Medical device-based neuromodulation for motor symptoms in Parkinson's disease: a systematic review and meta-analysis

To synthesize randomized clinical trial (RCT) evidence comparing the efficacy of medical device-based neuromodulation (MDBN) techniques for improving motor symptoms in Parkinson's disease (PD).

Device-based neuromodulation therapies, including deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), are used to target PD motor symptoms, but reported effect sizes vary substantially across trials.

A systematic review was conducted in accordance with PRISMA guidelines. RCTs evaluating MDBN for PD motor function, measured by the Unified Parkinson's Disease Rating Scale Part III (UPDRS3), were identified through MEDLINE, Embase, and Web of Science. A random-effects meta-analysis was performed for the primary outcome (UPDRS3). Risk of bias was assessed using the Cochrane RoB tool, and certainty of evidence with GRADE. Meta-regression examined methodological, population, and intervention variables associated with effect size variation.

Forty-seven RCTs (56 intervention comparisons; 2,638 participants) were included. Thirty trials investigated non-invasive neuromodulation (mainly rTMS and tDCS) and 17 invasive approaches (DBS). Meta-analysis of 39 effect sizes (from studies during L-Dopa ON, near-term follow-up) showed a small but significant improvement with active MDBN (SMD = -0.18, p = 0.008; I ² = 61%). Meta-regression showed larger effects in studies using intention-to-treat analysis and smaller effects when sham stimulation was used as a comparator.

MDBN is associated with modest yet significant motor improvements in PD. Effect size estimates are influenced by methodological characteristics, particularly analysis strategy and comparator selection. This is the first review in the field to calculate and incorporate separate effect sizes for each active intervention group in multi-arm trials, enabling more precise data inclusion.