Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures

Abstract

Objective: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS.

Methods: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri‑ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS.

Results: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99).

Significance: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.

Keywords: Autonomic nervous system; Cardiac; Epilepsy; FDS; Heart rate variability; Nonepileptic seizures.