To assess the prevalence, presentation, and neuroimaging correlates of cerebral visual impairment (CVI) and visual processing deficits associated with cerebral adrenoleukodystrophy (CALD).

X-linked adrenoleukodystrophy is a single gene disorder characterized by defective β-oxidation of very long chain fatty acids. Without treatment, the cerebral demyelinating phenotype, CALD, causes rapid neurologic decline, ultimately progressing to total neurologic disability within months to three years of symptom onset. With the advent of newborn screening and both allogeneic and experimental autologous stem cell transplantation, it is now possible to halt the progression of CALD at increasingly earlier timepoints in the natural history of the disease. Higher order visual processing deficits are a particularly relevant focus of study as they may serve as an early marker of neurologic decline and potentially identify an earlier window of opportunity for treatment.

Medical records were retrospectively reviewed for all male CALD patients seen at Massachusetts General Hospital between June 2005 and July 2020 (n=89). Neurological assessments and neuropsychological tests were reviewed to assess for signs and symptoms of CVI. Brain MRIs were reviewed to evaluate lesion burden.

Forty-nine percent of patients had findings suggestive of CVI, most commonly a deficit/decline in visual perceptual reasoning as assessed by formal neuropsychological testing (32%), a visual field cut (29%), or a deficit/decline in visual-motor integration (29%). Symptoms were not limited to a single pattern of lesion progression (e.g. posterior-predominant vs. anterior-predominant). Symptoms were prevalent in 31% of patients with very early lesions (Loes score ≤3). Symptoms presented as late as two years following hematopoietic stem cell transplantation (HSCT).

CVI is prevalent not just among untreated, advanced symptomatic CALD patients, but also in those with very early lesions who have undergone successful HSCT. Even patients considered ideal transplant candidates based on Loes score and overall clinical picture may not experience functionally optimal outcomes.