Abstract
BACKGROUND AND PURPOSE: Cerebral adrenoleukodystrophy is a devastating neurological disorder caused by mutations in the ABCD1 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, P < .001), early lesions can grow while appearing radiographically stable, lesions undergo sustained acceleration in progressive cerebral adrenoleukodystrophy (β = 0.10 mL/month2 [95% CI, 0.05−0.14 mL/month2], P < .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.
ABBREVIATIONS:
- CALD
- cerebral adrenoleukodystrophy
- HSCT
- hematopoietic stem cell transplantation
- LS
- Loes score
- t0
- time-zero
Footnotes
S.N. Niogi and F.S. Eichler are senior authors.
Statistical analysis was performed by Eric Mallack, MD, 175 Cambridge Street, Suite 340, Boston, MA 02114, and Gulce Askin, MPH, 402 E. 67th St, Level C2, New York, NY 10065.
All phases of this study were supported by the National Institute of Health and the Leblang Charitable Foundation. Dr Musolino is supported by a K08 (1K08NS094683-01), and Dr Mallack, by a K12 (5 K12 NS066274), both from the National Institute of Neurological Disorders and Stroke.
Disclosures: Eric J. Mallack—RELATED: Grant: National Institutes of Health/National Institute of Neurological Disorders and Stroke K12 Neurological Sciences Academic Development Award.* Patricia L. Musolino—RELATED: Grant: National Institute of Neurological Disorders and Stroke, Comments: K08.*. Marc Engelen—UNRELATED: Consultancy: Minoryx Therapeutics, Autobahn, bluebird bio, Comments: research collaboration with pharmaceutical companies developing drugs for X-linked adrenoleukodystrophy*; Grants/Grants Pending: Vidi Grant, Netherlands Organization for Scientific Research, Comments: grant for natural history study in adrenoleukodystrophy; Payment for Development of Educational Presentations: cerebral adrenoleukodystrophy education video on Medscape, Comments: commissioned by bluebird bio. Sumit N. Niogi—RELATED: Grant: K12 National Institutes of Health Award, Comments: The study was funded, in part, by a K12 National Institutes of Health Award to Weill Cornell Medicine with Dr Mallack as the Principal Investigator of the grant. I received no support through this grant mechanism.* Florian S. Eichler—UNRELATED: Consultancy: SwanBio Therapeutics; Patents (Planned, Pending Or Issued): adenoassociated virus serotype–mediated ABCD1 gene correction; Payment for Development of Educational Presentations: PRIME medical education company, Comments: for live webinars on adrenoleukodystrophy; OTHER RELATIONSHIPS: Principal Investigator of the adrenoleukodystrophy gene therapy sponsored by bluebird bio, site Principal Investigator of the trial MIN102 sponsored by Minoryx Therapeutics. *Money paid to the institution.
- © 2021 by American Journal of Neuroradiology
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