{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:18:27Z","timestamp":1780330707318,"version":"3.54.1"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Patients with lissencephaly typically present with severe psychomotor retardation and drug-resistant seizures. The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort and to evaluate the response to antiseizure medication (ASM). Therefore, we retrospectively evaluated 47 patients of five genetic forms (LIS1\/PAFAH1B1, DCX, DYNC1H1, TUBA1A, TUBG1) using family questionnaires, standardized neuropediatric assessments, and patients' medical reports.<\/jats:p><jats:p>\n          Results\u2003All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1\u201342.0), starting with epileptic spasms in 70%. Standard treatment protocols with hormonal therapy (ACTH or corticosteroids) and\/or vigabatrin were the most effective approach for epileptic spasms, leading to seizure control in 47%. Seizures later in the disease course were most effectively treated with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, resulting in seizure freedom in 20%. Regarding psychomotor development, lissencephaly patients presenting without epileptic spasms were significantly more likely to reach various developmental milestones compared to patients with spasms.<\/jats:p><jats:p>\n          Conclusion\u2003Classic lissencephaly is highly associated with drug-resistant epilepsy starting with epileptic spasms in most patients. The standard treatment protocols for infantile epileptic spasms syndrome lead to freedom from seizures in around half of the patients. Due to the association of epileptic spasms with an unfavorable course of psychomotor development, early and reliable diagnosis and treatment of spasms should be pursued. For epilepsies occurring later in childhood, ASM with valproic acid and lamotrigine, followed by vigabatrin and phenobarbital, appears to be most effective.<\/jats:p>","DOI":"10.1055\/s-0044-1789014","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T22:57:08Z","timestamp":1725058628000},"page":"410-419","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients"],"prefix":"10.1055","volume":"55","author":[{"given":"Christiane R.","family":"Proepper","sequence":"additional","affiliation":[{"name":"University Children's Hospital Regensburg (KUNO), University Hospital Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia M.","family":"Schuetz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Maria","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Krankenhaus Barmherzige Br\u00fcder Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja von","family":"Au","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bast","sequence":"additional","affiliation":[{"name":"Epilepsy Center Kork, Kehl, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Beaud","sequence":"additional","affiliation":[{"name":"Pediatric Practice, Garding, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Borggraefe","sequence":"additional","affiliation":[{"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"}]},{"given":"Friedrich","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Children's Hospital F\u00fcrth, F\u00fcrth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, St. Josefskrankenhaus, Freiburg im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Busse","sequence":"additional","affiliation":[{"name":"Social Pediatric Center, Evangelisches Krankenhaus M\u00fclheim\/Ruhr, M\u00fclheim an der Ruhr, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Kepler University Hospital, Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otfried","family":"Debus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clemenshospital, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Diepold","sequence":"additional","affiliation":[{"name":"Pediatric Practice, Northeim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fries","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asklepios Kinderklinik St. Augustin, St. Augustin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gero von","family":"Gersdorff","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine II, University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Haeussler","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Social Pediatrics, University Children's Hospital, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig-University Gie\u00dfen, Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Hartlieb","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurology, Neurorehabilitation and Epileptology, Schoen-Clinic, Vogtareuth, Germany"},{"name":"Research Center \u201cRehabilitation, Transition and Palliation,\u201d Paracelsus Medical University Salzburg, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Heiming","sequence":"additional","affiliation":[{"name":"Pediatric Practice, Barsinghausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Herkenrath","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kluger","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurology, Neurorehabilitation and Epileptology, Schoen-Clinic, Vogtareuth, Germany"},{"name":"Research Center \u201cRehabilitation, Transition and Palliation,\u201d Paracelsus Medical University Salzburg, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas H.","family":"Kreth","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Hospital for Children and Adolescents, gGmbH Klinikum Leverkusen, Leverkusen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kurlemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Bonifatius Hospital Lingen, Lingen (Ems), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Moeller","sequence":"additional","affiliation":[{"name":"Center for Developmental Diagnostics and Social Pediatrics, Wolfsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Morris-Rosendahl","sequence":"additional","affiliation":[{"name":"Genomic Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom"},{"name":"Clinical Genetics and Genomics, Royal Brompton Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Panzer","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Center for Epilepsy, DRK Westend Clinic Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Philippi","sequence":"additional","affiliation":[{"name":"Social Pediatric Center Frankfurt-Mitte, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Ruegner","sequence":"additional","affiliation":[{"name":"Pediatric Practice, Kirchberg\/Jagst, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Toepfer","sequence":"additional","affiliation":[{"name":"Pediatric Practice, Murnau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vieker","sequence":"additional","affiliation":[{"name":"Epileptology Focus Practice, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelheid","family":"Wiemer-Kruel","sequence":"additional","affiliation":[{"name":"Epilepsy Center Kork, Kehl, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Jena University Hospital, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Schuierer","sequence":"additional","affiliation":[{"name":"Center for Neuroradiology, University Clinics and Bezirksklinikum Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hehr","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Geis","sequence":"additional","affiliation":[{"name":"University Children's Hospital Regensburg 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Chiba","year":"2022","journal-title":"Neuroradiology"},{"issue":"03","key":"ref16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1528-1167.2008.01866.x","article-title":"Lamotrigine-valproic acid combination therapy for medically refractory epilepsy","volume":"50","author":"J J Moeller","year":"2009","journal-title":"Epilepsia"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/j.1528-1157.1998.tb01332.x","article-title":"Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy","volume":"39","author":"R G Beran","year":"1998","journal-title":"Epilepsia"},{"issue":"08","key":"ref18","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.1528-1157.1999.tb00832.x","article-title":"The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction","volume":"40","author":"F Pisani","year":"1999","journal-title":"Epilepsia"},{"issue":"06","key":"ref19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1055\/a-1909-2977","article-title":"Treatment of infantile spasm syndrome: update from the interdisciplinary guideline committee coordinated by the German-Speaking Society of Neuropediatrics","volume":"53","author":"G Ramantani","year":"2022","journal-title":"Neuropediatrics"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/ana.24594","article-title":"Response to treatment in a prospective national infantile spasms cohort","volume":"79","author":"K G Knupp","year":"2016","journal-title":"Ann Neurol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"772333","DOI":"10.3389\/fneur.2022.772333","article-title":"Hormonal therapy for infantile spasms: a systematic review and meta-analysis","volume":"13","author":"S Guang","year":"2022","journal-title":"Front 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Go","year":"2012","journal-title":"Neurology"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1789014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T23:53:49Z","timestamp":1736294029000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1789014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":22,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2025,1,7]]},"published-print":{"date-parts":[[2024,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1789014","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,30]]}}}