Cranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome

Hayflick, Susan J.; Penzien, Johann; Michl, Wolfgang; Sharif, Uzma M.; Rosman, N. Paul; Wheeler, Patricia G.

doi:10.1016/s0887-8994(01)00296-x

Cited by 59 publications

(23 citation statements)

References 7 publications

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“…The hyperintense central region indicates a primary tissue insult leading to necrosis or oedema, while the surrounding hypointense region represents high iron. In presymptomatic patients, the hyperintense lesions predominate; with disease progression, hypointensities appear and eventually dominate 33. The eye-of-the-tiger sign is highly specific to PKAN and is not observed in INAD or idiopathic NBIA, although similar changes may rarely be seen in neuroferritinopathy 34…”

Section: Neuroimagingmentioning

confidence: 99%

Clinical and genetic delineation of neurodegeneration with brain iron accumulation

Gregory

Polster

Hayflick

2008

Journal of Medical Genetics

329

318

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Neurodegeneration with brain iron accumulation (NBIA) describes a group of progressive neurodegenerative disorders characterised by high brain iron and the presence of axonal spheroids, usually limited to the central nervous system. Mutations in the PANK2 gene account for the majority of NBIA cases and cause an autosomal recessive inborn error of coenzyme A metabolism called pantothenate kinase associated neurodegeneration (PKAN). More recently, it was found that mutations in the PLA2G6 gene cause both infantile neuroaxonal dystrophy (INAD) and, more rarely, an atypical neuroaxonal dystrophy that overlaps clinically with other forms of NBIA. High brain iron is also present in a portion of these cases. Clinical assessment, neuroimaging, and molecular genetic testing all play a role in guiding the diagnostic evaluation and treatment of NBIA.

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Section: Neuroimagingmentioning

confidence: 99%

Clinical and genetic delineation of neurodegeneration with brain iron accumulation

Gregory

Polster

Hayflick

2008

Journal of Medical Genetics

329

318

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“…Until now, almost all individuals with PANK2 mutations have the "eye of the tiger" sign, and almost all individuals with the sign carry PANK2 mutations [25][26][27]. The MRI changes occur early in the course of the disease and have already been used to predict PKAN in presymptomatic sibs of affected individuals [28]. Fig.…”

Section: Imagingmentioning

confidence: 99%

Pantothenate Kinase-Associated Neurodegeneration

Hartig

Prokisch²,

Meitinger³

et al. 2012

CDT

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Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological examinations. The discovery of the disease causing mutations in PANK2 has linked the disorder to coenzyme A (CoA) metabolism. PANK2 is the only one out of four PANK genes encoding an isoform which localizes to mitochondria. At least two other NBIA genes (PLA2G6, C19orf12) encode proteins that share with PANK2 a mitochondrial localization and all are suggested to play a role in lipid homeostasis.With no causal therapy available for PKAN until now, only symptomatic treatment is possible. A multi-centre retrospective study with bilateral pallidal deep brain stimulation in patients with NBIA revealed a significant improvement of dystonia. Recently, studies in the PANK Drosophila model "fumble" revealed improvement by the compound pantethine which is hypothesized to feed an alternate CoA biosynthesis pathway. In addition, pilot studies with the iron chelator deferiprone that crosses the blood brain barrier showed a good safety profile and some indication of efficacy. An adequately powered randomized clinical trial will start in 2012.This review summarizes clinical presentation, neuropathology and pathogenesis of PKAN.

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“…12 Most interesting, iron deposition detectable by MR imaging may precede the development of clinical symptoms, as evidenced by the identification of an "eye-of-the-tiger" in presymptomatic mutation-positive siblings of children affected by PKAN. 13 In contrast, children with INAD may develop iron deposition later in their disease course or not at all. 14 The observation that the degree of iron deposition correlates incompletely with clinical symptoms suggests that though iron is a useful neuroimaging feature in NBIA, it likely is neither necessary nor sufficient to produce the disease phenotype.…”

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confidence: 99%

Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

Kruer¹,

Boddaert²,

Schneider³

et al. 2011

AJNR Am J Neuroradiol

191

161

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SUMMARY: NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.ABBREVIATIONS: ACP ϭ aceruloplasminemia; CNS ϭ central nervous system; FAHN ϭ fatty acid hydroxylase-associated neurodegeneration; INAD ϭ infantile neuroaxonal dystrophy; KRS ϭ KuforRakeb syndrome; NAD ϭ neuroaxonal dystrophy; NBIA ϭ neurodegeneration with brain iron accumulation; NFT ϭ neuroferritinopathy; PKAN ϭ pantothenate kinase-associated neurodegeneration; PLAN ϭ phospholipase-associated neurodegeneration; SENDA ϭ static encephalopathy of childhood with neurodegeneration in adulthood; WSS ϭ Woodhouse-Sakati syndrome B efore the widespread availability of MR imaging, a diagnosis of NBIA could be made only at the time of autopsy. In contrast, current diagnosis is facilitated by evaluation by using both T1-and T2-weighted sequences. As a paramagnetic substance, Fe 3ϩ catalyzes the nuclear spin relaxation of neighboring water protons. With standard clinical parameters, areas rich in iron appear hypointense on T2-weighted sequences, and isointense on T1 sequences. T2*-weighted acquisitions (gradient-echo sequences) may accentuate this degree of hypointensity ("blooming") and may be helpful in identifying NBIA disorders as may susceptibility-weighted images.1 In biologic iron-oxides, Fe 2ϩ typically has fewer unpaired electrons than Fe 3ϩ and is less effective in quenching T2-weighted signal intensity.2 Calcium may also appear isointense on T1 and hypointense on T2-weighted sequences, mimicking the appearance of iron. The 2 minerals are readily distinguished by CT, however, because Ca 2ϩ characteristically appears hyperintense to the surrounding brain parenchyma, while iron is isointense. In addition, iron typically appears markedly hypointense on both standard clinical diffusionweighted and apparent diffusion coefficient sequences. Other metals that may be deposited in neurodegenerative disorders, such as manganese and copper, have a distinct appearance on T1-and T2-weighted sequences, enabling a heuristic approach to diagnosis based on MR imaging parameters. The characteristics of these metals are summarized in Table 1. Despite the utility of MR imaging in this setting, it does not preclude the need for elemental analysis of neuropathologic specimens; rather, it enables putative diagnosis to be made during life.The radiographic appearance of the lesions themselves is of prime importance. Iron deposition occurs in mul...

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Cranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome

Cited by 59 publications

References 7 publications

Clinical and genetic delineation of neurodegeneration with brain iron accumulation

Clinical and genetic delineation of neurodegeneration with brain iron accumulation

Pantothenate Kinase-Associated Neurodegeneration

Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

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