Neurochemical correlates of functional decline in amyotrophic lateral sclerosis

Ian Cheong, Dinesh K. Deelchand, Lynn E. Eberly, Małgorzata Marjańska, Georgios Manousakis, Gaurav Guliani, David Walk, Gülin Öz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Objective To determine whether proton magnetic resonance spectroscopy (1 H-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 1 H-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. 1 H-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. 1 H-MRS was a better predictor of study withdrawal due to ALS progression than ALSFRS-R.

Original languageEnglish (US)
Pages (from-to)294-301
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume90
Issue number3
DOIs
StatePublished - Mar 1 2019

Bibliographical note

Publisher Copyright:
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords

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

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