Authors :
Presenting Author: Elise Collard, Msc – Université Catholique de Louvain, Institute of Neuroscience (IoNS), Clinical Neuroscience, Brussels, Belgium
Enrique Germany, PhD – PostDoc, Université Catholique de Louvain, Institute of Neuroscience (IoNS), Clinical Neuroscience, Brussels, Belgium; Antoine Nonclercq, PhD – 3Université libre de Bruxelles, BEAMS Department, Belgium; Riëm El Tahry, MD,PhD – PI, Université Catholique de Louvain, Institute of Neuroscience (IoNS), Clinical Neuroscience, Brussels, Belgium ,WEL Research Institute, Department Welbio, Avenue Pasteur 6, 1300 Wavre, Belgium, Cliniques Universitaires Saint-Luc, Center for Refractory Epilepsy, Department of Neurology, Brussels, Belgium
Rationale:
Epilepsy is the second most common chronic neurological disease associated with 50 million people affected (Jacoby et al., 2005). A third do not respond to antiepileptic drugs, and some patients are not eligible to surgically remove the epileptogenic focus, such as c
hildhood absence epilepsy, one of the most common forms of pediatric epilepsy, a form of idiopathic generalized epilepsy. In this case, vagus nerve stimulation (VNS) can be offered as an adjunctive treatment. Absence seizures can be accompanied by autonomous changes(Devinsky, 2004; Jansen et al., 2013; Roche-Labarbe et al., 2010). GAERS (Genetic Absence Epilepsy Rats from Strasbourg) is a well-validated genetic model of typical absence epilepsy (Danober et al., 1998). Its electrophysiological and behavioral characteristics match those observed in humans (Depaulis et al., 2016). We aim to study whether absence seizures can be detected through autonomous changes visible within vagus nerve neurogram recordings (VENG).Methods:
The left cervical vagus nerve was implanted with a cuff electrode (outer diam: 1.6mm, inner diam: 0.3mm, interelectrode distance: 4mm) for VENG recording. Epidural electrodes were implanted for scalp EEG monitoring [GND]: AP: -2, ML: +-3 [PL/PR]: AP: 5, ML: +-3 [REF]: AP: -6, ML: 0. Surgical procedure was performed under sevoflurane anesthesia. VENG and EEG were recorded for 24h in five months old freely moving GAERS rats (N=2) (Fig1). Ictal VENG segments were identified based on corresponding ictal EEG patterns. Absences lasting less than five seconds were not discarded. Root Mean Square (RMS) value of each VENG segment during absences was calculated and compared to the RMS value of the pre-ictal VENG segments (10 sec). The increase or decrease of the VENG signal compared to the pre-ictal phase is given in percentage RMS per hour (Fig.2A,B).
Results:
Both increased and decreased vagus nerve activity were observed during absences compared to the pre-ictal phase. Twenty four hour recordings for two rats are presented. 328 absences (Rat1) and 315 absences (Rat2) were recorded, lasting between five and forty six secones. In Rat1, 112 seizures were characterized by an increase of VENG RMS ranging from 17 to 95%, while 216 seizures had a decrease of VENG RMS ranging from -13% to -65%
(Fig. 2A). In Rat2, 94 seizures were characterized by an increase in VENG RMS ranging from 8% to 184%, while 221 seizures had a decrease of VENG RMS ranging from -44% to -71% (Fig.2B).
Conclusions:
Changes in vagus nerve activity are observed during absence seizures in the GAERS model. These VENG modifications could be used for the development of novel closed-loop VNS therapy.
Funding:
« Welbio » par WEL Research Institute Starting Grant