Article Text

Download PDFPDF
Research paper
Neurochemical correlates of functional decline in amyotrophic lateral sclerosis


Objective To determine whether proton magnetic resonance spectroscopy (1H-MRS) can detect neurochemical changes in amyotrophic lateral sclerosis (ALS) associated with heterogeneous functional decline.

Methods Nineteen participants with early-stage ALS and 18 age-matched and sex ratio-matched controls underwent ultra-high field 1H-MRS scans of the upper limb motor cortex and pons, ALS Functional Rating Scale-Revised (ALSFRS-R total, upper limb and bulbar) and upper motor neuron burden assessments in a longitudinal observational study design with follow-up assessments at 6 and 12 months. Slopes of neurochemical levels over time were compared between patient subgroups classified by the rate of upper limb or bulbar functional decline. 1H-MRS and clinical ratings at baseline were assessed for ability to predict study withdrawal due to disease progression.

Results Motor cortex total N-acetylaspartate to myo-inositol ratio (tNAA:mIns) significantly declined in patients who worsened in upper limb function over the follow-up period (n=9, p=0.002). Pons glutamate + glutamine significantly increased in patients who worsened in bulbar function (n=6, p<0.0001). Neurochemical levels did not change in patients with stable function (n=5–6) or in healthy controls (n=14–16) over time. Motor cortex tNAA:mIns and ALSFRS-R at baseline were significantly lower in patients who withdrew from follow-up due to disease progression (n=6) compared with patients who completed the 12-month scan (n=10) (p<0.001 for tNAA:mIns; p<0.01 for ALSFRS-R), with a substantially larger overlap in ALSFRS-R between groups.

Conclusion Neurochemical changes in motor areas of the brain are associated with functional decline in corresponding body regions. 1H-MRS was a better predictor of study withdrawal due to ALS progression than ALSFRS-R.

  • amyotrophic lateral sclerosis
  • motor cortex
  • proton MRS
  • longitudinal
  • 7 tesla
  • biomarker

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.