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Meta-Analysis
. 2021 May;44(3):728-739.
doi: 10.1002/jimd.12356. Epub 2021 Jan 9.

MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines

Eric J Mallack  1   2 , Bela R Turk  3 , Helena Yan  1 , Carrie Price  3 , Michelle Demetres  1 , Ann B Moser  3 , Catherine Becker  2 , Kim Hollandsworth  3 , Laura Adang  4 , Adeline Vanderver  4 , Keith Van Haren  5 , Maura Ruzhnikov  5 , Joanne Kurtzberg  6 , Gustavo Maegawa  7 , Paul J Orchard  8 , Troy C Lund  8 , Gerald V Raymond  3 , Molly Regelmann  9 , Joseph J Orsini  10 , Elisa Seeger  11 , Stephan Kemp  12 , Florian Eichler  2 , Ali Fatemi  3
Affiliations
Meta-Analysis

MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines

Eric J Mallack et al. J Inherit Metab Dis. 2021 May.

Abstract

Background: Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset. We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy.

Methods: To establish the most frequent age and diagnostic neuroimaging modality for CCALD, we completed a meta-analysis of relevant studies published between January 1, 1970 and September 10, 2019. We used the consensus development conference method to incorporate the resulting data into guidelines to inform the timing and techniques for neuroimaging surveillance. Final guideline agreement was defined as >80% consensus.

Results: One hundred twenty-three studies met inclusion criteria yielding 1285 patients. The overall mean age of CCALD diagnosis is 7.91 years old. The median age of CCALD diagnosis calculated from individual patient data is 7.0 years old (IQR: 6.0-9.5, n = 349). Ninety percent of patients were diagnosed between 3 and 12. Conventional MRI was most frequently reported, comprised most often of T2-weighted and contrast-enhanced T1-weighted MRI. The expert panel achieved 95.7% consensus on the following surveillance parameters: (a) Obtain an MRI between 12 and 18 months old. (b) Obtain a second MRI 1 year after baseline. (c) Between 3 and 12 years old, obtain a contrast-enhanced MRI every 6 months. (d) After 12 years, obtain an annual MRI.

Conclusion: Boys with adrenoleukodystrophy identified early in life should be monitored with serial brain MRIs during the period of highest risk for conversion to CCALD.

Keywords: MRI; adrenoleukodystrophy; cerebral; childhood; imaging; newborn screening; surveillance.

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Conflict of interest statement

CONFLICT OF INTEREST

E. S. is the Founder of the Aidan Jack Seeger Foundation (AJSF). The AJSF provided support for in-person meetings during which these guidelines were generated, presented, and revised. The other authors have no financial relationships or conflicts of interest relevant to this article to disclose.

Figures

FIGURE 1
FIGURE 1
Early and late-stage demyelinating lesions in childhood cerebral adrenoleukodystrophy. (a) Very early CCALD lesion in the splenium of the corpus callosum, T2-MRI. (b) Corresponding post-contrast T1-MRI. (c) More prominent early lesion with (d) clear lesional contrast-enhancement. The goal of surveillance is to identify and treat patients at this stage of disease. (e) Advanced parieto-occipital lesion crossing the splenium of the corpus callosum, T2-FLAIR, with (f) a garland of “leading edge” contrast enhancement on T1-post contrast MRI. Patients are often symptomatic at this stage
FIGURE 2
FIGURE 2
PRISMA flow diagram
FIGURE 3
FIGURE 3
Age of CCALD diagnosis calculated from the sub-analysis of individual patient data. Age of CCALD diagnosis was extracted from the sub-analysis of 349 individually reported cases. The median age of diagnosis is 7.0 years old (IQR: 6.0–9.5). 90.0% of the cases diagnosed are between 3 and 12 years of age, inclusive
See this image and copyright information in PMC

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