Saskia M Herbst1, Christiane R Proepper2, Tobias Geis3, Ingo Borggraefe4, Andreas Hahn5, Otfried Debus6, Martin Haeussler7, Gero von Gersdorff8, Gerhard Kurlemann9, Matthias Ensslen4, Nathalie Beaud10, Joerg Budde11, Michael Gilbert12, Ralf Heiming13, Rita Morgner14, Heike Philippi15, Sophia Ross16, Gertrud Strobl-Wildemann17, Kerstin Muelleder18, Paul Vosschulte19, Deborah J Morris-Rosendahl20, Gerhard Schuierer21, Ute Hehr2. 1. Center for and Institute of Human Genetics, University of Regensburg, Regensburg, Germany. Electronic address: saskia.herbst@ukr.de. 2. Center for and Institute of Human Genetics, University of Regensburg, Regensburg, Germany. 3. Department of Pediatric Neurology, Klinik St. Hedwig, University Children's Hospital Regensburg (KUNO), Regensburg, Germany. 4. Department of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Children's Hospital, University of Munich, Munich, Germany. 5. Department of Child Neurology, Gießen, Germany. 6. Clemenshospital, Children's Hospital, Münster, Germany. 7. Frühdiagnosezentrum Würzburg, University Children's Hospital, Würzburg, Germany. 8. University Hospital Cologne, Köln, Germany. 9. University Children's Hospital Muenster, Department of General Pediatrics, Neuropediatrics, Münster, Germany. 10. Department of Neuropediatrics, Westküstenklinikum Heide, Heide, Germany. 11. Department of Pediatrics St. Hedwig, St. Josefskrankenhaus Freiburg, Freiburg, Germany. 12. Pediatric Practice, Werne, Germany. 13. Pediatric Practice, Barsinghausen, Germany. 14. Pediatric Practice, Kirchberg, Germany. 15. Center of Developmental Neurology Frankfurt, Frankfurt, Germany. 16. Pediatric Neurology, University Children's Hospital Erlangen, Erlangen, Germany. 17. MVZ Human Genetics, Ulm, Germany. 18. Landes- Frauen- und Kinderklinik Linz, Linz, Austria. 19. Pediatric Practice, Münster, Germany. 20. Genomic Medicine, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, United Kingdom. 21. Center for Neuroradiology, Bezirksklinikum Regensburg, University Medical Center, Regensburg, Germany.
Abstract
BACKGROUND: Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year. AIM: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. METHOD: Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. RESULTS: All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. CONCLUSION: Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.
BACKGROUND:Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year. AIM: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. METHOD: Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. RESULTS: All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. CONCLUSION: Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.
Authors: Morten T Venø; Susanne T Venø; Kati Rehberg; Jessy V van Asperen; Bettina H Clausen; Ida E Holm; R Jeroen Pasterkamp; Bente Finsen; Jørgen Kjems Journal: Front Mol Neurosci Date: 2017-02-09 Impact factor: 5.639
Authors: Maria Durce C G Carvalho; Ricardo A A Ximenes; Ulisses R Montarroyos; Paula F S da Silva; Luciana P A Andrade-Valença; Sophie H Eickmann; Regina C Ramos; Maria Ângela W Rocha; Thalia V B de Araujo; Maria de Fátima P M de Albuquerque; Celina M T Martelli; Wayner V de Souza; Elizabeth B Brickley; Demócrito de B Miranda-Filho Journal: Epilepsia Date: 2020-02-17 Impact factor: 5.864
Authors: Renske Oegema; Tahsin Stefan Barakat; Martina Wilke; Katrien Stouffs; Dina Amrom; Eleonora Aronica; Nadia Bahi-Buisson; Valerio Conti; Andrew E Fry; Tobias Geis; David Gomez Andres; Elena Parrini; Ivana Pogledic; Edith Said; Doriette Soler; Luis M Valor; Maha S Zaki; Ghayda Mirzaa; William B Dobyns; Orly Reiner; Renzo Guerrini; Daniela T Pilz; Ute Hehr; Richard J Leventer; Anna C Jansen; Grazia M S Mancini; Nataliya Di Donato Journal: Nat Rev Neurol Date: 2020-09-07 Impact factor: 42.937