GPi-DBS for KMT2B-Associated Dystonia: Systematic Review and Meta-Analysis

Background: Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT-KMT2B. Objectives: We aimed to conduct a systematic review and meta-analysis to assess outcomes and identify predictors of good outcome following GPi-DBS in DYT-KMT2B. Methods: We searched MEDLINE, Cochrane and MDS-abstracts databases using the MeSH terms “KMT2B and DYT28”. We included studies that reported objective outcomes following GPi-DBS in DYT-KMT2B. The BFMDRS-M (Burke-Fahn-Marsden Dystonia Rating Scale- Movement) total scores pre- and post-surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta-analysis and used meta-regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS-M). Results: Initial searches screened 132 abstracts of which 34 full-text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow-up was 12 months (range: 1–264 months). GPi-DBS resulted in median BFMDRS-M improvement of 42.7% (range: −103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS-M was 41% (95% CI: 27%–57%). Male gender [β: 22.6, 95% CI: 8.0–37.3, P = 0.004), and higher pre-operative BFMDRS-M score [β: 0.62, 95% CI: 0.36–0.87, P < 0.001) were independently associated with better outcome. Conclusion: KMT2B-associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline.