Abstracts

Rationale: With the increased availability of gene panels and genetic/exome sequencing more cases of nonlesional genetic drug resistant epilepsy (DRE) are being discovered. It is generally accepted that patients with channelopathies are poor surgical candidates; however, there is insufficient evidence regarding the efficacy of epilepsy surgery in patients with channelopathies. This case series details two related patients with intractable focal epilepsy since childhood who failed epilepsy surgery, and illustrates the need for genetic testing as being part of the surgical evaluation in patients without a clear etiology.

Methods: Patient 1 is a 52-year-old female with focal aware seizures with left upper extremity motor symptoms with secondary generalization, and postictal confusion. She started having seizures in infancy. Past EEGs showed right frontoparietal epileptiform abnormalities. At the age of 36 she underwent surgical evaluation, having intracranial subdural grid placement. Seizure onset was localized to the medial right frontal cortex where she subsequently had resection. The pathology was inconclusive. Despite having the resection the patient had an increased frequency of seizures and required being on 3 antiseizure medications (ASMs). Patient 2 (who is the maternal grand nephew of Patient 1) is a 29-year-old male who started having seizures in infancy after vaccination. The seizures recurred at 3 years of age. EEGs showed right frontal and left centrotemporal epileptiform abnormalities, but with concordant MRI abnormalities. He was subsequently trialed on therapeutic doses of multiple ASMs, but seizures continued. At the age of 14 years old the patient had a phase 1 evaluation which showed bifrontal interictals and many seizures, but with elusive onset. Ictal SPECT failed to show a seizure focus, but a MEG showed right temporal discharges. Intracranial monitoring with subdural grid captured seizure activity broadly over the right temporal lobe. Right anterior temporal lobectomy was performed sparing the hippocampus. Pathology was normal. The patient continued having seizures despite intensive medical management.

Results: Patient 1 had recent genetic testing to confirm the diagnosis of Charcot-Marie-Tooth disease which showed a pathogenic variant with duplication of the PMP22 gene indicating the autosomal dominant CMT1A subtype. Incidentally, an SCN9A variant of uncertain significance, c.390G >T (p.Met130lle), was also present. Aberrations in the SCN9A gene, which encodes for the NAV1.7 sodium channel, have been associated with autosomal dominant genetic epilepsy with febrile seizures plus (GEFS+). Patient 2 also has the clinical manifestations of Charcot-Marie-Tooth, including distal peripheral neuropathy and pes-cavus.

Conclusions: In patients with intractable epilepsy without clear etiology, genetic testing should be considered as part of the surgical evaluation if a channelopathy is suspected.

Funding: Please list any funding that was received in support of this abstract.: None.