Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy

Karen L. Skjei Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Ephraim W. Church Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, Pennsylvania; and

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Brian N. Harding Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Mariarita Santi Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Katherine D. Holland-Bouley Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

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Robert R. Clancy Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Brenda E. Porter Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Gregory G. Heuer Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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Eric D. Marsh Perelman School of Medicine, University of Pennsylvania, Philadelphia;
Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia;

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OBJECT

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.

ABBREVIATIONS

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.
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