Responsive Thalamic Neurostimulation: A Systematic Review of a Promising Approach for Refractory Epilepsy

Abstract

IntroductionResponsive neurostimulation is an evolving therapeutic option for patients with treatment-refractory epilepsy. Open-loop, continuous stimulation of the anterior thalamic nuclei is the only approved modality, yet chronic stimulation rarely induces complete seizure remission and is associated with neuropsychiatric adverse effects. Accounts of off-label responsive stimulation in thalamic nuclei describe significant improvements in patients who have failed multiple drug regimens, vagal nerve stimulation, and other invasive measures. This systematic review surveys the currently available data supporting the use of responsive thalamic neurostimulation in primary and secondary generalized, treatment-refractory epilepsy.Materials and MethodsA systematic review was performed using the following combination of keywords and controlled vocabulary: (“Seizures”[Mesh] AND “Thalamus”[Mesh] AND “Deep Brain Stimulation”[Mesh]) OR (responsive neurostim* AND (thalamus[MeSH])) OR [responsive neurostimulation AND thalamus AND (epilepsy OR seizures)]. In addition, a search of the publications listed under the PubMed “cited by” tab was performed for all publications that passed title/abstract screening in addition to manually searching their reference lists.ResultsTen publications were identified describing a total of 29 subjects with a broad range of epilepsy disorders treated with closed-loop thalamic neurostimulation. The median age of subjects was 31 years old (range 10–65 years). Of the 29 subjects, 15 were stimulated in the anterior, 11 in the centromedian, and 3 in the pulvinar nuclei. Excluding 5 subjects who were treated for 1 month or less, median time on stimulation was 19 months (range 2.4–54 months). Of these subjects, 17/24 experienced greater than or equal to 50%, 11/24 least 75%, and 9/24 at least 90% reduction in seizures. Although a minority of patients did not exhibit significant clinical improvement by follow-up, there was a general trend of increasing treatment efficacy with longer periods on closed-loop thalamic stimulation.ConclusionThe data supporting off-label closed-loop thalamic stimulation for refractory epilepsy is limited to 29 adult and pediatric patients, many of whom experienced significant improvement in seizure duration and frequency. This encouraging progress must be verified in larger studies.

Escaping the Procrustean Bed: A Perspective on Pediatric Stereoelectroencephalography

“…Specifically, neuromodulatory options in otherwise poor surgical candidates have become frequent indications for SEEG. [26][27][28]…”

Using chronic recordings from a closed‐loop neurostimulation system to capture seizures across multiple thalamic nuclei

“…Closed‐loop stimulation has also been used to target thalamic nuclei and, generally, either bilateral CMT or bilateral ANT have been targeted. 5 , 6 …”

“…Closed-loop stimulation has also been used to target thalamic nuclei and, generally, either bilateral CMT or bilateral ANT have been targeted. 5,6 We present a patient with evidence of unilateral, broad fronto-temporal onset seizures that secondarily generalize in whom we implanted a closed-loop Responsive Neurostimulation System (RNS; Neuropace, Mountainview, CA) with leads spanning and stimulating multiple thalamic nuclei. The nuclei include the targeted ANT and CMT and the adjacent mediodorsal nucleus (MD) and pulvinar on the left side.…”

“…These trials have largely employed continuous or cycled open‐loop stimulation with current deep brain stimulation (DBS) systems, meaning no aspect of the ongoing target region activity is assessed before stimulation and stimulation is not adjusted according to that ongoing activity. Closed‐loop stimulation has also been used to target thalamic nuclei and, generally, either bilateral CMT or bilateral ANT have been targeted 5,6 …”