Silvana Franceschetti1, Roberto Michelucci, Laura Canafoglia, Pasquale Striano, Antonio Gambardella, Adriana Magaudda, Paolo Tinuper, Angela La Neve, Edoardo Ferlazzo, Giuseppe Gobbi, Anna Teresa Giallonardo, Giuseppe Capovilla, Elisa Visani, Ferruccio Panzica, Giuliano Avanzini, Carlo Alberto Tassinari, Amedeo Bianchi, Federico Zara. 1. From the Department of Neurophysiopathology and Epilepsy Centre (S.F., L.C., E.V., F.P., G.A.), IRCCS Foundation C. Besta Neurological Institute, Milan; Unit of Neurology (R.M.), IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna; Pediatric Neurology and Muscular Diseases Unit (P.S.), DINOGMI-Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, G. Gaslini Institute; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; Institute of Neurological Sciences (A.G.), National Research Council, Mangone, Cosenza; Epilepsy Centre (A.M.), Department of Neuroscience, University of Messina; IRCCS Institute of Neurological Sciences and Department of Biomedical and Neuromotor Sciences (P.T.), University of Bologna; Epilepsy Centre (A.L.N.), Azienda Ospedaliero Universitaria Consorziale, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Policlinico, Bari; Child Neurology Unit (G.G.), IRCCS delle Scienze Neurologiche, Bologna; Department of Neurology and Psychiatry (A.T.G.), Neurology Unit, La Sapienza University, Rome; Epilepsy Center (G.C.), Department of Child Neuropsychiatry, C. Poma Hospital, Mantua; University of Bologna (C.A.T.); Department of Neurology and Epilepsy Centre (A.B.), San Donato Hospital, Arezzo; and Istituto Gaslini (F.Z.), Laboratory of Neurogenetics, Genoa, Italy. Coinvestigators are listed on the Neurology® Web site at www.neurology.org.
Abstract
OBJECTIVE: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. METHODS: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. RESULTS: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. CONCLUSIONS: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.
OBJECTIVE: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. METHODS: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. RESULTS: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. CONCLUSIONS: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.
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