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

Abstract

ObjectiveGenetic 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.MethodsThis 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-TOR1A 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.ResultsDYT-TOR1A (68%, 38.4 points; p<0.001), DYT-THAP1 (37% 14.5 points; p<0.001) and NBIA/DYT-PANK2 (27%, 21.4 points; p<0.001) improved in BFMMS; only DYT-TOR1A improved in BFMDS (69%, 9.7 points; p<0.001). Improvement in DYT-TOR1A was significantly greater than in DYT-THAP1 (BFMMS −31%), NBIA/DYT-PANK2 (BFMMS −35%; BFMDS −53%) and CHOR/DYT-ADCY5 (BFMMS −36%; BFMDS −42%). Worse motor outcomes were associated with longer dystonia duration and older age at dystonia onset in DYT-TOR1A, longer dystonia duration in DYT/PARK-TAF1 and younger age at dystonia onset in DYT-SGCE.ConclusionsGPi DBS outcomes vary across monogenic dystonias. These data serve to inform patient selection and prognostic counselling.

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

“…Despite early intervention with DBS, the multi-country cohort experienced suboptimal outcomes in the long-term. This result appears to be contradictory to the earlier dystonia studies reporting the association between better outcomes and shorter disease duration before DBS (Isaias et al, 2011;Lumsden et al, 2013;Artusi et al, 2020). In the suboptimal responders included in the historical cohort, only those with very long disease duration before DBS were reported to have fixed skeletal deformities, and age at onset was similar between these two groups.…”

“…In 2000, excellent DBS outcomes in patients with DYT1 were first reported by Coubes et al ( 2000 ). Subsequently, retrospective studies and a meta-analysis suggested that TOR1A mutation-positive status was a clinical predictive factor for a better DBS outcome (Vasques et al, 2009 ; Andrews et al, 2010 ; Borggraefe et al, 2010 ; FitzGerald et al, 2014 ; Moro et al, 2017 ; Artusi et al, 2020 ). Additionally, in the largest cohort to date of patients with DYT1 dystonia who underwent GPi DBS ( n = 47), improvement in dystonia severity by >80% was maintained up to 7 years after surgery (Panov et al, 2013 ).…”

Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics

“…Multiple clinical trials [49][50][51] have established the efficacy of GPi DBS in primary generalized dystonia, finding that those having the DYT1 gene mutation have a better response to DBS. 52 Anatomy. Relevant anatomy and imaging considerations of the sensorimotor portion of the GPi have been previously discussed (see PD section).…”

ADCY5‐Induced Dyskinetic Storm Rescued with Pallidal Deep Brain Stimulation in a 46‐Year‐Old Man

“…6 DBS has recently been described as an effective therapy in ADCY5-related hyperkinesia, although clinical results seem to vary substantially. [7][8][9] Whether the heterogeneity of the benefit from DBS is attributed to additional genetic-related or operation-related factors (such as the exact electrode position) has to be explored in future clinical trials. Disclosures Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work.…”