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

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.

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

“…This discrepancy exemplifies the challenge that our program and our partnering SCCs faced when trying to enforce a uniform approach to monitor these cases when more formal consensus statements were yet to be published. Recommendations were eventually published, but the publication dates were well after screening had begun [14,15,19]. In the interim, our program worked collaboratively with specialists across California and consulted with other state screening programs [25] to provide draft guidelines until a national consensus could be reached.…”

“…Hematopoietic stem cell transplantation 2 of 13 (HSCT) has been shown to be an effective therapy to halt cerebral demyelination and prevent death if administered early, before neurologic progression [11][12][13]. Regular MRIs and adrenal testing are recommended to monitor for early signs of the disease in order to administer treatment when it is most effective [14][15][16][17][18][19].…”

Advanced Diagnostic System and Introduction of Newborn Screening of Adrenoleukodystrophy and Peroxisomal Disorders in Japan

“…Through these efforts, we diagnosed 29 male patients as Addison-only at diagnosis and 43 pre-symptomatic male patients, which led to appropriate follow-up (Figure 2) [8] based on guidelines and references [10][11][12]. More recently, with regard to the timing of starting the MRI follow-up, in order to examine more efficiently and with less burden, it has been suggested that the first examination be done at 12 to 18 months of age, the second after 1 year, and then every 6 months between 3 and 12 years of age [13]. These follow-up efforts lead to steroid replacement therapy and HSCT at the appropriate time to improve the prognosis in male patients with ALD.…”

“…Follow-up flowchart for patients with pre-symptomatic adrenoleukodystrophy[8]. * start MRI follow-up at 12 to 18 months of age[13].…”

Imaging in X-Linked Adrenoleukodystrophy

“…37 The hallmark of structural MRI is the ability to detect cerebral ALD lesions before clinical symptoms become apparent. Therefore, the current recommendation is to repeat brain MRI every 6 months up until the age of 12 years and yearly after that, 12,38 which is a great burden for patients.…”