86" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Riluzole2DACS.svg/390px-Riluzole2DACS.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Riluzole2DACS.svg/520px-Riluzole2DACS.svg.png 2x" data-file-width="512" data-file-height="169" /></a><figcaption>Chemical structure of <a href="/wiki/Riluzole" title="Riluzole">riluzole</a>, a medication that prolongs survival by 2–3 months<a href="#cite_note-CD001447-101">[101]</a></figcaption></figure> <a href="/wiki/Riluzole" title="Riluzole">Riluzole</a> has been found to modestly prolong survival by about 2–3 months.<a href="#cite_note-102">[102]</a><a href="#cite_note-CD001447-101">[101]</a> It may have a greater survival benefit for those with <a href="/wiki/Bulbar-onset_ALS" class="mw-redirect" title="Bulbar-onset ALS">bulbar-onset ALS</a>.<a href="#cite_note-CD001447-101">[101]</a> It may work by decreasing release of the excitatory <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> <a href="/wiki/Glutamate_(neurotransmitter)" title="Glutamate (neurotransmitter)">glutamate</a> from pre-synaptic neurons.<a href="#cite_note-Nature2017-10">[10]</a> The most common side effects are nausea and a lack of energy (<a href="/wiki/Asthenia" class="mw-redirect" title="Asthenia">asthenia</a>).<a href="#cite_note-CD001447-101">[101]</a> People with ALS should begin treatment with riluzole as soon as possible following their diagnosis.<a href="#cite_note-EFNS_2012-100">[100]</a> Riluzole is available as a tablet, liquid, or dissolvable oral film.<a href="#cite_note-alsa1-15">[15]</a> <a href="/wiki/Edaravone" title="Edaravone">Edaravone</a> has been shown to modestly slow the decline in function in a small group of people with early-stage ALS.<a href="#cite_note-103">[103]</a><a href="#cite_note-Therapeutic_Advances_in_Neurological_Disorders-104">[104]</a> It may work by protecting motor neurons from <a href="/wiki/Oxidative_stress" title="Oxidative stress">oxidative stress</a>.<a href="#cite_note-105">[105]</a> The most common side effects are bruising and gait disturbance.<a href="#cite_note-Therapeutic_Advances_in_Neurological_Disorders-104">[104]</a> Edaravone is available as an intravenous infusion or as an oral suspension.<a href="#cite_note-106">[106]</a> <a href="/wiki/Sodium_phenylbutyrate/ursodoxicoltaurine" title="Sodium phenylbutyrate/ursodoxicoltaurine">AMX0035</a> (Relyvrio) is a combination of <a href="/wiki/Sodium_phenylbutyrate" title="Sodium phenylbutyrate">sodium phenylbutyrate</a> and <a href="/wiki/Tauroursodeoxycholic_acid" class="mw-redirect" title="Tauroursodeoxycholic acid">taurursodiol</a>, which was initially shown to prolong the survival of patients by an average of six months.<a href="#cite_note-107">[107]</a> Relyvrio was withdrawn by the manufacturer in April 2024<a href="#cite_note-108">[108]</a> following the completion of the Phase 3 PHOENIX trial<a href="#cite_note-109">[109]</a> which did not show substantial benefit to ALS patients. <a href="/wiki/Tofersen" title="Tofersen">Tofersen</a> (Qalsody) is an <a href="/wiki/Antisense_oligonucleotide" class="mw-redirect" title="Antisense oligonucleotide">antisense oligonucleotide</a> that was approved for medical use in the United States in April 2023, for the treatment of SOD1-associated ALS.<a href="#cite_note-FDA_Qalsody-110">[110]</a> In a study of 108 patients with SOD1-associated ALS there was a non-significant trend towards a slowing of progression, as well as a significant reduction in neurofilament light chain,<a href="#cite_note-111">[111]</a> a putative ALS biomarker thought to indicate neuronal damage.<a href="#cite_note-112">[112]</a> A follow-up study and open-label extension suggested that earlier treatment initiation had a beneficial effect on slowing disease progression. Tofersen is available as an intrathecal injection into the <a href="/wiki/Lumbar_cistern" class="mw-redirect" title="Lumbar cistern">lumbar cistern</a> at the base of the spine.<a href="#cite_note-FDA_Qalsody-110">[110]</a> <div class="mw-heading mw-heading4"><h4 id="Symptomatic_treatments">Symptomatic treatments</h4>[<a href="/w/index.php?title=ALS&action=edit&section=22" title="Edit section: Symptomatic treatments">edit</a>]</div> Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and <a href="/wiki/Phlegm" title="Phlegm">phlegm</a>.<a href="#cite_note-British_Medical_Bulletin-97">[97]</a> <a href="/wiki/Gabapentin" title="Gabapentin">Gabapentin</a>, <a href="/wiki/Pregabalin" title="Pregabalin">pregabalin</a>, and <a href="/wiki/Tricyclic_antidepressants" class="mw-redirect" title="Tricyclic antidepressants">tricyclic antidepressants</a> (e.g., <a href="/wiki/Amitriptyline" title="Amitriptyline">amitriptyline</a>) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (<a href="/wiki/NSAIDs" class="mw-redirect" title="NSAIDs">NSAIDs</a>), <a href="/wiki/Acetaminophen" class="mw-redirect" title="Acetaminophen">acetaminophen</a>, and <a href="/wiki/Opioid" title="Opioid">opioids</a> can be used for nociceptive pain.<a href="#cite_note-Pain2017-35">[35]</a> Depression can be treated with <a href="/wiki/Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs) or tricyclic antidepressants,<a href="#cite_note-Nature2017-10">[10]</a> while <a href="/wiki/Benzodiazepines" class="mw-redirect" title="Benzodiazepines">benzodiazepines</a> can be used for anxiety.<a href="#cite_note-Support2016-5">[5]</a> There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD.<a href="#cite_note-Nature2017-10">[10]</a> <a href="/wiki/Baclofen" title="Baclofen">Baclofen</a> and <a href="/wiki/Tizanidine" title="Tizanidine">tizanidine</a> are the most commonly used oral drugs for treating spasticity; an <a href="/wiki/Intrathecal" class="mw-redirect" title="Intrathecal">intrathecal</a> baclofen pump can be used for severe spasticity.<a href="#cite_note-Nature2017-10">[10]</a> <a href="/wiki/Atropine" title="Atropine">Atropine</a>, <a href="/wiki/Scopolamine" title="Scopolamine">scopolamine</a>, amitriptyline or <a href="/wiki/Glycopyrrolate" class="mw-redirect" title="Glycopyrrolate">glycopyrrolate</a> may be prescribed when people with ALS begin having trouble swallowing their saliva (<a href="/wiki/Sialorrhea" class="mw-redirect" title="Sialorrhea">sialorrhea</a>).<a href="#cite_note-Nature2017-10">[10]</a> A 2017 review concluded that <a href="/wiki/Mexiletine" title="Mexiletine">mexiletine</a> is safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016.<a href="#cite_note-Therapeutic_Advances_in_Neurological_Disorders-104">[104]</a> <div class="mw-heading mw-heading3"><h3 id="Breathing_support">Breathing support</h3>[<a href="/w/index.php?title=ALS&action=edit&section=23" title="Edit section: Breathing support">edit</a>]</div> <div class="mw-heading mw-heading4"><h4 id="Non-invasive_ventilation">Non-invasive ventilation</h4>[<a href="/w/index.php?title=ALS&action=edit&section=24" title="Edit section: Non-invasive ventilation">edit</a>]</div> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:BIPAP.JPG" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/0/04/BIPAP.JPG/260px-BIPAP.JPG" decoding="async" width="260" height="203" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/04/BIPAP.JPG/390px-BIPAP.JPG 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/04/BIPAP.JPG/520px-BIPAP.JPG 2x" data-file-width="3840" data-file-height="2994" /></a><figcaption><a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">Non-invasive ventilation</a> supports breathing with a face or nasal mask connected to a ventilator.</figcaption></figure> <a href="/wiki/Non-invasive_ventilation" title="Non-invasive ventilation">Non-invasive ventilation</a> (NIV) is the primary treatment for respiratory failure in ALS<a href="#cite_note-Nature2017-10">[10]</a> and was the first treatment shown to improve both survival and quality of life.<a href="#cite_note-Support2016-5">[5]</a> NIV uses a face or nasal mask connected to a ventilator that provides intermittent positive pressure to support breathing. Continuous positive pressure is not recommended for people with ALS because it makes breathing more difficult.<a href="#cite_note-Care2017-16">[16]</a> Initially, NIV is used only at night<a href="#cite_note-Support2016-5">[5]</a> because the first sign of respiratory failure is decreased gas exchange (<a href="/wiki/Hypoventilation" title="Hypoventilation">hypoventilation</a>) during sleep; symptoms associated with this nocturnal hypoventilation include interrupted sleep, anxiety, morning headaches, and daytime fatigue.<a href="#cite_note-Sleep_Disorders_and_Respiratory_Function-93">[93]</a> As the disease progresses, people with ALS develop shortness of breath when lying down, during physical activity or talking, and eventually at rest.<a href="#cite_note-NeuroRehabilitation_2015-113">[113]</a> Other symptoms include poor concentration, poor memory, confusion, respiratory tract infections, and a weak cough. Respiratory failure is the most common cause of death in ALS.<a href="#cite_note-Support2016-5">[5]</a> It is important to monitor the respiratory function of people with ALS every three months because beginning NIV soon after the start of respiratory symptoms is associated with increased survival. This involves asking the person with ALS if they have any respiratory symptoms and measuring their respiratory function.<a href="#cite_note-Support2016-5">[5]</a> The most commonly used measurement is upright <a href="/wiki/Forced_vital_capacity" class="mw-redirect" title="Forced vital capacity">forced vital capacity</a> (FVC), but it is a poor detector of early respiratory failure and is not a good choice for those with bulbar symptoms, as they have difficulty maintaining a tight seal around the mouthpiece. Measuring FVC while the person is lying on their back (supine FVC) is a more accurate measure of diaphragm weakness than upright FVC.<a href="#cite_note-Sleep_Disorders_and_Respiratory_Function-93">[93]</a> Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of diaphragm strength that is not affected by bulbar muscle weakness.<a href="#cite_note-Care2017-16">[16]</a> If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime <a href="/wiki/Blood_gas_analysis" class="mw-redirect" title="Blood gas analysis">blood gas analysis</a><a href="#cite_note-Support2016-5">[5]</a> to look for <a href="/wiki/Hypoxemia" title="Hypoxemia">hypoxemia</a> (low oxygen in the blood) and <a href="/wiki/Hypercapnia" title="Hypercapnia">hypercapnia</a> (too much carbon dioxide in the blood).<a href="#cite_note-Care2017-16">[16]</a> If their daytime blood gas analysis is normal, they should then have nocturnal <a href="/wiki/Pulse_oximetry" title="Pulse oximetry">pulse oximetry</a> to look for hypoxemia during sleep.<a href="#cite_note-Support2016-5">[5]</a> Non-invasive ventilation prolongs survival longer than riluzole.<a href="#cite_note-114">[114]</a> A 2006 randomized controlled trial found that NIV prolongs survival by about 48 days and improves the quality of life; however, it also found that some people with ALS benefit more from this intervention than others. For those with normal or only moderately impaired bulbar function, NIV prolongs survival by about seven months and significantly improves the quality of life. For those with poor bulbar function, NIV neither prolongs survival nor improves the quality of life, though it does improve some sleep-related symptoms.<a href="#cite_note-Cochrane_NIV-92">[92]</a> Despite the clear benefits of NIV, about 25–30% of all people with ALS are unable to tolerate it, especially those with cognitive impairment or bulbar dysfunction.<a href="#cite_note-Sleep_Disorders_and_Respiratory_Function-93">[93]</a> Results from a large 2015 cohort study suggest that NIV may prolong survival in those with bulbar weakness, so NIV should be offered to all people with ALS, even if it is likely that they will have difficulty tolerating it.<a href="#cite_note-Lancet2017-9">[9]</a> <div class="mw-heading mw-heading4"><h4 id="Invasive_ventilation">Invasive ventilation</h4>[<a href="/w/index.php?title=ALS&action=edit&section=25" title="Edit section: Invasive ventilation">edit</a>]</div> Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (<a href="/wiki/Tracheostomy" class="mw-redirect" title="Tracheostomy">tracheostomy</a>) and inserting a <a href="/wiki/Tracheal_tube" title="Tracheal tube">tube</a> connected to a ventilator.<a href="#cite_note-Care2017-16">[16]</a> It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use.<a href="#cite_note-Support2016-5">[5]</a> While invasive ventilation prolongs survival, especially for those younger than 60, it does not treat the underlying neurodegenerative process. The person with ALS will continue to lose motor function, making communication increasingly difficult and sometimes leading to <a href="/wiki/Locked-in_syndrome" title="Locked-in syndrome">locked-in syndrome</a>, in which they are completely paralyzed except for their eye muscles.<a href="#cite_note-Care2017-16">[16]</a> About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life<a href="#cite_note-Conn2015-17">[17]</a> but most still consider it to be satisfactory. However, invasive ventilation imposes a heavy burden on caregivers and may decrease their quality of life.<a href="#cite_note-Care2017-16">[16]</a> Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe.<a href="#cite_note-ALS_Ethics-94">[94]</a> <div class="mw-heading mw-heading3"><h3 id="Therapy">Therapy</h3>[<a href="/w/index.php?title=ALS&action=edit&section=26" title="Edit section: Therapy">edit</a>]</div> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg" class="mw-file-description"><img alt="A man with ALS communicates with his wife by pointing to letters and words with a head mounted laser pointer." src="//upload.wikimedia.org/wikipedia/commons/thumb/3/36/Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg/260px-Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg" decoding="async" width="260" height="205" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/36/Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg/390px-Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/36/Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg/520px-Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg 2x" data-file-width="609" data-file-height="480" /></a><figcaption>A man with ALS communicates by pointing to letters and words using a head-mounted laser pointer.</figcaption></figure> <a href="/wiki/Physical_therapy" title="Physical therapy">Physical therapy</a> plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.<a href="#cite_note-Lewis_&_Rushanan-95">[95]</a><a href="#cite_note-asha-96">[96]</a> Occupational therapy and special equipment such as <a href="/wiki/Assistive_technology" title="Assistive technology">assistive technology</a> can also enhance people's independence and safety throughout the course of ALS.<a href="#cite_note-ajop-98">[98]</a> Gentle, low-impact <a href="/wiki/Aerobic_exercise" title="Aerobic exercise">aerobic exercise</a> such as performing activities of daily living, walking, swimming, and <a href="/wiki/Stationary_bicycle" title="Stationary bicycle">stationary bicycling</a> can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful <a href="/wiki/Spasticity" title="Spasticity">spasticity</a> and shortening (contracture) of muscles.<a href="#cite_note-115">[115]</a> Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles because muscle exhaustion can lead to a worsening of symptoms associated with ALS, rather than providing help to people with ALS.<a href="#cite_note-British_Medical_Bulletin-97">[97]</a> They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible.<a href="#cite_note-ajop-98">[98]</a> Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. This includes inspiratory muscle training, lung volume recruitment training, and manual assisted cough therapy aimed at increasing respiratory muscle strength as well as increasing survival rates.<a href="#cite_note-116">[116]</a> People with ALS who have difficulty speaking or swallowing may benefit from working with a <a href="/wiki/Speech-language_pathology" class="mw-redirect" title="Speech-language pathology">speech-language pathologist</a>.<a href="#cite_note-asha-96">[96]</a> These health professionals can teach people adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of <a href="/wiki/Augmentative_and_alternative_communication" title="Augmentative and alternative communication">augmentative and alternative communication</a> such as voice amplifiers, speech-generating devices (or voice output communication devices) or low-tech communication techniques such as head-mounted laser pointers, <a href="/wiki/Letter_board#Communication_Board" title="Letter board">alphabet boards</a> or yes/no signals.<a href="#cite_note-asha-96">[96]</a> <div class="mw-heading mw-heading3"><h3 id="Nutrition">Nutrition</h3>[<a href="/w/index.php?title=ALS&action=edit&section=27" title="Edit section: Nutrition">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Percutaneous_endoscopic_gastrostomy-tube.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/62/Percutaneous_endoscopic_gastrostomy-tube.jpg/220px-Percutaneous_endoscopic_gastrostomy-tube.jpg" decoding="async" width="220" height="165" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/62/Percutaneous_endoscopic_gastrostomy-tube.jpg/330px-Percutaneous_endoscopic_gastrostomy-tube.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/62/Percutaneous_endoscopic_gastrostomy-tube.jpg/440px-Percutaneous_endoscopic_gastrostomy-tube.jpg 2x" data-file-width="1000" data-file-height="750" /></a><figcaption>A <a href="/wiki/Gastrostomy" title="Gastrostomy">gastrostomy</a> tube is placed through the wall of the abdomen into the stomach.</figcaption></figure> Preventing <a href="/wiki/Weight_loss" title="Weight loss">weight loss</a> and <a href="/wiki/Malnutrition" title="Malnutrition">malnutrition</a> in people with ALS improves both survival and quality of life.<a href="#cite_note-Lancet2017-9">[9]</a> Weight loss in ALS is often caused by muscle wasting and increased resting energy expenditure. Weight loss may also be secondary to reduced food intake since <a href="/wiki/Dysphagia" title="Dysphagia">dysphagia</a> develops in about 85% of people with ALS at some point over the course of their disease.<a href="#cite_note-Care2017-16">[16]</a> Therefore, regular periodic assessment of the weight and swallowing ability in people with ALS is very important.<a href="#cite_note-Support2016-5">[5]</a> Dysphagia is often initially managed via dietary changes and modified swallowing techniques.<a href="#cite_note-Nature2017-10">[10]</a> People with ALS are often instructed to avoid dry or chewy foods in their diet and instead have meals that are soft, moist, and easy to swallow.<a href="#cite_note-NeuroRehabilitation_2015-113">[113]</a> Switching to thick liquids (like fruit nectar or smoothies) or adding thickeners (to thin fluids like water and coffee) may also help people facing difficulty swallowing liquids. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival,<a href="#cite_note-Therapeutic_Advances_in_Neurological_Disorders-104">[104]</a> but more research is still needed. A <a href="/wiki/Feeding_tube" title="Feeding tube">feeding tube</a> should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water.<a href="#cite_note-Nature2017-10">[10]</a> This can take the form of a <a href="/wiki/Gastrostomy" title="Gastrostomy">gastrostomy</a> tube, in which a tube is placed through the wall of the abdomen into the stomach, or (less commonly) a <a href="/wiki/Nasogastric_tube" class="mw-redirect" title="Nasogastric tube">nasogastric tube</a>, in which a tube is placed through the nose and down the esophagus into the stomach.<a href="#cite_note-Care2017-16">[16]</a> A gastrostomy tube is more appropriate for long-term use<a href="#cite_note-Support2016-5">[5]</a> than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers.<a href="#cite_note-Care2017-16">[16]</a> The feeding tube is usually inserted by a <a href="/wiki/Percutaneous_endoscopic_gastrostomy" title="Percutaneous endoscopic gastrostomy">percutaneous endoscopic gastrostomy</a> procedure (PEG). While there is weak evidence that PEG tubes improve survival in people with ALS, no <a href="/wiki/Randomized_controlled_trial" title="Randomized controlled trial">randomized controlled trials</a> (RCTs) have yet been conducted to indicate whether enteral tube feeding has benefits compared to continuation of feeding by mouth.<a href="#cite_note-:0-99">[99]</a> Nevertheless, PEG tubes are still offered with the intent of improving the person's quality of life<a href="#cite_note-Conn2015-17">[17]</a> by sustaining nutrition, hydration status, and medication intake.<a href="#cite_note-Support2016-5">[5]</a> <div class="mw-heading mw-heading3"><h3 id="End-of-life_care">End-of-life care</h3>[<a href="/w/index.php?title=ALS&action=edit&section=28" title="Edit section: End-of-life care">edit</a>]</div> <a href="/wiki/Palliative_care" title="Palliative care">Palliative care</a>, which relieves symptoms and improves the quality of life without treating the underlying disease, should begin shortly after someone is diagnosed with ALS.<a href="#cite_note-EFNS_2012-100">[100]</a> Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for <a href="/wiki/End-of-life_care" title="End-of-life care">end-of-life care</a> and can help avoid unwanted interventions or procedures.<a href="#cite_note-Conn2015-17">[17]</a> Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out <a href="/wiki/Advance_directive" class="mw-redirect" title="Advance directive">advance directives</a> indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes.<a href="#cite_note-Therapeutic_Advances_in_Neurological_Disorders-104">[104]</a> Late in the disease course, difficulty speaking due to muscle weakness (<a href="/wiki/Dysarthria" title="Dysarthria">dysarthria</a>) and cognitive dysfunction may impair their ability to communicate their wishes regarding care.<a href="#cite_note-Nature2017-10">[10]</a> Continued failure to solicit the preferences of the person with ALS may lead to unplanned and potentially unwanted emergency interventions, such as invasive ventilation. If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject.<a href="#cite_note-Conn2015-17">[17]</a> <a href="/wiki/Hospice_care" class="mw-redirect" title="Hospice care">Hospice care</a>, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death.<a href="#cite_note-Conn2015-17">[17]</a> It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking.<a href="#cite_note-Nature2017-10">[10]</a> Although many people with ALS fear choking to death (suffocating),<a href="#cite_note-Conn2015-17">[17]</a> they can be reassured that this occurs rarely, less than 1% of the time.<a href="#cite_note-117">[117]</a> Most patients die at home,<a href="#cite_note-Conn2015-17">[17]</a> and in the final days of life, opioids can be used to treat pain and <a href="/wiki/Dyspnea" class="mw-redirect" title="Dyspnea">dyspnea</a>, while <a href="/wiki/Benzodiazepine" title="Benzodiazepine">benzodiazepines</a> can be used to treat anxiety.<a href="#cite_note-Care2017-16">[16]</a> <div class="mw-heading mw-heading2"><h2 id="Epidemiology">Epidemiology</h2>[<a href="/w/index.php?title=ALS&action=edit&section=29" title="Edit section: Epidemiology">edit</a>]</div> ALS is the most common <a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">motor neuron disease</a> in adults and the third most common <a href="/wiki/Neurodegenerative_disease" title="Neurodegenerative disease">neurodegenerative disease</a><a href="#cite_note-Neuroscience2014-60">[60]</a> after <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a> and <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a>.<a href="#cite_note-118">[118]</a> Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000.<a href="#cite_note-119">[119]</a> In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000.<a href="#cite_note-120">[120]</a> The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women.<a href="#cite_note-Conspiracy-62">[62]</a> The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old.<a href="#cite_note-MMWR_2015-121">[121]</a> The number of new cases is about 0.8 people per 100,000 per year in east Asia and about 0.7 people per 100,000 per year in south Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent.<a href="#cite_note-Nature2017-10">[10]</a> There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America.<a href="#cite_note-Conspiracy-62">[62]</a> There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than the rest of the world, including <a href="/wiki/Guam" title="Guam">Guam</a>, the <a href="/wiki/Kii_Peninsula" title="Kii Peninsula">Kii Peninsula</a> of Japan, and <a href="/wiki/Western_New_Guinea" title="Western New Guinea">Western New Guinea</a>. The incidence in these areas has decreased since the 1960s;<a href="#cite_note-Orphanet2009-1">[1]</a> the cause remains unknown.<a href="#cite_note-Conspiracy-62">[62]</a> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Prevalence_of_ALS_in_the_United_States_by_age_group,_2012-2015.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg/330px-Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg" decoding="async" width="330" height="215" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg/495px-Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/ca/Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg/660px-Prevalence_of_ALS_in_the_United_States_by_age_group%2C_2012-2015.jpg 2x" data-file-width="1191" data-file-height="777" /></a><figcaption>Estimated prevalence of ALS in the United States by age group, 2012–2015<a href="#cite_note-MMWR_2015-121">[121]</a></figcaption></figure> People of all races and ethnic backgrounds may be affected by ALS,<a href="#cite_note-MMWR_2015-121">[121]</a> but it is more common in whites than in Africans, Asians, or Hispanics.<a href="#cite_note-Projected2016-122">[122]</a> In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West.<a href="#cite_note-MMWR_2015-121">[121]</a> Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks.<a href="#cite_note-Current_Issues_in_ALS_Epidemiology-123">[123]</a> There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is C9orf72, followed by SOD1, TARDBP, and FUS, while the most common ALS gene in Asia is SOD1, followed by FUS, C9orf72, and TARDBP.<a href="#cite_note-124">[124]</a> ALS can affect people at any age,<a href="#cite_note-Martin2017-53">[53]</a> but the peak incidence is between 50 and 75 years<a href="#cite_note-Lancet2017-9">[9]</a> and decreases dramatically after 80 years.<a href="#cite_note-Lancet2011-18">[18]</a> The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS; alternatively, ALS in the elderly might go undiagnosed because of <a href="/wiki/Comorbidities" class="mw-redirect" title="Comorbidities">comorbidities</a> (other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS.<a href="#cite_note-Current_Issues_in_ALS_Epidemiology-123">[123]</a> In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group.<a href="#cite_note-MMWR_2015-121">[121]</a> Sporadic ALS usually starts around the ages of 58 to 63 years, while genetic ALS starts earlier, usually around 47 to 52 years.<a href="#cite_note-Lancet2011-18">[18]</a> The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the world's population, especially in developing countries.<a href="#cite_note-Projected2016-122">[122]</a> <div class="mw-heading mw-heading2"><h2 id="History">History</h2>[<a href="/w/index.php?title=ALS&action=edit&section=30" title="Edit section: History">edit</a>]</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Jean-Martin_Charcot.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/6a/Jean-Martin_Charcot.jpg/170px-Jean-Martin_Charcot.jpg" decoding="async" width="170" height="225" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/6a/Jean-Martin_Charcot.jpg/255px-Jean-Martin_Charcot.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/6a/Jean-Martin_Charcot.jpg/340px-Jean-Martin_Charcot.jpg 2x" data-file-width="457" data-file-height="604" /></a><figcaption>The French neurologist <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a> coined the term amyotrophic lateral sclerosis in 1874.<a href="#cite_note-Rowland2001-20">[20]</a></figcaption></figure> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:1923_Lou_Gehrig.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/1923_Lou_Gehrig.png/170px-1923_Lou_Gehrig.png" decoding="async" width="170" height="226" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/1923_Lou_Gehrig.png/255px-1923_Lou_Gehrig.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/fb/1923_Lou_Gehrig.png/340px-1923_Lou_Gehrig.png 2x" data-file-width="719" data-file-height="957" /></a><figcaption>American baseball player <a href="/wiki/Lou_Gehrig" title="Lou Gehrig">Lou Gehrig</a>. In some countries, especially the United States, ALS is called "Lou Gehrig's disease".<a href="#cite_note-What's_in_a_name?-125">[125]</a></figcaption></figure> Descriptions of the disease date back to at least 1824 by <a href="/wiki/Charles_Bell" title="Charles Bell">Charles Bell</a>.<a href="#cite_note-Rowland2001-20">[20]</a> In 1850, <a href="/wiki/Fran%C3%A7ois-Amilcar_Aran" title="François-Amilcar Aran">François-Amilcar Aran</a> was the first to describe a disorder he named "progressive muscular atrophy", a form of ALS in which only the lower motor neurons are affected.<a href="#cite_note-126">[126]</a> In 1869, the connection between the symptoms and the underlying neurological problems were first described by <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a>, who initially introduced the term amyotrophic lateral sclerosis in his 1874 paper.<a href="#cite_note-Rowland2001-20">[20]</a> Flail arm syndrome, a regional variant of ALS, was first described by <a href="/wiki/Alfred_Vulpian" title="Alfred Vulpian">Alfred Vulpian</a> in 1886. Flail leg syndrome, another regional variant of ALS, was first described by <a href="/wiki/Pierre_Marie" title="Pierre Marie">Pierre Marie</a> and his student Patrikios in 1918.<a href="#cite_note-127">[127]</a> <div class="mw-heading mw-heading3"><h3 id="Diagnostic_criteria">Diagnostic criteria</h3>[<a href="/w/index.php?title=ALS&action=edit&section=31" title="Edit section: Diagnostic criteria">edit</a>]</div> In the 1950s, <a href="/wiki/Electrodiagnostic_testing" class="mw-redirect" title="Electrodiagnostic testing">electrodiagnostic testing</a> (EMG) and <a href="/wiki/Nerve_conduction_velocity" title="Nerve conduction velocity">nerve conduction velocity</a> (NCV) testing began to be used to evaluate clinically suspected ALS. In 1969 <a href="/wiki/Electromyography#History" title="Electromyography">Edward H. Lambert</a> published the first EMG/NCS diagnostic criteria for ALS, consisting of four findings he considered to strongly support the diagnosis.<a href="#cite_note-128">[128]</a> Since then a number of diagnostic criteria have been developed, which are mostly in use for research purposes for inclusion/exclusion criteria, and to stratify patients for analysis in trials. Research diagnostic criteria for ALS include the "El Escorial" in 1994,<a href="#cite_note-129">[129]</a> revised in 1998.<a href="#cite_note-130">[130]</a> In 2006, the "Awaji" criteria proposed using EMG and NCV tests to help diagnose ALS earlier,<a href="#cite_note-131">[131]</a> and most recently the "Gold Coast" criteria in 2019.<a href="#cite_note-132">[132]</a> <div class="mw-heading mw-heading3"><h3 id="Name">Name</h3>[<a href="/w/index.php?title=ALS&action=edit&section=32" title="Edit section: Name">edit</a>]</div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Motor_neuron_diseases" title="Motor neuron diseases">Motor neuron diseases</a></div> Amyotrophic comes from <a href="/wiki/Greek_language" title="Greek language">Greek</a>: a- means "no", myo- (from mûs) refers to "muscle", and trophḗ means "nourishment". Therefore, <a href="/wiki/Amyotrophy" title="Amyotrophy">amyotrophy</a> means "muscle malnourishment"<a href="#cite_note-What_is_ALS?-133">[133]</a> or the wasting of muscle tissue.<a href="#cite_note-134">[134]</a> Lateral identifies the locations in the spinal cord of the affected motor neurons. <a href="/wiki/Sclerosis_(medicine)" title="Sclerosis (medicine)">Sclerosis</a> means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.<a href="#cite_note-What_is_ALS?-133">[133]</a> ALS is sometimes referred to as Charcot's disease (not to be confused with <a href="/wiki/Charcot%E2%80%93Marie%E2%80%93Tooth_disease" title="Charcot–Marie–Tooth disease">Charcot–Marie–Tooth disease</a> or <a href="/wiki/Charcot_joint_disease" class="mw-redirect" title="Charcot joint disease">Charcot joint disease</a>), because <a href="/wiki/Jean-Martin_Charcot" title="Jean-Martin Charcot">Jean-Martin Charcot</a> was the first to connect the clinical symptoms with the pathology seen at autopsy.<a href="#cite_note-135">[135]</a> The British neurologist <a href="/wiki/Russell_Brain" class="mw-redirect" title="Russell Brain">Russell Brain</a> coined the term motor neurone disease in 1933 to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease.<a href="#cite_note-136">[136]</a> In some countries, especially the United States, ALS is called Lou Gehrig's disease<a href="#cite_note-What's_in_a_name?-125">[125]</a> after the American <a href="/wiki/Baseball" title="Baseball">baseball</a> player <a href="/wiki/Lou_Gehrig" title="Lou Gehrig">Lou Gehrig</a>, who was diagnosed with ALS in 1939.<a href="#cite_note-137">[137]</a> In the United States and continental Europe, the term ALS (as well as Lou Gehrig's disease in the US) refers to all forms of the disease, including "classical" ALS, <a href="/wiki/Progressive_bulbar_palsy" title="Progressive bulbar palsy">progressive bulbar palsy</a>, <a href="/wiki/Progressive_muscular_atrophy" title="Progressive muscular atrophy">progressive muscular atrophy</a>, and <a href="/wiki/Primary_lateral_sclerosis" title="Primary lateral sclerosis">primary lateral sclerosis</a>.<a href="#cite_note-UMN_Assessment-138">[138]</a><a href="#cite_note-Clinical_Features_of_ALS-32">[32]</a> In the United Kingdom and Australia, the term motor neurone disease refers to all forms of the disease while ALS only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement.<a href="#cite_note-UMN_Assessment-138">[138]</a> <div class="mw-heading mw-heading2"><h2 id="Society_and_culture">Society and culture</h2>[<a href="/w/index.php?title=ALS&action=edit&section=33" title="Edit section: Society and culture">edit</a>]</div> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><video id="mwe_player_0" poster="//upload.wikimedia.org/wikipedia/commons/thumb/d/d2/ALS_Ice_Bucket_Challenge.ogv/260px--ALS_Ice_Bucket_Challenge.ogv.jpg" controls="" preload="none" data-mw-tmh="" class="mw-file-element" width="260" height="146" data-durationhint="23" data-mwtitle="ALS_Ice_Bucket_Challenge.ogv" data-mwprovider="wikimediacommons" resource="/wiki/File:ALS_Ice_Bucket_Challenge.ogv"><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.480p.vp9.webm" type="video/webm; codecs="vp9, opus"" data-transcodekey="480p.vp9.webm" data-width="854" data-height="480" /><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.720p.vp9.webm" type="video/webm; codecs="vp9, opus"" data-transcodekey="720p.vp9.webm" data-width="1280" data-height="720" /><source src="//upload.wikimedia.org/wikipedia/commons/d/d2/ALS_Ice_Bucket_Challenge.ogv" type="video/ogg; codecs="theora, vorbis"" data-width="1280" data-height="720" /><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.144p.mjpeg.mov" type="video/quicktime" data-transcodekey="144p.mjpeg.mov" data-width="256" data-height="144" /><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.240p.vp9.webm" type="video/webm; codecs="vp9, opus"" data-transcodekey="240p.vp9.webm" data-width="426" data-height="240" /><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.360p.webm" type="video/webm; codecs="vp8, vorbis"" data-transcodekey="360p.webm" data-width="640" data-height="360" /><source src="//upload.wikimedia.org/wikipedia/commons/transcoded/d/d2/ALS_Ice_Bucket_Challenge.ogv/ALS_Ice_Bucket_Challenge.ogv.360p.vp9.webm" type="video/webm; codecs="vp9, opus"" data-transcodekey="360p.vp9.webm" data-width="640" data-height="360" /></video><figcaption>A student demonstrating the ice bucket challenge</figcaption></figure> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/List_of_people_with_motor_neuron_disease" title="List of people with motor neuron disease">List of people with motor neuron disease</a></div> In addition to the baseball player <a href="/wiki/Lou_Gehrig" title="Lou Gehrig">Lou Gehrig</a> and the theoretical physicist <a href="/wiki/Stephen_Hawking" title="Stephen Hawking">Stephen Hawking</a> (who notably lived longer than any other known person with the condition), a number of other notable individuals have or have had ALS.<a href="#cite_note-auto-64">[64]</a> Several books have been written and films have been made about patients of the disease as well. American sociology professor and ALS patient <a href="/wiki/Morrie_Schwartz" title="Morrie Schwartz">Morrie Schwartz</a> was the subject of the memoir <a href="/wiki/Tuesdays_with_Morrie" title="Tuesdays with Morrie">Tuesdays with Morrie</a> and the <a href="/wiki/Tuesdays_with_Morrie_(film)" title="Tuesdays with Morrie (film)">film of the same name</a>, and Stephen Hawking was the subject of the critically acclaimed biopic <a href="/wiki/The_Theory_of_Everything_(2014_film)" title="The Theory of Everything (2014 film)">The Theory of Everything</a>. In August 2014, the "<a href="/wiki/Ice_Bucket_Challenge" title="Ice Bucket Challenge">Ice Bucket Challenge</a>" to raise money for ALS research went <a href="/wiki/Viral_phenomenon" title="Viral phenomenon">viral</a> online.<a href="#cite_note-139">[139]</a> Participants filmed themselves filling a bucket full of ice water and pouring it onto themselves; they then nominated other individuals to do the same. Many participants donated to ALS research at the <a href="/wiki/ALS_Association" title="ALS Association">ALS Association</a>, the <a href="/wiki/ALS_Therapy_Development_Institute" title="ALS Therapy Development Institute">ALS Therapy Development Institute</a>, <a href="/wiki/ALS_Society_of_Canada" title="ALS Society of Canada">ALS Society of Canada</a>, or <a href="/wiki/Motor_Neurone_Disease_Association" title="Motor Neurone Disease Association">Motor Neurone Disease Association</a> in the UK.<a href="#cite_note-140">[140]</a> <div style="clear:left;" class=""></div> <div class="mw-heading mw-heading2"><h2 id="Research">Research</h2>[<a href="/w/index.php?title=ALS&action=edit&section=34" title="Edit section: Research">edit</a>]</div> The Muscular Dystrophy Association (<a class="external free" href="https://en.wikipedia.org/wiki/Muscular_Dystrophy_Association">https://en.wikipedia.org/wiki/Muscular_Dystrophy_Association</a>) (MDA) supports research aimed at advancing ALS research and improving patient care. This is part of its broader mission to address neuromuscular diseases, including funding research and support for affected individuals. <div class="mw-heading mw-heading2"><h2 id="References">References</h2>[<a href="/w/index.php?title=ALS&action=edit&section=35" title="Edit section: References">edit</a>]</div> <img alt="Public Domain" src="//upload.wikimedia.org/wikipedia/en/thumb/6/62/PD-icon.svg/12px-PD-icon.svg.png" decoding="async" width="12" height="12" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/6/62/PD-icon.svg/18px-PD-icon.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/6/62/PD-icon.svg/24px-PD-icon.svg.png 2x" data-file-width="196" data-file-height="196" /> This article incorporates text from this source, which is in the <a href="/wiki/Public_domain" title="Public domain">public domain</a>: <style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://web.archive.org/web/20041118185803/http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_amyotrophiclateralsclerosis.htm">"Amyotrophic Lateral Sclerosis Fact Sheet"</a>. 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Clinical Neurophysiology. 127 (7): 2643–2660. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.clinph.2016.04.025">10.1016/j.clinph.2016.04.025</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/27291884">27291884</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:3757685">3757685</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Clinical+Neurophysiology&rft.atitle=Assessment+of+the+upper+motor+neuron+in+amyotrophic+lateral+sclerosis&rft.volume=127&rft.issue=7&rft.pages=2643-2660&rft.date=2016-07&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A3757685%23id-name%3DS2CID&rft_id=info%3Apmid%2F27291884&rft_id=info%3Adoi%2F10.1016%2Fj.clinph.2016.04.025&rft.aulast=Huynh&rft.aufirst=W&rft.au=Simon%2C+NG&rft.au=Grosskreutz%2C+J&rft.au=Turner%2C+MR&rft.au=Vucic%2C+S&rft.au=Kiernan%2C+MC&rft_id=https%3A%2F%2Fdoi.org%2F10.1016%252Fj.clinph.2016.04.025&rfr_id=info%3Asid%2Fen.wikipedia.org%3AALS" class="Z3988"> </li> <li id="cite_note-139"><a href="#cite_ref-139">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAlexander2014" class="citation news cs1">Alexander E (20 August 2014). <a rel="nofollow" class="external text" href="https://web.archive.org/web/20140821095115/http://www.independent.co.uk/news/people/george-bush-delivers-possibly-the-best-als-ice-bucket-challenge-yet-9680934.html">"George Bush delivers possibly the best ALS ice bucket challenge yet"</a>. The Independent. Archived from <a rel="nofollow" class="external text" href="https://www.independent.co.uk/news/people/george-bush-delivers-possibly-the-best-als-ice-bucket-challenge-yet-9680934.html">the original</a> on 21 August 2014. Retrieved 20 August 2014.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Independent&rft.atitle=George+Bush+delivers+possibly+the+best+ALS+ice+bucket+challenge+yet&rft.date=2014-08-20&rft.aulast=Alexander&rft.aufirst=E&rft_id=https%3A%2F%2Fwww.independent.co.uk%2Fnews%2Fpeople%2Fgeorge-bush-delivers-possibly-the-best-als-ice-bucket-challenge-yet-9680934.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3AALS" class="Z3988"> </li> <li id="cite_note-140"><a href="#cite_ref-140">^</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFWicks2014" class="citation journal cs1">Wicks P (December 2014). <a rel="nofollow" class="external text" href="https://doi.org/10.3109%2F21678421.2014.984725">"The ALS ice bucket challenge – can a splash of water reinvigorate a field?"</a>. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. 15 (7–8): 479–480. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.3109%2F21678421.2014.984725">10.3109/21678421.2014.984725</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25431828">25431828</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:207581186">207581186</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Amyotrophic+Lateral+Sclerosis+%26+Frontotemporal+Degeneration&rft.atitle=The+ALS+ice+bucket+challenge+%E2%80%93+can+a+splash+of+water+reinvigorate+a+field%3F&rft.volume=15&rft.issue=7%E2%80%938&rft.pages=479-480&rft.date=2014-12&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A207581186%23id-name%3DS2CID&rft_id=info%3Apmid%2F25431828&rft_id=info%3Adoi%2F10.3109%2F21678421.2014.984725&rft.aulast=Wicks&rft.aufirst=P&rft_id=https%3A%2F%2Fdoi.org%2F10.3109%252F21678421.2014.984725&rfr_id=info%3Asid%2Fen.wikipedia.org%3AALS" class="Z3988"> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2>[<a href="/w/index.php?title=ALS&action=edit&section=36" title="Edit section: External links">edit</a>]</div> <a href="/wiki/File:Commons-logo.svg" class="mw-file-description"><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/12px-Commons-logo.svg.png" decoding="async" width="12" height="16" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/18px-Commons-logo.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/24px-Commons-logo.svg.png 2x" data-file-width="1024" data-file-height="1376" /></a> Media related to <a href="https://commons.wikimedia.org/wiki/Category:Amyotrophic_lateral_sclerosis" class="extiw" title="commons:Category:Amyotrophic lateral sclerosis">Amyotrophic lateral sclerosis</a> at Wikimedia Commons <ul><li><a rel="nofollow" class="external text" href="https://www.als.org/">ALS Association Official Website</a></li> <li><a rel="nofollow" class="external text" href="https://www.als.net/">ALS Therapy Development Institute</a></li> <li><a rel="nofollow" class="external text" href="https://www.als-mnd.org/">International Alliance of ALS/MND Associations</a></li> <li><a rel="nofollow" class="external text" href="https://symposium.mndassociation.org/">International Symposium on ALS/MND</a></li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1236075235">.mw-parser-output .navbox{box-sizing:border-box;border:1px solid #a2a9b1;width:100%;clear:both;font-size:88%;text-align:center;padding:1px;margin:1em auto 0}.mw-parser-output .navbox .navbox{margin-top:0}.mw-parser-output .navbox+.navbox,.mw-parser-output .navbox+.navbox-styles+.navbox{margin-top:-1px}.mw-parser-output .navbox-inner,.mw-parser-output .navbox-subgroup{width:100%}.mw-parser-output .navbox-group,.mw-parser-output .navbox-title,.mw-parser-output .navbox-abovebelow{padding:0.25em 1em;line-height:1.5em;text-align:center}.mw-parser-output .navbox-group{white-space:nowrap;text-align:right}.mw-parser-output .navbox,.mw-parser-output .navbox-subgroup{background-color:#fdfdfd}.mw-parser-output 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dt:last-child::after,.mw-parser-output .hlist dd li:last-child::after,.mw-parser-output .hlist dt dd:last-child::after,.mw-parser-output .hlist dt dt:last-child::after,.mw-parser-output .hlist dt li:last-child::after,.mw-parser-output .hlist li 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/Q206901" class="extiw" title="d:Q206901">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#1982355687">8B60.0</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#/G12.2">G12.2</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-CM" title="ICD-10-CM">10-CM</a>: <a rel="nofollow" class="external text" href="https://icd10cmtool.cdc.gov/?fy=FY2024&query=G12.21">G12.21</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=335.20">335.20</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/105400">105400</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=D000690">D000690</a></li><li><a href="/wiki/Diseases_Database" title="Diseases Database">DiseasesDB</a>: <a rel="nofollow" class="external text" href="http://www.diseasesdatabase.com/ddb29148.htm">29148</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/000688.htm">000688</a></li><li><a href="/wiki/EMedicine" title="EMedicine">eMedicine</a>: <a rel="nofollow" class="external text" href="https://emedicine.medscape.com/neuro/14-overview">neuro/14</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/emerg/topic24.htm#">emerg/24</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/pmr/topic10.htm#">pmr/10</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/Motor-Neurone-Disease-(MND)">ALS</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/NBK1450/">Amyotrophic lateral sclerosis</a></li><li><a href="/wiki/Radiopaedia" title="Radiopaedia">Radiopaedia</a>: <a rel="nofollow" class="external text" href="https://radiopaedia.org/articles/amyotrophic-lateral-sclerosis-3">amyotrophic-lateral-sclerosis-3</a></li><li><a href="/wiki/Orphanet" title="Orphanet">Orphanet</a>: <a rel="nofollow" class="external text" href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=803">803</a></li><li>Scholia: <a class="external text" href="https://tools.wmflabs.org/scholia/topic/Q206901">Q206901</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="Diseases_of_the_nervous_system,_primarily_CNS" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed 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: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 href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">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="Amyotrophic_lateral_sclerosis" 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:Amyotrophic_lateral_sclerosis" title="Template:Amyotrophic lateral sclerosis"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Amyotrophic_lateral_sclerosis" title="Template talk:Amyotrophic lateral sclerosis"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Amyotrophic_lateral_sclerosis" title="Special:EditPage/Template:Amyotrophic lateral sclerosis"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Amyotrophic_lateral_sclerosis" style="font-size:114%;margin:0 4em"><a href="/wiki/Amyotrophic_lateral_sclerosis" class="mw-redirect" title="Amyotrophic lateral sclerosis">Amyotrophic lateral sclerosis</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">General</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/Genetics_of_amyotrophic_lateral_sclerosis" title="Genetics of amyotrophic lateral sclerosis">Genetics of ALS</a></li> <li><a href="/wiki/Amyotrophic_lateral_sclerosis_research" title="Amyotrophic lateral sclerosis research">ALS research</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Organizations in the United States</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/ALS_Association" title="ALS Association">ALS Association</a></li> <li><a href="/wiki/ALS_Therapy_Development_Institute" title="ALS Therapy Development Institute">ALS Therapy Development Institute</a></li> <li><a href="/wiki/Les_Turner_ALS_Foundation" title="Les Turner ALS Foundation">Les Turner ALS Foundation</a></li> <li><a href="/wiki/Muscular_Dystrophy_Association" title="Muscular Dystrophy Association">Muscular Dystrophy Association</a></li> <li><a href="/wiki/Project_ALS" title="Project ALS">Project ALS</a></li> <li><a href="/wiki/Prize4Life" title="Prize4Life">Prize4Life</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">International organizations</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/ALS_Society_of_Canada" title="ALS Society of Canada">ALS Society of Canada</a></li> <li><a href="/wiki/Motor_Neurone_Disease_Association" title="Motor Neurone Disease Association">Motor Neurone Disease Association</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Events</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/ALS_Awareness_Month" title="ALS Awareness Month">ALS Awareness Month</a></li> <li><a href="/wiki/Ice_Bucket_Challenge" title="Ice Bucket Challenge">Ice Bucket Challenge</a></li> <li><a href="/wiki/Annual_ALS_Awareness_Game" class="mw-redirect" title="Annual ALS Awareness Game">Annual ALS Awareness Game</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">People</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/O.J._Brigance" class="mw-redirect" title="O.J. Brigance">O.J. Brigance</a></li> <li><a href="/wiki/Paul_Cellucci" title="Paul Cellucci">Paul Cellucci</a></li> <li><a href="/wiki/Dwight_Clark" title="Dwight Clark">Dwight Clark</a></li> <li><a href="/wiki/Jay_S._Fishman" title="Jay S. Fishman">Jay Fishman</a></li> <li><a href="/wiki/Pete_Frates" title="Pete Frates">Pete Frates</a></li> <li><a href="/wiki/Lou_Gehrig" title="Lou Gehrig">Lou Gehrig</a></li> <li><a href="/wiki/Richard_Glatzer" title="Richard Glatzer">Richard Glatzer</a></li> <li><a href="/wiki/Steve_Gleason" title="Steve Gleason">Steve Gleason</a></li> <li><a href="/wiki/Stephen_Hawking" title="Stephen Hawking">Stephen Hawking</a></li> <li><a href="/wiki/Stephen_Heywood" title="Stephen Heywood">Stephen Heywood</a></li> <li><a href="/wiki/Stephen_Hillenburg" title="Stephen Hillenburg">Stephen Hillenburg</a></li> <li><a href="/wiki/Jacob_Javits" title="Jacob Javits">Jacob Javits</a></li> <li><a href="/wiki/Jason_Becker" title="Jason Becker">Jason Becker</a></li> <li><a href="/wiki/Augie_Nieto" title="Augie Nieto">Augie Nieto</a></li> <li><a href="/wiki/Jon_Stone" title="Jon Stone">Jon Stone</a></li> <li><a href="/wiki/Kevin_Turner_(running_back)" title="Kevin Turner (running back)">Kevin Turner</a></li> <li><a href="/wiki/Henry_A._Wallace" title="Henry A. 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