(269) Pre-ictal heart rate variability alterations in focal and generalized seizures and response to vagus nerve stimulation

Rationale: Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug-resistant epilepsy (DRE) patients since 1997, yet the prediction of treatment response before implantation is still a subject of ongoing research. Focusing on the mechanism of action (MOA) of VNS might provide characteristics for VNS response. This study investigated whether pre-ictal heart rate variability (HRV) alterations are associated with VNS response and whether these alterations were different in focal versus generalized seizures.

Methods: DRE patients underwent video-electroencephalography (EEG) and ECG recording before VNS implantation. Recorded seizures were categorized in either focal or generalized onset. HRV parameters (time, non-linear, and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60min before seizure onset) and pre-ictal (10min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of treatment in patients with focal and generalized seizures.

Results: Twenty-nine patients with a total of 117 seizures were evaluated,12 patients were classified as VNS responders (seizure reduction ≥ 50% after one year of VNS). In focal onset seizures (85/117) time domain and non-linear HRV variables decreased significantly in VNS non-responders (p=0.024, p=0.005, p=0.005) during the pre-ictal time frame. In generalized seizures (32/117) high frequency (HF) power increased significantly in the pre-ictal time frame in both VNS responders and VNS non-responders (p=0.017, p=0.004).

Conclusions: VNS non-responders were characterized by a significant decrease of pre-ictal HRV in focal onset seizures suggesting a sudden autonomic imbalance due to epileptic activity targeting central autonomic brain regions, which might be due to an impaired central autonomic function that makes it unlikely to respond to VNS. Generalized onset seizures showed a significant increase in HF power – a parasympathetic overdrive in both VNS responders and VNS non-responders that can be interpreted as a severe autonomic imbalance potentially leading to cardiovascular and breathing issues that are known to be involved in Sudden Unexpected Death in Epilepsy (SUDEP).

Funding: Please list any funding that was received in support of this abstract.: No funding was received.