{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:22:48Z","timestamp":1782433368571,"version":"3.54.5"},"reference-count":84,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"},{"name":"SEQMD project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Lafora disease is a rare genetic disorder characterized by a disruption in glycogen metabolism. It manifests as progressive myoclonus epilepsy and cognitive decline during adolescence. Pathognomonic is the presence of abnormal glycogen aggregates that, over time, produce large inclusions (Lafora bodies) in various tissues. This study aims to describe the clinical and histopathological aspects of a novel Lafora disease patient, and to provide an update on the therapeutical advancements for this disorder. A 20-year-old Libyan boy presented with generalized tonic\u2013clonic seizures, sporadic muscular jerks, eyelid spasms, and mental impairment. Electroencephalography showed multiple discharges across both brain hemispheres. Brain magnetic resonance imaging was unremarkable. Muscle biopsy showed increased lipid content and a very mild increase of intermyofibrillar glycogen, without the polyglucosan accumulation typically observed in Lafora bodies. Despite undergoing three lines of antiepileptic treatment, the patient\u2019s condition showed minimal to no improvement. We identified the homozygous variant c.137G&gt;A, p.(Cys46Tyr), in the EPM2B\/NHLRC1 gene, confirming the diagnosis of Lafora disease. To our knowledge, the presence of lipid aggregates without Lafora bodies is atypical. Lafora disease should be considered during the differential diagnosis of progressive, myoclonic, and refractory epilepsies in both children and young adults, especially when accompanied by cognitive decline. Although there are no effective therapies yet, the development of promising new strategies prompts the need for an early and accurate diagnosis.<\/jats:p>","DOI":"10.3390\/brainsci13121679","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T03:48:41Z","timestamp":1701834521000},"page":"1679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lafora Disease: A Case Report and Evolving Treatment Advancements"],"prefix":"10.3390","volume":"13","author":[{"given":"Carola Rita","family":"Ferrari Aggradi","sequence":"first","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5300-174X","authenticated-orcid":false,"given":"Martina","family":"Rimoldi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Medical Genetics Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Velardo","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megi","family":"Meneri","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"},{"name":"Stroke Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Iacobucci","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9293-6823","authenticated-orcid":false,"given":"Michela","family":"Ripolone","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-8084","authenticated-orcid":false,"given":"Laura","family":"Napoli","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Ciscato","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Moggio","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo Pietro","family":"Comi","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"},{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"},{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5425-969X","authenticated-orcid":false,"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"},{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0797-8282","authenticated-orcid":false,"given":"Elena","family":"Abati","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/s-0035-1552620","article-title":"Progressive Myoclonus Epilepsies","volume":"35","year":"2015","journal-title":"Semin. 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