Case Report: Responsive Neurostimulation of the Centromedian Thalamic Nucleus for the Detection and Treatment of Seizures in Pediatric Primary Generalized Epilepsy.
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SUBMITTER: Welch WP
PROVIDER: S-EPMC8113700 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20-30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.
| S-EPMC9381751 | biostudies-literature
Project description:Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2-11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation.
| S-EPMC8608991 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment.MethodsThe baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified.ResultsTwenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy.SignificanceThis case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.
| S-EPMC8483259 | biostudies-literature
Project description:Seizures have traditionally been considered hypersynchronous excitatory events and epilepsy has been separated into focal and generalized epilepsy based largely on the spatial distribution of brain regions involved at seizure onset. Epilepsy, however, is increasingly recognized as a complex network disorder that may be distributed and dynamic. Responsive neurostimulation (RNS) is a recent technology that utilizes intracranial electroencephalography (EEG) to detect seizures and delivers stimulation to cortical and subcortical brain structures for seizure control. RNS has particular significance in the clinical treatment of medically refractory epilepsy and brain-computer interfaces in epilepsy. Closed loop RNS represents an important step forward to understand and target nodes in the seizure network. The thalamus is a central network node within several functional networks and regulates input to the cortex; clinically, several thalamic nuclei are safe and feasible targets. We highlight the network theory of epilepsy, potential targets for neuromodulation in epilepsy and the first reported use of RNS as a first generation brain-computer interface to detect and stimulate the centromedian intralaminar thalamic nucleus in a patient with bilateral cortical onset of seizures. We propose that advances in network analysis and neuromodulatory techniques using brain-computer interfaces will significantly improve outcomes in patients with epilepsy. There are numerous avenues of future direction in brain-computer interface devices including multi-modal sensors, flexible electrode arrays, multi-site targeting, and wireless communication.
| S-EPMC6079216 | biostudies-literature
Project description:The centromedian (CM) nucleus is an intralaminar thalamic nucleus that is considered as a potentially effective target of deep brain stimulation (DBS) and ablative surgeries for the treatment of multiple neurological and psychiatric disorders. However, the structure of CM is invisible on the standard T1- and T2-weighted (T1w and T2w) magnetic resonance images, which hamper it as a direct DBS target for clinical applications. The purpose of the current study is to demonstrate the use of quantitative susceptibility mapping (QSM) technique to image the CM within the thalamic region. Twelve patients with Parkinson's disease, dystonia, or schizophrenia were included in this study. A 3D multi-echo gradient recalled echo (GRE) sequence was acquired together with T1w and T2w images on a 3-T MR scanner. The QSM image was reconstructed from the GRE phase data. Direct visual inspection of the CM was made on T1w, T2w, and QSM images. Furthermore, the contrast-to-noise ratios (CNRs) of the CM to the adjacent posterior part of thalamus on T1w, T2w, and QSM images were compared using the one-way analysis of variance (ANOVA) test. QSM dramatically improved the visualization of the CM nucleus. Clear delineation of CM compared to the surroundings was observed on QSM but not on T1w and T2w images. Statistical analysis showed that the CNR on QSM was significantly higher than those on T1w and T2w images. Taken together, our results indicate that QSM is a promising technique for improving the visualization of CM as a direct targeting for DBS surgery.
| S-EPMC6962173 | biostudies-literature
Project description: Not available
| S-EPMC8327384 | biostudies-literature
Project description:Responsive neurostimulation (RNS) is an effective therapy for people with drug-resistant focal epilepsy. In clinical trials, RNS therapy results in a meaningful reduction in median seizure frequency, but the response is highly variable across individuals, with many receiving minimal or no benefit. Understanding why this variability occurs will help improve use of RNS therapy. Here we advocate for a reexamination of the assumptions made about how RNS reduces seizures. This is now possible due to large patient cohorts having used this device, some long-term. Two foundational assumptions have been that the device's intracranial leads should target the seizure focus/foci directly, and that stimulation should be triggered only in response to detected epileptiform activity. Recent studies have called into question both hypotheses. Here, we discuss these exciting new studies and suggest future approaches to patient selection, lead placement, and device programming that could improve clinical outcomes.
| S-EPMC10654422 | biostudies-literature
Project description:BackgroundEpilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a 'cold-spot' and a 'sweet-spot', which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation.ObjectiveWe investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients.MethodsBy using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups.ResultsThe sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders.ConclusionCerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy.
| S-EPMC10563482 | biostudies-literature
Project description:Autoimmune encephalitis (AE) frequently presents with seizures in the acute setting. Seizures are often refractory to anti-seizure medications (ASM) but have been shown to be responsive to immunomodulatory therapies. A subset of patients with AE continues to have refractory epilepsy, recently named "autoimmune-associated epilepsy (AAE)," for years after the acute AE presentation. Optimal treatment for AAE has not been determined. Furthermore, the efficacy of neuromodulation and immunotherapy has not been well established in AAE. Here, we report a patient with probable autoantibody negative AE who initially presented with new onset refractory status epilepticus (NORSE). After his acute presentation, he continued to have frequent seizures that were refractory to four ASMs at therapeutic doses. A responsive neurostimulation (RNS®, NeuroPace) system was implanted for diagnostic and therapeutic purposes, with minimal change in seizure frequency. Due to continued frequent seizures despite ASMs and neurostimulation, he underwent a trial of immunotherapy consisting of high-dose intravenous (IV) corticosteroids and intravenous immunoglobulin (IVIG). Despite the addition of immunotherapy to his treatment regimen, the patient experienced no significant clinical or electrographic change in seizure frequency. This case does not support the use of immunotherapy for treatment of AAE and illustrates the need for consensus guidelines in the management of patients with AAE. Further, the use of electrocorticography (ECoG) data provided an objective surrogate measure of seizure frequency; this may support the role for early neuromodulation in the management of AAE.
| S-EPMC9666681 | biostudies-literature
Project description:Responsive neurostimulation is a promising treatment for drug-resistant focal epilepsy; however, clinical outcomes are highly variable across individuals. The therapeutic mechanism of responsive neurostimulation likely involves modulatory effects on brain networks; however, with no known biomarkers that predict clinical response, patient selection remains empiric. This study aimed to determine whether functional brain connectivity measured non-invasively prior to device implantation predicts clinical response to responsive neurostimulation therapy. Resting-state magnetoencephalography was obtained in 31 participants with subsequent responsive neurostimulation device implantation between 15 August 2014 and 1 October 2020. Functional connectivity was computed across multiple spatial scales (global, hemispheric, and lobar) using pre-implantation magnetoencephalography and normalized to maps of healthy controls. Normalized functional connectivity was investigated as a predictor of clinical response, defined as percent change in self-reported seizure frequency in the most recent year of clinic visits relative to pre-responsive neurostimulation baseline. Area under the receiver operating characteristic curve quantified the performance of functional connectivity in predicting responders (≥50% reduction in seizure frequency) and non-responders (<50%). Leave-one-out cross-validation was furthermore performed to characterize model performance. The relationship between seizure frequency reduction and frequency-specific functional connectivity was further assessed as a continuous measure. Across participants, stimulation was enabled for a median duration of 52.2 (interquartile range, 27.0-62.3) months. Demographics, seizure characteristics, and responsive neurostimulation lead configurations were matched across 22 responders and 9 non-responders. Global functional connectivity in the alpha and beta bands were lower in non-responders as compared with responders (alpha, pfdr < 0.001; beta, pfdr < 0.001). The classification of responsive neurostimulation outcome was improved by combining feature inputs; the best model incorporated four features (i.e. mean and dispersion of alpha and beta bands) and yielded an area under the receiver operating characteristic curve of 0.970 (0.919-1.00). The leave-one-out cross-validation analysis of this four-feature model yielded a sensitivity of 86.3%, specificity of 77.8%, positive predictive value of 90.5%, and negative predictive value of 70%. Global functional connectivity in alpha band correlated with seizure frequency reduction (alpha, P = 0.010). Global functional connectivity predicted responder status more strongly, as compared with hemispheric predictors. Lobar functional connectivity was not a predictor. These findings suggest that non-invasive functional connectivity may be a candidate personalized biomarker that has the potential to predict responsive neurostimulation effectiveness and to identify patients most likely to benefit from responsive neurostimulation therapy. Follow-up large-cohort, prospective studies are required to validate this biomarker. These findings furthermore support an emerging view that the therapeutic mechanism of responsive neurostimulation involves network-level effects in the brain.
| S-EPMC9123848 | biostudies-literature