title: MR Spectroscopy in Patients with Hereditary Diffuse Leukoencephalopathy with Spheroids and Asymptomatic Carriers of Colony-stimulating Factor 1 Receptor Mutation.
abstract: OBJECTIVE
  Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare neurodegenerative disorder with various clinical presentations. Mutation of the colony-stimulating factor 1 receptor (CSF1R) gene is considered to be a cause of this autosomal dominant disorder. The purpose of this study was to report magnetic resonance spectroscopy (MRS) findings in patients with HDLS and asymptomatic carriers and to clarify the use of MRS in this disease.
  
  
  METHODS
  In this retrospective, institutional review board-approved study, we included four consecutive patients, genetically diagnosed with HDLS, and two asymptomatic carriers after acquiring informed consent. We performed single-voxel MRS of the left centrum semiovale on a 3-T clinical scanner. We also included a sex-matched normal dataset. We quantified N-acetylaspartate (NAA), creatine, choline-containing compounds (Cho), glutamine, glutamate (Glu), myo-inositol (Ins), glutathione, lactate (Lac), and gamma-amino butyric acid using LCModel. We performed statistical analysis, and P value <0.05 was considered significant.
  
  
  RESULTS
  In HDLS cases, MRS revealed decreased NAA and Glu concentrations, which probably reflected neuronal damage and/or loss, and a subsequent reduction of neurotransmitters. A patient with HDLS also had increased Cho and Ins concentrations, indicating gliosis, and increased Cho concentration was also observed in an asymptomatic carrier. This suggests that metabolic changes had already occurred in an asymptomatic state.
  
  
  CONCLUSIONS
  We demonstrated changes in metabolite concentrations not only in patients with HDLS but also in asymptomatic CSF1R mutation carriers. Our study indicates that MRS is a potentially useful tool for the analysis of metabolic and pathophysiological findings of HDLS, even during the early stages of disease.
authors.affiliation: Department of Radiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sako
authors.affiliation: Department of Neurology, Jikei University School of Medicine.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Terasawa
authors.affiliation: MR Applications and Workflow Asia Pacific, GE Healthcare Japan Corporation.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Waka
authors.initials: W
authors.lastname: Sakai
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Ai
authors.initials: A
authors.lastname: Tsukamoto-Miyashiro
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsui
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Department of Radiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001927:Brain Diseases / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging* / Q000235:genetics*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
chemical_list: D001224:Aspartic Acid; D016173:Macrophage Colony-Stimulating Factor; C000179:N-acetylaspartate
keywords: Mescher-Garwood point-resolved spectroscopy; colony stimulating factor-1 receptor; hereditary diffuse leukoencephalopathy with spheroids; magnetic resonance imaging