{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:51:58Z","timestamp":1791773518509,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Among the etiologies of focal epilepsy, mutations of the GATOR1 complex genes\u2014comprising\n                    <jats:italic>NPRL3<\/jats:italic>\n                    ,\n                    <jats:italic>NPRL2<\/jats:italic>\n                    , and\n                    <jats:italic>DEPDC5<\/jats:italic>\n                    \u2014are known to result in overactivation of mTORC1. A recent study highlighted an association between ictal and postictal central apnea (ICA) and pathogenic variants of\n                    <jats:italic>DEPDC5<\/jats:italic>\n                    . Here, we analyzed data from 134 patients across two independent cohorts diagnosed with focal epilepsy who underwent video\u2010electroencephalographic long\u2010term monitoring (VLTM) with cardiorespiratory polygraphy. Genetic testing results done for clinical\u2013diagnostic purposes were reviewed in patients with epilepsy of unknown etiology and patients with magnetic resonance imaging (MRI)\u2010defined\/suspected focal cortical dysplasia (FCD). In 46 patients, we recorded at least one seizure associated with ICA. Genetic testing was performed in 21 of 22 MRI\u2010negative patients with ICA, revealing variants in mTOR pathway genes in 10 cases (48%), including\n                    <jats:italic>DEPDC5<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096),\n                    <jats:italic>NPRL3<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093), and\n                    <jats:italic>MTOR<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091). Regarding MRI\u2010positive patients with ICA (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200924), an acquired lesional etiology was found in 11. Of 13 patients with MRI\u2010defined FCD, genetic testing was carried out in seven, all of whom had negative results. Moreover, no pathogenic variants were detected in the 14\u2010MRI negative patients without ICA. Our findings confirm that variants in mTOR pathway genes (not only in\n                    <jats:italic>DEPDC5<\/jats:italic>\n                    ) are present in patients with ICA and underline the potential risk of sudden unexpected death in epilepsy. These results also highlight the importance of performing respiratory polygraphy during VLTM to document ictal apnea.\n                  <\/jats:p>","DOI":"10.1111\/epi.18646","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T16:30:14Z","timestamp":1758299414000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peri\u2010ictal respiratory dysfunction: Expanding the association between\n                    <scp>mTOR<\/scp>\n                    pathway disorders and ictal central apnea"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0981-4788","authenticated-orcid":false,"given":"Margherita","family":"Burani","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3585-5872","authenticated-orcid":false,"given":"Giada","family":"Giovannini","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-7363","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3090-6247","authenticated-orcid":false,"given":"Matteo","family":"Pugnaghi","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Affronte","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Taruffi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Madrassi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Scolastico","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-1599","authenticated-orcid":false,"given":"Alice","family":"Ballerini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6280-7526","authenticated-orcid":false,"given":"Anna Elisabetta","family":"Vaudano","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurophysiology Unit and Epilepsy Center, Neuroscience Department Modena Azienda Ospedaliera\u2010Universitaria  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Florindo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Medicine and Surgery University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Ambrosini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit, Department of Neuroscience IRCCS San Martino Hospital  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-3920","authenticated-orcid":false,"given":"Gian Marco","family":"Duma","sequence":"additional","affiliation":[{"name":"Epilepsy and Clinical Neurophysiology Unit Scientific Institute IRCCS E. Medea  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Osanni","sequence":"additional","affiliation":[{"name":"Epilepsy and Clinical Neurophysiology Unit Scientific Institute IRCCS E. Medea  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Danieli","sequence":"additional","affiliation":[{"name":"Epilepsy and Clinical Neurophysiology Unit Scientific Institute IRCCS E. Medea  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Mambretti","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Scientific Institute IRCCS E. Medea  Bosisio Parini Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Epilepsy and Clinical Neurophysiology Unit Scientific Institute IRCCS E. 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