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.
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.
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.
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.
EEG = electroencephalography; GEFS+ = generalized epilepsy with febrile seizures plus; ILAE = International League Against Epilepsy; MCD = malformation of cortical development; MTS = mesial temporal sclerosis; SMEI = severe myoclonic epilepsy of infancy.
BlümckeI, , ThomM, , AronicaE, , ArmstrongDD, , VintersHV, & PalminiA, et al.: The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia52:158–174, 2011
BlümckeI, ThomM, AronicaE, ArmstrongDD, VintersHV, PalminiA, : The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia52:158–174, 201110.1111/j.1528-1167.2010.02777.x)| false
CeulemansBP, ClaesLR, LagaeLG: Clinical correlations of mutations in the SCN1A gene: from febrile seizures to severe myoclonic epilepsy in infancy. Pediatr Neurol30:236–243, 200410.1016/j.pediatrneurol.2003.10.012)| false
HayashiM, , SugaiK, , KuriharaE, & TamagawaK: An autopsy case of severe myoclonic epilepsy of infancy, who died of acute encephalopathy associated with influenza infection. Epilepsia45:Suppl 865, 2004
HayashiM, SugaiK, KuriharaE, TamagawaK: An autopsy case of severe myoclonic epilepsy of infancy, who died of acute encephalopathy associated with influenza infection. Epilepsia45:Suppl 865, 2004)| false
KrsekP, MatonB, KormanB, Pacheco-JacomeE, JayakarP, DunoyerC, : Different features of histopathological subtypes of pediatric focal cortical dysplasia. Ann Neurol63:758–769, 200810.1002/ana.21398)| false
Le GalF, KorffCM, Monso-HinardC, MundMT, MorrisM, MalafosseA, : A case of SUDEP in a patient with Dravet syndrome with SCN1A mutation. Epilepsia51:1915–1918, 201010.1111/j.1528-1167.2010.02691.x)| false
Van PoppelK, PatayZ, RobertsD, ClarkeDF, McGregorA, PerkinsFF, : Mesial temporal sclerosis in a cohort of children with SCN1A gene mutation. J Child Neurol27:893–897, 201210.1177/0883073811435325)| false
WieserHG, , BlumeWT, , FishD, , GoldensohnE, , HufnagelA, & KingD, et al.: ILAE Commission Report Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia42:282–286, 2001
WieserHG, BlumeWT, FishD, GoldensohnE, HufnagelA, KingD, : ILAE Commission Report Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia42:282–286, 2001)| false
WolffM, Cassé-PerrotC, DravetC: Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuro-psychological findings. Epilepsia47:Suppl 245–48, 200610.1111/j.1528-1167.2006.00688.x)| false