Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration.
7 Tesla MRI
glutamate
magnetic resonance spectroscopy
mitochondrial membrane protein-associated neurodegeneration (MPAN)
neurodegeneration with brain iron accumulation (NBIA)
quantitative susceptibility mapping, iron
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
26
02
2019
revised:
20
07
2019
accepted:
24
07
2019
pubmed:
14
9
2019
medline:
18
12
2020
entrez:
14
9
2019
Statut:
ppublish
Résumé
Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia. The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN. In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Mitochondrial membrane protein-associated neurodegeneration is an autosomal-recessive disorder caused by C19orf12 mutations and characterized by iron deposits in the basal ganglia.
OBJECTIVES
The aim of this study was to quantify iron concentrations in deep gray matter structures using quantitative susceptibility mapping MRI and to characterize metabolic abnormalities in the pyramidal pathway using
METHODS
We present data of 4 clinically affected membrane protein-associated neurodegeneration patients (mean age: 21.0 ± 2.9 years) and 9 heterozygous gene mutation carriers (mean age: 50.4 ± 9.8 years), compared to age-matched healthy controls. MRI assessments were performed on a 7.0 Tesla whole-body system, consisting of whole-brain gradient-echo scans and short echo time, single-volume MR spectroscopy in the white matter of the precentral/postcentral gyrus. Quantitative susceptibility mapping, a surrogate marker for iron concentration, was performed using a state-of-the-art multiscale dipole inversion approach with focus on the globus pallidus, thalamus, putamen, caudate nucleus, and SN.
RESULTS AND CONCLUSION
In membrane protein-associated neurodegeneration patients, magnetic susceptibilities were 2 to 3 times higher in the globus pallidus (P = 0.02) and SN (P = 0.02) compared to controls. In addition, significantly higher magnetic susceptibility was observed in the caudate nucleus (P = 0.02). Non-manifesting heterozygous mutation carriers exhibited significantly increased magnetic susceptibility (relative to controls) in the putamen (P = 0.003) and caudate nucleus (P = 0.001), which may be an endophenotypic marker of genetic heterozygosity. MR spectroscopy revealed significantly increased levels of glutamate, taurine, and the combined concentration of glutamate and glutamine in membrane protein-associated neurodegeneration, which may be a correlate of corticospinal pathway dysfunction frequently observed in membrane protein-associated neurodegeneration patients. © 2019 International Parkinson and Movement Disorder Society.
Substances chimiques
C19orf12 protein, human
0
Membrane Proteins
0
Mitochondrial Proteins
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
142-150Informations de copyright
© 2019 International Parkinson and Movement Disorder Society.
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