[Skip to Content]
[Skip to Content Landing]
Original Investigation
December 3, 2018

Association of Pallidal Neurostimulation and Outcome Predictors With X-linked Dystonia Parkinsonism

Author Affiliations
  • 1Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
  • 2Department of Neurology, University Hospital Lübeck, Lübeck, Germany
  • 3Department of Neurosurgery, University Hospital Lübeck, Lübeck, Germany
  • 4Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 5Department of Neurology and Psychiatry, University of Santo Tomas Hospital, Manila, Philippines
  • 6Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines
  • 7Institute for Neurosciences, St. Luke's Medical Center, Quezon City and Global City, Philippines
  • 8Asian Hospital and Medical Center, Muntinlupa City, Philippines
  • 9Department of Neurology, University Hospital Würzburg, Würzburg, Germany
  • 10Department of Neurology, Charité- Universitätsmedizin Berlin, Berlin, Germany
JAMA Neurol. 2019;76(2):211-216. doi:10.1001/jamaneurol.2018.3777
Key Points

Questions  Is deep brain stimulation (DBS) an efficient therapeutic option in severe X-linked dystonia parkinsonism and what are predictors for the postoperative outcome?

Findings  In this cohort study, pallidal DBS resulted in an improvement of dystonia and, to a lesser extent, parkinsonism. Deep brain stimulation was less effective in patients with more pronounced caudate atrophy.

Meaning  Pallidal DBS should be considered a first-line treatment in medically intractable X-linked dystonia parkinsonism, and given the association of poorer treatment outcomes in patients with more advanced neurodegeneration, DBS should potentially be considered during the earlier stages of the disease.


Importance  Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy.

Objective  To determine the efficacy of GPi-DBS in a cohort of patients with XDP in a prospective study and identify predictors of postoperative outcomes.

Design, Setting, and Participants  This observational prospective cohort study enrolled patients in February 2013 and was completed in December 2014. The patients were followed up for up to 46 months. Patients from the Philippines were treated in a single center in Lübeck, Germany and followed up in the Philippines. Sixteen men with XDP (mean [SD] age, 40.9 [7.3] years; disease duration, 1-6 years) from the Philippines with predominant dystonia were selected.

Exposures  All patients underwent bilateral GPi-DBS in Lübeck, Germany.

Main Outcomes and Measures  Clinical assessment included the motor parts of the Burke-Fahn-Marsden scale (BFMDRS-M) and the Unified Parkinson’s Disease Rating Scale (UPDRS-III). T1-based basal ganglia volumetry was performed and correlated with postoperative outcomes.

Results  The study participants included 16 Filipino men (mean age, 40.9 years). Masked video ratings revealed significant improvements of dystonia severity 1 week (−55%; range, −94% to 59%; P < .01) and 6 months (−59%; range, −100% to 22%; P < .001) after surgery. The UDPRS-III score also improved, albeit to a lesser extent (−19%; range, −54% to 95%; and −27%; range, −70% to 124%; respectively). Unmasked long-term follow-up confirmed the continued efficacy of GPi-DBS up to 46 months after surgery. Important secondary end points improved, including activities of daily living, pain severity, weight, and quality of life. Caudate atrophy was a predictor of a less beneficial outcome (r = 0.817, P = .004).

Conclusions and Relevance  Internal globus pallidus DBS had a positive association in XDP with predominant dystonia (the primary end point) and contributed to an improved quality of life (the secondary end point). The response to DBS occurred within 1 week. Given the inverse correlation of postoperative benefit and caudate atrophy, GPi-DBS should be considered early during the disease course. Close international collaboration, training, and funding from multiple sources enabled the sustainable follow-up of patients with XDP in the Philippines.