Article Text

Download PDFPDF
Cerebral degeneration predicts survival in amyotrophic lateral sclerosis
  1. S Kalra1,
  2. A Vitale3,
  3. N R Cashman2,
  4. A Genge3,
  5. D L Arnold3
  1. 1Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada
  2. 2Centre for Research in Neurodegeneration, University of Toronto, Toronto, Ontario, Canada
  3. 3Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
  1. Correspondence to:
 S Kalra
 2E3.18 Walter C. Mackenzie Health Sciences Centre, 8440-112 Street, Edmonton, Alberta, Canada T6G 2B7;sanjay.kalra{at}


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.

  • ALS, amyotrophic lateral sclerosis
  • ALSFRS, Amyotrophic Lateral Sclerosis Functional Rating Scale
  • NAA, N-acetylaspartate
  • FVC, forced vital capacity
  • LMN, lower motor neurone
  • UMN, upper motor neurone
  • MRS, proton magnetic resonance spectroscopy
  • MRSI, magnetic resonance spectroscopic imaging
  • NAA, N-acetylaspartate

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 11 July 2006

  • Funding: This study was partly funded by the Amyotrophic Lateral Sclerosis Association of America.

  • Competing interests: None.

  • Ethical approval: This study was approved by the Montreal Neurological Institute and Hospital Ethics Committee.