Related Experiment Video
Updated: Sep 22, 2025
Author Spotlight: Studying Clinical Characters and Epilepsy Outcomes After Frontal Disconnection in Patients with MOGHE
Published on: August 16, 2024
Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy: Timing and Treatment
Eric James Mallack1, Keith P Van Haren2, Anna Torrey2
1From the Department of Pediatrics (E.J.M., A.T.), Division of Child Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital; Department of Pediatrics (E.J.M.), Memorial Sloan Kettering Cancer Center, New York, NY; Department of Neurology (K.P.V.H.), Stanford University Schoolds of Medicine, Lucile Packard Children's Hospital, CA; Department of Pediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, the Netherlands; Department of Genetic Medicine (G.V.R.), Johns Hopkins University, Baltimore, MD; The Moser Center for Leukodystrophies (A.F.), Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD; and Department of Neurology (F.S.E.), Harvard Medical School, Massachusetts General Hospital, Boston. ejm9009@med.cornell.edu.
Insights
This study tracked brain lesion progression in boys with presymptomatic childhood-onset cerebral adrenoleukodystrophy (CCALD). Early detection and treatment, particularly with hematopoietic stem-cell transplant, significantly improved outcomes, preventing symptom onset.
Area of Science:
- Neurology
- Genetics
- Pediatric Medicine
Background:
- Childhood-onset cerebral adrenoleukodystrophy (CCALD) is a rare genetic disorder affecting the nervous system.
- Early diagnosis of presymptomatic CCALD is crucial for timely intervention.
- Understanding the natural history of CCALD lesion development and enhancement is key to optimizing treatment strategies.
Purpose of the Study:
- To characterize the natural history of brain lesions in presymptomatic CCALD.
- To analyze the timing of lesional enhancement in relation to diagnosis.
- To evaluate standard-of-care practices, including hematopoietic stem-cell transplant and gene therapy, for presymptomatic CCALD.
Main Methods:
- A multicenter cohort study of boys with presymptomatic CCALD (Neurologic Function Score = 0, Loes Score [LS] = 0.5-9.0, age <13 years).
- Two time-to-event survival analyses: lesion onset to enhancement, and enhancement to treatment.
- Subgroup analysis of patients with early CCALD evidence (LS ≤ 1) and those diagnosed between 2016-2021.
Main Results:
- Seventy-one boys diagnosed with presymptomatic CCALD had a median age of 6.4 years.
- 50% showed lesional enhancement at diagnosis; median time to enhancement was 6.0 months for others.
- Median time from enhancement to treatment was 3.8 months, with 4.2% developing symptoms before treatment. Earlier LS scores correlated with younger age and faster treatment.
Conclusions:
- Refined understanding of lesion development, enhancement, and treatment timing in presymptomatic CCALD.
- Data provide benchmarks for standardizing clinical care.
- Findings aid in designing future clinical trials for CCALD interventions.
Background And Objectives:
We 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).
Methods:
We 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.
Results:
Seventy-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).
Discussion:
Our 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.
Related Concept Videos
01:22Alzheimer's Disease: Treatment
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:22Lysosomal Hydrolases