Objective: Review DBS benefit in genetically confirmed dystonias.

Background: Deep brain stimulation (DBS) is an established option for genetic dystonias such as DYT-1. While literature on the potential benefit in other genetic dystonias is growing, the rarity of the individual syndromes makes evidence scarce.

Method: We systematically reviewed all published cases and case series of genetically confirmed dystonia that underwent DBS. A total of 396 cases with adequate pre- and post-operative clinical information were analyzed to evaluate motor outcomes. Treatment was considered beneficial when there was greater than 30% improvement on validated dystonia scales after DBS with at least 12 months of follow-up.

Results: Subjects with DYT-1 dystonia obtained the most benefit from DBS. Subjects with KMT2B, XDP, PKAN, GNAL, and DYT-11 mutations also benefited from DBS, while those with KCTD17, RDP, and PDE2A mutations did not have a sustained benefit. Although reports of DYT-6 suggested delayed improvement, there was limited confirmed improvement after DBS within the first year of follow up. Over 90% of DBS placements targeted GPI. STN was used for 17% of those with PKAN dystonia, 33% of those with RDP dystonia, and the one confirmed case of DRD dystonia.

Conclusion: The genetic etiology of dystonia appears to be a determinant of DBS response, with the greatest response seen in DYT-1. Dystonia-plus syndromes, which have additional movement or neurological features, may also be considered for DBS to potentially improve dystonia as seen in recently described dystonia syndromes such as KMT2B and anecdotal reports of positive outcomes in dystonia in Wilson’s Disease. This study supports the importance of genetic diagnosis of dystonia in the assessment of DBS eligibility and possibly target selection, such as in RDP and XDP, which have distinct pathophysiologies from Parkinson’s disease or primary dystonia resulting in poor response in the former and improvements in dystonia but not parkinsonism in the latter. A potential confounder is the reliance on rating scales which may not entirely capture quality of life and complete DBS response. Our results require validation by a prospective epidemiologic study of genetic characteristics, DBS response using both movement and quality of life scales, and possible functional or tractography based imaging for better target selection.

References: Rughani AI, Lozano AM. Surgical treatment of myoclonus dystonia syndrome. Mov Disord. 2013 Mar;28(3):282-7. doi: 10.1002/mds.25326. Epub 2013 Feb 7. PMID: 23401150 Meyer E, Carss KJ, Rankin J, Nichols JM, Grozeva D, Joseph AP, Mencacci NE, et al Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet. 2017 Feb;49(2):223-237. doi: 10.1038/ng.3740. Epub 2016 Dec 19. Panov F, Gologorsky Y, Connors G, Tagliati M, Miravite J, Alterman RL. Deep brain stimulation in DYT1 dystonia: a 10-year experience. Neurosurgery. 2013 Jul;73(1):86-93; discussion 93.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-confirmed-genetic-dystonias-a-comprehensive-review/