Deep brain stimulation and intrathecal/intraventricular baclofen for glutaric aciduria type 1: A scoping review, individual patient data analysis, and clinical trials review

Glutaric aciduria type 1 (GA1) is an autosomal recessive disease frequently leading to dystonia. Deep brain stimulation (DBS), intrathecal baclofen (ITB), and intraventricular baclofen (IVB) are the current interventional treatment options for refractory dystonia. We performed a scoping review, individual patient data (IPD) analysis, and clinical trials review to summarize the existing literature on these interventions in this population, characterize outcomes, and suggest directions for future investigation. PubMed, Embase, and Scopus were searched following PRISMA guidelines. IPD were extracted from studies providing IPD for GA1 patients. ClinicalTrials.gov was reviewed. Of 139 articles, 7 studies with 10 patients were included. In study‐level data, 2/4 (50.0%) DBS studies found no improvement in dystonia and 3/3 (100%) on baclofen found decreased dystonia and enteral medication regimen. In the IPD analysis, four studies with 5 patients (2 IVB, 2 DBS, 1 ITB) were included. The average percent reduction in dystonia was 29.9% ± 32.5% (median:18%, IQR:18%–29.2%). Function improved in 4 (80.0%) patients. All patients with reported changes in enteral dystonia‐related medication regimen (3/3, 100%) reported reduction in medication usage. No patients (0%) had perioperative complications. Mean follow‐up length was 14.8 ± 12.2 months. No interventional clinical trials were found. ITB, IVB, and DBS represent present neuromodulatory approaches for the treatment of GA1. ITB and IVB reduce dystonia, while DBS has a heterogeneous effect. ITB and IVB improved function and reduced enteral medication regimens. These findings must be viewed with caution considering limited data and a serious risk of bias. Further large‐scale studies are necessary to determine indications for ITB, IVB, and DBS and elucidate treatment algorithms.