Hallervorden-Spatz disease

Clinical History

The patient presented with progressively increasing motor difficulties, gait impairment, slowing of voluntary movements, dsytonic posturing, speech problems (dysarthria), and mental deterioration over the previous two years.

Imaging Findings

The patient presented with progressively increasing motor difficulties, gait impairment, slowing of voluntary movements, dsytonic posturing, speech problems (dysarthria), and mental deterioration over the previous two years.

Computed tomography (CT) of the brain was performed, which revealed mild cerebral atrophy with bilateral punctuate calcifications of the globus pallidi. A cranial MRI study of the patient was performed on a 1.5T MR scanner. SE T1-weighted images, FSE proton-density (PD) and T2-weighted images, FLAIR sequence in the axial plane, FSE T2-weighted images and FLAIR sequence in the coronal plane, and SE T1-weighted images in the sagittal plane were obtained. This MRI study of the brain revealed symmetrical hypointense signal intensity changes bilaterally along the globus pallidi and nigro-striatal pathways associated with hyperintense signal changes of the globus pallidi, giving a characteristic "eye of the tiger" appearance.

Discussion

Hallervorden-Spatz disease (HSD) is a rare metabolic disorder characterised by autosomal recessive transmission, although some sporadic cases are rarely described. The onset of disease is usually at late adolescence, however both younger and older patients have been reported in the literature. The disease is characterised by relentless progression of extra-pyramidal symptoms such as gait impairment, rigidity of the limbs, slowing of voluntary movements, choreo-athetosis, dystonic posturing, spasticity, tremors, dysarthria, and mental deterioration, leading to an intellectual decline at a young age. Optic nerve atrophy, retinal degeneration and pyramidal signs are other associated findings.

CT studies usually show symmetrical hypodensity in the mildly atrophic basal ganglia, however high-density calcifications in the globus pallidi without any atrophy have also been described.

MRI studies reveal the iron deposits as hypointense areas on T2-weighted images mainly along the basal ganglia and substantia nigra. Areas of gliosis, demyelination, neuronal loss, and axonal swelling are seen as high signal intensity areas on T2-weighted images. Initially, hyperintense areas are seen in the globus pallidi and substantia nigra. Later, as the disease progresses, a hypointense rim is seen around it, due to iron deposition, causing a characteristic "eye of the tiger" sign.

Pathological studies show generalised atrophy of the brain with decreased size of the caudate nucleus, substantia nigra, and tegmentum. Histological examination of the brain reveals neuronal loss, axonal swelling (also known as axonal spheroids secondary to the appearance of axonal cells showing vacuolated cytoplasm), gliosis and iron deposits in the globus pallidi, substantia nigra, caudate nucleus, amygdala, hippocampus and pons.

A deficiency of cysteine dioxygenase has been reported in HSD; this causes a subsequent accumulation of cysteine, which chelates iron in the globus pallidi. Free radicals of iron and cysteine damage neuronal cell membranes, leading to swelling of the terminal portions of axons due to accumulation of damaged cellular constituents and products. The resulting axonal spheroids lead to break-up of myelin sheaths and reactive gliosis.

Differential Diagnosis List

Final Diagnosis

Hallervorden-Spatz disease

URL:	https://www.eurorad.org/case/1804
DOI:	10.1594/EURORAD/CASE.1804
ISSN:	1563-4086