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Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity

Lookup NU author(s): Dr Michael Keogh, Dr Benjamin Aribisala, Dr Jiabao He, Dr Clare Morris, Professor Grainne Gorman, Professor Rita HorvathORCiD, Professor Patrick Chinnery, Professor Andrew BlamireORCiD


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Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders.

Publication metadata

Author(s): Keogh MJ, Aribisala BS, He J, Tulip E, Butteriss D, Morris C, Gorman G, Horvath R, Chinnery PF, Blamire AM

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2015

Volume: 262

Issue: 10

Pages: 2232-2240

Print publication date: 01/10/2015

Online publication date: 04/07/2015

Acceptance date: 20/06/2015

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer


DOI: 10.1007/s00415-015-7832-2


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Funder referenceFunder name
European Commission FP7 programme
Medical Research Council
National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust
National Institute for Health Research Biomedical Research Centre for Ageing and Age-Related Disease award
Newcastle University
096919Z/11/ZWellcome Trust Centre for Mitochondrial Research
G0601943Medical Research Council (UK) Centre for Translational Muscle Disease research