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Abstract
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.
Glossary
- ALD=
- X-linked adrenoleukodystrophy;
- CALD=
- cerebral adrenoleukodystrophy;
- CCALD=
- childhood cerebral adrenoleukodystrophy;
- HSCT=
- hematopoietic stem-cell transplant;
- IRB=
- institutional review board;
- KM=
- Kaplan-Meier;
- LO=
- Lorenzo's Oil;
- LS=
- Loes Score;
- NFS=
- Neurologic Function Scale
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Submitted and externally peer reviewed. The handling editor was Renee Shellhaas, MD, MS.
- Received October 16, 2021.
- Accepted in final form March 4, 2022.
- © 2022 American Academy of Neurology
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