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Abstract
Background Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia.
Methods Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson’s Disease Rating Scale (UPDRS).
Results The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (PFDR<0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen.
Conclusions GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.
- MOVEMENT DISORDERS
- DYSTONIA
- PET, FUNCTIONAL IMAGING
Data availability statement
Data are available on reasonable request. The result maps are available from the corresponding author on request. The individual patient data cannot be made publicly available according to the institutional regulations and national legislation.
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Data availability statement
Data are available on reasonable request. The result maps are available from the corresponding author on request. The individual patient data cannot be made publicly available according to the institutional regulations and national legislation.
Footnotes
Twitter @EmmaHonkanen, @JJoutsa
Contributors EAH, MMR and JJ designed the study. EAH, JR, EP, MK, OE and JJ collected the data. EAH, JA, HE, MMR and JJ analysed the data. All authors took part in the interpretation of the results. EAH and JJ wrote the first draft. All authors critically revised the paper and approved the final version. EAH and JJ are guarantors of the work.
Funding The present work was supported by the Finnish Medical Foundation and Turku University Hospital (VTR-funds).
Competing interests The authors report no relevant competing interests. EAH was supported by The Finnish Parkinson Foundation, Turku University Foundation, The Finnish Medical Foundation and Turku University Hospital (VTR funds). EP is a member of the MDS Non-Motor Parkinson’s Disease Study Group, is a PI in Finland in International Adroit-study (Abbott DBS Registry of Outcomes for Indications over Time) and has received funding from Government research grant (TYH). HD was supported by the Nündel Foundation. JV reports grants and personal fees from Medtronic, grants and personal fees from Boston Scientific, personal fees from Abbott outside the submitted work. JV was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295). VK serves as an advisory board member of AbbVie, has received travel expenses from Nordic Infucare AB and research funding from the Finnish Alcohol Research Foundation, the Päivikki and Sakari Sohlberg Foundation, the International Parkinson and Movement Disorder Society, and Finnish governmental research funding (VTR). MMR reports grant support and honoraria for speaking from Medtronic and Boston Scientific, outside the submitted and was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295). JJ received grants from the Finnish Medical Foundation, Instrumentarium Research Foundation, Finnish Foundation for Alcohol Studies, University of Turku (Sigrid Juselius Foundation, Private Donation) and Turku University Hospital (ERVA funds), a congress travel grant from Abbott and Abbvie, lecturer honoraria from Lundbeck and Novartis, and consulting fees from Summaryx.
Provenance and peer review Not commissioned; externally peer reviewed.
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