title: Cerebral proton magnetic resonance spectroscopy in infantile Alexander disease.
abstract: Alexander disease (AD) is a rare genetic disorder of the central nervous system due to a dysfunction of astrocytes. The most common infantile form presents as a progressive leukodystrophy with macrocephalus. Recently, heterozygous de novo mutations in the gene encoding glial fibrillary acidic protein (GFAP) have been demonstrated to be associated with AD. We used localized proton magnetic resonance spectroscopy (MRS) to assess metabolic abnormalities in grey and white matter, basal ganglia, and cerebellum of 4 patients with infantile AD and GFAP mutations. Strongly elevated concentrations of myo-inositol in conjunction with normal or increased choline-containing compounds in all regions investigated point to astrocytosis and demyelination. Neuroaxonal degeneration, as reflected by a reduction of N-acetylaspartate, was most pronounced in cerebral and cerebellar white matter. The accumulation of lactate in affected white matter is in line with infiltrating macrophages. Metabolic alterations demonstrated by in vivo proton MRS are in excellent agreement with known neuropathological features of AD.
authors.affiliation: Dept. of Paediatrics and Neuropaediatrics, Children's Hospital, Robert-Koch-Str. 40, 37075 Göttingen, Germany. hanefeld@med.uni-goettingen.de
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Peter
authors.initials: P
authors.lastname: Dechent
authors.forename: Moritz
authors.initials: M
authors.lastname: Meins
authors.forename: Mechthild
authors.initials: M
authors.lastname: Haupt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sperner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.forename: Jens
authors.initials: J
authors.lastname: Frahm
authors.forename: Folker
authors.initials: F
authors.lastname: Hanefeld
mesh_terms: D038261:Alexander Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005911:Gliosis / Q000473:pathology; D006801:Humans; D007223:Infant; D007294:Inositol / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology; D011859:Radiography
chemical_list: D001224:Aspartic Acid; D019344:Lactic Acid; D007294:Inositol; C000179:N-acetylaspartate