Peripheral Neuropathy in Parkinson’s Disease Treated with Device-Assisted Therapies: How Often It Is Reported Depends on How It Is Sought. A Systematic Review and Meta-Analysis

Background/Objectives: Peripheral neuropathy (PN) is an increasingly recognized complication of device-assisted therapies for advanced Parkinson’s disease, with reported frequencies ranging from 1% to nearly 50% and no pooled estimate available. We aimed to estimate how often PN is reported under device-assisted therapy and whether its frequency is associated with levodopa exposure, catechol-O-methyltransferase (COMT) inhibition, and vitamin status. Methods: PubMed, Scopus, and Web of Science were searched without date restriction, and the reference lists of 21 reviews were screened. Studies reporting a peripheral nerve outcome under any device-assisted therapy were eligible, and proportions were pooled using random-effects models (PROSPERO CRD 1375888). Results: Seventy-five studies with 7106 patients were included. The pooled frequency under levodopa–carbidopa intestinal gel (LCIG) was 13.2% (95% confidence interval 9.8 to 17.6), against one case among 272 patients under levodopa-entacapone-carbidopa intestinal gel (LECIG). Frequency rose with levodopa dose (odds ratio 1.28 per 100 mg/day) and treatment duration (1.30 per 12 months). Neither COMT inhibition nor prophylactic B-vitamin supplementation was associated with lower frequency. Reported frequency ranged from 3.9%, where PN was recorded only when volunteered, to 33.6%, where all patients were tested. Conclusions: How intensively PN is sought appears to be a major determinant of how often it is found.