Cardiac Phenomena During Kainic-acid Induced Epilepsy and Lamotrigine Antiepileptic Therapy

Rationale: Pathologic ECG events are known to accompany seizures and to persist in several chronic epilepsy syndromes. The contribution of antiepileptic drugs (AEDs) to these events and the implications in the etiology of sudden-unexpected death in epilepsy (SUDEP) continue to be a matter of debate. We therefore investigated cardiac parameters during kainic-acid (KA) induced experimental epilepsy and antiepileptic treatment with lamotrigine (LTG).

Methods: Epilepsy was induced in seven C57Bl/6 mice by injections of KA (20 mg/kg) on days 1 and 5, which produced severe acute seizures and spontaneous seizures 10 days later. Treatment with LTG (30 mg/kg) was initiated on day 11 and repeated on day 12. Continuous ECGs and ECoGs were collected telemetrically from freely moving mice.

Results: Mice displayed pre-ictal but not ictal tachycardia. The squared coefficient of variation (SCV) of R-R intervals was significantly elevated 30s before and during seizures compared to control conditions. LTG produced a significant reversible increase in SCV and LF/HF ratio during slow-wave sleep (SWS), potentially indicative of sympatho-vagal imbalance during this state of vigilance, in which epileptic patients are known to be particularly vulnerable to SUDEP.

Significance: The KA model used in this study permits the investigation of cardiac phenomena during epilepsy, as it features many effects found in human epileptic patients. Increased LF/HF, a known risk factor for cardiac disease, which is often found in epileptic patients, was observed as a side-effect of LTG treatment during SWS, suggesting that LTG may promote imbalance of the autonomous nervous system in epileptic mice.