Abstract
Objective: To assess the prevalence, presentation, and neuroimaging correlates of cerebral visual impairment (CVI) and visual processing deficits associated with cerebral adrenoleukodystrophy (CALD).
Background: 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.
Design/Methods: 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.
Results: 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).
Conclusions: 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.
Disclosure: The institution of Ms. Corre has received research support from American Academy of Neurology Institute. Ms. Corre has received personal compensation in the range of $500-$4,999 for serving as a Neurodevelopmental Disabilities Scholar with Child Neurology Foundation. Ms. Bambery has nothing to disclose. Dr. Bennett has nothing to disclose. Haley Andonian has nothing to disclose. Mr. Kelly has nothing to disclose. An immediate family member of Dr. Eichler has received personal compensation for serving as an employee of UpToDate. Dr. Eichler has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for SwanBio Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Eichler has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Origin Biosciences. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orchard Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Autobahn Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bluebird Bio. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. Dr. Eichler has received stock or an ownership interest from SwanBio Therapeutics. The institution of Dr. Eichler has received research support from Bluebird Bio. The institution of Dr. Eichler has received research support from Minoryx Therpeutics. The institution of Dr. Eichler has received research support from Sio Therapeutics. Dr. Eichler has received intellectual property interests from a discovery or technology relating to health care.
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