title: MR imaging and proton spectroscopy of neuronal injury in late-onset GM2 gangliosidosis.
abstract: OBJECTIVE
  Despite the ubiquity of G(M2) gangliosides accumulation in patients with late-onset G(M2) gangliosidosis (G(M2)G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients.
  
  
  METHODS
  During a single imaging session, 9 patients with late-onset G(M2)G and 8 age-matched normal volunteers underwent the following protocol: (1) T1- and T2-weighted and fluid-attenuated inversion recovery MR images, as well as (2) multivoxel proton MR spectroscopy (1H-MR spectroscopy) to quantify the distribution of the n-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were obtained.
  
  
  RESULTS
  The patients' NAA levels in the thalamus (6.5 +/- 1.9 mmol/L) and NAWM (5.8 +/- 2.1 mmol/L) were approximately 40% lower than the controls' (P = .003 and P = .005), whereas the Cr and Cho reductions ( approximately 30% and approximately 26%) did not reach significance (P values of .06-.1). All cerebellar metabolites, especially NAA and Cr, were much (30%-90%) lower in the patients, which reflects the atrophy.
  
  
  CONCLUSIONS
  In late-onset G(M2)G, NAA decreases are detectable in NAGM and NAWM even absent morphologic (MR imaging) abnormalities. Because the accumulation of G(M2) gangliosides can be reduced pharmacologically, 1H-MR spectroscopy might be a sensitive and specific for detecting and quantifying neuroaxonal injury and monitoring response to emerging treatments.
authors.affiliation: Department of Radiology, New York University, New York, NY 10016, USA.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.forename: Annette O
authors.initials: AO
authors.lastname: Nusbaum
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.forename: John
authors.initials: J
authors.lastname: Gianutsos
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: Oded
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001284:Atrophy; D001369:Axons / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D005260:Female; D020143:Gangliosidoses, GM2 / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D010487:Periaqueductal Gray / Q000473:pathology; D011522:Protons; D013788:Thalamus / Q000378:metabolism
chemical_list: D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine