Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy.
OBJECTIVE
Mutations in the sodium channel alpha 1 subunit gene (SCN1A) have been associated with a wide range of epilepsy phenotypes including Dravet syndrome. There currently exist few histopathological and surgical outcome reports in patients with this disease. In this case series, the authors describe the clinical features, surgical pathology, and outcomes in 6 patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection prior to uncovering the genetic basis of their epilepsy.


METHODS
Medical records of SCN1A mutation-positive children with treatment-resistant epilepsy who had undergone resective epilepsy surgery were reviewed retrospectively. Surgical pathology specimens were reviewed.


RESULTS
All 6 patients identified carried diagnoses of intractable epilepsy with mixed seizure types. Age at surgery ranged from 18 months to 20 years. Seizures were refractory to surgery in every case. Surgical histopathology showed evidence of subtle cortical dysplasia in 4 of 6 patients, with more neurons in the molecular layer of the cortex and white matter.


CONCLUSIONS
Cortical resection is unlikely to be beneficial in these children due to the genetic defect and the unexpected neuropathological finding of mild diffuse malformations of cortical development. Together, these findings suggest a diffuse pathophysiological mechanism of the patients' epilepsy which will not respond to focal resective surgery.
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Karen L
KL
Skjei
Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, Pennsylvania; and.
Ephraim W
EW
Church
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Brian N
BN
Harding
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Mariarita
M
Santi
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Katherine D
KD
Holland-Bouley
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Robert R
RR
Clancy
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Brenda E
BE
Porter
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Gregory G
GG
Heuer
Perelman School of Medicine, University of Pennsylvania, Philadelphia;|Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia;
Eric D
ED
Marsh
D000293:Adolescent; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000503:physiopathology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D000069279:Drug Resistant Epilepsy / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology / Q000601:surgery; D008499:Medical Records; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D012189:Retrospective Studies; D017211:Treatment Failure; D055815:Young Adult
D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human
Dravet syndrome; EEG = electroencephalography; GEFS+ = generalized epilepsy with febrile seizures plus; ILAE = International League Against Epilepsy; MCD = malformation of cortical development; MTS = mesial temporal sclerosis; SCN1A mutations; SMEI = severe myoclonic epilepsy of infancy; cortical malformations; epilepsy surgery; histopathology