Loss of long-term benefit from VIM-DBS in essential tremor: A secondary analysis of repeated measurements

Abstract

Aims: Deep brain stimulation (DBS) in the ventral intermediate nucleus (Vim-DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long-term efficacy of Vim-DBS. This study aimed to explore whether Vim-DBS shows long-term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects. Methods: In a repeated-measures meta-analysis of 533 patients from 18 studies, Vim-DBS efficacy was evaluated at ≤6 months, 7–12 months, 1–3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS; total score, motor score, hand-function score, and activities of daily living [ADL] score). Secondary outcomes were the long-term predictive factors. Results: The TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand-function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long-term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand-function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long-term results. Conclusion: This study provides level 3a evidence that long-term Vim-DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.