Seizures in childhood cerebral adrenoleukodystrophy.

Aim: To describe seizure prevalence in childhood cerebral adrenoleukodystrophy (CCALD) and the relationship to disease severity/progression.

Method: This was a retrospective observational cross-sectional study of patients with CCALD at two leukodystrophy centers between 2008 and 2024 compared to patients with X-linked adrenoleukodystrophy (X-ALD) without cerebral lesions. Patients with CCALD were under 18 years old, had genetically confirmed X-ALD, and had brain magnetic resonance imaging (MRI) consistent with CCALD. Statistics included: descriptive values (mean, median, range) and clinical variables compared using Wilcoxon rank-sum tests for patient age, MRI score, functional status, electroencephalogram (EEG) findings, and seizure characteristics.

Results: Of 86 male children with CCALD, 25 (29%) experienced seizures, of whom 22 (88%) received their X-ALD diagnosis after onset of CCALD symptoms, and 45% (10/22) of these were diagnosed directly because of seizure. Seizure severity correlated with worse functional status and MRI/Loes score; no seizures occurred with Loes score less than 6. All reported seizures were motor. In those with seizures with available EEG (n = 15), diffuse slowing was more common than epileptiform discharges (73.3% vs. 26.7% respectively). Of the 53 patients with X-ALD without cerebral involvement, only 5.7% experienced seizures at any age.

Interpretation: Seizures in CCALD are not uncommon, indicating that X-ALD should be considered for male children presenting with first-time seizure. Seizures and seizure severity increase with advancing disease.