Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
STN-SNr co-stimulation in Parkinson's disease: a systematic review and meta-analysis of motor and freezing-of-gait outcomes.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод пока не подготовлен
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Kong Lingjie, Li Pengxing, Bi Yuewei, Gong Le, Ren Yutong, Wang Yaning, Guo Yi
Аннотация
BACKGROUND: Freezing of gait (FoG) and axial impairments often persist in Parkinson's disease despite optimized medication and subthalamic nucleus deep brain stimulation (STN-DBS). We systematically reviewed whether adding substantia nigra pars reticulata (SNr) stimulation improves motor and FoG outcomes.
METHODS: Following PRISMA 2020 and PROSPERO registration (CRD420261343479), six databases were searched through 1 May 2026. Primary outcomes compared STN-SNr co-stimulation with STN-only stimulation; stimulation-off or baseline comparisons were secondary. Two reviewers independently screened studies, extracted data, and assessed risk of bias. UPDRS-III and FoG were pooled as mean differences (MDs) and Hedges' g, respectively, accounting for paired data and within-study dependence. Certainty was assessed using GRADE.
RESULTS: Ten studies (nine randomized trials and one observational study) included 109 unique evaluable participants; two single-patient case reports were summarized narratively. UPDRS-III showed no between-group difference across seven studies (73 participants; MD - 0.10, 95% CI - 1.01 to 0.81; I² = 0%; low certainty). FoG showed no additional benefit across six studies (86 participants; Hedges' g - 0.23, 95% CI - 1.04 to 0.59; I²_total = 85.6%; very low certainty). Secondary baseline comparisons favored co-stimulation for UPDRS-III (MD - 13.55) and FoG (Hedges' g - 0.60), but did not isolate an incremental SNr effect.
CONCLUSIONS: Low-certainty evidence suggests no clinically important difference in global motor outcomes, while very-low-certainty evidence does not demonstrate a consistent additional FoG benefit. Improvements versus stimulation-off or baseline cannot establish an incremental SNr effect. Larger phenotype-stratified trials with objective gait endpoints and systematic adverse-event reporting are needed.
METHODS: Following PRISMA 2020 and PROSPERO registration (CRD420261343479), six databases were searched through 1 May 2026. Primary outcomes compared STN-SNr co-stimulation with STN-only stimulation; stimulation-off or baseline comparisons were secondary. Two reviewers independently screened studies, extracted data, and assessed risk of bias. UPDRS-III and FoG were pooled as mean differences (MDs) and Hedges' g, respectively, accounting for paired data and within-study dependence. Certainty was assessed using GRADE.
RESULTS: Ten studies (nine randomized trials and one observational study) included 109 unique evaluable participants; two single-patient case reports were summarized narratively. UPDRS-III showed no between-group difference across seven studies (73 participants; MD - 0.10, 95% CI - 1.01 to 0.81; I² = 0%; low certainty). FoG showed no additional benefit across six studies (86 participants; Hedges' g - 0.23, 95% CI - 1.04 to 0.59; I²_total = 85.6%; very low certainty). Secondary baseline comparisons favored co-stimulation for UPDRS-III (MD - 13.55) and FoG (Hedges' g - 0.60), but did not isolate an incremental SNr effect.
CONCLUSIONS: Low-certainty evidence suggests no clinically important difference in global motor outcomes, while very-low-certainty evidence does not demonstrate a consistent additional FoG benefit. Improvements versus stimulation-off or baseline cannot establish an incremental SNr effect. Larger phenotype-stratified trials with objective gait endpoints and systematic adverse-event reporting are needed.