Abstracts

Rationale: Patients with drug resistant epilepsy are potential candidates for resective epilepsy surgery. Factors that influence the outcome of epilepsy surgery have been studied extensively. Despite this seizure freedom occurs in only ~65% of optimal candidates. There are now more studies on surgical outcomes of patients with specific genetic syndromes, yet the role of routine genetic testing in preoperative evaluations remains unclear. To study this, we retrospectively examined genetic evaluations in patients referred for surgical evaluations during a period over which there was a significant increase in the availability of genetic testing. We present data from the first and the last year of the study.

Methods: After IRB approval, patients admitted to the Johns Hopkins Hospital epilepsy monitoring unit for the purpose of pre-surgical evaluation in the years 2012 and 2020 were identified through EEG logs, hospital scheduling records, and medical charts. Patients without epilepsy and those admitted for spell characterization were excluded. Patient demographics, clinical epilepsy details, electroencephalography (EEG) findings, neuroimaging results and other ancillary tests were collected. If genetic testing was performed, reason for testing, type of test and results were collected. For those who underwent surgery, the outcome of surgery was classified by the Engel surgical outcome scale. We compared characteristics of patients who were considered for genetic testing versus who were not and trends over time.

Results: Thirty-six patients in 2012 (23 female) and 60 patients in 2020 (27 female) were included. In 2012, 4/36 (11.1%) of presurgical patients were considered for genetic testing compared to 15/60 (25%) in 2020, p=0.069. The overall diagnostic yield of genetic testing was 31.2% (5/16); 25% in 2012 and 40% in 2020. The reasons for considering genetic evaluation were intractable epilepsy (10/19, 52%), positive family history (3/19, 16%), “epilepsy plus” (3/19, 16%), and if a genetic syndrome was suspected (2/19, 22%). Patients considered for genetic testing had a younger age of epilepsy onset (mean=7.21 years) compared to patients who were not (mean=17.06 years, p=0.0049), and there was a trend towards having bilateral, generalized, or non-lateralizing scalp EEG findings (47% vs 24%, p=0.08). A non-lesional MRI did not change consideration of genetic testing, p=0.6. Six out of 19 patients who were considered for genetic testing underwent epilepsy surgery and 4 had favorable outcomes. Of these, 2 patients had tumors, 1 had Rasmussen’s Encephalitis, and 1 had Tuberous Sclerosis Complex. Genetic testing was positive in 1/2 patients with a poor outcome, revealing a pathogenic variant in NPRL3. Two patients with pathogenic variants in CACNA1A and RAI1 were rejected for further surgical evaluation, primarily based on the genetic test result.

Conclusions: Preliminary analysis of our study showed that nearly 1/3 of the patients who were referred for presurgical evaluation and underwent genetic testing had a result that revealed an underlying genetic etiology. There was a trend towards more frequent consideration of genetic testing over time and testing changed the plan in some cases.

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