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

Abstract

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

Converging on a Neuromodulation Target for Tremor

“…These papers each take a different approach, including a large retrospective analysis of DBS tremor outcomes by Nowacki and colleagues, 17 a neuroimaging marker that may identify the preferred tremor target in individual patients by Neudorfer and colleagues, 18 and a prospective randomized trial comparing the two tremor targets by Kvernmo and colleagues. 19 Remarkably, these three papers all agree that the optimal target for tremor is not the classic target in the VIM nucleus of the thalamus, but in the PSA, aligning with the location of white matter fibers connecting the cerebellum with the thalamus (Fig) . The first of these studies 17 performed the largest analysis of DBS electrode locations for tremor to date, including 119 patients from five European centers. Some centers targeted the VIM while others targeted the PSA, resulting in variability in lead location and tremor 19 They implanted a single DBS electrode to cover both the traditional VIM target (with dorsal contacts) and a more ventral/posterior target in the PSA.…”

“…19 Remarkably, these three papers all agree that the optimal target for tremor is not the classic target in the VIM nucleus of the thalamus, but in the PSA, aligning with the location of white matter fibers connecting the cerebellum with the thalamus (Fig) . The first of these studies 17 performed the largest analysis of DBS electrode locations for tremor to date, including 119 patients from five European centers. Some centers targeted the VIM while others targeted the PSA, resulting in variability in lead location and tremor 19 They implanted a single DBS electrode to cover both the traditional VIM target (with dorsal contacts) and a more ventral/posterior target in the PSA. Patients were randomized to one of the targets for the first 3 months, and then switched to the second target for the next 3 months.…”

“…Three papers in this issue of the ANNALS of NEUROLOGY add to our knowledge regarding the optimal DBS target for tremor. These papers each take a different approach, including a large retrospective analysis of DBS tremor outcomes by Nowacki and colleagues, 17 a neuroimaging marker that may identify the preferred tremor target in individual patients by Neudorfer and colleagues, 18 and a prospective randomized trial comparing the two tremor targets by Kvernmo and colleagues 19 . Remarkably, these three papers all agree that the optimal target for tremor is not the classic target in the VIM nucleus of the thalamus, but in the PSA, aligning with the location of white matter fibers connecting the cerebellum with the thalamus (Fig 1).…”

“…The third study by Kvernmo et al was a randomized double‐blind cross‐over trial of VIM versus PSA DBS in 45 patients with tremor 19 . They implanted a single DBS electrode to cover both the traditional VIM target (with dorsal contacts) and a more ventral/posterior target in the PSA.…”

Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia

“…Deep brain stimulation (DBS) of the ventralis intermedius nucleus (VIM) and subthalamic projections harboring the dentatothalamic tract (DTT) is highly effective in essential tremor (ET) ( 2 ). However, its effect in heredodegenerative ataxias associated with tremor such as spinocerebellar ataxias (SCA) or fragile X ataxia (FXTAS) remains poorly explored ( Table 1 ).…”