Neurodegeneration with Brain Iron Accumulation on MRI: An Adult Case of α-Mannosidosis

Zoons, Evelien; Koning, Tom J. de; Abeling, N. G. G. M.; Tijssen, Marina A. J.

doi:10.1007/8904_2011_78

Cited by 12 publications

(5 citation statements)

References 11 publications

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“…The three patients here described, MD-137 ( FUCA1 ), MD-020 ( GLB1 ), and MD-153 ( TPP1 ), suffered from lysosomal diseases. Additionally, a subject with α-mannosidosis, also a lysosomal storage disease, who presented hypointensity signals in the GP was published [ 48 ]. Taken together, NBIA on MRI seems not to be so rare in some lysosomal disorders, especially in GM1-gangliosidosis, since so far, five unrelated cases are known (including our proband).…”

Section: Discussionmentioning

confidence: 99%

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Martínez‐Rubio

Hinarejos

Sancho

et al. 2022

IJMS

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Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

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Section: Discussionmentioning

confidence: 99%

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Martínez‐Rubio

Hinarejos

Sancho

et al. 2022

IJMS

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show abstract

“…In this context, the accuracy of automated brain morphometry methods is also important for the comprehension of the pathophysiology of neurological and neuropsychiatric disorders with basal ganglia involvement, such as Parkinson's syndrome, Huntington's disease, dystonia, various tremor forms, Tourette's syndrome and schizophrenia ( Utter and Basso, 2008 ). There is substantial controversy in the literature about the magnitude, directionality and neurobiological interpretation of basal ganglia structural changes in both healthy ageing and in diseased brain ( Koolschijn et al, 2009; Mars et al, 2011; Zoons et al, 2012 ). The majority of these studies assessed basal ganglia anatomy using T1-weighted (T1w) imaging data, which turned out to be methodologically challenging ( Wonderlick et al, 2009; Babalola et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Disentangling in vivo the effects of iron content and atrophy on the ageing human brain

et al. 2014

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Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer – MT, from healthy subjects (n = 96, aged 21–88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.

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“…However, only small numbers of patients have been described and/or Fe accumulation is inconsistent, and neuropathological proof of Fe accumulation is lacking in these disorders [2]. Caution is necessary in the interpretation of T2/T2*-weighted MRIs as has been shown for mannosidosis; this disorder was considered in the differential diagnosis of NBIA [257] but a semiquantitative analysis in a group of mannosidosis patients showed that the hyposignal appearance of the deep gray matter is only relative and rather caused by an increased signal from the surrounding white matter [258].…”

Section: Neurodegenerations With Brain Iron Accumulation (Nbia) Groupmentioning

confidence: 99%

Cerebral Iron Deposition in Neurodegeneration

et al. 2022

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Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson’s disease, Friedreich’s disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood–brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.

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Neurodegeneration with Brain Iron Accumulation on MRI: An Adult Case of α-Mannosidosis

Cited by 12 publications

References 11 publications

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Disentangling in vivo the effects of iron content and atrophy on the ageing human brain

Cerebral Iron Deposition in Neurodegeneration

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