ANT-DBS in epilepsy shows no effect on selected neuropsychiatric tests.

OBJECTIVES: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) is an established option in treatment-resistant epilepsy and obtained FDA approval in 2018. Increased psychiatric comorbidity is well known in epilepsy. The main objective of this study was to investigate possible neuropsychiatric treatment-related changes in patients receiving ANT-DBS. MATERIALS AND METHODS: Bilateral ANT electrodes were implanted in 18 adult patients with refractory epilepsy in a randomized, double-blinded study. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the next six months (open phase), both groups received active stimulation. Neuropsychiatric assessment was conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). RESULTS: Comparing preoperative status (T1) and 12 months (T3), postoperative outcome in all patients did not show significant differences between the two groups for any of the applied tests. Groupwise comparisons across the two first time points (the blinded period, representing the randomized controlled trial) showed no significant differences between the two groups in any of the neuropsychiatric parameters studied. Comparing test results after 6 months of stimulation in both groups (sum of ON group T1 to T2 and OFF group T2 to T3) did not show significant changes for any of the psychiatric assessments. CONCLUSIONS: Our results indicate that ANT-DBS has limited effect concerning psychiatric issues. Subjective side effects were, however, reported in individual patients.

Cognitive change after DBS in refractory epilepsy: A randomized-controlled trial.

OBJECTIVES: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) reduces seizure frequency in patients with refractory epilepsy. There are, however, few studies on treatment-related changes in cognitive functions. The main objective of this study was to investigate cognitive changes in patients receiving ANT-DBS. We also explored whether possible effects were related to stimulation duration and whether change in seizure frequency was associated with cognitive changes. MATERIALS AND METHODS: Bilateral ANT electrodes were implanted in 18 patients with refractory epilepsy, aged 18-52 years. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the following 6-month open phase, both groups received stimulation. Neuropsychological assessments were conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). RESULTS: Groupwise comparisons across the three time points revealed changes in performance in two of 22 cognitive test scores: motor speed and sustained attention. We found no significant group differences in cognitive change from T1 to T2. Patients reported fewer symptoms of executive dysfunction after 12 months of stimulation. Patients showing significant improvement in seizure frequency had better performance in a measure of verbal learning. CONCLUSION: Our results indicate that ANT-DBS has very limited effects on cognitive functioning, as measured by formal tests after 6- or 12-month stimulation. ANT-DBS may have a positive influence on executive function. Our findings provide limited support for an association between change in seizure frequency and cognitive functioning.

Direct visual targeting versus preset coordinates for ANT-DBS in epilepsy.

OBJECTIVES: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) may be used against refractory focal epilepsy, but only two randomized double-blinded trials have been performed. The Oslo study was discontinued prematurely since reduction in seizure frequency was less than expected. The aim of the present study was to review the targeting used in the Oslo study and to identify the actual positions of the contacts used for stimulation. MATERIAL AND METHODS: BrainLab MRI data were available from 12 Oslo study patients. Based on MRI the coordinates of the center of the ANT were identified. The coordinates were considered as the visually identified preferred target and were compared with the target originally used for ANT electrode implantation and with the actual electrode positions estimated from post-operative CT scans. RESULTS: We found considerable differences between the visually identified preferred target, the originally planned target, and the actual electrode position. The total distance between the active electrode position and the visually identified preferred target was on average 3.3 mm on the right and 2.9 mm on the left side. CONCLUSION: Indirect targeting based on preset coordinates may contribute to explain the modest effect of ANT-DBS on seizure frequency seen in the Oslo study. Observed differences between the center of the ANT and the actual electrode position may at least in part be explained by variations in position and size of the ANT. Direct identification of the target using better MRI imaging protocols is recommended for future ANT-DBS surgery.

Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study.

OBJECTIVES: The safety and effect on seizure frequency of anterior thalamic nucleus deep brain stimulation were studied in this prospective, randomized, double-blinded study. Patients were followed for 12 months. The first 6 months were blinded with regard to active stimulation or not. After 6 months, all patients received active stimulation. MATERIAL AND METHODS: Bilateral ANT electrodes were implanted into 18 patients suffering from focal, pharmacoresistant epilepsy. Antiepileptic treatment was kept unchanged from three months prior to operation. The Liverpool seizure severity scale (LSSS) was used to measure the burden of epilepsy. RESULTS: There was no significant difference between the 2 groups at the end of the blinded period at 6 months. However, when considering all patients and comparing 6 months of stimulation with baseline, there was a significant, 22% reduction in the frequency of all seizures (P = 0.009). Four patients had ≥50% reduction in total seizure frequency and 5 patients ≥50% reduction in focal seizures after 6 months of stimulation. No increased effect over time was shown. LSSS at 6 months compared to baseline showed no significant difference between the 2 groups, but a small, significant reduction in LSSS was found when all patients had received stimulation for 6 months. CONCLUSIONS: Our study supports results from earlier studies concerning DBS as a safe treatment option, with effects even in patients with severe, refractory epilepsy. However, our results are not as encouraging as those reported from many other, mainly unblinded, and open studies.