BACKGROUND
Interindividual variability in motor outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) remains incompletely understood. Glymphatic-related imaging abnormalities have been reported in PD, but their relevance to neuromodulation response is unclear.
OBJECTIVES
To investigate whether preoperative glymphatic function, assessed using the Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) index, is associated with motor outcomes after STN-DBS and whether hemispheric asymmetry provides additional explanatory value.
METHODS
We retrospectively evaluated 74 advanced PD patients undergoing bilateral STN-DBS with ≥6 months follow-up. Preoperative assessment included 3 T MRI-derived ALPS measures, Fazekas score, perivascular space burden, MDS-UPDRS-III, levodopa responsiveness, and metabolic markers. Primary outcome was percentage motor improvement at follow-up. Multivariable regression models assessed ALPS associations after adjustment for levodopa responsiveness and measured clinical covariates.
RESULTS
Lower ALPS asymmetry index (AI) was independently associated with greater percentage motor improvement (standardized β = -0.508, p < 0.001), while greater preoperative levodopa responsiveness was also associated with improvement (β = 0.740, p < 0.001). Lower ALPS-AI was additionally associated with axial motor improvement and responder status at both ≥50% and ≥ 33% thresholds. All four principal levodopa-adjusted ALPS-AI associations remained significant after Benjamini-Hochberg correction (all pFDR≤0.0069). Mean ALPS index, Fazekas score, and perivascular space burden were not associated with motor outcomes.
CONCLUSIONS
Preoperative glymphatic asymmetry was associated with motor outcomes after STN-DBS independently of levodopa responsiveness and measured clinical covariates. ALPS-derived asymmetry may capture outcome variability not reflected by conventional imaging, although prospective validation and evaluation alongside lead localization, stimulation parameters, and programming factors are required.
Gulce Cosku Yilmaz Cakan, Ali Bayram, B. Samancı et al.· Movement Disorders Clinical...· 0 citations
OBJECTIVE
Although the centromedian nucleus of the thalamus (CM) is an increasingly considered deep brain stimulation (DBS) target for drug-resistant epilepsy (DRE), there is significant variability in programming practices, which may contribute to heterogenous outcomes. We systematically described stimulation parameters for CM-DBS and their association with seizure outcomes to inform a standardized, evidence-informed programming framework.
METHODS
We performed a Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA)-guided systematic review and meta-analysis of published studies pertaining to CM-DBS including all dates through March 2026. Eligible studies included patients with DRE treated with CM-DBS, extractable seizure outcomes, and reported stimulation parameters. Study-level data and extractable patient-level data were synthesized. The primary outcome was percent seizure reduction at the last follow-up. Using random-effects meta-analysis we summarized study-level efficacy and performed regression analyses to assess associations with diagnosis, seizure semiology, and stimulation parameters.
RESULTS
Thirty studies including 269 individuals met inclusion criteria. Median seizure reduction was 71.5% and 200 participants (74.6%) with seizure outcome data were responders (>50% seizure reduction), which likely represents an upper bound on true efficacy given the predominance of non-randomized studies at serious-to-critical risk of bias. Generalized tonic-clonic seizures were associated with greater seizure reduction. Tonic seizures were associated with worse outcome, yet this was attenuated after accounting for study clustering. Stimulation parameters varied substantially across studies. No single nominal stimulation parameter demonstrated a robust clinically actionable association with outcome; however, estimated total electrical energy delivered was associated with greater seizure reduction on multivariable modeling, yet this was attenuated when accounting for clustering between studies.
SIGNIFICANCE
These findings map the landscape of programming of CM-DBS, while emphasizing the need for standardized reporting of stimulation parameters, contact localization, and stimulation exposure to enable prospective optimization. On this basis, we propose a pragmatic, evidence-informed programming framework for CM-DBS that emphasizes postoperative contact localization, standardized initial stimulation settings, and stepwise titration of stimulation exposure.
M. AlQahtani, Michal Stern-Zimmer, P. Jain et al.· Epilepsia· 0 citations
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