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. 2025 Feb 14;143(1):53-62.
doi: 10.3171/2024.10.JNS24753. Print 2025 Jul 1.

Connectomic-guided stereotactic radiosurgery thalamotomy for tremor: a patient-specific approach to enhance outcomes

Erik H Middlebrooks  1   2 , Vishal Patel  1 , Richard A Popple  3 , Harrison C Walker  4 , Evan M Thomas  3   5 , Sarah A Brinkerhoff  4 , Ashley R Anderson  3 , Hrishikesh D Deshpande  6 , Benjamin A McCullough  4 , Natividad P Stover  4 , Victor W Sung  4 , Anthony P Nicholas  4 , David G Standaert  4 , Talene Yacoubian  4 , Marissa N Dean  4 , Jaimie A Roper  7 , Sanjeet S Grewal  2 , Marshall T Holland  8 , J Nicole Bentley  8 , Barton L Guthrie  8 , Markus Bredel  3
Affiliations

Connectomic-guided stereotactic radiosurgery thalamotomy for tremor: a patient-specific approach to enhance outcomes

Erik H Middlebrooks et al. J Neurosurg. .

Abstract

Objective: Stereotactic radiosurgery (SRS) is an effective treatment for refractory tremor. However, the lack of reliable patient-specific targeting biomarkers leads to varying outcomes. Although connectomic-based targeting is commonly used in deep brain stimulation, its application in SRS is limited. This study aimed to develop a new targeting approach by using patient-specific structural connectivity to improve outcomes after SRS.

Methods: The authors performed a retrospective study of patients in a prospective trial for frameless virtual-cone SRS on a linear accelerator for essential tremor or tremor-dominant Parkinson disease. The primary endpoint was percentage improvement in Fahn-Tolosa-Marin tremor rating scale scores contralateral to the treatment side. Probabilistic tractography assessed connectivity from each thalamic voxel to the primary motor cortex (M1), primary sensory cortex (S1), and supplemental motor area/premotor cortex (SMA/PMC). Group-level comparisons were conducted to evaluate the relationship between the sweet spot for maximum contralateral tremor improvement and areas maximally connected to M1, S1, and SMA/PMC. Multiple regression analysis assessed the relationship between the lesion centerpoint coordinates and the maximally connected voxel to M1, S1, and SMA/PMC at the individual level.

Results: The analysis included 27 patients with a mean follow-up of 17.9 ± 11.1 months. The sweet spot for maximal contralateral tremor improvement at the group level was in the region most connected to M1 cortex. Smaller y-distances (anterior-posterior) from the lesion center to the M1 maximally connected voxel significantly correlated with tremor improvement at the single-subject level (p < 0.001). However, the authors found no significant correlation between the lesion y-coordinate and the maximally connected voxel to SMA/PMC and S1, nor between the x-distances from the lesions to the SMA/PMC, M1, and S1 voxels (p > 0.07).

Conclusions: This study demonstrates that patient-specific connectivity between the treatment target and M1 correlates with treatment outcomes. The authors' approach provides a practical targeting method for SRS thalamotomy for tremor.

Keywords: Parkinson disease; connectomics; functional neurosurgery; radiosurgery; thalamotomy; tremor.

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