Title | A Longitudinal Analysis of Early Lesion Growth in Presymptomatic Patients with Cerebral Adrenoleukodystrophy. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Mallack EJ, Askin G, van de Stadt S, Caruso PA, Musolino PL, Engelen M, Niogi SN, Eichler FS |
Journal | AJNR Am J Neuroradiol |
Volume | 42 |
Issue | 10 |
Pagination | 1904-1911 |
Date Published | 2021 10 |
ISSN | 1936-959X |
Keywords | Adolescent, Adrenoleukodystrophy, Adult, Child, Child, Preschool, Humans, Magnetic Resonance Imaging, Male, Mutation, Phenotype, Retrospective Studies, Young Adult |
Abstract | BACKGROUND AND PURPOSE: Cerebral adrenoleukodystrophy is a devastating neurological disorder caused by mutations in the gene. Our aim was to model and compare the growth of early cerebral lesions from longitudinal MRIs obtained in presymptomatic patients with progressive and arrested cerebral adrenoleukodystrophy using quantitative MR imaging-based lesion volumetry. MATERIALS AND METHODS: We retrospectively quantified and modeled the longitudinal growth of early cerebral lesions from 174 MRIs obtained from 36 presymptomatic male patients with cerebral adrenoleukodystrophy. Lesions were manually segmented using subject-specific lesion-intensity thresholding. Volumes were calculated and plotted across time. Lesion velocity and acceleration were calculated between sequentially paired and triplet MRIs, respectively. Linear mixed-effects models were used to assess differences in growth parameters between progressive and arrested phenotypes. RESULTS: The median patient age was 7.4 years (range, 3.9-37.0 years). Early-stage cerebral disease progression was inversely correlated with age (ρ = -0.6631, < .001), early lesions can grow while appearing radiographically stable, lesions undergo sustained acceleration in progressive cerebral adrenoleukodystrophy (β = 0.10 mL/month [95% CI, 0.05-0.14 mL/month], < .001), and growth trajectories diverge between phenotypes in the presymptomatic time period. CONCLUSIONS: Measuring the volumetric changes in newly developing cerebral lesions across time can distinguish cerebral adrenoleukodystrophy phenotypes before symptom onset. When factored into the overall clinical presentation of a patient with a new brain lesion, quantitative MR imaging-based lesion volumetry may aid in the accurate prediction of patients eligible for therapy. |
DOI | 10.3174/ajnr.A7250 |
Alternate Journal | AJNR Am J Neuroradiol |
PubMed ID | 34503945 |
PubMed Central ID | PMC8562733 |
Grant List | K08 NS094683 / NS / NINDS NIH HHS / United States K12 NS066274 / NS / NINDS NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)