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Abstract Details

Genetic Variation Associated with Post-operative Seizure Freedom in Temporal Lobe Epilepsy
Epilepsy/Clinical Neurophysiology (EEG)
Epilepsy/Clinical Neurophysiology (EEG) Posters (7:00 AM-5:00 PM)
073
To identify single nucleotide polymorphisms (SNPs) associated with post-operative seizure freedom in temporal lobe epilepsy (TLE) patients.

Surgical resection is the treatment of choice for up to 80% of pharmaco-resistant TLE; however, heterogeneity in response demands improvements in the prediction of postoperative seizure outcomes. Genomic approaches may reveal novel mechanisms to create a more personalized approach to epilepsy surgery.

 
We selected 107 TLE patients who underwent surgical resection and had brain tissue exome data available for analysis. Seizure freedom was defined as Engel 1a or 1b at time of last follow-up (minimum of 6 months). Common variant SNPs (n=109) in ten epilepsy risk genes not previously studied in TLE surgical outcomes—SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1—were tested for association with post-operative seizure freedom using logistic regression. A false discovery rate (FDR) P <  .25 was used as an exploratory significance threshold. Genotype-Tissue Expression (GTEx) data were used to investigate whether significant SNPs may be expression quantitative trait loci (eQTLs). 
43% of patients were considered seizure free. Three SNPs located in ABCB1 (i.e., rs10276036, rs11975994, rs1128503) were associated with post-operative seizure freedom in TLE patients  (P < .25), and each showed evidence of being eQTLs for ABCB1, RUNDC3B, and ADAM22 in the cerebellum (P < .001). The C allele for the lead SNP, rs10276036, conferred a 0.44 reduction in odds of seizure recurrence post-surgery [95% CI:0.26-0.78; FDR P = 0.239]. 
ABCB1 has been heavily implicated in multidrug resistance. While TLE patients in this study were pharmacoresistant, it is notable that the three ABCB1 SNPs differentiated seizure-free and seizure-recurrent groups. Our SNP-outcome association is corroborated by previous observations that deletions in RUNDC3b and LGL1-ADAM22 protein complexes associate with epilepsy phenotypes. Future studies are underway including multi-omic and functional validation of ABCB1, RUNDC3B, and ADAM22.
Authors/Disclosures
Shreya Louis, MD, MS
PRESENTER 		Dr. Louis has nothing to disclose.
Robyn Busch Robyn Busch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier Inc.. Robyn Busch has received research support from National Institutes of Health. Robyn Busch has received research support from American Epilepsy Society. Robyn Busch has received research support from Cleveland Clinic. Robyn Busch has received research support from Ohio Department of Higher Â鶹´«Ã½Ó³»­. Robyn Busch has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Marcia E. Morita-Sherman, MD (Eisai) An immediate family member of Dr. Morita-Sherman has received personal compensation for serving as an employee of Forrester Research. Dr. Morita-Sherman has received personal compensation for serving as an employee of Eisai Inc.. An immediate family member of Dr. Morita-Sherman has stock in Forrester Research. The institution of Dr. Morita-Sherman has received research support from Cleveland Clinic.
No disclosure on file
No disclosure on file
Imad M. Najm, MD (Cleveland Clinic) Dr. Najm has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai Inc. Dr. Najm has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai Inc. Dr. Najm has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Eisai Inc.
No disclosure on file
Lara Jehi, MD (Cleveland Clinic Epilepsy Center) Dr. Jehi has nothing to disclose.
No disclosure on file