{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:29:39Z","timestamp":1792664979374,"version":"4.5.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the electro-clinical longitudinal data and CSF A\u03b242, p-tau<jats:sub>181<\/jats:sub> and t-tauAg, amyloid, and <jats:sup>18<\/jats:sup>F-FDG PET of five unrelated LD families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 \u00b1 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily\/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF A\u03b242, amyloid PET) and neurodegenerative (CSF p-tau<jats:sub>181<\/jats:sub> and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer's disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer's disease type.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1202971","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T09:28:53Z","timestamp":1687944533000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Giuseppe","family":"d'Orsi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Farolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Muccioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Modoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Allegri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Garibotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Di Claudio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Di Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Benvenuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bisulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.1684\/epd.2016.0842","article-title":"Lafora disease","volume":"18","author":"Turnbull","year":"2016","journal-title":"Epileptic Disord."},{"key":"B2","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41582-018-0057-0","article-title":"Lafora disease - 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