Abstract
Clinical benefits of pallidal deep brain stimulation (GPi DBS) in dystonia increase relatively slowly suggesting slow plastic processes in the motor network. Twenty-two patients with dystonia of various distribution and etiology treated by chronic GPi DBS and 22 healthy subjects were examined for short-latency intracortical inhibition of the motor cortex elicited by paired transcranial magnetic stimulation. The relationships between grey matter volume and intracortical inhibition considering the long-term clinical outcome and states of the GPi DBS were analysed. The acute effects of GPi DBS were associated with a shortening of the motor response whereas the grey matter of chronically treated patients with a better clinical outcome showed hypertrophy of the supplementary motor area and cerebellar vermis. In addition, the volume of the cerebellar hemispheres of patients correlated with the improvement of intracortical inhibition which was generally less effective in patients than in controls regardless of the DBS states. Importantly, good responders to GPi DBS showed a similar level of short-latency intracortical inhibition in the motor cortex as healthy controls whereas non-responders were unable to increase it. All these results support the multilevel impact of effective DBS on the motor networks in dystonia and suggest potential biomarkers of responsiveness to this treatment.
Highlights
Deep brain stimulation of the globus pallidus internus (GPi DBS) is an effective symptomatic treatment for pharmacoresistant dystonic syndromes[1,2,3], where pathophysiological mechanisms of action are not yet fully understood
Relationship between the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS) and brain morphology evaluated by voxel based morphometry (VBM)
Our dystonia patients treated with chronic GPi DBS showed distinct changes in the short latency cortical inhibition (SICI) as well as in the motor evoked potential (MEP) onset latency accompanied by significant brain morphology changes
Summary
Deep brain stimulation of the globus pallidus internus (GPi DBS) is an effective symptomatic treatment for pharmacoresistant dystonic syndromes[1,2,3], where pathophysiological mechanisms of action are not yet fully understood. Several mechanisms have been discussed, describing an alteration of inhibitory circuits at the cortical, brainstem and spinal level[10,11] or reporting impaired sensorimotor integration[12,13] These functional changes in dystonia are accompanied by various structural abnormalities[14] especially in brain regions including the primary sensorimotor cortex, basal ganglia, thalamus and cerebellum[14,15,16,17]. Excitability was evaluated using paired TMS to elicit a short-latency intracortical inhibition (SICI) in the motor cortex of the hand muscles to assess the acute effects of the GPi DBS18,19 This technique was previously used in dystonia patients to show affected cortical excitability in various dystonic syndromes[20,21] no acute effects of GPi DBS on the SICI were detected[22,23,24]. We expected that GPi DBS may induce local grey matter density changes especially in areas belonging to the sensorimotor circuits
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