Deep Brain Stimulation and Intractable Epilepsy
Deep Brain Stimulation and Intractable Epilepsy
Partial epilepsies in humans are usually well controlled by anti-epileptic drugs (AEDs) in about 70% of cases, but the remaining 30% become refractory.1 About 50% of the latter are suitable for resective surgery, 2 which can lead to satisfactory results. However, many of these patients cannot be operated on unless there is an unacceptable deficit, especially when the epileptogenic zone involves speech, memory, or motor areas. Moreover, patients presenting with multifocal or generalized epilepsy who fail with AEDs are not suitable for surgery.
For these reasons, and because the development of new AEDs is unlikely to control all of them, new techniques such as deep brain stimulation, cortical stimulation or local drug delivery are under development to improve the number of successfully treated patients.
Deep brain stimulation (DBS) was originally developed to treat Parkinson’s disease, essential tremor and, more recently, dystonia. In this respect, several nuclei have been targeted—the ventral intermediate nucleus (VIM), the internal part of the pallidum (GPi) and the sub-thalamic nucleus (STN). This surgery is wellestablished and routinely and safely performed worldwide, and is now available for new indications including intractable epilepsy. But the question remains whether there are sufficient experimental and clinical data to suggest that this new treatment could be proposed for these patients.
There is now a large and convincing body of literature describing the modulating effect of chemical and physical lesion of the basal ganglia, thalamus, and posterior hypothalamus on generalized epileptic models in rats (for review, see Deransart and Depaulis, 20023). From movement disorder surgery it is now considered, even if the mechanisms are still debated, that high-frequency stimulation (HFS) of a nuclear structure mimics the clinical effect of its lesion but only few data are so far available concerning the effect of HFS-DBS in these animal models. Moreover, most of these authors have challenged DBS in generalized epileptic models but only a few studies have concentrated on focal neocortical or limbic epilepsy. Nevertheless, it has been established that HFS of the anterior nucleus of the thalamus, the mammillary nucleus, the centromedian nucleus, the superior colliculus, and the sub-thalamic nucleus has an anti-epileptic effect in the pentylenetetrazole model,4,5), the Gaers model (genetic absence epileptic rats from Strasbourg),6,7 and the pilocarpine8 and kainic acid models.9,10
In humans, several structures have been explored since the 1970s for the treatment of mainly multi-focal, frontal, or generalized epilepsy. In this respect, authors have reported their experience with DBS of the cerebellum,11–17), the centromedian nucleus,16,18 the anterior nucleus of the thalamus,18–23 and the striatum,23 with some divergent results.
Preliminary data reported with DBS of the anterior nucleus of the thalamus were convincing enough to initiate a national trial that is currently being conducted in the US.
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