Objective: To investigate the effects of GPi-DBS on brain glucose metabolism locally at the stimulation site and across the whole brain in patients with cervical dystonia.

Background: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but the mechanism of action is not fully understood.

Method: Eleven cervical dystonia patients with GPi-DBS underwent brain ¹⁸F-fluorodeoxyglucose PET imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the stimulation site and voxel-by-voxel across the whole brain. Clinical symptom severity in each condition and overall treatment response were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).

Results: The mean (SD) best treatment response to DBS during the treatment was 81 (22)% [TWSTRS severity scale mean (SD) decrease 12 (5.4) points]. The TWSTRS score was 3.2 (3.9) points lower DBS on compared to DBS off (p=0.02). At the stimulation site in the GPi, stimulation was associated with increased glucose metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03). However, metabolic activation at the stimulation site did not correlate with acute change in motor symptom severity or overall therapeutic response (p>0.9). In the whole brain analysis, stimulation increased glucose metabolism in the GPi, subthalamic nucleus, putamen, primary somatosensory cortex and primary motor cortex (P_FDR<0.05). Acute change in symptom severity correlated with increase in glucose metabolism in the sensorimotor cortex and overall treatment response in the supplementary motor area (P_FDR<0.05).

Conclusion: The results provide direct support for the hypothesis that GPi-DBS activates a sensorimotor brain network, and that its clinical efficacy is mediated through activation of the remote nodes of this network rather than local effects at the stimulation site. Our findings lend insight into the mechanism of action of GPi-DBS in cervical dystonia and may help to identify new treatment targets that could also be reached using noninvasive brain stimulation.

This abstract has been presented previously on March 7, 2022 at 2nd Expert Summit on the Future of Deep Brain Stimulation, Wurzburg, Germany.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gpi-dbs-induced-brain-metabolic-activation-in-cervical-dystonia/