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

Abstract

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.

Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments

“…Patients with Huntington's disease or other forms of chorea such as Chorea-acanthocytosis can experience improvements in movement with bilateral GPi DBS as suggested by many case reports and some case series [86][87][88][89]. Beneficial effects occur both for axial and limb chorea.…”

Deep brain stimulation in Huntington’s disease: Assessment of potential targets

“…Cislaghi et al [33] reported significant improvement in chorea with worsening of bradykinesia at 4 year follow-up after bilateral GPi DBS in a patient with the Westphal variant of HD. A recent long-term prospective open-label study evaluated the beneficial effects of bilateral GPi DBS on chorea in seven patients with refractory HD [34]. In this study, the mean improvement in chorea (Unified Huntington's Disease Rating Scale) was 58.34% (p = 0.018) and 59.8% (p = 0.040) at 1 and 3 years following bilateral GPi DBS, respectively [34].…”

“…A recent long-term prospective open-label study evaluated the beneficial effects of bilateral GPi DBS on chorea in seven patients with refractory HD [34]. In this study, the mean improvement in chorea (Unified Huntington's Disease Rating Scale) was 58.34% (p = 0.018) and 59.8% (p = 0.040) at 1 and 3 years following bilateral GPi DBS, respectively [34]. Progressive worsening of symptoms such as bradykinesia and dystonia with disease progression and no improvement with DBS therapy were noted in this study.…”

“…Progressive worsening of symptoms such as bradykinesia and dystonia with disease progression and no improvement with DBS therapy were noted in this study. In addition, DBS-induced bradykinesia was managed with reprogramming of the stimulation parameters (reduction of pulse width or bipolar settings) [34].…”

The non–Huntington disease choreas

“…A significant benefit to chorea was reported, although this was limited by disease progression. 19 As the therapeutic principles for the treatment of chorea are often extrapolated from HD to other disorders, DBS is increasingly being considered in patients with medication-resistant chorea of other etiologies.…”