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Aktuelle Neurologie 2016; 43(08): 501-510
DOI: 10.1055/s-0042-116022
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Vagusnervstimulation in der Behandlung von Epilepsiepatienten

Vagus Nerve Stimulation in the Treatment of Epilepsy
M. Hirsch
1   Abteilung Prächirurgische Epilepsiediagnostik – Epilepsiezentrum, Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Deutschland
,
P. Reinacher
2   Abteilung Stereotaktische und Funktionelle Neurochirurgie, Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Deutschland
,
A. Schulze-Bonhage
1   Abteilung Prächirurgische Epilepsiediagnostik – Epilepsiezentrum, Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Deutschland
› Author Affiliations
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Publication History

Publication Date:
18 October 2016 (online)

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Zusammenfassung

Weil ca. ein Drittel der Epilepsiepatienten sich als pharamakorefraktär erweist und nicht allen diesen Patienten ein epilepsiechirurgischer Eingriff angeboten werden kann, werden weitere Behandlungsmöglichkeiten benötigt. Die Vagusnervstimulation (VNS) ist seit 1994 ein fester Bestandteil in der palliativen Behandlung von Epilepsiepatienten. In 2 Studien wurde bei fokalen Epilepsien eine signifikant bessere Wirksamkeit einer 30 Hz-Stimulation gegenüber einer Applikation subtherapeutischer seltener Einzelreize nachgewiesen (Evidenzklasse I); offene Verlaufsbeobachtungen zeigen mit der Stimulationsdauer zunehmende Responderraten (bis zu 50–60% nach 2 Jahren). Die Effektivität der VNS ist damit vergleichbar mit der Gabe eines zusätzlichen Medikamentes. Eine komplette Anfallsfreiheit wird selten erreicht (2–8% der Patienten). Studien mit kleinen Fallzahlen belegen auch eine gute Wirkung der VNS bei genetischen (idiopathischen generalisierten) Epilepsien. Es wird angenommen, dass die hauptsächliche Wirkung durch eine Neuromodulation bei chronischer Intervallstimulation entfaltet wird. Zusätzlich wird von manchen Patienten eine akute Wirkung auf die Anfallsdauer bzw. Anfallsschwere der mittels eines Magneten im Anfall aktivierten zusätzlichen Stimulationen angegeben. Der aktive Einsatz eines Magneten im Anfall ist jedoch durch verschiede Faktoren limitiert. Dies war die Rationale für die Entwicklung eines closed-loop-VNS-Systems, welches einen Anfall anhand bei Epilepsiepatienten häufig auftretender iktaler Tachykardien detektieren kann und selbstständig einen Stimulationszyklus appliziert. 2 Studien wiesen eine gute Funktion dieses VNS-Systems bei geeigneten Patienten nach. Die VNS wird in der Regel gut vertragen mit hohen Langzeitretentionsraten der Anwendung. Die häufigsten stimulationsbedingten Nebenwirkungen wie Heiserkeit, Parästhesien, Husten, Dyspnoe sind mit der Zeit deutlich rückläufig. Die Raten kardialer Nebenwirkungen und die Operationsrisiken sind sehr niedrig. Vorsicht ist geboten bei Patienten mit einem Schlaf-Apnoe-Syndrom, weil die VNS die Beschwerden verschlechtern kann. Ein antidepressiver Effekt der VNS gilt als belegt, weshalb auch eine Zulassung zur Behandlung der Depression unabhängig von der Diagnose einer Epilepsie besteht. Die sensible Innervation der Concha des Ohres durch den Ramus auricularis des N. vagus ist Grundlage für die Wirkung eines neuerdings erhältlichen Gerätes zur transkutanen Vagusnervstimulation. Eine randomisierte, kontrollierte Studie zur Wirksamkeit der transkutanen VNS bei 76 Patienten konnte keine Überlegenheit der hochdosierten Stimulation gegenüber der Kontrollgruppe nachweisen, obgleich sich eine positive Wirkung abzeichnete; Die Studie verfügte zum Wirksamkeitsnachweis nicht über genügend statistische power. Auch für die transkutane VNS werden antidepressive Effekte berichtet, daneben auch positive Effekte auf die Kognition.

Abstract

Because about a third of epilepsy patients are drug resistant and epilepsy surgery can not be offered to all these patients, additional treatment options are needed. Since 1994, vagus nerve stimulation (VNS) has been an integral part of the palliative treatment of patients with epilepsy. In 2 studies a significantly better efficacy in treatment of focal epilepsy was verified for 30 Hz Stimulation as compared to the application of subtherapeutic rare single impulses (evidence class I); open history observations show that with increasing duration of stimulation, there is an increase in responder rates (up to 50–60% after 2 years). The effectiveness of VNS is therefore comparable to administration of an additional drug. Complete seizure freedom is rarely achieved (2–8% of patients). Studies with small numbers of patients also show a good effect of VNS in genetic (idiopathic generalized) epilepsy. It is believed that the main effect results from neuromodulation through chronic interval stimulation. In addition, patients reported an acute effect on seizure duration and severity by additional stimulations activated by a magnet in the course of the seizure. The active use of a magnet during a seizure, however, is limited by various factors. This was the rationale for the development of a closed-loop VNS system that can detect ictal tachycardia that frequently occurs in patients during an epileptic seizure and independently triggers a stimulation cycle. 2 studies have demonstrated the VNS system to function well in appropriate patients. The VNS is generally well tolerated with high long-term retention rates of application. The most common stimulation-induced side effects such as hoarseness, paresthesia, cough, and dyspnea clearly decline with time. The rate of cardiac side effects and the risks of surgery are very low. Caution is advised in patients with sleep apnea syndrome because the VNS may worsen the symptoms. An antidepressant effect of VNS is considered as established so that it has received approval for treatment of depression independent of the diagnosis of epilepsy. The sensory innervation of the concha of the ear by the auricular branch of the vagus nerve is the basis for the action of a newly available device for transcutaneous vagus nerve stimulation. A randomized, controlled study of the efficacy of transcutaneous VNS in 76 patients could not demonstrate superiority of high-dose stimulation compared with the control group, although there were signs of a positive effect. The proof-of-efficacy study does not have sufficient statistical power. Besides antidepressant effects, transcutaneous VNS has also been reported to have positive effects on cognition.

Schlüsselwörter

Epilepsie - Vagusnervstimulation - transkutan - closed-loop

Keywords

epilepsy - transcutaneous - closed-loop - vagus nerve stimulation
 

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