TY - JOUR
T1 - Brain iron and metabolic abnormalities in C19orf12 mutation carriers
T2 - A 7.0 tesla MRI study in mitochondrial membrane protein–associated neurodegeneration
AU - Dusek, Petr
AU - Mekle, Ralf
AU - Skowronska, Marta
AU - Acosta-Cabronero, Julio
AU - Huelnhagen, Till
AU - Robinson, Simon Daniel
AU - Schubert, Florian
AU - Deschauer, Marcus
AU - Els, Antje
AU - Ittermann, Bernd
AU - Schottmann, Gudrun
AU - Madai, Vince I.
AU - Paul, Friedemann
AU - Klopstock, Thomas
AU - Kmiec, Tomasz
AU - Niendorf, Thoralf
AU - Wuerfel, Jens
AU - Schneider, Susanne A.
N1 - Publisher Copyright:
© 2019 International Parkinson and Movement Disorder Society
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 1H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. 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.
AB - 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 1H MR spectroscopy in clinically manifesting membrane protein-associated neurodegeneration patients and asymptomatic C19orf12 gene mutation heterozygous carriers. 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.
KW - 7 Tesla MRI
KW - glutamate
KW - magnetic resonance spectroscopy
KW - mitochondrial membrane protein–associated neurodegeneration (MPAN)
KW - neurodegeneration with brain iron accumulation (NBIA)
KW - quantitative susceptibility mapping, iron
UR - http://www.scopus.com/inward/record.url?scp=85073801425&partnerID=8YFLogxK
U2 - 10.1002/mds.27827
DO - 10.1002/mds.27827
M3 - Article
C2 - 31518459
AN - SCOPUS:85073801425
SN - 0885-3185
VL - 35
SP - 142
EP - 150
JO - Movement Disorders
JF - Movement Disorders
IS - 1
ER -