Thalamic neuromodulation for epilepsy: A clinical perspective

Ilyas, Adeel; Tandon, Nitin; Lhatoo, Samden D.

doi:10.1016/j.eplepsyres.2022.106942

Cited by 9 publications

(9 citation statements)

References 56 publications

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“…Our results show that different thalamic sites are involved differently in the very early stage of seizure propagation. This agrees with the extant literature, where thalamic participation in the epileptogenic networks of focal epilepsies has been documented (Ilyas et al ., 2022; Piper et al .,2022). Pioneering past studies have shown increased synchrony between cortical and thalamic ictal activity in temporal lobe seizures, and that in a majority of cases the thalamic activity was driven by cortical activity (Guye et al ., 2006).…”

Section: Discussionsupporting

confidence: 93%

Multisite Thalamic Recordings to Characterize Seizure Propagation in the Human Brain

Kaboodvand

Veit

et al. 2022

Preprint

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Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in patients with refractory focal epilepsy, but it is not uniformly effective. One important uncertainty is to what extent thalamic subregions other than the ANT are recruited earlier and more prominently in the propagation of seizures in patients with presumed temporal lobe epilepsy (TLE). To address this unknown, we studied 11 patients with clinical manifestations of TLE planned to undergo invasive stereo-encephalography (sEEG) monitoring. We extended cortical electrodes to reach thalamic nuclear subdivisions in the anterior (ANT), middle (mediodorsal) and or posterior (pulvinar) sites. This multisite thalamic sampling was without any adverse events. Intracranial EEG (iEEG) recordings confirmed seizure onset in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, thereby highlighting the importance of iEEG for more accurate localization of seizure foci. Visual review of EEGs documented early and prominent involvement of specific thalamic sites. Seizures originating from the same brain origin produced a stereotyped thalamic EEG signature. Visual review of EEGs, validated with single-pulse corticothalamic evoked potentials, documented early and prominent involvement of thalamic sites that would have not been predicted given the anatomy of seizure onset zones. Pulvinar was involved earlier and more prominently than other sampled nuclear subgroups in 60% of patients, even though all patients had a presumed diagnosis of TLE prior to invasive monitoring. Our findings document the feasibility and safety of multisite sampling from the human thalamus and suggest that the anatomy of thalamic involvement may not be entirely predictable on the basis of clinical information or lobar localization of seizures. Future clinical trials can establish whether offering more personalized targets for thalamic neuromodulation will lead to greater meaningful improvements in outcome.

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Section: Discussionsupporting

confidence: 93%

Multisite Thalamic Recordings to Characterize Seizure Propagation in the Human Brain

Kaboodvand

Veit

et al. 2022

Preprint

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“…This analysis supports the hypothesis that thalamic neuromodulation remains a safe and effective treatment option for pediatric patients, in line with previous literature in this population comprised of small case studies and systematic reviews. [12][13][14][15]17 In our meta-analysis, 67% of all patients achieved a treatment response of at least a 50% reduction in baseline seizures, and 42% of patients experienced at least a 75% reduction in baseline seizures. When comparing thalamic target, age, and laterality, we found no significant association with seizure outcome among patients.…”

Section: Discussionmentioning

confidence: 70%

“…11 Multiple deep brain targets for stimulation have shown considerable promise in achieving therapeutic response in adult patients, namely the centromedian nucleus (CMN), anterior thalamic nucleus (ANT), subthalamic nucleus, hippocampus, zona incerta, posterolateral hypothalamus, and mammillothalamic tract. 11,12 Although not yet FDA-approved, several neurosurgical groups have explored neuromodulation in children with severe, refractory seizures. Single-center studies have reported promising outcomes, with a substantial percentage of patients achieving seizure reduction rates of >50%.…”

Section: Introductionmentioning

confidence: 99%

“…Neuromodulation techniques, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have emerged as a promising therapeutic approach for some drug‐resistant epilepsies 11 . Multiple deep brain targets for stimulation have shown considerable promise in achieving therapeutic response in adult patients, namely the centromedian nucleus (CMN), anterior thalamic nucleus (ANT), subthalamic nucleus, hippocampus, zona incerta, posterolateral hypothalamus, and mammillothalamic tract 11,12 . Although not yet FDA‐approved, several neurosurgical groups have explored neuromodulation in children with severe, refractory seizures.…”

Section: Introductionmentioning

confidence: 99%

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Predictors of therapeutic response following thalamic neuromodulation for drug‐resistant pediatric epilepsy: A systematic review and individual patient data meta‐analysis

Sharma,

Parfyonov,

Tiefenbach

et al. 2024

Epilepsia

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We sought to perform a systematic review and individual participant data meta‐analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug‐resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy‐four (84%) patients were implanted bilaterally. The median time to last follow‐up was 12 months (interquartile range = 6.75–26.25). Sixty‐nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

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“…The treatment of drug-resistant, intractable epilepsies has entered a new frontier with the use of thalamic neuromodulation (Ilyas et al, 2022 ). Early targeting of the anterior (ANT) nucleus with DBS used an open-loop stimulation approach to treat several types of intractable epilepsy ( Feigen and Eskandar ).…”

Section: Thalamic Neuromodulation For Intractable Epilepsies: a New F...mentioning

confidence: 99%

Editorial: All roads lead to Rome: Harnessing thalamic neuromodulation for difficult-to-treat neurological disorders

Watson

Kopell²

2023

Front. Hum. Neurosci.

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Thalamic neuromodulation for epilepsy: A clinical perspective

Cited by 9 publications

References 56 publications

Multisite Thalamic Recordings to Characterize Seizure Propagation in the Human Brain

Multisite Thalamic Recordings to Characterize Seizure Propagation in the Human Brain

Predictors of therapeutic response following thalamic neuromodulation for drug‐resistant pediatric epilepsy: A systematic review and individual patient data meta‐analysis

Editorial: All roads lead to Rome: Harnessing thalamic neuromodulation for difficult-to-treat neurological disorders

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