Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

Abstract

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...

Lessons from a pair of siblings with BPAN

“…[1][2][3][4][5][6] Beta-propeller protein-associated neurodegeneration (BPAN, NBIA5, OMIM: 300894) has been estimated to account for~7% of all cases of NBIA. 7 Besides being the only type of NBIA with an X-linked dominant pattern of inheritance, BPAN has distinctive clinical and brain imaging findings.…”

Contribution of metals to brain MR signal intensity: review articles

“…Although various factors other than iron content also affect the estimated iron concentration in the brain on MRI, MRI is used to diagnose many kinds of iron-storage diseases, such as neurodegeneration with brain iron accumulation (NBIA) [65][66][67][68], Alzheimer's disease [69,70], Parkinson's disease [71,72], multiple sclerosis [73,74], Friedreich's ataxia [75,76], and Huntington's disease [53,77]. NBIA is a group of neurodegenerative diseases characterized by iron accumulation in the basal ganglia.…”

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging

“…Brain MRI usually shows bilateral "eye-of-the-tiger" sign. CT scan shows bilateral calcifications and corresponding to the central spot visible on MRI 21 .…”

“…Clinical features include parkinsonism-dystonia syndrome with variable response to dopaminergic medications and neuropsychiatric symptoms 9 . Brain MRI may be normal or may disclose iron accumulation in globus pallidus, substantia nigra and striatum 21 .…”