Abstract Details

Title Natural History of Neurological and Neuroimaging Progression in Childhood Cerebral X-Linked Adrenoleukodystrophy (CCALD).

Topic Child Neurology and Developmental Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-043

Objective Analysis of a large cohort of boys with childhood cerebral X-linked adrenoleukodystrophy (ALD) with the goal to define the rate of neurological disease progression and its correlation with magnetic resonance imaging (MRI) severity.

Background ALD is a rare peroxisomal disorder due to mutations in ABCD1presenting with distinct and variable phenotypes ranging from the rapidly progressive fatal childhood cerebral form (CCALD) to the slowly progressive adult-onset adrenomyeloneuropathy. Furthermore, while an MRI severity score, referred to Loes score is utilized to determine disease pathology, its correlation with neurological disease severity and progression is not known.

Design/Methods

Retrospective analysis of the Neurological Function Score (NFS) and the Loes MRI severity score of an existent database of 689 boys (<18 years) with CCALD. Individuals with normal neuroimaging or who had undergone bone marrow transplantation were excluded. Bootstrapping technique was used with 100 random samples with the aim to explore whether the Loes score can predict changes in NFS.

Results 455 patients had CCALD at the time of first visit with an average age of 8.6 years while 234 patients were asymptomatic or had Addison’s disease only. The most common findings were aphasia(71%), vision impairment(70%) and running difficulties(69%). 64 patients had both NFS and Loes scores at baseline and at least one follow-up and in this group, a strong correlation between maximum recorded NFS and Loes score was observed. The bootstrap model yielded a Loes score slope of 0.92 with an average expected NFS change of 1.71 (predicted NFS=1.71+(0.92) x change in MRI).

Conclusions There is a high correlation between the Loes MRI score and NFS, with Loes score changes being predictive neurological progression. This data can serve as a basis for future trial designs and demonstrates that the Loes score is a surrogate marker of disease progression in CCALD.

Authors/Disclosures
Mohammed A. Almuqbil, MD, FAAN (King Saud bin Abdulaziz University for Health Sciences) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
John Henderson	No disclosure on file
Gerald Raymond, MD (Johns Hopkins)	Dr. Raymond has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Bluebird bio. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Travere. Dr. Raymond has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with Dept of HHS.
Seyed A. Fatemi, MD, MBA (Kennedy Krieger Institute, Johns Hopkins Medical Institute)	Dr. Fatemi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for RCO law. The institution of Dr. Fatemi has received research support from Minoryx. The institution of Dr. Fatemi has received research support from Viking Therapeutics. The institution of Dr. Fatemi has received research support from Swanbio Therapeutics . The institution of Dr. Fatemi has received research support from Autobahn Therapeutics. The institution of Dr. Fatemi has received research support from Nuvelution. The institution of Dr. Fatemi has received research support from NIH. The institution of Dr. Fatemi has received research support from A Cure for Ellie Foundation. The institution of Dr. Fatemi has received research support from Brian's Hope Foundation . Dr. Fatemi has received intellectual property interests from a discovery or technology relating to health care. Dr. Fatemi has a non-compensated relationship as a Director (Board member) with ALDConnect that is relevant to AAN interests or activities.

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