{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:50:36Z","timestamp":1793213436124,"version":"4.5.0"},"reference-count":86,"publisher":"American Medical Association (AMA)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,6,9]]},"abstract":"<jats:sec id=\"ab-jrv260009-1\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness due to degeneration of upper motor neurons in the brain and lower motor neurons in the brainstem and spinal cord. It affects approximately 25\u202f000 individuals in the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv260009-2\">\n                    <jats:title>Observations<\/jats:title>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis is characterized by progressive painless muscle weakness that typically begins in a focal region of the body, such as limb muscle weakness causing hand weakness or foot drop (65%), cranial muscle weakness causing speech or swallowing problems (20%-25%), or axial muscle weakness causing bent posture (5%-10%), and spreads to other body regions over time. The disease usually manifests with dysfunction indicative of both upper motor neurons (causing muscle stiffness and spasticity) and lower motor neurons (causing weakness, fasciculations, atrophy, and flaccidity). After onset, weakness spreads through the musculature and typically causes death due to respiratory muscle weakness. Among people with ALS, approximately 85% have sporadic ALS, which is not associated with known environmental or genetic factors, and 15% have familial ALS. Amyotrophic lateral sclerosis is diagnosed based on clinical features, which can be supported by results of electromyography. More than 60 genes have been associated with ALS, and most are autosomal dominant. Pathogenic variants in chromosome 9 open reading frame 72 (\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      ) are found in 40% of all familial ALS cases, and pathogenic variants in superoxide dismutase 1 (\n                      <jats:italic toggle=\"yes\">SOD1<\/jats:italic>\n                      ) are found in 20% of patients with familial ALS. Patients with ALS survive a mean of 3 to 5 years after diagnosis, and there are currently no curative therapies. Clinical care primarily focuses on symptom management and quality of life. Three US Food and Drug Administration (FDA)\u2013approved disease-modifying therapies are available in the United States. Riluzole and edaravone are oral medications that slow ALS progression by up to 2 to 4 months, and tofersen is an intrathecally administered gene therapy for patients with\n                      <jats:italic toggle=\"yes\">SOD1<\/jats:italic>\n                      gene variants. Specialized multidisciplinary teams, comprising neurologists, nurses, therapists, dietitians, and social workers, are associated with improved survival (4-7 months) and quality of life.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv260009-3\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disorder of upper and lower motor neurons. No curative therapies exist. Two oral medications, riluzole and edaravone, are approved by the FDA and modestly decrease disease progression in sporadic ALS. Tofersen, an intrathecally administered gene-based therapy, is also FDA approved and slows disease progression in patients with\n                      <jats:italic toggle=\"yes\">SOD1<\/jats:italic>\n                      pathogenic gene variants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2026.6385","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T16:30:12Z","timestamp":1778517012000},"page":"1970","source":"Crossref","is-referenced-by-count":13,"title":["Amyotrophic Lateral Sclerosis"],"prefix":"10.1001","volume":"335","author":[{"given":"John","family":"Ravits","sequence":"first","affiliation":[{"name":"ALS Clinical and Translational Research Programs, Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Ferrey","sequence":"additional","affiliation":[{"name":"ALS Clinical and Translational Research Programs, Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Gundogdu","sequence":"additional","affiliation":[{"name":"ALS Clinical and Translational Research Programs, Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wali","family":"Qayoumi","sequence":"additional","affiliation":[{"name":"ALS Clinical and Translational Research Programs, Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Zale","sequence":"additional","affiliation":[{"name":"ALS Clinical and Translational Research Programs, Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"jrv260009r1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/17582024.2025.2546761","article-title":"You look at life through a different lens: a phenomenological study of living with amyotrophic lateral sclerosis.","volume":"16","author":"Morgan","year":"2026","journal-title":"Neurodegener Dis Manag"},{"issue":"5-6","key":"jrv260009r2","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1080\/21678421.2023.2165947","article-title":"Epidemiology and economic burden of amyotrophic lateral sclerosis in the United States: a literature review.","volume":"24","author":"Berry","year":"2023","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"5","key":"jrv260009r3","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1002\/mus.70023","article-title":"The burden of motor neuron diseases in the United States, 1990-2021: a systematic analysis of the Global Burden of Disease study 2021.","volume":"72","author":"Oh","year":"2025","journal-title":"Muscle Nerve"},{"issue":"6","key":"jrv260009r4","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1136\/jnnp.51.6.778","article-title":"Comparison of sporadic and familial disease amongst 580 cases of motor neuron disease.","volume":"51","author":"Li","year":"1988","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"jrv260009r5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.2147\/CLEP.S37505","article-title":"Risk factors for amyotrophic lateral sclerosis.","volume":"7","author":"Ingre","year":"2015","journal-title":"Clin Epidemiol"},{"issue":"1","key":"jrv260009r6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/ane.13345","article-title":"Military service and related risk factors for amyotrophic lateral sclerosis.","volume":"143","author":"McKay","year":"2021","journal-title":"Acta Neurol Scand"},{"issue":"10","key":"jrv260009r7","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1212\/WNL.0b013e3181b6bbbd","article-title":"ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration.","volume":"73","author":"Ravits","year":"2009","journal-title":"Neurology"},{"issue":"11","key":"jrv260009r8","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","article-title":"The phenotypic variability of amyotrophic lateral sclerosis.","volume":"10","author":"Swinnen","year":"2014","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"jrv260009r9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s42466-025-00389-w","article-title":"Motor phenotypes of amyotrophic lateral sclerosis\u2014a three-determinant anatomical classification based on the region of onset, propagation of motor symptoms, and the degree of upper and lower motor neuron dysfunction.","volume":"7","author":"Meyer","year":"2025","journal-title":"Neurol Res Pract"},{"issue":"4","key":"jrv260009r10","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1136\/jnnp-2019-322541","article-title":"Primary lateral sclerosis: consensus diagnostic criteria.","volume":"91","author":"Turner","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"jrv260009r11","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41572-023-00447-0","article-title":"Frontotemporal lobar degeneration.","volume":"9","author":"Grossman","year":"2023","journal-title":"Nat Rev Dis Primers"},{"issue":"7","key":"jrv260009r12","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1212\/WNL.59.7.1077","article-title":"The overlap of amyotrophic lateral sclerosis and frontotemporal dementia.","volume":"59","author":"Lomen-Hoerth","year":"2002","journal-title":"Neurology"},{"issue":"7","key":"jrv260009r13","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1212\/01.WNL.0000055861.95202.8D","article-title":"Are amyotrophic lateral sclerosis patients cognitively normal?","volume":"60","author":"Lomen-Hoerth","year":"2003","journal-title":"Neurology"},{"key":"jrv260009r14","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jocn.2022.04.009","article-title":"Pseudobulbar affect in neurodegenerative diseases: a systematic review and meta-analysis.","volume":"100","author":"Nabizadeh","year":"2022","journal-title":"J Clin Neurosci"},{"issue":"2","key":"jrv260009r15","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209623","article-title":"Progressive cerebrocerebellar uncoupling in sporadic and genetic forms of amyotrophic lateral sclerosis.","volume":"103","author":"Tahedl","year":"2024","journal-title":"Neurology"},{"issue":"12","key":"jrv260009r16","doi-asserted-by":"publisher","first-page":"5677","DOI":"10.1007\/s00415-023-11954-1","article-title":"Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review.","volume":"270","author":"Bombaci","year":"2023","journal-title":"J Neurol"},{"issue":"7","key":"jrv260009r17","doi-asserted-by":"publisher","first-page":"3953","DOI":"10.1007\/s00415-024-12455-5","article-title":"Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.","volume":"271","author":"Bjelica","year":"2024","journal-title":"J Neurol"},{"key":"jrv260009r18","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/bs.irn.2017.04.009","article-title":"Nonmotor symptoms in amyotrophic lateral sclerosis: a systematic review.","volume":"134","author":"Fang","year":"2017","journal-title":"Int Rev Neurobiol"},{"key":"jrv260009r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117054","article-title":"Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis.","volume":"417","author":"Richards","year":"2020","journal-title":"J Neurol Sci"},{"issue":"5","key":"jrv260009r20","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis.","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"issue":"3","key":"jrv260009r21","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/mus.22175","article-title":"The Awaji criteria for diagnosis of ALS.","volume":"44","author":"de Carvalho","year":"2011","journal-title":"Muscle Nerve"},{"issue":"14","key":"jrv260009r22","doi-asserted-by":"publisher","first-page":"e1610","DOI":"10.1212\/WNL.0000000000007242","article-title":"Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials.","volume":"92","author":"van den Berg","year":"2019","journal-title":"Neurology"},{"issue":"8","key":"jrv260009r23","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/j.clinph.2020.04.005","article-title":"A proposal for new diagnostic criteria for ALS.","volume":"131","author":"Shefner","year":"2020","journal-title":"Clin Neurophysiol"},{"issue":"6","key":"jrv260009r24","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1212\/CPJ.0000000000000957","article-title":"Delivering bad news in amyotrophic lateral sclerosis: proposal of specific technique ALS ALLOW.","volume":"11","author":"Edwards","year":"2021","journal-title":"Neurol Clin Pract"},{"issue":"1-2","key":"jrv260009r25","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1080\/21678421.2024.2397517","article-title":"How to break the news in amyotrophic lateral sclerosis\/motor neuron disease: practical guidelines from experts.","volume":"26","author":"O\u2019Connell","year":"2025","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"3","key":"jrv260009r26","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.clinph.2007.09.143","article-title":"Electrodiagnostic criteria for diagnosis of ALS.","volume":"119","author":"de Carvalho","year":"2008","journal-title":"Clin Neurophysiol"},{"issue":"7","key":"jrv260009r27","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1016\/j.clinph.2016.03.024","article-title":"Lower motor neuron dysfunction in ALS.","volume":"127","author":"de Carvalho","year":"2016","journal-title":"Clin Neurophysiol"},{"issue":"3","key":"jrv260009r28","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1002\/mus.27567","article-title":"Amyotrophic lateral sclerosis mimics.","volume":"66","author":"Kwan","year":"2022","journal-title":"Muscle Nerve"},{"key":"jrv260009r29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cnp.2023.12.003","article-title":"Diagnosis and differential diagnosis of MND\/ALS: IFCN handbook chapter.","volume":"9","author":"de Carvalho","year":"2023","journal-title":"Clin Neurophysiol Pract"},{"issue":"10","key":"jrv260009r30","doi-asserted-by":"publisher","DOI":"10.1111\/ene.70382","article-title":"Diagnostic and prognostic value of blood and cerebrospinal fluid biomarkers in amyotrophic lateral sclerosis: a systematic review and meta-analysis.","volume":"32","author":"Obara","year":"2025","journal-title":"Eur J Neurol"},{"issue":"1","key":"jrv260009r31","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/ana.25276","article-title":"Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion.","volume":"84","author":"Benatar","year":"2018","journal-title":"Ann Neurol"},{"issue":"5","key":"jrv260009r32","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1097\/WCO.0000000000001294","article-title":"The genetics of amyotrophic lateral sclerosis.","volume":"37","author":"Nijs","year":"2024","journal-title":"Curr Opin Neurol"},{"issue":"9","key":"jrv260009r33","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1093\/brain\/awad120","article-title":"Genetic variability in sporadic amyotrophic lateral sclerosis.","volume":"146","author":"Van Daele","year":"2023","journal-title":"Brain"},{"issue":"3","key":"jrv260009r34","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S1474-4422(25)00026-2","article-title":"Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.","volume":"24","author":"Mizielinska","year":"2025","journal-title":"Lancet Neurol"},{"issue":"1","key":"jrv260009r35","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1474-4422(24)00479-4","article-title":"Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention.","volume":"24","author":"Benatar","year":"2025","journal-title":"Lancet Neurol"},{"issue":"5","key":"jrv260009r36","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/S1474-4422(25)00109-7","article-title":"Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.","volume":"24","author":"Balendra","year":"2025","journal-title":"Lancet Neurol"},{"issue":"2","key":"jrv260009r37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S1474-4422(24)00517-9","article-title":"Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.","volume":"24","author":"Moens","year":"2025","journal-title":"Lancet Neurol"},{"issue":"11","key":"jrv260009r38","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1002\/acn3.51895","article-title":"Evidence-based consensus guidelines for ALS genetic testing and counseling.","volume":"10","author":"Roggenbuck","year":"2023","journal-title":"Ann Clin Transl Neurol"},{"issue":"9","key":"jrv260009r39","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/s41576-023-00592-y","article-title":"Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.","volume":"24","author":"Ak\u00e7imen","year":"2023","journal-title":"Nat Rev Genet"},{"key":"jrv260009r40","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1189470","article-title":"Current insights in the molecular genetic pathogenesis of amyotrophic lateral sclerosis.","volume":"17","author":"Zhou","year":"2023","journal-title":"Front Neurosci"},{"issue":"5","key":"jrv260009r41","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s00401-019-02077-x","article-title":"The basis of clinicopathological heterogeneity in TDP-43 proteinopathy.","volume":"138","author":"Kawakami","year":"2019","journal-title":"Acta Neuropathol"},{"issue":"7628","key":"jrv260009r42","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: from genes to mechanism.","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"issue":"15","key":"jrv260009r43","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1212\/WNL.0b013e3181bc0141","article-title":"Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.","volume":"73","author":"Miller","year":"2009","journal-title":"Neurology"},{"issue":"9","key":"jrv260009r44","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1056\/NEJM199403033300901","article-title":"A controlled trial of riluzole in amyotrophic lateral sclerosis.","volume":"330","author":"Bensimon","year":"1994","journal-title":"N Engl J Med"},{"issue":"5","key":"jrv260009r45","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/S1474-4422(18)30054-1","article-title":"Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study.","volume":"17","author":"Fang","year":"2018","journal-title":"Lancet Neurol"},{"issue":"7-8","key":"jrv260009r46","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1080\/21678421.2020.1771734","article-title":"Real-world evidence of riluzole effectiveness in treating amyotrophic lateral sclerosis.","volume":"21","author":"Andrews","year":"2020","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"7","key":"jrv260009r47","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/S1474-4422(17)30163-1","article-title":"Edaravone: a new treatment for ALS on the horizon?","volume":"16","author":"Hardiman","year":"2017","journal-title":"Lancet Neurol"},{"issue":"7","key":"jrv260009r48","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S1474-4422(17)30115-1","article-title":"Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.","volume":"16","author":"Abe","year":"2017","journal-title":"Lancet Neurol"},{"issue":"3","key":"jrv260009r49","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/mus.28448","article-title":"Efficacy and safety of once daily dosing vs approved on\/off dosing of edaravone oral suspension up to 48?weeks in patients with amyotrophic lateral sclerosis (study MT-1186-A02).","volume":"72","author":"Rothstein","year":"2025","journal-title":"Muscle Nerve"},{"issue":"3","key":"jrv260009r50","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/mus.28451","article-title":"Safety extension study of edaravone oral suspension in patients with amyotrophic lateral sclerosis for up to an additional 96?weeks of treatment.","volume":"72","author":"Genge","year":"2025","journal-title":"Muscle Nerve"},{"issue":"2","key":"jrv260009r51","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1001\/jamaneurol.2021.4893","article-title":"Safety and effectiveness of long-term intravenous administration of edaravone for treatment of patients with amyotrophic lateral sclerosis.","volume":"79","author":"Witzel","year":"2022","journal-title":"JAMA Neurol"},{"issue":"5","key":"jrv260009r53","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1007\/s10072-025-07994-2","article-title":"Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.","volume":"46","author":"Hamad","year":"2025","journal-title":"Neurol Sci"},{"issue":"12","key":"jrv260009r54","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide tofersen for SOD1 ALS.","volume":"387","author":"Miller","year":"2022","journal-title":"N Engl J Med"},{"issue":"2","key":"jrv260009r55","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1001\/jamaneurol.2025.4946","article-title":"Long-term tofersen in SOD1 amyotrophic lateral sclerosis.","volume":"83","author":"Miller","year":"2026","journal-title":"JAMA Neurol"},{"issue":"3","key":"jrv260009r56","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s10072-020-05011-2","article-title":"Multidisciplinary care in amyotrophic lateral sclerosis: a systematic review and meta-analysis.","volume":"42","author":"de Almeida","year":"2021","journal-title":"Neurol Sci"},{"issue":"6","key":"jrv260009r57","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16264","article-title":"European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).","volume":"31","author":"Van Damme","year":"2024","journal-title":"Eur J Neurol"},{"key":"jrv260009r58","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/B978-0-12-824535-4.00007-0","article-title":"Palliative care principles in ALS.","volume":"191","author":"Shoesmith","year":"2023","journal-title":"Handb Clin Neurol"},{"issue":"5","key":"jrv260009r59","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/mus.27779","article-title":"Pulmonary care for ALS: progress, gaps, and paths forward.","volume":"67","author":"Ackrivo","year":"2023","journal-title":"Muscle Nerve"},{"issue":"1","key":"jrv260009r60","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1177\/0269216317709965","article-title":"Caregiver burden in amyotrophic lateral sclerosis: a systematic review.","volume":"32","author":"de Wit","year":"2018","journal-title":"Palliat Med"},{"issue":"5","key":"jrv260009r61","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006981.pub3","article-title":"Treatment for sialorrhea (excessive saliva) in people with motor neuron disease\/amyotrophic lateral sclerosis.","volume":"5","author":"James","year":"2022","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"jrv260009r62","doi-asserted-by":"publisher","DOI":"10.1590\/1516-3180.2022.0470.r1.100423","article-title":"Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review.","volume":"142","author":"Cunha-Correia","year":"2023","journal-title":"Sao Paulo Med J"},{"issue":"3","key":"jrv260009r63","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1007\/s13311-016-0508-5","article-title":"Enhanced bulbar function in amyotrophic lateral sclerosis: the Nuedexta treatment trial.","volume":"14","author":"Smith","year":"2017","journal-title":"Neurotherapeutics"},{"issue":"5","key":"jrv260009r64","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1002\/ana.22093","article-title":"Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect.","volume":"68","author":"Pioro","year":"2010","journal-title":"Ann Neurol"},{"issue":"16","key":"jrv260009r65","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1212\/WNL.0000000000002507","article-title":"A randomized trial of mexiletine in ALS: safety and effects on muscle cramps and progression.","volume":"86","author":"Weiss","year":"2016","journal-title":"Neurology"},{"key":"jrv260009r66","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26117","article-title":"Mexiletine for muscle cramps in amyotrophic lateral sclerosis: a randomized, double-blind crossover trial.","author":"Oskarsson","year":"2018","journal-title":"Muscle Nerve"},{"issue":"7","key":"jrv260009r67","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1007\/s00415-015-7811-7","article-title":"Improving survival in amyotrophic lateral sclerosis: future treatments in a modern service.","volume":"262","author":"Hrastelj","year":"2015","journal-title":"J Neurol"},{"key":"jrv260009r68","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/B978-0-12-824535-4.00012-4","article-title":"Neurology ethics at the end of life.","volume":"191","author":"Mazzola","year":"2023","journal-title":"Handb Clin Neurol"},{"issue":"1-2","key":"jrv260009r69","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jns.2012.08.011","article-title":"Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis.","volume":"323","author":"Spataro","year":"2012","journal-title":"J Neurol Sci"},{"issue":"11","key":"jrv260009r70","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1212\/WNL.0000000000002786","article-title":"Physician-assisted death: a Canada-wide survey of ALS health care providers.","volume":"87","author":"Abrahao","year":"2016","journal-title":"Neurology"},{"issue":"9","key":"jrv260009r71","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1080\/15265161.2022.2105422","article-title":"Neurologic diseases and medical aid in dying: aid-in-dying laws create an underclass of patients based on disability.","volume":"23","author":"Shavelson","year":"2023","journal-title":"Am J Bioeth"},{"issue":"2","key":"jrv260009r72","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/ana.24096","article-title":"Long-term survival in amyotrophic lateral sclerosis: a population-based study.","volume":"75","author":"Pupillo","year":"2014","journal-title":"Ann Neurol"},{"issue":"1-2","key":"jrv260009r73","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1080\/21678421.2022.2067777","article-title":"Respiratory onset in amyotrophic lateral sclerosis: clinical features and spreading pattern.","volume":"24","author":"Pinto","year":"2023","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"9","key":"jrv260009r74","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1212\/WNL.0000000000002251","article-title":"How common are ALS plateaus and reversals?","volume":"86","author":"Bedlack","year":"2016","journal-title":"Neurology"},{"issue":"7-8","key":"jrv260009r75","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/21678421.2018.1457059","article-title":"\u201cALS reversals\u201d: demographics, disease characteristics, treatments, and co-morbidities.","volume":"19","author":"Harrison","year":"2018","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"jrv260009r76","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev-med-041217-010829","article-title":"Therapeutic antisense oligonucleotides are coming of age.","volume":"70","author":"Bennett","year":"2019","journal-title":"Annu Rev Med"},{"issue":"1","key":"jrv260009r77","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s43856-023-00419-1","article-title":"Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders.","volume":"4","author":"Lauffer","year":"2024","journal-title":"Commun Med (Lond)"},{"issue":"4","key":"jrv260009r78","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1007\/s13311-022-01247-2","article-title":"Antisense oligonucleotides for the study and treatment of ALS.","volume":"19","author":"Boros","year":"2022","journal-title":"Neurotherapeutics"},{"issue":"10494","key":"jrv260009r79","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1016\/S0140-6736(25)00513-6","article-title":"Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series.","volume":"405","author":"Shneider","year":"2025","journal-title":"Lancet"},{"issue":"1","key":"jrv260009r80","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1038\/ncomms2303","article-title":"A role for calpain-dependent cleavage of TDP-43 in amyotrophic lateral sclerosis pathology.","volume":"3","author":"Yamashita","year":"2012","journal-title":"Nat Commun"},{"issue":"6637","key":"jrv260009r81","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1126\/science.abq5622","article-title":"Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies.","volume":"379","author":"Baughn","year":"2023","journal-title":"Science"},{"issue":"7899","key":"jrv260009r82","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41586-022-04424-7","article-title":"TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.","volume":"603","author":"Ma","year":"2022","journal-title":"Nature"},{"issue":"7899","key":"jrv260009r83","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41586-022-04436-3","article-title":"TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.","volume":"603","author":"Brown","year":"2022","journal-title":"Nature"},{"issue":"9","key":"jrv260009r84","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1038\/s41591-022-01956-3","article-title":"Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1\/2a trial.","volume":"28","author":"Baloh","year":"2022","journal-title":"Nat Med"},{"issue":"9","key":"jrv260009r85","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1080\/14712598.2024.2392307","article-title":"Current status and new avenues of stem cell\u2013based preclinical and therapeutic approaches in amyotrophic lateral sclerosis.","volume":"24","author":"Mazzini","year":"2024","journal-title":"Expert Opin Biol Ther"},{"issue":"3","key":"jrv260009r86","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1007\/s00415-022-11464-6","article-title":"Towards clinical application of implantable brain-computer interfaces for people with late-stage ALS: medical and ethical considerations.","volume":"270","author":"Vansteensel","year":"2023","journal-title":"J Neurol"},{"key":"jrv260009r52","unstructured":"Ferrer. Ferrer reports top-line results from phase III ADORE study in ALS. Accessed March 16, 2026. https:\/\/www.ferrer.com\/en\/results-study-ADORE-ALS"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2848974\/jama_ravits_2026_rv_260009_1780326654.34037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:19:25Z","timestamp":1781018365000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2848974"}},"subtitle":["A Review"],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":86,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2026,6,9]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2026.6385","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}