Thalamic organization in essential tremor patients with neuropathy: implication for functional neurosurgery

Background Mechanisms underlying the suboptimal effect of ventral intermediate nucleus deep brain stimulation in patients with essential tremor and co-morbid peripheral neuropathy remain unclear. Objectives We compared disease-related (location and extension of the ventral intermediate nucleus) and surgery-related (targeting, intraoperative testing) factors in essential tremor patients with and without peripheral polyneuropathy treated with deep brain stimulation of the ventral intermediate nucleus, testing whether the overlap between volume of tissue activated and ventral intermediate nucleus (target coverage) was associated with clinical outcomes. Methods Preoperative diffusion magnetic resonance imaging was used for thalamic segmentation, based on preferential cortical connectivity. The target coverage was estimated using a finite element model. Tremor severity was scored at rest, posture, action, and handwriting at baseline, 6, and 12 months. Tremor improvement <50% at 12 months was deemed suboptimal. Vertex-wise shape analysis and edge analysis were performed to compare the ventral intermediate nucleus location and extension. Results 9.7% (18/185) of essential tremor patients treated with deep brain stimulation had co-morbid polyneuropathy. These patients showed a more medial (p=0.03) and anterior (p=0.04) location of the ventral intermediate nucleus, lower target coverage (p=0.049), and worse clinical outcomes (p=0.006) compared to those without polyneuropathy. No differences were observed in the volume of tissue activated between the two groups. Optimal clinical outcomes were associated with greater target coverage (optimal coverage >48%). Conclusions In essential tremor, co-morbid polyneuropathy may result in suboptimal deep brain stimulation outcomes and lower target coverage, likely related to a reorganization of the ventral thalamic nuclei.