Disrupting abnormal electrical activity with deep brain stimulation: is epilepsy the next frontier?

Department of Neurosurgery, University of Florida, Gainesville, Florida, USA.
Neurosurgical FOCUS (Impact Factor: 2.14). 08/2010; 29(2):E7. DOI: 10.3171/2010.4.FOCUS10104
Source: PubMed

ABSTRACT Given the tremendous success of deep brain stimulation (DBS) for the treatment of movement and neuropsychiatric disorders, clinicians have begun to open up to the possible use of electrical stimulation for the treatment of patients with uncontrolled seizures. This process has resulted in the discovery of a wide array of DBS targets, including the cerebellum, hypothalamus, hippocampus, basal ganglia, and various thalamic nuclei. Despite the ambiguity of the mechanism of action and the unknowns surrounding potentially ideal stimulation settings, several recent trials have empirically demonstrated reasonable efficacy in selected cases of medication-refractory seizures. These exciting results have fueled a number of studies aimed at firmly establishing DBS as an effective treatment for selected cases of intractable epilepsy, and many companies are aiming at Food and Drug Administration approval. We endeavor to review the studies in the context of the various DBS targets and their relevant circuitry for epilepsy. Based on the unfolding research, DBS has the potential to play an important role in treating refractory epilepsy. The challenge, as in movement disorders, is to assemble interdisciplinary teams to screen, implant, and follow patients, and to clarify patient selection. The future will undoubtedly be filled with optimization of targets and stimulation parameters and the development of best practices. With tailored therapeutic approaches, epilepsy patients have the potential to improve with DBS.

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    ABSTRACT: INTRODUCTION: Diffusion tensor imaging (DTI) techniques demonstrated diffuse bilateral temporal and extra-temporal abnormalities of white matter in patients presenting mesial temporal lobe epilepsy with hippocampal sclerosis (HS). The aim of this study was to assess these diffusion changes following temporal lobe surgery, by applying a novel voxel-based tract-based spatial statistics (TBSS) technique for whole-brain analysis of fractional anisotropy (FA) and mean diffusivity (MD). Second, region-of-interest analysis (ROI) was performed to improve statistical power. MATERIAL AND METHODS: The study included 22 patients with unilateral HS. Twelve patients underwent temporal lobe surgery. Follow up MRI was done in a mean interval of 4 months. Voxelwise pre-operative FA asymmetry in all 22 patients was assessed within subjects between lesional and contralateral hemispheres. The whole-brain post-operative dataset of 10 seizure-free patients was compared with the corresponding pre-operative dataset using voxel-wise statistical analysis. Additionally, regional analysis at the fornices was done with skeleton-based region of interest (SROI). RESULTS: Within a mean interval time of 6.3 months after surgery, 10 of 12 patients were seizure free (83.3%). The voxelwise comparison between lesional and contralateral hemispheres was consistent with previous studies showing a more widespread diffusion alteration in the lesional hemisphere. Voxel-wise comparison between post and pre-operative dataset did not show supra-thresholded voxels. SROI statistical analysis showed significant decrease in FA and increase in MD in the ipsilateral fornix. Significant increase in FA was observed in the contralateral fornix after surgery. CONCLUSION: The ipsi-lesional fornix showed decreased FA and increased MD after surgery, consistent with Wallerian degeneration. In contrast, contra-lesional fornix demonstrated increase in FA. This observation is important for our understanding of the fate of the remaining brain tissue following removal of an epileptic focus. Postoperative increase in FA may reflect structural reorganization in response to epilepsy surgery. The discrepancy between SROI and voxelwise statistics emphasizes the difference of statistical sensitivity between voxelwise and ROI analyses.
    Epilepsy research 03/2011; 94(3). DOI:10.1016/j.eplepsyres.2011.02.001 · 2.19 Impact Factor
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    ABSTRACT: Given the tremendous success of deep brain stimulation (DBS) for the treatment of movement and neuropsychiatric disorders, clinicians have begun to open up to the possible use of electrical stimulation for the treatment of patients with uncontrolled seizures. DBS of various neural targets has been investigated in clinical studies and animal studies, including the anterior nucleus of thalamus (ANT), cerebellum, hippocampus, subthalamic nucleus (STN), centromedian nucleus of the thalamus (CMT), caudate nucleus (CN). Recently, a large and multicenter trial (SANTE: Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) was conducted and subsequently with encouraging results, making ANT the most well-established target for DBS in the treatment of epilepsy to date. Here, we endeavor to review mainly the animal studies and clinical studies of ANT DBS to further explore the more reliable target.
    Brain research bulletin 03/2011; 85(3-4):81-8. DOI:10.1016/j.brainresbull.2011.03.020 · 2.97 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation.
    04/2011; 2011:414682. DOI:10.4061/2011/414682