Paroxysmal fast activity is a biomarker of treatment response in DBS for Lennox-Gastaut syndrome.

Abstract

Epilepsy treatment trials typically rely on seizure diaries to determine seizure frequency, but these are time-consuming and difficult to accurately maintain. Fast, reliable, and objective biomarkers of treatment response are needed, particularly in Lennox-Gastaut syndrome (LGS) where high seizure frequency and co-morbid cognitive and behavioural issues are additional obstacles to accurate diary-keeping. Here, we measured generalised paroxysmal fast activity (GPFA), a key interictal electrographic feature of LGS, and correlated GPFA burden with seizure diaries during a thalamic deep brain stimulation (DBS) treatment trial (ESTEL). GPFA and electrographic seizure counts from intermittent, 24-hour EEGs were compared to 3-monthly diary-recorded seizure counts in 17 young adults with LGS (mean age ±1SD=24.9±6.6) in the ESTEL study, a randomised clinical trial of DBS lasting 12 months (comprising a 3-month baseline and 9 months of post-implantation follow-up). Baseline median seizures measured by diaries was 2.6 (IQR:1.4-5) per day, compared to 284 (IQR:120.5-360) electrographic seizures per day, confirming that diaries capture only a small fraction of seizure burden. Across all patient EEGs, the average number of GPFA discharges per hour of sleep was 138 (IQR:72-258). GPFA duration and frequency, quantified over 2-hour windows of sleep EEG, were significantly associated with diary-recorded seizure counts over 3-month intervals (p<0.001, η²p = 0.30-0.48). For every one GPFA discharge, there were 20-25 diary seizures witnessed over 3 months. There was high between-patient variability in the ratio between diary seizure burden and GPFA burden; however, within individual patients, the ratio was similar over time, such that the percentage change from pre-DBS baseline in seizure diaries strongly correlated with the percentage change in GPFA. When seeking to optimise treatment in patients with LGS, monitoring changes in GPFA may allow rapid titration of treatment parameters, rather than waiting for feedback from seizure diaries.