Nigropallidal iron accumulation in pantothenate kinase-associated neurodegeneration demonstrated by susceptibility-weighted imaging

Abstract

Neurodegeneration with brain iron accumulation (NBIA, formerly known as Hallervorden-Spatz syndrome) defines a group of genetic disorders characterized by brain iron deposition. The major form of NBIA is pantothenatekinase associated neurodegeneration, or PKAN, caused by mutations in the PANK2 gene [1, 2]. The other known causes of NBIA include neuroferritinopathy, infantile neuroaxonal dystrophy, and aceruloplasminemia [2, 3]. Because of extensive phenotypic overlap, the clinical diagnosis of different subtypes of NBIA can be challenging, particularly in the early stages [2, 3]. Previous MRI studies with an emphasis on T2-weighted imaging (T2WI) demonstrated a central region of hyperintensity in the globus pallidus with surrounding hypointensity, called an eye-of-the-tiger sign [1, 2]. Newer MR imaging technologies, susceptibility-weighted imaging (SWI), has been shown to be superior in its ability to demonstrate brain iron deposition than other conventional MR imaging [4]. We report herein SWI findings in a patient with PKAN2 gene mutation to characterize the patterns of iron deposition in this disorder. A 17-year-old boy presented with dysarthria and progressive generalized dystonia for 2 years. Initially, he developed twisting postures in his right hand, which progressively worsened and spread to involve the neck, trunk, and his left arm. His birth, perinatal, growth and development histories were unremarkable. There was no family history of neurological disorders. On examination, he showed blepharospasm, retrocollis, and backward tilting of the trunk. He complained of severe pain in his left shoulder which took an intermittent dystonic posture with internal rotation. He also had dystonic posture in both hands and feet. However, he could walk without difficulty. The result of neuropsychological tests showed mild mental retardation. Ophthalmic examination revealed no Kayser-Fleisher rings, optic neuropathy, or pigmentary retinopathy. His motor, sensory, and cerebellar function tests were normal. Deep tendon reflexes were normoactive, and plantar reflexes were flexor bilaterally. Routine laboratory tests were all normal as well as measurements of serum ceruloplasmin, CK, ferritin, and lactate levels. EEG was normal. Brain magnetic resonance imaging showed the eye-of-the-tiger sign on T2-weighted imaging (Fig. 1a). Susceptibility-weighted images dramatically showed the tracts of iron deposition from substantia nigra to globus pallidus (Fig. 1c–f). Genetic testing confirmed compound heterozygous mutations in exon 3 [c. (999A [ G), p. (K335E)] and exon 4 [c. (1270_1272del), p. (L424del)] in the PKAN2 gene. MRI has been particularly useful in distinguishing the forms of NBIA. The eye-of-the-tiger sign (Fig. 1a) is specific for PKAN and showed a high correlation with the presence of a PANK2 mutation [1, 2]. However, the J.-H. Lee (&) D.-S. Kim Department of Neurology, Medical Research Institute, Pusan National University Yangsan Hospital, Beomo-ri, Mulgum-eup, Gyeongnam 626-770, Korea e-mail: drleejae@hanmail.net; jhlee.neuro@pusan.ac.kr