Objective: We aimed to evaluate the efficacy of GPi-DBS in patients with monogenic autosomal dominant dystonia associated with mutations in TOR1A(DYT1), THAP(DYT6),and KMT2B (DYT28) genes.

Background: DBS is indicated for severe medically refractory dystonia causing significant patient disability [1]. Among the factors influencing outcome of surgery are disease duration, severity of preoperative motor symptoms, presence of fixed skeletal deformities or structural brain lesions, and GPi-volume. Patients with isolated dystonia usually respond to DBS better than with combined one, although results vary in different genetic types [2,3,4,5,6].

Method: 37 patients with monogenic dystonia were included in the study: 20 patients with DYT1 (age of onset 11.0±9.6, disease duration 12.7±12.1, age at surgery 23.9±14.1 years); 7 patients with DYT6 (age of onset 11.1±7.3, disease duration 18.6±9.6, age at surgery 29.7±15.3 years), and 10 patients with DYT28-dystonia (age of onset 5.7±2.3, disease duration 6.6±7.7, age at surgery 12.3±8.5 years). Dystonia severity was measured according to Burke-Fahn-Marsden dystonia rating scale (motor score) and preoperatively comprised 58.0±18.4, 59.0±18.9, and 73.6±13.3, respectively. All patients underwent implantation of GPi-electrodes for bilateral DBS. We assessed patients at the last follow-up ranging from 0.5 to 10 years (mean 3.3±2.6 years).

Results: As for clinical characteristics, patients with DYT28-dystonia had earlier disease onset, shorter disease duration, younger age at surgery, and more severe dystonic symptoms compared to DYT1 and DYT6-patients. DYT1-patients had longer follow-up than the others. Mean alleviation of motor disturbances following GPi-DBS was 62.5±17.0% in DYT1, 44.6±17.4% in DYT6, and 36.9±20.5% in DYT28-dystonia. In this particular group of patients, we found correlation of absolute motor improvement with preoperative dystonia severity, but not with age of onset or disease duration (r=0.44, p<0.05).

Conclusion: In patients with different monogenic dystonias, clinical manifestation and severity are heterogeneous. GPi-DBS efficacy in patients with DYT1-dystonia seems to be greater than in DYT6 or DYT28-dystonia. In case of severe pharmacoresistant dystonia, GPi-DBS should be considered early, especially in monogenic variants for which surgery is effective. Early recognition of corresponding dystonic phenotype (genetic testing) and timely referral for DBS may improve dystonia management.

References: 1. Jinnah HA. Medical and Surgical Treatments for Dystonia. Neurol Clin. 2020;38(2):325-348. doi: 10.1016/j.ncl.2020.01.003
2. Tisch S. Deep brain stimulation in dystonia: factors contributing to variability in outcome in short and long term follow-up. Curr Opin Neurol. 2022;35(4):510-517. doi: 10.1097/WCO.0000000000001072
3. Chudy D, Raguž M, Vuletić V, Rački V, Papić E, Nenadić Baranašić N, Barišić N. GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature. Front Neurol. 2023;14:1151900. doi: 10.3389/fneur.2023.1151900
4. Tisch S, Kumar KR. Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome. Front Neurol. 2021;11:630391. doi: 10.3389/fneur.2020.630391
5. Chen W, Fan H, Lu G. The Efficacy and Predictors of Using GPi-DBS to Treat Early-Onset Dystonia: An Individual Patient Analysis. Neural Plast. 2021;2021:9924639. doi: 10.1155/2021/9924639
6. Artusi CA, Dwivedi A, Romagnolo A, Bortolani S, Marsili L, Imbalzano G, Sturchio A, Keeling EG, Zibetti M, Contarino MF, Fasano A, Tagliati M, Okun MS, Espay AJ, Lopiano L, Merola A. Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2020;91(4):426-433. doi: 10.1136/jnnp-2019-322169

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-of-globus-pallidus-internus-for-monogenic-dystonia/