{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:23:37Z","timestamp":1783700617235,"version":"3.55.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":43,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Familial adult myoclonic epilepsy type 2 is a hereditary condition characterized by cortical tremor, myoclonus and epilepsy. It belongs to the spectrum of cortical myoclonus and the sensorimotor cortex hyperexcitability represents an important pathogenic mechanism underlying this condition. Besides pericentral cortical structures, the impairment of subcortical networks seems also to play a pathogenetic role, mainly via the thalamo-cortical pathway. However, the mechanisms underlying cortical\u2013subcortical circuits dysfunction, as well as their impact on clinical manifestations, are still unknown. Therefore, the main aims of our study were to systematically study with an extensive electrophysiological battery, the cortical sensorimotor, as well as thalamo-cortical networks in genetically confirmed familial adult myoclonic epilepsy patients and to establish reliable neurophysiological biomarkers for the diagnosis.<\/jats:p>\n               <jats:p>In 26 familial myoclonic epilepsy subjects, harbouring the intronic ATTTC repeat expansion in the StAR-related lipid transfer domain-containing 7 gene, 17 juvenile myoclonic epilepsy patients and 22 healthy controls, we evaluated the facilitatory and inhibitory circuits within the primary motor cortex using single and paired-pulse transcranial magnetic stimulation paradigms. We also probed the excitability of the somatosensory, as well as the thalamo-somatosensory cortex connection by using ad hoc somatosensory evoked potential protocols. The sensitivity and specificity of transcranial magnetic stimulation and somatosensory evoked potential metrics were derived from receiver operating curve analysis. Familial adult myoclonic epilepsy patients displayed increased facilitation and decreased inhibition within the sensorimotor cortex compared with juvenile myoclonic epilepsy patients (all P\u2009&amp;lt;\u20090.05) and healthy controls (all P\u2009&amp;lt;\u20090.05). Somatosensory evoked potential protocols also displayed a significant reduction of early high-frequency oscillations and less inhibition at paired-pulse protocol, suggesting a concomitant failure of thalamo-somatosensory cortex circuits. Disease onset and duration and myoclonus severity did not correlate either with sensorimotor hyperexcitability or thalamo-cortical measures (all P\u2009&amp;gt;\u20090.05). Patients with a longer disease duration had more severe myoclonus (r\u2009=\u20090.467, P\u2009=\u20090.02) associated with a lower frequency (r\u2009=\u2009\u22120.607, P\u2009=\u20090.001) and higher power of tremor (r\u2009=\u20090.479, P\u2009=\u20090.02). Finally, familial adult myoclonic epilepsy was reliably diagnosed using transcranial magnetic stimulation, demonstrating its superiority as a diagnostic factor compared to somatosensory evoked potential measures. In conclusion, deficits of sensorimotor cortical and thalamo-cortical circuits are involved in the pathophysiology of familial adult myoclonic epilepsy even if these alterations are not associated with clinical severity. Transcranial magnetic stimulation-based measurements display an overall higher accuracy than somatosensory evoked potential parameters to reliably distinguish familial adult myoclonic epilepsy from juvenile myoclonic epilepsy and healthy controls.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac037","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T20:12:07Z","timestamp":1644610327000},"source":"Crossref","is-referenced-by-count":27,"title":["Abnormal sensorimotor cortex and thalamo-cortical networks in familial adult myoclonic epilepsy type 2: pathophysiology and diagnostic implications"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-4741","authenticated-orcid":false,"given":"Raffaele","family":"Dubbioso","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy"},{"name":"IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Tomasevic","sequence":"additional","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen University, Kobenhavn, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonilda","family":"Bilo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Esposito","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit, AORN Cardarelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-3744","authenticated-orcid":false,"given":"Fiore","family":"Manganelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"issue":"1","key":"2022022618502765200_fcac037-B1","doi-asserted-by":"crossref","first-page":"4920","DOI":"10.1038\/s41467-019-12671-y","article-title":"Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to 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