Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy

Abstract

Background and ObjectivesWe sought to characterize the natural history and standard-of-care practices between the radiologic appearance of brain lesions, the appearance of lesional enhancement, and treatment with hematopoietic stem-cell transplant or gene therapy among boys diagnosed with presymptomatic childhood-onset cerebral adrenoleukodystrophy (CCALD).MethodsWe analyzed a multicenter, mixed retrospective/prospective cohort of patients diagnosed with presymptomatic CCALD (Neurologic Function Score = 0, Loes Score [LS] = 0.5–9.0, and age <13 years). Two time-to-event survival analyses were conducted: (1) time from CCALD lesion onset-to-lesional enhancement and (2) time from enhancement-to-treatment. The analysis was repeated in the subset of patients with (1) the earliest evidence of CCALD, defined as an MRI LS ≤ 1, and (2) patients diagnosed between 2016 and 2021.ResultsSeventy-one boys were diagnosed with presymptomatic cerebral lesions at a median age of 6.4 years [2.4–12.1] with a LS of 1.5 [0.5–9.0]. Fifty percent of patients had lesional enhancement at diagnosis. In the remaining 50%, the median Kaplan-Meier (KM)-estimate of time from diagnosis-to-lesional enhancement was 6.0 months (95% CI 3.6–17.8). The median KM-estimate of time from enhancement-to-treatment is 3.8 months (95% CI 2.8–5.9); 2 patients (4.2%) developed symptoms before treatment. Patients with a diagnostic LS ≤ 1 were younger (5.8 years [2.4–11.5]), had a time-to-enhancement of 4.7 months (95% CI 2.7–9.30), and were treated in 3.8 months (95% CI 3.1–7.1); no patients developed symptoms before treatment. Time from CCALD diagnosis-to-treatment decreased over the course of the study (ρ = −0.401, p = 0.003).DiscussionOur findings offer a more refined understanding of the timing of lesion formation, enhancement, and treatment among boys with presymptomatic CCALD. These data offer benchmarks for standardizing clinical care and designing future clinical trials.

Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy

“…In the Research Article entitled “Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy: Timing and Treatment” by Mallack et al, 1 the title of Figure 5 should be “Diagnostic LS ≤ 1.0: Time From CCALD Diagnosis-to-Enhancement.” The publisher regrets the error.…”