Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy
Introduction
The most forms of epilepsy can be considered as a result of an imbalance of the excitatory and inhibitory processes in the brain due to the debilitation of inhibitory processes [1]. The existence of a control system responsible for seizure arrest has been suggested by some authors [2]. Therefore, the artificial enhancement of the activity of this control system might lead to a beneficial therapeutic effect for patients who do not respond to medication.
Review of the ample experimental data along with a handful of clinical attempts shows that some brain structures are able to express inhibitory (suppressive) influences on both interictal and ictal epileptic electrical activity. The caudate nucleus [3], [4], [5], cerebellar cortex and cerebellar nuclei [6], [7], [8], thalamic anterior nuclear complex and centromedian nucleus [9], [10], [11] are the most studied brain structures with the ability to suppress epileptic discharges. A new trend of therapeutic electrical stimulation of cortical or deep epileptic foci has been described in the both experimental [12], [13] and clinical [14], [15], [16], [17] studies.
It was suggested that in the brain of many intractable epilepsy patients, instead of a restricted epileptic focus, there might be a multifocal epileptic system [18], [19], [20]. In these patients, even if epilepsy surgery is indicated, many problems arise often precluding them from radical surgery, i.e. multifocality of seizures, localization of epileptic foci within eloquent cortical areas, possible postsurgical memory impairment, etc. In such cases, an artificial increase of the activity of a brain inhibitory system, used alone, or in combination with different types of ablative surgery, might successfully treat the intractable epilepsy patient [14].
Analysis of the existing experimental and scarce clinical data reveals that there is an uncertainty about the parameters of stimulation and reproducibility of the results of stimulation, as well as about the stability and longevity of the inhibitory effects of stimulation on the epileptic activity. The main question remains to be answered: whether therapeutic brain stimulation will only prevent or stop epileptic seizures, giving only relief from symptoms, or will it influence the underlying disease mechanisms and foster an inhibitory process directed at lowering the “seizure tendency,” and ultimately cure the patient.
The aim of this article is not to present “anecdotal” cases of brain stimulation in epilepsy patients, or detect a specific “inhibitory” brain structure and implement a new method of treatment. The objective of this long-term (more than 20 years) series of studies is to present the electrophysiological and clinical evidence regarding the ability of some brain structures to prevent, suppress epileptic activity, and stop human epileptic activity and seizures. These include the evaluation of clinical and electrophysiological effects of electrical stimulation of head of the caudate nucleus (HCN), cerebellar dentate nucleus (CDN), centromedian nucleus (CM), and neocortical and temporal lobe mesiobasal epileptic foci. Based on these data we will discuss possible mechanisms and goals of therapeutic brain electrical stimulation in epilepsy.
Section snippets
Patients
The effects of HCN, CDN, CM eletrostimulation, and direct cortical and temporal lobe mesiobasal epileptic foci on the interictal and ictal brain electrical activity were studied during the diagnostic evaluations of 150 adult intractable epilepsy patients (age range 21–40 years, mean age 24 years, duration of illness 8–21 years, mean duration 14 years) with chronically (for 2–8 weeks) implanted diagnostic intracerebral electrodes, as well as during intrasurgical stereoelectroencephalographic
Head of caudate nucleus stimulation
Short relative high-frequency (HF) stimulation (2–5 s, 30–100 Hz) of both the dorsal and ventral parts of the HCN elicited the appearance or enhancement of epileptiform spike and/or sharp wave activity of preexisting EEG and SEEG of HCN and rhinencephalic brain structures. Conversely, 2–6 s duration low-frequency stimulation (4–8 Hz) of the ventral part of HCN decreased the frequency of sharp transients in the interictal epileptic activity and terminated the epileptic discharges in the mesiobasal
Head of caudate nucleus stimulation
The results of our studies of intractable epilepsy patients indicated that low-frequency stimulation of HCN in intractable epilepsy patients is able to suppress interictal epileptic activity, focal amygdalahippocampal discharges, and even the spread and generalization of seizures. Our study revealed that the inhibitory effect on the epileptic activity was more reliably achieved with stimulation of the ventral part of the HCN and can be bilateral with the unilateral stimulation. Morphological
Acknowledgements
The authors thank Vernon L. Towle, Ph.D., Jean-Paul Spire, M.D., John Milton, M.D., Ph.D., and John Hunter, Ph.D. for their comments and help in manuscript preparation. We also wish to make mention the late academician Peter Saradzhishvili, founder and Director of the Institute of Clinical and Experimental Neurology in Tbilisi and permanent Chairman of Epilepsy Problem Commission of the Academy of Science of the former USSR, who was the initiator of this work.
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