Enhancing Asleep Deep Brain Stimulation Targeting for Essential Tremor Using Machine Learning: The OPTIVIM Phase 2 Study.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) is an effective treatment of essential tremor, but the optimal target and how to reach it with the best accuracy remain controversial. The OptimDBS algorithm is based on Kernel Ridge Regression and was trained on a database of patients who underwent DBS with optimal postoperative outcomes. Using 3-dimensional T1-weighted MRI as the only input, it calculates the stereotactic coordinates of an effective DBS target for treating tremor. The aim of the study was to evaluate the efficacy and safety of OptimDBS-guided asleep DBS without peroperative clinical and electrophysiological controls in an independent cohort of patients. METHODS: The OPTIVIM study was a prospective, single-arm, multicenter Phase 2 trial. The primary outcome was tremor reduction and improvement in activities of daily living as assessed by the Fahn-Tolosa-Marin scale 3 months after surgery. Secondary outcomes included reduction in tremor amplitude on accelerometry, quality of life (modified Parkinson's Disease Questionnaire-39), ataxia (Scale for the Assessment and Rating of Ataxia), adverse events, and anatomic location of active contacts and the volume of tissue activated, all measured 3 months after surgery. RESULTS: Twenty-two patients from 2 centers were enrolled. Fahn-Tolosa-Marin scores improved by 61.3% (95% CI: 53.7%-68.9%). Accelerometry (mean ± SD) showed a reduction in postural tremor amplitude of 81% ± 56% on the right side and 84% ± 35% on the left side. Modified Parkinson's Disease Questionnaire-39 scores (median [Q1-Q3]) improved by 55% [24.3%-77.8%]. Scale for the Assessment and Rating of Ataxia scores remained stable (median [Q1-Q3], preoperative vs postoperative: 4 [3-6] vs 3 [2-6]). There were no serious adverse events. Active contacts were located in the posterior subthalamic area (59%) or the ventral-intermediate nucleus of the thalamus (20%), with 100% of volume of tissue activated overlapping the ventral-intermediate nucleus of the thalamus or posterior subthalamic area. CONCLUSION: The results of OptimDBS-guided asleep DBS seem to be comparable with those reported in the literature for awake and asleep DBS and ablative techniques. Long-term evaluations with larger cohorts are needed to confirm these results.