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(Radiology. 2000;217:895-896.)
© RSNA, 2000

Signs in Imaging

The Eye-of-the-Tiger Sign1

R. Paul Guillerman, MD

1 From the Department of Radiology, Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039. Received May 12, 1999; accepted July 13. Address correspondence to the author (e-mail: guilr0@chmcc.org).

Index terms: Basal ganglia, MR • Brain, diseases, 142.121411, 142.88 • Brain, gray matter, 142.88 • Brain, iron • Brain, MR, 142.121411 • Hallervorden-Spatz syndrome, 142.88 • Signs in Imaging


   APPEARANCE
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EXPLANATION
 DISCUSSION
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On T2-weighted magnetic resonance (MR) images, marked low signal intensity circumscribes the globus pallidus. This low signal intensity surrounds a central region of high signal intensity in the anteromedial globus pallidus, producing an eye-of-the-tiger appearance (Figure) (1). The central region of high signal intensity may be better appreciated with certain pulse sequences (2).



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  		Figure 1. Transverse T2-weighted MR image depicts a low-signal-intensity ring (arrow) surrounding a central high-signal-intensity region (arrowhead) in the medial aspect of the globus pallidus, producing an eye-of-the-tiger appearance.

 

   EXPLANATION
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DISCUSSION
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The eye-of-the-tiger sign is most commonly described in Hallervorden-Spatz syndrome, where the ring of marked hypointensity involving the globus pallidus on T2-weighted MR images is due to excess iron accumulation. Iron is absent from the central nervous system at birth, but deposits occur throughout life in healthy adults, with the highest concentrations occurring in the globus pallidus primarily in the form of the metalloprotein ferritin (3,4). This iron deposition is pathologically intensified in Hallervorden-Spatz syndrome, while iron levels in blood and cerebrospinal fluid remain normal (5). Superparamagnetic iron substances such as ferritin have unpaired orbital electrons, which result in positive magnetic susceptibilities, a decrease in T2, and low signal intensity on T2-weighted images (6). Calcium deposition does not appear to be a substantial contributor to the basal ganglionic mineralization process in Hallervorden-Spatz syndrome (2).

The central high signal intensity of the globus pallidus in Hallervorden-Spatz syndrome has been attributed to gliosis, increased water content, and neuronal loss with disintegration, vacuolization, and cavitation of the neuropil (1,2,7,8). These processes lengthen T2, which produces high signal intensity on T2-weighted images.


   DISCUSSION
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The term Hallervorden-Spatz syndrome encompasses several disorders, each of which shares the clinical features of progressive extrapyramidal dysfunction and dementia with the pathologic triad of iron deposition, axonal spheroids, and gliosis in the globus pallidus (9). Hallervorden-Spatz disease is the familial pediatric neurodegenerative disorder characterized by rigidity, dystonia, impaired postural reflexes, and progressive dementia (10). Other distinct clinicopathologic disorders in the scope of Hallervorden-Spatz syndrome include dementia, tetraparesis, and neurofibrillary tangles (9); retinitis pigmentosa and acanthocytosis with or without lipid abnormalities, including hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, pallidal degeneration, or HARP, syndrome (11,12); X-linked disorders associated with mental retardation and Dandy-Walker malformation (13); disorders with Lewy bodies (14); and adult-onset disorders (9).

Hallervorden-Spatz syndrome is classified pathologically as a neuroaxonal dystrophy because of the presence of axonal spheroids. However, other neuroaxonal dystrophies do not manifest excess iron deposition in the globus pallidus (9) and would be expected to lack the eye-of-the-tiger sign at MR imaging. This is a useful differentiating point since infantile neuroaxonal dystrophy may have a clinical manifestation similar to that of Hallervorden-Spatz syndrome (15).

In Hallervorden-Spatz syndrome, histopathologic studies have revealed iron deposits in the perivascular spaces, walls of the lenticulostriate vessels, axonal spheroids, microglia, and macrophages in the neuropil (9,14,16). The subcellular localization of accumulated iron in Hallervorden-Spatz syndrome has not been determined, but the iron deposits may be associated with material bound to membranes derived from lysosomes (17).

The pathophysiologic basis of excess iron accumulation and toxicity in Hallervorden-Spatz syndrome is hypothetical at present. An enzymatic block in the metabolic pathway from cysteine to taurine has been reported (18). The resultant cysteine accumulation in the globus pallidus may chelate iron; the combined excess of cysteine and iron generates free radicals that damage neuronal membranes (18). Superoxide dismutase activity detected in axonal spheroids in the basal ganglia may facilitate the oxidative stress related to iron accumulation that exceeds the binding capacity of ferritin (16). As familial cases exist, a genetic basis has also been postulated, and a gene associated with Hallervorden-Spatz syndrome has been mapped to chromosome 20p12.3-p13 (5), although the protein encoded by this gene has not yet been characterized.

The eye-of-the-tiger sign is most commonly referenced in association with Hallervorden-Spatz syndrome, but the sign has been reported in other extrapyramidal parkinsonian disorders, including cortical–basal ganglionic degeneration (19), early-onset levodopa-responsive parkinsonism (20), and Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy) (21). Prior to MR imaging, the diagnosis of Hallervorden-Spatz syndrome was suspected at clinical examination and was confirmed only at postmortem examination. Computed tomography of Hallervorden-Spatz syndrome shows nonspecific striatal atrophy (22) and globus pallidus mineralization (23). The eye-of-the-tiger sign allows the specific MR imaging diagnosis of Hallervorden-Spatz syndrome or related extrapyramidal parkinsonian disorders in the presence of supporting clinical signs (24).


   FOOTNOTES
 
A trainee (resident or fellow) wishing to submit a manuscript for Signs in Imaging should first write to the Editor for approval of the sign to be prepared, to avoid duplicate preparation of the same sign.


   REFERENCES
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 APPEARANCE
 EXPLANATION
 DISCUSSION
 REFERENCES
 

  1. Sethi KD, Adams RJ, Loring DW, El Gammal T. Hallervorden-Spatz syndrome: clinical and magnetic resonance imaging correlations. Ann Neurol 1988; 24:692-694.[Medline]
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  18. Perry TL, Norman VW, Young S, et al. Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus. Ann Neurol 1985; 18:482-489.[Medline]
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