Teaching Case

A 5-year-old boy was admitted to the emergency department for subacute ataxia and bradypsychia. Personal history included acute recurrent laryngitis, speech difficulty during the last 9 months and left eye strabismus in the past 3 months.

An emergent cranial unenhanced Computerized Tomography (CT) was performed and revealed extensive bilateral calcifications in bilateral parieto-occipital white matter, with some thicker foci in the medial aspect of the hyperdense areas. Abdominal ultrasound was normal.

A cranial Magnetic Resonance imaging (MRI) was carried out two days later with T1WI, T2WI, FLAIR, SWI, diffusion, ASL perfusion, and contrast-enhanced T1. The MR images demonstrated an extensive and confluent bilateral parieto-occipital white matter abnormal signal intensity suggestive of demyelination, with involvement of the posterior corpus callosum and sparing of arcuate fibres. The lesions also involved the posterior internal capsules and the pyramidal tracts within the brainstem. Presence of calcifications could be verified on susceptibility-weighted image (SWI). Presence of diffusion restriction and gadolinium enhancement was present in the anterior edge of the demyelinating lesions, reflecting the severe inflammation and blood-brain barrier disruption.

Background

X-linked adrenoleukodystrophy [X-ALD] is the most common peroxisomal disorder. characterized by impaired beta-oxidation of very long-chain fatty acids, with consequent accumulation all tissues, including the white matter of the brain, the spinal cord and adrenal cortex [1]. It is caused by mutations in the ABCD1 gene located on the X-chromosome. Nowadays, a classification in children and adults is described in several clinical phenotypes [2].

Clinical Perspective

Cerebral ALD is the most rapidly progressive and devastating phenotype, usually presents in boys older than 2.5 years, with deficits in cognitive abilities and decline of school performance. As the disease progresses, more neurologic deficits appear, with hyperactive behaviour, apraxia, visual and auditory impairment, hemiparesis or spastic tetraparesis, cerebellar ataxia and seizures. Death often occurs two to four years after onset of symptoms [2, 3]. Postmortem histopathological examination reveals extensive demyelination with perivascular infiltration of lymphocytes and macrophages that resembles, to some extent, the demyelinating lesions seen in multiple sclerosis [2].

Imaging Perspective

Brain MRI shows the abnormal signal intensity involving the corpus callosum, parieto-occipital white matter, pyramidal tracts within the brainstem, pons, and internal capsules. This pattern with symmetrical peri-ventricular "butterfly wings" like lesions is seen in about 80% of cases. Enhancement usually occurs in a second stage when the disease starts to progress rapidly, reflecting severe inflammation and disruption of the blood-brain barrier. In the absence of biomarkers to predict this evolution, brain MRI remains the only tool to detect this evolution in an early stage. A scoring system to grade the demyelinating abnormalities on brain MRI has been developed by Loes [4]. Atypical imaging patterns have been described, such as frontal predominant involvement [5], asymmetrical pattern, or isolated involvement of tracts or cerebellum. Symmetrical calcifications have been rarely reported and may be an early sign of progression to inflammatory stage [6].

Outcome

Our patient presented already with advanced disease, with LOES score 14 in the initial MR imaging. Metabolic study disclosed elevated very long-chain fatty acids. Next Generation Sequencing analyses proved the ABCD1 mutation. Owing to the quite recent diagnosis, the patient is still alive, but even with experimental therapy, he is presenting a rapid progression of the disease.

Take home message / Teaching Points

Characteristic MR imaging features of childhood cerebral X-linked ALD have been well documented, although most radiologists have limited experience.

The typical location of calcifications on the initial CT may also help in narrowing the differential diagnoses in correlation with an appropriate clinical context.

All patient data have been completely anonymized throughout the entire manuscript and related files.