Deep Brain Stimulation for Arm Tremor: A Randomized Trial Comparing Two Targets

Objective: Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra-individual efficacy of VIM- versus PSA-DBS on tremor suppression and arm function.

Methods: We performed a randomized, double-blind, crossover trial at Oslo University Hospital in patients (18-80 years) with isolated or combined action tremor affecting at least one arm. Four-contact DBS leads were implanted (bi- or unilaterally) with a trajectory to cover the VIM (upper two contacts) and PSA (lower two contacts). Patients were randomized (1:1 ratio) post-surgery to: Group 1, VIM-stimulation months 0-3 (period 1), then PSA-stimulation months 4-6 (period 2); Group 2, PSA-stimulation first, then VIM-stimulation. Primary endpoint was the difference in improvement from baseline to the end of the VIM- versus PSA-period in the sum of the dominant arm tremor scores of the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), items 5/6 + 10-14.

Results: Forty-five patients were randomized to Group 1 (n = 23) or 2 (n = 22). In the primary endpoint per-protocol analysis (mixed model, n = 40), mean difference in the sum FTMTRS score improvement for the dominant arm was -2.65 points (95% CI -4.33 to -0.97; p = 0.002). The difference in favour of PSA stimulation was highly significant in period 2, but not period 1.

Interpretation: Our randomized trial demonstrated that PSA stimulation provided superior tremor suppression compared with VIM stimulation. A period effect reducing tremor for up to three months in both groups was most likely attributed to a post-surgery stun effect. ANN NEUROL 2022;91:585-601.