Lies Mollet

Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model

J. Neurochem. (2011) 117, 461–469.

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: Pilot trial at Ghent University Hospital

PURPOSE Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable stimulus generator and an electrode for combined stimulation and recording. In this feasibility study, three patients were implanted with ADNS-300 for therapeutic VNS. In addition, compound action potentials (CAPs) were recorded to evaluate activation of the vagus nerve in response to VNS. METHODS Three patients were implanted with a cuff-electrode around the left vagus nerve, that was connected to a rechargeable pulse generator under the left clavicula. Two weeks after surgery, therapeutic VNS (0.25-1.25 mA, 500 μs, 30s on, 10 min off and 30Hz) was initiated and stimulus-induced CAPs were recorded. RESULTS The ADNS-300 system was successfully implanted in all three patients and patients were appropriately stimulated during six months of follow-up. A reduction in seizure frequency was demonstrated in two patients (43% and 40% in patients 1 and 3, respectively), while in patient 2 seizure frequency remained unchanged. CAPs could be recorded in patients 1 and 2, proving stimulation-induced activation of the vagus nerve. CONCLUSION This feasibility study demonstrates that the ADNS-300 system can be used for combined therapeutic stimulation (in 3/3 patients) and recording of CAPs in response to VNS (in 2/3 patients) up to three weeks after surgery. Implantation in a larger number of patients will lead to a better understanding of the electrophysiology of the vagus nerve, which in turn could result in more adequate and individualized VNS parameter choice.

ELECTROPHYSIOLOGICAL RESPONSES FROM VAGUS NERVE STIMULATION IN RATS

The mechanism of action of vagus nerve stimulation (VNS) for pharmacoresistant epilepsy is unknown and the therapeutic outcome is highly variable. We investigated stimulation-induced vagus nerve electrophysiological responses in rats using various stimulation parameters. Conduction velocity, I(50), rheobase and chronaxie were calculated. We identified an early and late component corresponding to an afferent compound action potential (CAP) and a remote laryngeal motor-evoked potential (LMEP), respectively. The conduction velocity (CAP: 26.2 ± 1.4 m/s; LMEP: 32.4 ± 2.4 m/s) and I(50) (CAP: 2.4 ± 0.3 mA; LMEP: 1.8±0.2 mA) were significantly different for both components, the rheobase (CAP: 140±30 μA; LMEP: 110±26 μA) and chronaxie (CAP: 66±7 μs; LMEP: 73±9 μs) were not. Using a pulse of 10 μs, the CAP saturated between 4-5 mA. Our method can be used to record VNS-induced electrophysiological responses in rats and provides an objective biomarker for electrical stimulation with various parameters in an experimental set-up. Our findings are potentially useful for clinical purposes in the sense that combination of VNS and recording of vagal nerve CAPs may help clinicians to determine the individual optimal intensity required to fully activate fast-conducting afferent fibers.

Repeated assessment of larynx compound muscle action potentials using a self-sizing cuff electrode around the vagus nerve in experimental rats.

RATIONALE Vagus nerve stimulation (VNS) is an adjunctive treatment for patients with refractory epilepsy. In more than 30% of the patients VNS has no therapeutic effect. The goal of this study was to find an objective parameter that can be used as an indicator of effective stimulation of the vagus nerve. METHODS The electrophysiological response to VNS was recorded from the vagus nerve, recurrent laryngeal nerve and larynx muscles. Nerve lesions and muscle relaxing agent were used to find the source of the electrophysiological response. A cuff-electrode for chronic stimulation and recording was implanted for chronic recording of the VNS-induced electrophysiological response after implantation. Dose-response curves were determined daily during a follow-up period of 2 months. RESULTS VNS induced an electrophysiological response around 3 ms after start of the stimulation. This response was identified as a larynx compound action potential (LCMAP) LCMAP could be recorded immediately after surgery in 11/21 rats, while in the other 10/21 rats, a recovery period with an average of 25 days was required. Once the LCAMP could be recorded, the latency and overall characteristics of the doses response curves of the LCMAP remained stable during the entire follow-up period. CONCLUSIONS In this study, we provide an objective electrophysiological parameter for vagus nerve activation. LCAMP may indicate recovery of the vagus nerve after implantation, which may help to determine when uptitration of VNS therapy can be initiated. LCAMP could be of value in future experiments for objectification of VNS in animal models for epilepsy.

Intensity-dependent modulatory effects of vagus nerve stimulation on cortical excitability

Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy. It remains unknown whether VNS efficacy is dependent on output current intensity. The present study investigated the effect of various VNS output current intensities on cortical excitability in the motor cortex stimulation rat model. The hypothesis was that output current intensities in the lower range are sufficient to significantly affect cortical excitability.

Vagus nerve stimulation has antidepressant effects in the kainic acid model for temporal lobe epilepsy

Molecular Imaging of Inflammation Reveals Differences Between Drug-Resistant and Drug-Sensitive Animals in a Chronic Model of Temporal Lobe Epilepsy