Analysis of Interindividual Lesion Progression Variability in Adult Cerebral Adrenoleukodystrophy

Area of Science:

• Neurology
• Radiology
• Genetics

Background:

• Cerebral adrenoleukodystrophy (cALD) is a severe X-linked adrenoleukodystrophy (X-ALD) phenotype causing rapid white matter destruction.
• Treatment options for adult cALD are limited, and monitoring MRI changes is crucial for guiding therapy and trials.
• Data on MRI change progression in adult cALD is scarce compared to childhood cases.

Purpose of the Study:

• To characterize the natural history of cerebral lesion progression in adult male patients with X-linked adrenoleukodystrophy (X-ALD).
• To identify predictors of lesion progression in adult cALD.
• To provide data for personalized treatment strategies and clinical trial design.

Main Methods:

• Multicenter retrospective cohort study of adult men with confirmed X-ALD.
• Inclusion of patients with at least two MRI scans showing lesion progression over a minimum 3-month untreated follow-up.
• Lesion volumes segmented using 3D U-Net, compared with Loes score, and analyzed for predictors like gadolinium enhancement and serum neurofilament light chain (sNfL).

Main Results:

• Analysis included 48 patients and 338 MRI scans, revealing an exponential lesion progression rate of 3.4% per month with significant interindividual variability.
• Lesion growth was slower in non-enhancing lesions (0.9%/month) and varied by initial location.
• Increased sNfL levels correlated better with absolute lesion volume and progression rate than with the Loes score.

Conclusions:

• Adult cALD lesion growth is exponential with substantial variability.
• Primary lesion location, contrast enhancement, and sNfL levels are potential predictors of lesion progression.
• Findings support personalized treatment approaches and inform future clinical trial designs for adult X-ALD.