VNS Therapy for Refractory Epilepsy

Background: More than 50 million people worldwide suffer from epilepsy, and approximately 30% of them are considered as drug-resistant (refractory), as the seizures are not in control with two adequately used antiepileptic drug schedules. Vagus nerve stimulation (VNS) is a promising treatment option for these patients. Neuromodulation therapies in the treatment of epilepsy are under substantial research, and the mechanisms of actions and details of function are still not fully understood.

Aims: The purpose of this study is to elucidate the functions of VNS therapy including the efficacy and the details concerning the automatic stimulation (responsive VNS, rVNS) properties. Other goals are to assess the power usage aspects of the treatment with different settings and after initiating automatic stimulation mode, and to gain a better understanding of the behavior of responsive stimulations in epilepsy patients.

Materials and Methods: Altogether 42 patients with refractory epilepsy were included in four studies. Follow-up time was highly variant, from 13 days to more than 11 years. The clinical and stimulation-related data were analyzed with SPSS, Excel, and Matlab softwares. We used nonparametric statistical tests and elucidated the results with illustrations.

Results: In the first study we found that in 90% of the patients the response to ANT-DBS (deep brain stimulation of the anterior nucleus of the thalamus) therapy was similar to VNS therapy (progressively better, partial response, no response) in patients with refractory epilepsy. In the second study, we found the initiation of automatic stimulation mode leading to better seizure control in 36.4 % of the patients. Therefore we were able to alter other stimulation settings, which led to significantly reduced battery usage. In the third study, we confirmed the altered stimulator settings affecting the number of stimulations and total charge delivered in the patient, especially when altering the OFF-time and the autostimulation threshold, and a possible difference between the function of rVNS in the temporal lobe and other epilepsy patients. In the fourth study, we found circadian patterns in automatic stimulations in most of the patients resembling the pattern of cortisol secretion. Our results support the finding that response to VNS therapy improves over time.

Conclusions: Vagus nerve stimulation is a promising treatment option for patients with refractory epilepsy. The automatic stimulation mode of VNS offers better seizure control with possibly lesser power usage than the older models. The responses to VNS and ANT-DBS therapies show similarities. There is circadian rhythmicity in the autostimulation activations in rVNS therapy. Shortening the OFF- time and lowering the threshold rate leads to a larger number of stimulations delivered.