Implanted neurostimulation devices are gaining traction as palliative treatment options for certain forms of drug-resistant epilepsy, but clinical utility of these devices is hindered by incomplete mechanistic understanding of their therapeutic effects. Approved devices for anterior thalamic nuclei deep brain stimulation (ANT DBS) are thought to work at a network level, but limited sensing capability precludes characterization of neurophysiological effects outside the thalamus. Here, we describe a patient with drug-resistant temporal lobe epilepsy who was implanted with a responsive neurostimulation device (RNS System), involving hippocampal and ipsilateral temporal neocortical leads, and subsequently received ANT DBS. Over 1.5 years, RNS System electrocorticography enabled multiscale characterization of neurophysiological effects of thalamic stimulation. In brain regions sampled by the RNS System, ANT DBS produced acute, phasic, frequency-dependent responses, including suppression of hippocampal low frequency local field potentials. ANT DBS modulated functional connectivity between hippocampus and neocortex. Finally, ANT DBS progressively suppressed hippocampal epileptiform activity in relation to the extent of hippocampal theta suppression, which informs stimulation parameter selection for ANT DBS. Taken together, this unique clinical scenario, involving hippocampal recordings of unprecedented chronicity alongside ANT DBS, sheds light on the therapeutic mechanism of thalamic stimulation and highlights capabilities needed in next-generation devices.
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| http://dx.doi.org/10.1016/j.ebr.2021.100467 | DOI Listing |
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Objective: Stereotactic neuromodulation, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have emerged as some of the more promising means for managing drug-resistant epilepsy. This study serves as a comprehensive analysis of DBS of the anterior nucleus of the thalamus (ANT), centromedian thalamic nucleus (CMT), and hippocampus and RNS for seizure reduction in adult intractable epilepsy.
Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted of PubMed, Cochrane Library, and Embase databases from January 2000 to January 2024 to objectively assess the effectiveness of the various neuromodulation modalities on seizure reduction.
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From the Department of Neurology and Neurological Sciences (R.M., E.L.V.S., Z.L., S.N., M.D.-G., R.S.F., J.P.) and Department of Neurosurgery (A.D., V.B.), Stanford University School of Medicine; Department of Neurology (R.M.), University of Southern California, Los Angeles; and California Pacific Medical Center (T.W.), San Francisco.
Background And Objectives: Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has been shown to be effective in treating some patients with medically refractory epilepsy. However, it remains unknown how seizures spread through the ANT relative to other thalamic nuclei. This study aimed to investigate, through simultaneous recordings from both ANT and pulvinar (PLV) nucleus, their roles in seizure propagation.
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Department of Neurology, University of Arizona, Banner University Medical Center, Phoenix, AZ, USA.
Purpose: Anterior nucleus of the thalamus (ANT) is the only deep brain stimulation (DBS) target that is approved by the FDA for treatment of drug-resistant epilepsy (DRE). Hippocampus (HC) and centromedian nucleus (CMN) have been reported as potential DBS targets for DRE. This study aimed to assess the effectiveness and predictors of response among DRE patients treated with DBS in general and among ANT, HC and CMN DBS-targets.
View Article and Find Full Text PDFDeep brain stimulation mitigates memory deficits in a rodent model of traumatic brain injury.
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December 2024
Sunnybrook Research Institute, Toronto, ON, Canada; Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada. Electronic address:
Article Synopsis
- Traumatic brain injury (TBI) can lead to long-term deficits in attention and memory, and deep brain stimulation (DBS) is being explored as a potential therapy for improving these cognitive impairments.* -
- The study tested whether early DBS after TBI in male rats can prevent memory decline and promote neuroprotection by evaluating behavioral tests and measuring brain cell health and neurotrophic factors.* -
- Results showed that while DBS improved performance in some maze tests and increased levels of BDNF and hippocampal cell counts, it did not significantly enhance memory in other tests or reduce inflammatory cytokine levels in the brain.*
Combination of or Transition between Deep Brain Stimulation and Responsive Neurostimulation for the Treatment of Drug-Resistant Epilepsy.
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Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Introduction: Neuromodulation is an important treatment modality for patients with drug-resistant epilepsy who are not candidates for resective or ablative procedures. However, randomized controlled trials and real-world studies reveal that a subset of patients will experience minimal reduction or even an increase in seizure frequency after neuromodulation. We describe our experience with patients who undergo a second intracranial neuromodulation procedure after unsatisfactory initial response to intracranial neuromodulation.
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