{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:57:40Z","timestamp":1791442660684,"version":"4.3.3"},"reference-count":40,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013669","name":"Ionis Pharmaceuticals","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100013669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Pract Neurol"],"accepted":{"date-parts":[[2025,4,6]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Alexander disease is a rare, genetic and ultimately fatal neurological disorder that arises from pathogenic variants in the glial fibrillary acidic protein (\n                    <jats:italic>GFAP<\/jats:italic>\n                    ) gene. Its presenting symptoms often differ according to age at onset. Although Alexander disease typically presents in young children with seizures and developmental delays, its presentation in adults may include bulbar signs, ataxia and autonomic dysfunction. Because of the heterogeneous and non-specific symptoms associated with adult-onset Alexander disease, the diagnosis typically requires comprehensive clinical and neuroimaging evaluation as well as confirmatory genetic testing. Here, we present detailed case descriptions of patients who first presented with symptoms of Alexander disease as adults, with guidance on recognising distinctive clinical and radiological characteristics associated with the later-onset form. Timely recognition and referral of patients with Alexander disease will enable earlier interventions that may mitigate disease severity or slow disease progression if such interventions become available.\n                  <\/jats:p>","DOI":"10.1136\/pn-2024-004490","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T13:20:20Z","timestamp":1746969620000},"page":"507-515","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Diagnosing Alexander disease in adults"],"prefix":"10.1136","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0615-7159","authenticated-orcid":false,"given":"David S","family":"Lynch","sequence":"first","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK"},{"name":"National Hospital for Neurology and Neurosurgery, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Wade","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alise K","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mellen Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Institute of Neurology, London, UK"},{"name":"Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokatsu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan"},{"name":"Department of Neurology, Japan Community Healthcare Organization Kobe Central Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Collins","sequence":"additional","affiliation":[{"name":"Ionis, Carlsbad, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Edwards","sequence":"additional","affiliation":[{"name":"Ionis, Carlsbad, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy T","family":"Waldman","sequence":"additional","affiliation":[{"name":"Division of Neurology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"2025111304551253000_25.6.507.1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107402","article-title":"Glial fibrillary acidic protein is pathologically modified in Alexander disease","volume":"300","author":"Lin","year":"2024","journal-title":"J Biol 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directions","volume":"14","author":"Muthusamy","year":"2023","journal-title":"Front Neurol"},{"key":"2025111304551253000_25.6.507.9","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-75383-4","article-title":"A systematic review and meta-analysis of GFAP gene variants in Alexander disease","volume":"14","author":"Grossi","year":"2024","journal-title":"Sci Rep"},{"key":"2025111304551253000_25.6.507.10","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1177\/08830738231210040","article-title":"Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease","volume":"38","author":"Joung","year":"2023","journal-title":"J Child Neurol"},{"key":"2025111304551253000_25.6.507.11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.32598\/bcn.2021.1551.1","article-title":"Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case 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