‘Eye-of-the-Tiger’ Sign and Classic Pantothenate Kinase Associated Neurodegeneration

Abstract

A five-year-old girl presented with one-year history of gradual onset repeated falls while walking, dysarthria, increasing stiffness, toe walking and abnormal posturing of limbs. There was no diurnal variation and symptoms progressively worsened. On examination, she had masklike facies with horizontal smile and generalized dystonia. Ocular examination revealed waxy pallor of the disc, arteriolar attenuation and alteration in retinal pigmentation with normal foveal reflex suggesting retinitis pigmentosasine-pigmento ( Fig. 1). Magnetic resonance imaging (MRI) of brain revealed bilateral symmetrical hypointensity in the globus-pallidus with central hyperintensity, giving an 'eyeof-tiger' appearance on T2 weighted and FLAIR images (Fig. 2). Retinitis pigmentosa in eyes and characteristic MRI findings gave the diagnosis of Pantothenate kinase associated neurodegeneration (PKAN).PKAN, formerly known as Hallovorden-Spatz syndrome is an autosomal recessive disorder caused by mutation of the pantothenate kinase-2 gene [1]. The MRI finding, 'eye-of-the-tiger'sign is pathognomonic of classic PKAN [2]. The hypointensity on T2 weighted image is because of iron deposition and the central hyperintensity is due to the glioses and spongioses due to cell death [3]. There is an absolute correlation between the presence of a mutation in PANK2 and the eye-of-the-tiger sign; that is, all patients with the PANK2 mutation have this MR imaging pattern, which also is not seen in any mutation-negative patients [4].Eye-of-tiger-sign can sometimes be seen in few cases of neuroferritinopathy, but in these cases careful scurtinization will reveal involvement of other basal ganglia nuclei (caudate and putamen), thalamus and cerebral cortex which is not seen in PKAN [1]. Another condition, where the 'eye of tiger' like appearance is seen is dihydropteridine reductase deficiency in which there will be associated features like cortical calcifications and cysts. Even the clinical presentation varies with microcephaly, parkinsonism, oculogyric crisis and disturbed psychomotor development [5]. The eye-of-the-tiger sign can also be seen in non-NBIA conditions such as corticobasal ganglia degeneration and progressive supranuclear palsy [1]. However the clinical features like age of onset differentiate these from PKAN.In conclusion, though important neuroimaging finding like 'eye-of-the-tiger' sign can be seen in other conditions, the presence of this finding along with other clinical clues Fig. 1 Ophthalmoscopic findings of right fundus: Retinal examination shows waxy pallor of the disc, arteriolar attenuation and alteration in retinal pigmentation. Macula is normal with normal foveal reflex. Features are consistent with retinitis pigmentosa sine pigmento M. Kamate (*) : R. Mali : V. Tonne : S. Bubanale