A 9-months-old boy, born full-term to a G1P1 mother via caesarian section, presented with history of delayed development, hypertonia and hyperreflexia
Non-contrast MRI demonstrated diffuse neuroparenchymal volume loss predominantly in the supratentorial region. Bilaterally symmetrical T2 hyperintensity was seen in the periventricular and deep white matter with sparing of the subcortical U fibres. Patchy T2 hyperintensities were seen in the midbrain and pons (predominantly along corticospinal tracts). Mild diffuse thinning of corpus callosum and mild volume loss of bilateral caudate nucleus was noted. Cystic changes were seen in bilateral periventricular frontal white matter. Symmetrical halos of alternating T2 hyper/hypo intensities were seen in the dentate nucleus of cerebellum. Symmetrical enlargement of the intracranial segment of optic nerves and optic chiasm was also seen. Mild bilateral symmetrical T2-hypointensity were seen in bilateral thalami. In laboratory evaluation, there was very little activity (2SD below the reference value) of galactocerebroside ß-galactosidase in blood leukocytes, confirming the diagnosis of Krabbe‘s disease.
Globoid cell leukodystrophy, also known as Krabbe disease is a progressive degenerative leukodystrophy of the CNS and peripheral nervous system characterised by the presence of unique "globoid" cells in the demyelinating lesions . It is an autosomal-recessive lysosomal storage disease caused by deficiency of the enzyme galactocerebroside β-galactosidase.
Enzyme deficiency results in abnormal accumulation of galactosyl cerebrosides within the lysosomes of Schwann cells and oligodendrocytes. This eventually results in apoptosis with secondary abnormal activation of microglia and macrophages with subsequent demyelination and gliosis. The multinucleated macrophages are known as globoid cells .
It is more commonly seen in females. It can be divided according to the age of onset into infantile, juvenile, and adult forms. The clinical manifestation varies according to age of presentation . The infantile form is the most common, usually presenting between 3 and 6 months with extreme irritability and feeding difficulties . Neonatal variant is rapidly progressive and almost invariably fatal .
On Imaging, in NCCT, bilaterally symmetric increased attenuation (due to globoid accumulation + calcification) in the thalami, basal ganglia, internal capsule, corticospinal tracts, and dentate nuclei of the cerebellum can sometimes be identified even prior to the development of visible abnormalities on standard MR sequences .
Classic MR findings in GLD are corticospinal tract hyperintensity on T2/FLAIR with confluent symmetric demyelination in the deep periventricular WM. The subcortical U-fibers are typically spared. Bithalamic hypointensity on T2WI which can appear hyperintense on T1 is common. Alternating "halo" or ring-like hypo intensities on T1WI and hyperintensities on T2WI can be identified in the cerebellar WM surrounding the dentate nuclei . Another distinctive feature of GLD is enlargement of the intracranial optic nerves and chiasm. Diffusely enlarged, enhancing cranial nerves and cauda equina nerve roots have also been reported in GLD. Diffusion tensor imaging (DTI) may demonstrate reduced fractional anisotropy in the corticospinal tracts before other abnormalities appear. MR spectroscopy findings vary with age, including increased choline, myoinositol, and lactate and reduced NAA in affected areas; these are common yet non-specific .
Overall outcome of this disease is poor. Hematopoietic stem cell transplantation halts progression in mild cases and can delay disease progression .
Take home message: Krabbe's disease should be considered in the diagnosis of early-onset infantile seizures and in older children with spasticity and ataxia.
Teaching points: Corticospinal tract involvement in MRI, hyperdense thalami in CT which appears T1 hyperintense, alternating "halos" around dentate nuclei, enlargement of optic nerve/chiasm, ± other cranial nerves are the important findings of Krabbe's disease .
 Correlation of Neurodevelopmental Features and MRI Findings in Infantile Krabbe's Disease : American Journal of Roentgenology: Vol. 192, No. 1 (AJR). Ajronline.org. https://www.ajronline.org/doi/full/10.2214/ajr.07.3885. Published 2020. Accessed June 27, 2020.
 Leukodystrophy in Children: A Pictorial Review of MR Imaging Features | RadioGraphics. Pubs.rsna.org. https://pubs.rsna.org/doi/full/10.1148/radiographics.22.3.g02ma01461. Published 2020. Accessed June 27, 2020.
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