Secondary Worsening Following DYT1 Dystonia Deep Brain Stimulation: A Multi-country Cohort

Abstract

Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline.

Subthalamic Nucleus Deep Brain Stimulation for Dystonia: Evidence, Pros and Cons

“…Off stimulation evaluation showed worsening of dystonia, despite missing the 30% improvement threshold, thus indicating some continued benefit. All 11 patients underwent further DBS surgeries, either targeting the STN or the GPi, Additional leads did not offer meaningful improvement, if the initial leads were optimally placed (82).…”

Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome

“…Cif et al described secondary worsening after several years in a subgroup of DYT1 dystonia patients with good initial response at 12 months ( 34 ). A recent multicentre study reported secondary worsening in DYT1 dystonia after GPi DBS in 11 of 132 patients at 6 months to 3 years after DBS and was associated with younger age of onset, faster disease progression and cranial involvement ( 38 ).…”

Deep Brain Stimulation Treating Dystonia: A Systematic Review of Targets, Body Distributions and Etiology Classifications

“…In our present study, the pooled AER after GPi-DBS was numerically lower than that after STN-DBS, but the difference was not significant. This outcome might partly be due to the different stimulation parameters used in GPi-DBS and STN-DBS considering the stimulation-related AEs (Tsuboi et al, 2020). More studies are needed to explore the relationship between programming parameters and safety.…”