SAN DIEGO—An implantable device can reduce seizures and improve quality of life in patients with epilepsy for whom epilepsy surgery is not an option, according to research presented at the 66th Annual Meeting of the American Epilepsy Society. Implantable devices are not likely to help patients become seizure-free, however.
Vagus Nerve Stimulation Reduces Seizure Rate
The vagus nerve stimulator (VNS) is the only approved device for epilepsy in the United States and Canada, noted Barbara C. Jobst, MD, Director of the Dartmouth Epilepsy Program at Dartmouth-Hitchcock in Lebanon, New Hampshire. The typical treatment is a cycle of 30 seconds of stimulation, followed by three minutes of inactivity. The stimulus is delivered to the left vagal nerve at the level of the carotid bifurcation. If this treatment is ineffective, the neurologist may decide to use rapid cycling: a cycle of 21 seconds of stimulation, followed by 1.8 minutes of inactivity.
A minority of patients become seizure-free with VNS. The initial controlled trial of the treatment showed a modest seizure reduction of approximately 27%. In comparison, medications are associated with a median seizure reduction of between 30% and 45% in controlled trials.
Data indicate that the efficacy of VNS increases significantly with time. In long-term VNS studies with follow-up comparable to that of medication studies, mean seizure reduction increases to more than 60%. In contrast, seizure-free rates are the same in short- and long-term studies of antiepileptic drugs. But patients who experience no effects or adverse effects from VNS may drop out of long-term studies, thereby biasing the results, noted Dr. Jobst.
VNS has good tolerability overall, said Dr. Jobst. Approximately 17% of patients with epilepsy have their VNS removed. The device is associated with minor side effects such as hoarseness and dysphagia, but these conditions improve with time. The device also may have a positive effect on cognition and alertness, added Dr. Jobst.
Children May Benefit From VNS
Children respond more favorably to VNS than adults, and younger children seem to respond most favorably, said Dr. Jobst. Patients who have failed epilepsy surgery, often considered the most difficult patient population, also have a reduction in seizure frequency of more than 50% with VNS. VNS is equally effective in benign, generalized epilepsies. Patients with Lennox–Gastaut syndrome or epileptic encephalopathy respond less favorably, but have seizure-frequency reduction rates greater than 25%.
Patients with simple partial seizures tend to respond the best to VNS, and patients with tuberosclerosis or post-traumatic epilepsy also may respond well, said Dr. Jobst. VNS response rate seems to decrease as epilepsy duration increases, she added. Generalized tonic–clonic seizures are negative predictors of a favorable response.
VNS Entails Fewer Complications Than Callosotomy
One 2006 study compared outcomes between 21 patients with generalized epilepsy who received VNS implantation and 50 patients who had a callosotomy. The overall responder rate for VNS was 40%, but the rate was slightly higher for tonic–clonic and tonic–atonic seizures. The overall responder rate for callosotomy was nearly 80%, and 17% of those patients had a class 1 outcome, said Dr. Jobst.
Callosotomy was associated with a 20% rate of complications, however, compared with 8% for VNS. "The complications of a callosotomy are much more severe" and include death and hemiparesis, compared with site infection or defective batteries for VNS, said Dr. Jobst. Callosotomy is associated with a greater rate of seizure reduction than VNS, so risks and benefits have to be weighed carefully.
Deep Brain Stimulation as Treatment for Epilepsy
A deep brain stimulator (DBS) approved in Europe, but not in the US, may be another treatment option for patients with epilepsy. After implantation into the anterior nucleus of the thalamus, the device applies intermittent or continuous stimulation at high frequency.
Compared with sham stimulation, a DBS reduced seizure frequency by 29%. As with VNS, the effect of a DBS appears to increase over time. In the long-term SANTE study, median seizure reduction was greater than 60%, and the rate of seizure-free patients was about 12%.
The tolerability of a DBS is similar to that of VNS. Approximately 17% of DBSs were explanted in the long term. Common side effects include paresthesias and infection. About 4.5% of patients who received DBS implantation had intracranial hemorrhage, but none of the hemorrhages was of long-term clinical significance.
In the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy study, the median seizure reduction of DBS in temporal lobe epilepsy was significant compared with neocortical epilepsy, but not significant compared with controls, according to Dr. Jobst. Patients with complex partial seizures responded well, and patients with the most severe seizures generally improved the most.