Objective: We investigated Volumes of Neural Activation (VNAs) in dystonia subjects under effective bilateral pallidum deep brain stimulation (DBS). We aimed to disentangle the sweet spot for dystonia suppression within the internal globus pallidus.

Background: GPi-DBS is an established therapy for generalized and segmental dystonia. Average improvement of dystonia severity amounts to 50-60%, but outcomes are often variable and clinical studies report up to 25% non-responders (< 25% motor improvement). Variability in electrode placement may account for a large proportion of outcome variability. So far no study has been able to identify an “optimal efficacy volume” within the GPi.

Methods: Nine subjects with dystonia (2 segmental/7 generalized dystonia, mean BFMDRS 33.5 points) under chronic bilateral GPi-DBS were stratified for chronic motor improvement (median reduction of 76.4% after 22.6 months). We simulated VNAs (axon diameter of 2.5 µm) for each lead based on chronic stimulation parameters in subject’s related MRI space. Each VNA was associated with its corresponding contralateral hemibody and total axial BFMDRS improvement score. All patient images were registered to a common patient average MRI (PAM) of the ventral striatum and subpallidal area (created by registration and normalization of 18 disease specific T2/T1 IR weighted MRI volumes). Patients were split into two groups related to the stimulation-induced improvement, with > 80% hemibody BFMDRS score donoting “superresponders” and <80% “average responders”, respectively. Mean VNAs were created for each patient group by aggregating all the VNAs of that particular group.

Results: Model-based analysis showed a mean VNA of the superresponder group located within and below the ventroposterior GPi. Stereotactic coordinates of the VNA locus was lateral: 18.2, anterior: 3.3 and inferior 3.3 (based on AC-PC in mm). The mean VNA of the “average responder” group was located more lateral and extended into the GPe, whereas VNAs of superresponders spared the GPe and were confined to the internal pallidum and subpallidal space.

Conclusions: Our data corroborate previous findings of a more medial electrode location in GPi being associated with better outcomes (Tisch et al.). The VNA of superresponders suggests a relevant contribution of subpallidal white matter (e.g. ansa lenticularis) to the antidystonic effect of DBS in addition to stimulation of the classical target within ventroposterior GPi.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sweet-spot-of-antidystonic-effect-in-pallidal-neurostimulation/