MRI brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy

Abstract

Objective: To describe the brain MRI findings in asymptomatic patients with childhood cerebral adrenoleukodystrophy (CCALD).

Methods: We retrospectively reviewed a series of biochemically or genetically confirmed cases of adrenoleukodystrophy followed at our institution between 2001 and 2015. We identified and analyzed 219 brain MRIs from 47 asymptomatic boys (median age 6.0 years). Patient age, MRI scan, and brain lesion characteristics (e.g., contrast enhancement, volume, and Loes score) were recorded. The rate of lesion growth was estimated using a linear mixed effect model.

Results: Sixty percent of patients (28/47) showed brain lesions (median Loes score of 3.0 points; range 0.5-11). Seventy-nine percent of patients with CCALD (22/28) had contrast enhancement on first lesional or subsequent MRI. Lesion progression (Loes increase of ≥0.5 point) was seen in 50% of patients (14/28). The rate of lesion growth (mL/mo) was faster in younger patients (r = -0.745; p < 0.0001). Older patients (median age 14.4 y/o) tended to undergo spontaneous arrest of disease. Early lesions grew 46× faster when still limited to the splenium, genu of the corpus callosum, or the brainstem (p = 0.001).

Conclusion: We provide a description of CCALD lesion development in a cohort of asymptomatic boys. Understanding the early stages of CCALD is crucial to optimize treatments for children diagnosed by newborn screening.

Figure 1. Conversion to childhood cerebral adrenoleukodystrophy on MRI

Development of a T2-hyperintense lesion in the splenium of a 4-year-old boy (A) and genu of a 5.3-year-old boy (B) from previously normal imaging (Loes score of 0).

Figure 2. Loes scores and patterns of enhancement on MRI

(A) A 5.5-year-old boy with a T2-hyperintense lesion in the splenium, Loes score of 2, and ring-like enhancement on T1-weighted postcontrast MRI. (B) A 4.3-year-old boy with a lesion in the splenium, Loes score of 3, and patchy enhancement. (C) A 7.4-year-old boy with a lesion in the splenium extending into the parieto-occipital white matter, Loes score of 11, with peripheral enhancement.

Figure 3. Early detection of childhood cerebral adrenoleukodystrophy on MRI

(A) An 8-year-old boy with a T2-hyperintense lesion in the splenium of the corpus callosum, Loes score of 1. (B) A 7.2-year-old boy with a lesion in the genu of the corpus callosum, Loes score of 1. (C) An 8.2-year-old boy with a lesion in the left frontopontine projection fibers, Loes score of 0.5. Contrast enhancement can be appreciated in all cases.

Figure 4. Development of contrast enhancement in a cerebral adrenoleukodystrophy lesion

A 6.9-year-old boy, nonenhancing lesion in the splenium of the corpus callosum, Loes score of 1, develops contrast enhancement on the following MRI 5.6 months later.

Figure 5. Correlation of lesion growth rate and age

A strong, negative relationship between rate of lesion growth (mL/mo) and patient age (years) at first abnormal MRI can be appreciated (r = −0.745; p < 0.0001).