Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis.

OBJECTIVE

Genetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common monogenic dystonias.

METHODS

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. We searched PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-surgical and post-surgical assessments using the Burke-Fahn-Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke-Fahn-Marsden Disability Score (BFMDS). We performed (i) meta-analysis for each gene mutation; (ii) weighted ordinary linear regression analyses to compare BFMMS and BFMDS outcomes between DYT- and other monogenic dystonias, adjusting for age and disease duration and (iii) weighted linear regression analysis to estimate the effect of age, sex and disease duration on GPi DBS outcomes. Results were summarised with mean change and 95% CI.

RESULTS

DYT- (68%, 38.4 points; p<0.001), DYT- (37% 14.5 points; p<0.001) and NBIA/DYT- (27%, 21.4 points; p<0.001) improved in BFMMS; only DYT- improved in BFMDS (69%, 9.7 points; p<0.001). Improvement in DYT- was significantly greater than in DYT- (BFMMS -31%), NBIA/DYT- (BFMMS -35%; BFMDS -53%) and CHOR/DYT- (BFMMS -36%; BFMDS -42%). Worse motor outcomes were associated with longer dystonia duration and older age at dystonia onset in DYT-, longer dystonia duration in DYT/PARK- and younger age at dystonia onset in DYT-.

CONCLUSIONS

GPi DBS outcomes vary across monogenic dystonias. These data serve to inform patient selection and prognostic counselling.