title: Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity.
abstract: 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.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, England, UK. michael.keogh@newcastle.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Keogh
authors.affiliation: Institute of Cellular Medicine and Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, England, UK.
authors.forename: B S
authors.initials: BS
authors.lastname: Aribisala
authors.affiliation: Institute of Cellular Medicine and Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, England, UK.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, England, UK.
authors.forename: E
authors.initials: E
authors.lastname: Tulip
authors.affiliation: Department of Neuroradiology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, England, UK.
authors.forename: D
authors.initials: D
authors.lastname: Butteriss
authors.affiliation: Medical Toxicology Centre, Wolfson Building, Claremont Place, Newcastle University, Newcastle upon Tyne, NE2 4AA, England, UK.
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.affiliation: Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, England, UK.
authors.forename: G
authors.initials: G
authors.lastname: Gorman
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, England, UK.
authors.forename: R
authors.initials: R
authors.lastname: Horvath
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, England, UK.|Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, England, UK.
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.affiliation: Institute of Cellular Medicine and Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, England, UK. andrew.blamire@newcastle.ac.uk.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D002421:Caudate Nucleus / Q000378:metabolism*; D002531:Cerebellum / Q000473:pathology*; D005260:Female; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D007501:Iron
keywords: Iron; Morphometry; Neuroferritinopathy; Relaxometry; Voxel