Spectroscopic markers of neurodegeneration in the mesial prefrontal cortex predict survival in ALS

Abstract

Background and objective: N-acetylaspartate (NAA) and myo-inositol (mIns) are spectroscopic markers of neuronal integrity and astrogliosis, respectively. We performed a survival analysis to determine the prognostic value of the NAA/mIns metabolite ratio in ALS after a period of two and five years. Methods: Twenty-four patients with ALS (two with ALS-FTD) were recruited to participate in a high-field MR spectroscopy study of the mesial prefrontal cortex. Univariate and multivariate Cox proportional hazards analyses were used to assess NAA/mIns as a predictor of survival alongside other demographic and clinical measures. Census dates were set at two and five years after the time of MR scan for each patient. Survival curves were calculated using the Kaplan–Meier method. Results: After a five-year observation period, 19 patients had died and five were still alive. Median survival time from date of scan was 1.95 years. Univariate and multivariate Cox analysis showed NAA/mIns to be a significant independent predictor of survival at two years after scanning, but not at five years. Conclusion: Cerebral degeneration in the mesial prefrontal cortex as detected by the NAA/mIns metabolite ratio is predictive of survival in ALS in a time-dependent manner.

Keywords:

• MR spectroscopy
• ALS
• survival

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was funded by the ALS Association of America, ALS Society of Canada, the MSI Foundation of Alberta, the University of Alberta Hospital Foundation, and the Shelly Mrkonjic ALS Research Fund.