Preoperative Putamen Volume Predicts GPi-DBS Response in HIE-Related Dystonia-Dyskinesia, Study Finds

A recent retrospective cohort analysis has identified preoperative putaminal atrophy on MRI as a significant independent predictor of suboptimal motor outcomes following globus pallidus internus deep brain stimulation (GPi-DBS) in patients with dystonia-dyskinesia syndrome (DDS) secondary to perinatal hypoxic-ischemic encephalopathy (HIE). Published in Movement Disorders, the findings offer clinicians an actionable preoperative imaging criterion to guide patient selection and set realistic expectations for surgical benefit.¹

Study Overview

Led by Gaëtan Poulen, MD, PhD, a neurosurgeon at Montpellier University Hospital, the study retrospectively analyzed 73 patients with HIE-related DDS who underwent GPi-DBS between 2003 and 2023. Patients were required to be at least 6 years of age at surgery; genetic etiologies and non-HIE causes of DDS were excluded. The mean age at surgery was 23 years old (range, 6–65); 30 patients were younger than 18 years old.

Outcomes were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability subscales and the Barry-Albright Dystonia Scale (BADS) at baseline and at 1, 5, 10, and 15 years. Preoperative 1.5T MRI scans were assessed qualitatively for putaminal atrophy and quantitatively in 54 cases using manual volumetric segmentation.

Key Findings

Across the full cohort, GPi-DBS produced a statistically significant improvement in BFMDRS motor scores at 1 year (58.5 to 48.8; P <.0001), with gains persisting through 15 years of follow-up. Outcomes differed markedly by atrophy severity, however. Patients with severe putaminal atrophy (n = 33) had significantly higher preoperative BFMDRS motor scores (mean 70.7 [±19.9] vs 45.5 [±16]; P <.0001) and meaningfully smaller postoperative improvements compared with those with no or mild atrophy (n = 31), in whom gains were sustained through 5 years (P <.0001).

Volumetric analysis confirmed inverse correlations between putamen volume and preoperative clinical severity (r = −.52 to −0.58; P <.0001) and positive correlations with percentage of motor improvement at 1-year and 5-year follow-up (r = .28–.45; P <.05 for all). On multivariate regression, putaminal volume was the only independent predictor of clinical improvement at 1 year (β = 7.26–8.08; P = .017–.046; R² ≈ .14–.20); age, sex, and preoperative severity failed to reach significance. Post-hoc ROC analysis identified a preoperative BFMDRS motor score threshold of 59.7 (sensitivity 84.6%, specificity 88.8%) as a surrogate marker for severe putaminal atrophy.

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Clinical Context

HIE affects approximately 1.5 to 8 per 1000 live births in developed countries and is a leading cause of neonatal mortality and long-term neurodevelopmental morbidity.² DDS is a prominent sequela of HIE, but pharmacological management is often inadequate in this population.³ GPi-DBS has emerged as an interventional option for refractory cases, though outcomes have been heterogeneous and reliable preoperative predictors of response have remained elusive.⁴ Network mapping studies in dyskinetic cerebral palsy suggest that structural connectivity between the putamen and pallidothalamo-cortical circuits is central to DBS efficacy,⁵ lending biological support to the volumetric associations reported in this study.

Interpretation

All told, these data suggest that severe post-anoxic basal ganglia damage may compromise pallidothalamo-cortical circuit integrity to a degree that limits GPi-DBS efficacy. Preoperative putaminal volume, measurable on standard clinical MRI, may function as a practical, scalable biomarker for candidate selection. Notably, the study documented 2 patients with exceptional motor improvement exceeding 91%, demonstrating that meaningful benefit remains attainable in carefully selected individuals.

Limitations

The retrospective, single-center design limits generalizability, and volumetric analysis was feasible in only 54 of 73 patients. Follow-up patient numbers diminished substantially at 10 and 15 years (n = 17 and n = 14, respectively), reducing long-term statistical power. Existing outcome instruments (BFMDRS, BADS) were developed for primary dystonia and may inadequately capture functional gains in complex mixed motor disorders like DDS.

Future Research

The authors noted that prospective multicenter studies incorporating standardized preoperative MRI volumetry and functional connectivity profiling may be needed to validate putaminal volume as a formal selection criterion. In addition, they mentioned that the development of disease-specific outcome instruments for DDS could strengthen future benefit assessments.

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REFERENCES
1. Grasso M, Moser PO, Sauvageot S, et al. Putamen Atrophy as a Predictive Factor of Efficacy of GPi-DBS in Dystonia-Dyskinesia Syndrome Secondary to Perinatal Anoxic Encephalopathy. Mov Disord. Published online March 18, 2026. doi:10.1002/mds.70275
2. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86(6):329-338. doi:10.1016/j.earlhumdev.2010.05.010
3. Poulen G, Chan-Seng E, Sanrey E, Coubes P. Deep Brain Stimulation and Hypoxemic Perinatal Encephalopathy: State of Art and Perspectives. Life (Basel). 2021;11(6):481. Published 2021 May 25. doi:10.3390/life11060481
4. Koy A, Kühn AA, Schiller P, et al. Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation. Mov Disord. 2023;38(9):1736-1742. doi:10.1002/mds.29516
5. de Almeida Marcelino AL, Al-Fatly B, Tuncer MS, Krägeloh-Mann I, Koy A, Kühn AA. Lesion distribution and network mapping in dyskinetic cerebral palsy. Brain Commun. 2025;7(3):fcaf228. Published 2025 Jun 13. doi:10.1093/braincomms/fcaf228