Objective: To characterize DBS tractographic patterns in a patient with novel DYT-6 mutation with rapid response to stimulation.

Background: GPi DBS is an effective treatment for dystonia. While specific types of dystonia such as DYT-1, Tardive dystonia and PKAN have demonstrated significant clinical benefits from GPi-DBS, DYT-6, linked to a missense mutation of the THAP1 gene, has had a more modest response. In these patients, diffusion-tensor imaging research revealed structural abnormalities involving localized reductions in FA in white matter pathways adjacent to the sensorimotor cortex and in the dorsal pons, as well as reduced integrity of cerebello-thalamo-cortical fiber tracts, suggestive of somatotopically relevant changes.

Methods: We report the case of a 28 year-old woman with DYT-6 dystonia with right hand cramping onset at age 15, with a novel DYT-6 pathogenic mutation already reported. She underwent bilateral GPi-DBS and experienced a significant and unusually rapid clinical improvement. Her symptoms consisted of generalized, predominantly cervical, dystonia. Data collected included preoperative and postoperative MRI and CT scans, including diffusion-tensor imaging. All images were co-registered to localize the contacts using DBSproc within AFNI. Volumes of tissue activated (VTA) were calculated based on stimulating contact locations and parameters at 6-month after DBS. Probabilistic tractography was performed on the networks of VTA and whole brain grey-matter ROIs defined using Freesurfer.

Results: The patient demonstrated clinical benefit starting within 2 weeks from DBS stimulation initiation, which persisted at her latest follow-up (baseline: BFM=8.5, TWSTRS severity=18; 2 month-8 month: BFM=3-2.5, TWSTRS =13-13, 65%-71% improvement on BFM). The stimulating contact locations were (23, 6, -2) and (-23, 7, 3) in the Talairach space [center of masses of GPi: (±20, 5, 0)]. The stimulation reached the ventral DC areas, putamen, brainstem, thalamus and precentral and postcentral gyri. Furthermore, tracts to the motor and somatosensory areas were localized to the medial regions, matching the body representation of her symptoms.

Conclusions: Connectivity patterns suggest that stimulation reached brain areas previously implicated in imaging studies of DYT-6 patients, suggesting this could be an indicator for successful clinical outcome. This could partly explain the unusually rapid response in this case.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tractographic-patterns-of-effective-pallidal-dbs-in-dyt-6-dystonia-a-case-study/