Pallidus Stimulation for Chorea-Acanthocytosis: A Systematic Review and Meta-Analysis of Individual Data

Abstract

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington's Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

Keywords: Chorea; Chorea-acanthocytosis; Deep brain stimulation; Dystonia; Globus pallidus internus; Individual patient data.

Figure 1.

The ChAc mechanism and pallidus stimulation. A: ChAc, a neurodegenerative disease caused by a mutation in the VPS13A gene, is marked by the presence of acanthocytes in blood and choreiform movements. B: GPi-DBS for the treatment of ChAc. GPi-DBS, deep brain stimulation of globus pallidus interna; IPG, implanted pulse generator; ChAc, chorea-acanthocytosis.

Figure 2.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of the included studies.

Figure 3.

Frequency histograms of stimulation parameters. A: Relative frequency as a percentage of deep brain stimulation amplitude in volts from 52 electrodes. B: Relative frequency as a percentage of pulse widths in microseconds from 52 electrodes. C: Relative frequency as a percentage of frequencies utilized in Herz from 52 electrodes.