An individual patient analysis of the efficacy of using GPi-DBS to treat Huntington's disease

Abstract

Objective: The efficacy of globus pallidus internus-deep brain stimulation (GPi-DBS) for the treatment of Huntington's disease (HD) has not been validated in large-scale studies. We conducted an individual patient analysis to pool outcomes of all of the published HD-GPi-DBS studies.

Methods: PubMed, Embase and the Cochrane Library were searched for relevant articles. The Unified Huntington's Disease Rating Scale (UHDRS)-motor and UHDRS-chorea improvements were analyzed during different follow-up periods. Secondary outcomes, including UHDRS-motor subitem scores and functional assessment results, were also analyzed. Correlation and regression analyses were conducted to find improvement predictors. This study was registered in PROSPERO (CRD42018105995).

Results: Eighteen studies including 39 patients with 124 visits were analyzed. GPi-DBS significantly improved the UHDRS-motor score in <3 months (p = 0.001), 3-9 months (p < 0.001), and 9-12 months (p < 0.001), but did not continue in later follow-ups. UHDRS-chorea was significantly improved even in the >30-month follow-up (p = 0.003). Functional assessment was not improved 12 months postoperatively (p = 0.196). The Westphal variant of HD (W-HD) gained no motor benefits 6 months postoperatively (p = 0.178). The Westphal variant was the only risk factor for DBS efficacy (p = 0.044). The rate of stimulation-related adverse events was 87.2%.

Conclusions: GPi-DBS has a stable effect on chorea symptoms in HD patients. Chorea-dominant patients may be the best candidates for surgery, while attention should be paid to postoperative stimulation-related complications. Given that GPi-DBS has limited effects on other motor symptoms, W-HD patients are not surgical candidates.

Keywords: Deep brain stimulation; Globus pallidus internus; Huntington’s disease; Individual patient data; Meta-analysis.