Deep brain stimulation for Huntington's disease: long-term results of a prospective open-label study

Clinical article

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  • 1 Functional Neurosurgery Unit, Neurosurgery Department,
  • | 5 Neurology Department, and
  • | 6 Medical Genetics Department, University Hospital of Montpellier;
  • | 2 Institut de Génomique Fonctionnelle, INSERM, UMR-S 661, CNRS UMR 5203;
  • | 3 University of Montpellier 1, Montpellier, France; and
  • | 4 Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
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Object

To date, experience of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Huntington's disease (HD) has been limited to a small number of case reports. The aim of this study was to analyze long-term motor outcome of a cohort of HD patients treated with GPi DBS.

Methods

Seven patients with pharmacologically resistant chorea and functional impairment were included in a prospective open-label study from 2008 to 2011. The main outcome measure was the motor section of the Unified Huntington's Disease Rating Scale. The primary end point was reduction of chorea.

Results

Patients underwent MRI-guided bilateral GPi implantation. The median duration of follow-up was 3 years. A significant reduction of chorea was observed in all patients, with sustained therapeutic effect; the mean improvement on the chorea subscore was 58.34% at the 12-month follow-up visit (p = 0.018) and 59.8% at the 3-year visit (p = 0.040). Bradykinesia and dystonia showed a nonsignificant trend toward progressive worsening related to disease evolution and partly to DBS. The frequency of stimulation was 130 Hz for all patients. DBS-induced bradykinesia was managed by pulse-width reduction or bipolar settings. Levodopa mildly improved bradykinesia in 4 patients. Regular off-stimulation tests confirmed a persistent therapeutic effect of DBS on chorea.

Conclusions

GPi DBS may provide sustained chorea improvement in selected HD patients with pharmacologically resistant chorea, with transient benefit in physical aspects of quality of life before progression of behavioral and cognitive disorders. DBS therapy did not improve dystonia or bradykinesia. Further studies including quality of life measures are needed to evaluate the impact of DBS in the long-term outcome of HD.

Abbreviations used in this paper:

DBS = deep brain stimulation; DRS = Dementia Rating Scale; FA = Functional Assessment; GPi = globus pallidus internus; HD = Huntington's disease; HR-QoL = health-related quality of life; IPG = implantable pulse generator; IS = Independence Scale; TFC = Total Functional Capacity; UHDRS = Unified Huntington's Disease Rating Scale.

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