Abstract
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.
| Original language | English |
|---|---|
| Journal | JAMA Neurology |
| Volume | 76 |
| Issue number | 2 |
| Pages (from-to) | 211-216 |
| Number of pages | 6 |
| ISSN | 2168-6149 |
| DOIs | |
| Publication status | Published - 01.02.2019 |
Funding
received research funding from the German Research Foundation (BR 4328/2-1), the Collaborative Center for X-linked Dystonia-Parkinsonism, and the Else-Kröner Fresenius Stifung (2017_HA17). He received speaker’s honoraria from Grünnethal, TEVA, and UCB and a travel grant from Bayer. Dr Moll served as a consultant to and received lecture honoraria from Abbott/St Jude and has occasionally received travel reimbursements from Medtronic. He also served as a medicoscientific consultant to Alpha Omega. Dr Jamora is on the advisory boards of the Philippine offices of Lundbeck and Torrent and has received honoraria for lectures from the Philippine offices of Abbott, Allergan, Medichem, Natrapharm, and Sun Pharma and the international offices of Novartis, UCB, and Lundbeck. He has received research grants from the Collaborative Center for XDP (CCXDP). He has ongoing clinical trials for Allergan and Ipsen as a primary site investigator in Manila. Dr Hanssen has received travel grants from Actelion, Merz, and Abbott. Dr Münchau received grants from Pharm Allergan, Ipsen, Merz Pharmaceuticals, and Actelion. He received honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, GlaxoSmithKline, and Desitin. He was supported from nonprofit foundations or societies, including the Possehl-Stiftung (Lübeck), Dystonia Coalition (United States), Tourette Syndrome Association (Germany), European Huntington Disease Network, and the N.E.MO. Charity, that support the research of pediatric movement disorders. He received academic research support from Deutsche Forschungsgemeinschaft (MU 1692/3-1; SFB 936) and the University of Lübeck. Dr Weißbach received funding from the German Research Foundation (DFG; WE 5919 1-1) and the University of Lübeck (H03-2016). Dr Tronnier received honoraria from St Jude, Medtronic, EISAI, and Codman for scientific presentations. He is a member of the advisory boards of EISAI and Medtronic. Dr Klein serves as a medical advisor to Centogene and Biogen. No other disclosures are reported. Funding Support: This work was supported by the Collaborative Center for X-linked Dystonia-Parkinsonism, the Else Kröner Fresenius Foundation (2017_HA17), and a grant from the University Hospital Schleswig-Holstein, Campus Lübeck. St Judes Medical and Medtronic provided deep brain stimulation systems. Dr Klein is supported by a career development award from the Hermann and Lilly Schilling Foundation. Costs for the imaging studies and patient travel were absorbed by the Deutsche Forschungsgemeinschaft (SFB936; Drs Klein and Münchau and FOR2488; Drs Klein and Brüggemann). Research Foundation; DFG) provided funds for travel for patients and caregivers participating in the
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being -
SDG 10 Reduced Inequalities
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
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