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J Neurol Neurosurg Psychiatry 2006;77:1253-1255 doi:10.1136/jnnp.2006.090696
  • Paper

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}ualberta.ca
  • Received 12 February 2006
  • Accepted 27 June 2006
  • Revised 29 May 2006
  • Published Online First 11 July 2006

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.

Footnotes

  • 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.

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