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The importance of the vagus nerve - stimulation in epilepsy therapy 

Schmidt D, Elger CE, Stefan H, Bergmann A, Bauer G, Brandl U, Despland P, Dorn T, Ernst JP, Flierl A, Holthausen H, McClelland G, Körner E, Kramer G, Meencke HJ, Mamoli B, Merschhemke M , Noachtar S, Ott E, Pohlmann-Eden B, Runge U, Mann J Scherr, Schnizer M, Tettenborn B, Wieser HG 

Summary 

The stimulation of the left vagus nerve in the neck area by means of an implanted pacemaker reduced the number of medically and surgically intractable seizures angehbarer not good, especially in focal epilepsy and Lennox-Gastaut syndrome, and 40% of all patients by 50%. The number of seizures, shall, within three months by about 25%, and in some patients experiencing an effect on only after six months.

With the VNS can be achieved in individual cases, seizure freedom. The patient may vary with a magnet stimulation as needed. 

Advantage of the vagus nerve stimulation (VNS) is well tolerated; the Implanatation is generally well tolerated. Postoperative infections occur in approximately 2%. It is usually for the duration of stimulation depending on their strength to a quieter, slightly hoarse voice. On exertion or chronic obstructive pulmonary disease can occur in individual cases, with greater stimulation of respiratory distress. In the pre-existing dysphagia risk of aspiration is increased during stimulation. Interactions with anticonvulsants or other drugs are not observed. 

A prediction about the likely success in individual cases, as with drug therapy, also not yet possible. After 3-5 years, depending on the stress-required a surgical battery replacement.

Before implantation should be ensured that the seizures with medication standard therapy are not treatable and further that no operationally angehbares epilepsy syndrome is present. The VNS does not come into question when state after vagotomy. 

The VNS is recommended for children, adolescents and adults whose epileptic seizures are severe and the medication and surgery are not treated well. Even after an unsuccessful operation, the SSF are used successfully. 

Introduction 

The introduction of new antiepileptic drugs and the improvement of surgical therapy, including the vagus nerve - Stimulation (VNS) is the standard treatment of epilepsy has improved in recent years (Schmidt and Elger, 1999). As pleasing as this extension is, it provides the physician with the task, one achieved at the individual patient tailored treatment strategy. It is understood, the treatment of epilepsy with the regulation to start antiepileptic drugs, which are successful in about 60-70%. Does the medication is not the goal should be checked in time including an EEG intensive monitoring if there is one of the good operating performance angehbaren epilepsy syndromes. These include primarily the medial temporal lobe, which operated for about two-thirds of all patients is mind. But also extratemporal epilepsies and so-called catastrophic epilepsies in infancy and childhood are more elaborate after preliminary investigation to operate successfully (Stefan, 1999, Engel, 1996). But considering that only about one-third of patients with pharmaco-resistant epilepsy ultimately come to a resective epilepsy surgery in question, the potential application of VNS is clear. For the remaining patients is more than palliative surgical method available to the VNS. To November 1998 over 3400 patients have been implanted worldwide, which corresponds to approximately 3800 patient-years (Schachter, 1999). Detailed summaries are published (Ben-Menachem, 1998, Kramer and Schachter, 1999, MacLachlan 1998, Schachter 1998, 1999). In the following, the importance of VNS by a German group of experts is presented briefly. 

Efficacy and side effects of vagus nerve stimulation 

With pharmaco-resistant epilepsy seizures is a surgical resection is not appropriate or possible, or that the operation provided no satisfactory result, the chronic intermittent VNS provides the neck after implantation of a pacemaker, an effective and well tolerated palliative alternative. It is a stimulating electrode on the left vagus nerve attached, with beneath the skin is a generator similar to a pacemaker connected to every 5 minutes 30 seconds stimulates the vagus nerve (Fig. 1). About 80% of the afferent nerve fibers of the seizure of the brain-specific regulation of the noradrenergic system, probably involving the locus coeruleus-modulated (Krahl et al., 1999). However, the mechanism is still not fully understood (Schachter 1999). 

In any case, the number of attacks - proved-through controlled trials to significantly reduce some months (Table 1). Seizure freedom is thereby achieved only in exceptional cases. All 454 patients from the study E01-5 were followed for three years after implantation. After 1, 2 and 3 years were still 96.4%, treated 84.7% and 72.1%. The number of patients with only half as many attacks rose to 44.1% in the third year (Morris et al., 1998). In some patients, the effect for 3 years after implantation. 

An analysis of 26 consecutive patients who were treated after unsuccessful epilepsy surgery with the VNS, showed improvement in 16 cases of seizure control by 50%, even when unsuccessful previous surgery patients with partial seizures. If the seizure focus is not associated with a structural lesion or if it is not because of its proximity to functionally dispensable cortex can not be completely resected, the VNS should be considered as an additional method considered (Frost et al., 1998). In patients with "drop attacks" and partial seizures should be considered prior to the VNS Kallosotomie. 

Side effects 

Although no serious side effects are known, the VNS is not without its drawbacks. Hoarseness, sore throat, cough, dyspnea, paresthesia, muscle pain and headache may affect up to one third of patients experience temporary (Ramsay et al., 1994, Uthman et al., 1993, Handforth et al., 1998). The following side effects have been reported voice alteration (29.3%), paresthesia (11.7%) in the first year, second year 19.3% and 5.9% voice alteration and coughing in the 3rd Years 3.2% dyspnea (Morris et al., 1998). A big advantage is that the implantation of stimulation electrodes and the generator is a small routine intervention (Table 2). Nevertheless, the patient should of course be generally operable and free of any serious obstructive lung dysfunction or dysphagia. For pre-existing dysphagia can occur during stimulation to increased dysphagia with aspiration (Lundgren et al 1998). Of course, should not be preceded by vagotomy. At 454 implants at five centers in the U.S., there were no serious postoperative complications. An infection caused 8 times (1.8%) to explantation in another five cases (1.1%) could be avoided explantation. Direct affection of the N. vagus resulted in 3 patients (0.7%) in transient hoarseness or vocal cord paralysis. In 3 other patients (0.7%) experienced a transient hypoesthesia in the neck or a left-sided facial paralysis. It was generally very well tolerated implantation (Bruce et al., 1998). An increased mortality risk does not exist (Annegers et al., 1998). The acceptance of the system for patients is excellent. About 70% want to void the battery usually after three years, a battery change (Schachter 1999). 

Vagus nerve stimulation in children 

Of particular importance is the effect on seizures in children with Lennox-Gastaut syndrome (Helmers et al 1998, LaBar et al., 1998). Although controlled trials have yet been reported in as many as 6 out of 18 children more than 90% seizure reduction (Murphy et al, 1995). In another 6 children were down less than 90%. In the remaining children, no improvement has been achieved. Side effects were in all children hoarseness during stimulation, wound infection in one of 18 children, inactivation of the metal strip of credit cards, as well as cosmetic aspects due to the bulging of the skin by the implanted pacemaker.However, the device had to be explanted for various reasons at the back half of the children. Rarely leads to a strengthening of a pre-existing hyperactivity or an increase in pre-existing dysphagia. The maximum seizure inhibition is achieved only after several months, and the effect increases during the first year and a half continuously even further. Sixty children and adolescents with focal epilepsy in most age of 3.5 to 18 years old at the time of implantation were examined. The median seizure frequency decreased within 18 months to 42%. At 20% voting changes occurred in 7% and paresthesias. Otherwise, the implantation was well tolerated. Between the different types of seizures or epilepsy of various etiologies each found no differences in response to VNS. Conclusions of the authors: Overall, VNS appears in pediatric refractory epilepsy as effective and well tolerated in adults to be (Hornig et al, 1998).. 

Importance of the vagus nerve stimulation in epilepsy therapy 

According to available data from controlled studies in patients with pharnmakoresistenten focal epilepsy and clinical observations of patients with pharmaco-resistant symptomatic generalized epilepsies (LaBar et al., 1998), can currently find in summary that the VNS is a palliative surgical treatment method in the effectiveness of the new antiepileptic drugs is similar, and in patients in coming, which currently can not be successfully treated with medication or by resection