Executive Functions May Predict Outcome in Deep Brain Stimulation of Anterior Nucleus of Thalamus for Treatment of Refractory Epilepsy

Abstract

BackgroundDeep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an emerging treatment option for patients suffering from refractory epilepsy. ANT has extensive connections with hippocampus and retrosplenial cingulum, areas associated mainly with spatial memory and with anterior cingulum which is important in executive functions. As refractory epilepsy is often associated with cognitive decline and neuronal damage, the decreased connectivity between ANT and remote structures might impact on the effects of DBS.ObjectiveWe hypothesized that the neuropsychological profile could reflect the connectivity of ANT and further predict the efficacy of ANT DBS. We evaluated the cognitive performance of patients with refractory epilepsy with DBS to evaluate whether neuropsychological profiles could reflect the connectivity of ANT and further predict the efficacy of ANT DBS.MethodSixteen patients with refractory epilepsy treated with ANT DBS with at least 2 years of follow-up were included in the study. Patients underwent a neuropsychological evaluation as a part of the protocol and their clinical outcome was determined by seizure frequency in the last 6 months compared to baseline. The patients were classified as responders if there was a ≥50% reduction in the frequency of the predominant seizure type, otherwise as nonresponders.ResultsThere were 12 responders and 4 nonresponders for ANT DBS treatment in the study population. Nonresponders performed worse than responders in neuropsychological tasks measuring executive functions and attention, such as the Trail-Making Test.ConclusionBetter executive functions and attention seemed to predict improved clinical outcome after the ANT DBS surgery. Based on our preliminary descriptive findings and the anatomical connectivity hypothesis, we suggest that deficits in executive functions may relate to an inferior outcome. This finding might offer new tools for refining the selection of patients with refractory epilepsy scheduled to undergo ANT DBS surgery. Moreover, it highlights the need for further investigations of neural connectivity in epilepsy.

Improving the effectiveness of ANT DBS therapy for epilepsy with optimal current targeting

“…This might have caused a selection bias that might explain the relatively high amount of SUDEP in our study, as included has been patients with a significant seizure load over time, a matter that is often associated with cognitive decline and neuronal damage 36 . These changes might lead to decreased connectivity between ANT and remote structures, which might impact on the effects of DBS 37 . Thus, ANT DBS should not be used as a last resort therapy, but to be considered in the early stages of refractory epilepsy.…”

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus

“…8 However, it is not known whether the anticonvulsant activity of the ANT-DBS varies by subregions or whether adjacent thalamic nuclei that receive the DBS current spread from the ANT could participate in the antiseizure effect. 9 The exact location of the stimulating lead, 10 the desynchronization of the ipsilateral hippocampal activity by ANT-DBS, 11 the neuropsychological profile probably reflecting large-scale networks, 12 the frequency of thalamic interictal epileptiform discharges, 13 and local single cell firing patterns in the ANT have been reported to have a relation to the ANT-DBS response. 14 We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of DBS.…”

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

“…During the first survey round, no consensus was achieved on the parameters that could improve ANT-DBS therapy outcome, including [42] PATIENTS PREDICTORS Age at seizure onset [42] Age at seizure onset [26] -Age at the time of ANT-DBS implantation [26,42] -Disease duration from the age of seizure onset to age at the time of ANT-DBS [26,42] Temporal lobe epilepsy [17,18,43] Seizure aetiology [26] Sex [42] Normal MRI without structural abnormality [43] Normal MRI without structural abnormality [42] Partial seizures or secondarily generalized seizures [42] Less impaired patients [21] Lateralized EEG abnormalities (TLE) [42] Prior surgery / VNS treatment [17,18] Note: studies listed in Table 1 included different numbers of patients, thus a direct comparison might be inaccurate. different electrode target positions, micro-electrode guided implantation, awake implantation, and ictal side treatment.…”

“…Although ANT-DBS treatment is a safe and effective treatment for DRE patients, predictors for positive outcome are still scarce. Previous reports suggested that defined electrode location within the ANT [28,31], temporal epilepsy syndromes [17,18,29,42,43] especially with later age at disease onset, lateralized EEG abnormalities, and ictal side treatment [42], patients with limited impairment [21], as well as positive performance in executive function tests [45] might be associated with a favourable outcome. Accordingly, the EP members approved ANT-DBS treatment in DRE patients with TLE who are no candidates for resective surgery and those who did not sufficiently benefit from resection/VNS therapy.…”

“…The concept of DBS targeting the anterior thalamic nuclei (ANT-DBS) as a treatment of DRE has been examined with positive results in the studies of Cooper et al [14,15] and Upton et al [16], the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) randomized controlled trial [17,18] and a series of open-label clinical studies [19][20][21][22][23][24][25][26][27][28][29][30][31]. With the SANTE study, ANT-DBS has obtained Class I evidence and a CE mark as adjunctive treatment for reducing the frequency of focal onset seizures of adults with DRE in Europe [32] and FDA approval in the United States since April 2018 [33].…”