Epilepsy in dentatorubral-pallidoluysian atrophy: A systematic review and meta-analysis

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the ATN1 gene. The juvenile onset type often presents with epilepsy, including progressive myoclonic epilepsy (PME). However, evidence on epilepsy in DRPLA remains limited. This systematic review and meta-analysis aimed to summarize clinical characteristics of DRPLA-related epilepsy.

We systematically searched MEDLINE (PubMed), CENTRAL, Embase, Ichushi, and ClinicalTrials.gov for studies on DRPLA-related epilepsy, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The review protocol was registered with the Open Science Framework. Any study design reporting at least one case of DRPLA-related epilepsy was eligible, including case reports, case series, cohort studies, and clinical trials. Eligible studies underwent screening and full-text assessment, followed by inclusion in descriptive and meta-analytic syntheses. Meta-analyses included only studies reporting ≥5 DRPLA patients.

A total of 181 studies encompassing 1191 patients met the eligibility criteria. DRPLA patients with epilepsy had a younger onset age (16.9 [95% confidence interval (CI) = 13.76-20.76] vs. 45.5 years [95% CI = 42.77-48.47]) and more CAG repeats (66.7 [95% CI = 63.63-69.84] vs. 59.2 [95% CI = 55.67-62.92]) than those without epilepsy. DRPLA patients with epilepsy showed a higher likelihood of paternal versus maternal inheritance (odds ratio = 2.47 [95% CI = .97-6.27]). Focal seizures were frequently observed (40.0%-76.5%) alongside myoclonic and generalized tonic-clonic seizures. Electroencephalographic findings included slow bursts (38.0%), photoparoxysmal responses (36.6%), and interictal epileptiform discharges (77.5%). Giant somatosensory-evoked potentials, typically seen in PME, were observed in only two patients and absent in 27. Among antiseizure medications, perampanel and levetiracetam were more frequently reported as effective than sodium channel blockers.

This review synthesizes fragmented evidence on DRPLA-related epilepsy and highlights key clinical and electrophysiological patterns. Despite limitations from small-scale studies, these findings support more informed clinical care and underscore the need for larger cohort studies.