Efficacy and safety of multiple-target deep brain stimulation in non-parkinsonian movement disorders: a systematic review

Abstract

Introduction: To analyze studies employing multiple-target deep brain stimulation (DBS) for non-parkinsonian movement disorders and identify potential indications, therapeutic outcomes, and associated side effects.

Methods: We systematically screened PubMed and included studies involving patients treated with DBS targeting at least two brain regions, synchronous stimulation of ≥2 regions, patient data regarding symptoms/disease, and reported outcomes. Exclusion criteria included animal studies and reports lacking original data.

Results: Twenty-seven studies were identified, included and analyzed; general trends were noted for each disorder. For essential tremor multi-target DBS (VIM+VOA/VOP) demonstrated promising outcomes regarding symptom improvement and reduction of side-effects. For multiple Sclerosis Tremor limited evidence suggested positive outcomes, comparable to standard DBS. The VIM/VOP border has been highlighted as a promising target. Regarding holmes Tremor although limited to case reports, multi-target DBS yielded favorable outcomes with minimal adverse effects. Finaly for dystonia multi-target DBS (GPi+VIM, GPi+VO) effectively addressed tremor and dystonic features. Statistically significant advantages were demonstrated over single-target stimulation in myoclonus-dystonia and hemidystonia.

Conclusion: While variability in target selection, methodologies, and outcomes precludes a meta-analysis, evidence supports the potential role of multi-target DBS in cases where single-target stimulation is inadequate. Promising target combinations, such as GPi+VIM (myoclonus-dystonia) and VIM+VOA (essential tremor), warrant further clinical exploration. The heterogeneity and predominance of case reports highlight the need for high-quality, controlled studies to refine indications and optimize strategies for multi-target DBS.

Keywords: Dual-target DBS; Dystonia; Essential tremor; Holme’s tremor; Movement disorders; Multiple Sclerosis; Multiple-target DBS.