Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic–clonic seizure during cortical stimulation in patients with focal epilepsy

Stimulation-evoked focal to bilateral tonic–clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS. •The risk of stimulation-evoked FBTCS during cortical stimulation is relatively low.•A strong reduction in AEDs increases the risk of stimulation-evoked FBTCS.•Avoiding total AED withdraw may prevent patients from stimulation-evoked FBTCS.•No stimulus with an intensity of less than 5mA evoked a FBTCS.