Anterior Nucleus of Thalamus Deep Brain Stimulation: A Clinical-Based Analysis of the Ideal Target in Drug-Resistant Epilepsy

Abstract

<b><i>Introduction:</i></b> Deep brain stimulation of the anterior nucleus of thalamus (ANT-DBS) is an approved procedure for drug-resistant epilepsy. However, the preferred location inside ANT is not well known. In this study, we investigated the relationship between stereotactical coordinates of stimulated contacts and clinical improvement, in order to define the ideal target for ANT-DBS. <b><i>Methods:</i></b> Individual contact’s coordinates were obtained in the Montreal Neurological Institute (MNI) 152 space, with the utilization of advanced normalization tools and co-registration of pre- and postoperative MRI and CT images in open-source toolbox lead-DBS with the “Atlas of the Human Thalamus.” Each contact’s pair was either classified as a responder (≥50% seizure reduction and absence of intolerable adverse effects) or nonresponder, with a minimum follow-up of 11 continuous months of stimulation. <b><i>Results:</i></b> A total of 19 contacts’ pairs were tested in 14 patients. The responder rate was 9 out of 14 patients (64.3%). In 4 patients, a change in contacts’ pairs was needed to achieve this result. A highly encouraging location inside ANT (HELIA) was delimited in MNI space, corresponding to an area in the anterior and inferior portion of the anteroventral (AV) nucleus, medially to the endpoint of the mammillothalamic tract (ANT-mtt junction) (<i>x</i> [3.8; 5.85], <i>y</i> [−2.1; −6.35] and <i>z</i> [6.2; 10.1] in MNI space). Statistically significant difference was observed between responders and nonresponders, in terms of the number of coordinates inside this volume. Seven responders and two nonresponders had at least 5 of 6 coordinates (2 electrodes) inside HELIA (77.8% sensitivity and 80% specificity). In 3 patients, changing to contacts that were better placed inside HELIA changed the status from nonresponder to responder. <b><i>Conclusions:</i></b> A relationship between stimulated contacts’ coordinates and responder status was observed in drug-resistant epilepsy. The possibility to target different locations inside HELIA may help surpass anatomical variations and eventually obtain increased clinical benefit.

Deep brain stimulation of anterior nucleus and centromedian nucleus of thalamus in treatment for drug-resistant epilepsy

“…In the studies which followed the SANTE trial, the median seizure frequency reduction ranged from 50% to as much as 80.3%, with a responder rate exceeding 70-80% of patients [18,21,22,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. The outcomes of ANT DBS studies are set out in Table 1.…”

“…Although the evidence for the clinical effectiveness of VNS and DBS exists, the exact mechanisms of action remain unexplained [37]. PET studies during VNS have shown increased cerebral bloodflow in the thalamus [44].…”