{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:57:26Z","timestamp":1781175446056,"version":"3.54.1"},"reference-count":13,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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":["Epileptic Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in\n                      <jats:italic>COL4A1\/2<\/jats:italic>\n                      compromise vascular basement membrane integrity, causing intrauterine hemorrhage and infarction leading to extensive structural brain lesions. Vascular disruptions during critical windows of neuronal migration can result in malformations of cortical development (MCD), which may drive epileptogenicity. While surgery is established for drug\u2010resistant focal epilepsy,\n                      <jats:italic>COL4A1\/2<\/jats:italic>\n                      patients with widespread or bilateral MRI abnormalities are frequently deemed ineligible. In selected patients, this necessitates a refined surgical rationale, shifting from strictly curative goals to \u201cnon\u2010curative\u201d strategies focused on seizure mitigation and functional preservation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective multicenter study analyzed six previously unpublished patients (3\n                      <jats:italic>COL4A1<\/jats:italic>\n                      , 3\n                      <jats:italic>COL4A2<\/jats:italic>\n                      ) from three German epilepsy centers. We evaluated presurgical diagnostics (MRI, PET), surgical techniques, histopathology, and outcomes. Results were contextualized with a review of 11 previously published cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients experienced daily seizures and developmental delay prior surgery. MRI revealed bilateral abnormalities in 4\/6 patients (e.g., ventriculomegaly, white matter lesions). Surgical procedures included hemispherotomy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) and posterior quadrant disconnection\/resection (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092). Mean follow\u2010up was 5\u2009years 11\u2009months (range 2\u2009years 10\u2009months\u20138\u2009years 9\u2009months). Seizure freedom (ILAE 1) was achieved in 2\/6 patients (33%), both of whom had unilateral lesions. While patients with bilateral lesions remained at ILAE 4, 83% showed postoperative developmental improvement. Histopathology confirmed cortical malformations in three patients (FCD IIId, mMCD II, GW\u2010matter blurring), supporting the hypothesis that secondary cortical malformations, rather than macroscopic lesions, drive epileptogenicity. No surgical or neurovascular complications were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Epilepsy surgery is a feasible and safe treatment option for\n                      <jats:italic>COL4A1\/2<\/jats:italic>\n                      \u2010associated epilepsy. While curative in patients with unilateral lesions, bilateral cases can benefit from a \u201cnon\u2010curative\u201d approach focused on seizure mitigation and neurodevelopmental protection. Multimodal imaging, specifically FDG\u2010PET, can be helpful in identifying highly epileptogenic cortical areas within widespread structural damage and serve as a basis for surgical planning.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70271","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:07:52Z","timestamp":1781172472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epilepsy surgery in pediatric patients with complex\n                    <i>COL4A1\/2<\/i>\n                    \u2010associated epilepsy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-3527","authenticated-orcid":false,"given":"Jan P.","family":"Nieke","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Koerber\u2010Rosso","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine KJF Klinikum Josefinum  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4622-8695","authenticated-orcid":false,"given":"Lena\u2010Luise","family":"Becker","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Department of Pediatric Neurology  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center for Chronically Sick Children  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, German Epilepsy Center for Children and Adolescents  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Institute of Cell\u2010 and Neurobiology  Berlin Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ) Partner Site  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Jacob","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University of Munich, School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-8823","authenticated-orcid":false,"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich  Munich Germany"},{"name":"Institute of Human Genetics, Technical University of Munich, School of Medicine and Health  Munich Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9429-9878","authenticated-orcid":false,"given":"Sara","family":"Schenk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics TUM University Hospital\/Munich Municipal Hospital Group  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-0788","authenticated-orcid":false,"given":"Ingmar","family":"Bluemcke","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Member of European Reference Network EpiCARE University Hospitals Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-3033","authenticated-orcid":false,"given":"Nicholas","family":"Fearns","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-8006","authenticated-orcid":false,"given":"Christina","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Children's Hospital University of Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-994X","authenticated-orcid":false,"given":"Gerhard","family":"Kluger","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurology, Neurorehabilitation, and Epileptology Schoen Clinic Vogtareuth  Vogtareuth Germany"},{"name":"Department of Pediatrics, Research Programme for Rehabilitation, Transition and Palliation of Neurologically Ill Children Paracelsus Medical University Salzburg  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-0146","authenticated-orcid":false,"given":"Manfred","family":"Kudernatsch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Research Programme for Rehabilitation, Transition and Palliation of Neurologically Ill Children Paracelsus Medical University Salzburg  Salzburg Austria"},{"name":"Center for Neurosurgery, Epilepsy Surgery, Spinal Surgery and Scoliosis Schoen Clinic Vogtareuth  Vogtareuth Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-450X","authenticated-orcid":false,"given":"Mathias","family":"Kunz","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"},{"name":"Department of Neurosurgery University Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-6327","authenticated-orcid":false,"given":"Soheyl","family":"Noachtar","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1527-9350","authenticated-orcid":false,"given":"Jan","family":"R\u00e9mi","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-5671","authenticated-orcid":false,"given":"Moritz","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich  Munich Germany"},{"name":"Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital LMU Munich  Munich Germany"},{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1756-423X","authenticated-orcid":false,"given":"Joerg Christian","family":"Tonn","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"},{"name":"Department of Neurosurgery University Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-7484","authenticated-orcid":false,"given":"Christian","family":"Vollmar","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center LMU Munich  Munich Germany"},{"name":"Department of Neurosurgery University Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-4844","authenticated-orcid":false,"given":"Steffen","family":"Syrbe","sequence":"additional","affiliation":[{"name":"Heidelberg University, Medical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Pediatric Epileptology  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2780-6560","authenticated-orcid":false,"given":"Victoria San","family":"Antonio\u2010Arce","sequence":"additional","affiliation":[{"name":"Freiburg Epilepsy Center, Medical Center, Member of the ERN EpiCARE \u2013 University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg im Breisgau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-206X","authenticated-orcid":false,"given":"Angela","family":"Kaindl","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Department of Pediatric Neurology  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center for Chronically Sick Children  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, German Epilepsy Center for Children and Adolescents  Berlin Germany"},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Institute of Cell\u2010 and Neurobiology  Berlin Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ) Partner Site  Berlin 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