title: Cerebral degeneration predicts survival in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To determine the relationship of cerebral degeneration with survival in amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  Patients with probable or definite ALS underwent magnetic resonance spectroscopic imaging (MRSI) of the brain between July 1996 and May 2002, and were followed prospectively until March 2004. Creatine (Cr), choline (Cho) and the neuronal marker N-acetylaspartate (NAA) were quantified as ratios in the motor cortex.
  
  
  RESULTS
  In 63 patients compared with 18 healthy people, NAA/Cho was reduced by 13% (p<0.001), NAA/Cr was reduced by 5% (p = 0.01) and Cho/Cr was increased by 8% (p = 0.01). NAA/Cho was used for survival analysis, given its larger effect size and superior test accuracy (a sensitivity of 67% and a specificity of 83%). Median survival after MRSI was 24 months. Multivariate analysis showed reduced survival for lower NAA/Cho (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.08 to 0.72, p = 0.01), older age (HR 1.03, 95% CI 1.00 to 1.06, p = 0.04) and shorter symptom duration (HR 0.96, 95% CI 0.93 to 0.99, p = 0.01). Patients with NAA/Cho <2.11 had a reduced survival of 19.4 v 31.9 months (HR 2.05, 95% CI 1.12 to 4.03, p = 0.02).
  
  
  CONCLUSIONS
  Cerebral degeneration is predictive of reduced survival in ALS.
authors.affiliation: Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada. sanjay.kalra@ualberta.ca
authors.forename: S
authors.initials: S
authors.lastname: Kalra
authors.forename: A
authors.initials: A
authors.lastname: Vitale
authors.forename: N R
authors.initials: NR
authors.lastname: Cashman
authors.forename: A
authors.initials: A
authors.lastname: Genge
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality* / Q000473:pathology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000737:chemistry / Q000473:pathology*; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013534:Survival
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate