{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:02:33Z","timestamp":1790071353873,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Levetiracetam (LEV) is an antiseizure medication approved for focal and generalized epilepsy. Despite its efficacy, neuropsychiatric adverse effects (NP\u2010AEs) may lead to treatment discontinuation. Quantitative electroencephalographic (qEEG) graph\u2010theoretical analysis has emerged as a valuable tool for identifying neurophysiological markers of treatment response. We investigated whether baseline network metrics could identify drug\u2010naive people with focal epilepsy (PwE) at risk of developing clinically significant LEV\u2010related NP\u2010AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter retrospective longitudinal study across three Italian centers. From an original LEV monotherapy cohort of 134 PwE, we identified all 31 eligible patients who developed clinically significant LEV\u2010related NP\u2010AEs within the first month after LEV initiation (AE+) and matched them by age and sex with 31 patients without NP\u2010AEs (AE\u2212). All participants underwent resting\u2010state EEG within 30\u2009days before LEV. We compared relative power spectral density (PSD) and weighted phase lag index (wPLI) connectivity\u2010derived graph\u2010theoretical metrics (clustering coefficient, global efficiency, path length, modularity, node strength) using linear mixed\u2010effects models. Baseline variables showing significant between\u2010group differences were included in an elastic\u2010net penalized logistic regression model. Model performance was evaluated using nested cross\u2010validation and permutation testing (1000 permutations).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Relative PSD showed no differences between groups. The AE+ group showed higher baseline theta\u2010band wPLI\u2010derived clustering coefficient (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.032), characteristic path length (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.033), and node strength (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.03) than AE\u2212. In the elastic net model, theta\u2010band graph\u2010theoretical metrics predicted NP\u2010AE occurrence with an accuracy of .71 (95% confidence interval [CI] = .60\u2013.82) and an area under the curve of .71 (95% CI = .57\u2013.83). Permutation testing confirmed that model discrimination exceeded chance level (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Baseline theta\u2010band qEEG functional network organization emerged as a significant neurophysiological predictor of LEV\u2010related NP\u2010AEs. These findings suggest that pretreatment EEG may capture a neurophysiological vulnerability phenotype associated with LEV tolerability, supporting the potential role of network\u2010level biomarkers in guiding individualized treatment decisions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70486","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:15:00Z","timestamp":1790068500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting levetiracetam neuropsychiatric adverse effects using graph\u2010theoretical electroencephalographic network metrics in drug\u2010naive focal epilepsy: A multicenter longitudinal study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1311-013X","authenticated-orcid":false,"given":"Marco","family":"Sferruzzi","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3668-469X","authenticated-orcid":false,"given":"Lorenzo","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9833-9886","authenticated-orcid":false,"given":"Margherita Anna Grazia","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Research Unit of Intelligent Technologies for Health and Wellbeing, Engineering Department Campus Bio\u2010Medico, University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-8761","authenticated-orcid":false,"given":"Francesca","family":"Izzi","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurology Unit, Policlinico Tor Vergata University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-5581","authenticated-orcid":false,"given":"Fabio","family":"Placidi","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Neurology Unit, Policlinico Tor Vergata University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9624-6854","authenticated-orcid":false,"given":"Biagio Maria","family":"Sancetta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-555X","authenticated-orcid":false,"given":"Emanuele","family":"Cerulli Irelli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-779X","authenticated-orcid":false,"given":"Patrizia","family":"Pulitano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-5925","authenticated-orcid":false,"given":"Vincenzo","family":"Di Lazzaro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Fondazione Policlinico Universitario Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0328-7815","authenticated-orcid":false,"given":"Mario","family":"Tombini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Fondazione Policlinico Universitario Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6160-4348","authenticated-orcid":false,"given":"Giovanni","family":"Assenza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Research Unit of Neurology, Neurobiology, Neurophysiology University Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Fondazione Policlinico Universitario Campus Bio\u2010Medico di Roma  Rome 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