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: 2.11). 08/2010; 29(2):E7. DOI: 10.3171/2010.4.FOCUS10104
Source: PubMed


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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    • "This treatment has become a therapeutic option for pathologies that are associated with chronic pain and movement disorders [2] as well as for refractory depression [3] or epilepsy [4]. Such patients can be treated with direct electrical stimulation at the vagus nerve [5, 6] or at deep nuclei of the hypothalamus [4, 7–9]. The use of DBS in humans entails the implantation of a generator of electric current (commonly under the collarbone) and bilateral electrodes that transmit a continuous current to precise stereotaxic coordinates into the brain [10]. "
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    ABSTRACT: Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication.
    Clinical and Developmental Immunology 10/2013; 2013(5–8):698634. DOI:10.1155/2013/698634 · 2.93 Impact Factor
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    ABSTRACT: The series included five patients who had suffered 8 to 23 years of severe, medically intractable seizures without remission, severe socioeconomic handicaps, and an average of over one seizure a day on hospital observation and by history. All had combinations of partial and general seizures with focal and/or bilaterally synchronous epileptiform activity consistently on multiple electroencephalograms (EEG's). One patient had nearly continuous myoclonic activity. Serum levels of phenytoin, primidone, and phenobarbital were adjusted to therapeutic ranges. Three patients had additional medication (diazepam, ethosuximide). Cerebellar biopsy in three patients showed reduction in Purkinje cells. After implantation of cerebellar stimulators, seizure frequency was evaluated in hospital during three or four admissions for 4- to 6-wks' periods over the ensuing 15 to 21 months. No slow trends toward improvement or deterioration were noted. No significant differences in seizure frequency were found when comparing intervals of about 7 days of on-and-off stimulation both in the double-blind and unblinded conditions. No changes in EEG or Intelligence or Memory Quotients occurred unaccounted for by variations in serum levels of antiepileptic drugs. Despite the lack of objective improvement, patient and family acceptance of cerebellar stimulation was positive to enthusiastic. A rise in CSF norepinephrine and a fall in gamma aminobutyric acid (GABA) accompanied cerebellar stimulation and may be related to the results.
    Journal of Neurosurgery 04/1978; 48(3):407-16. DOI:10.3171/jns.1978.48.3.0407 · 3.74 Impact Factor
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