Neurochemical correlates of functional decline in amyotrophic lateral sclerosis

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Cortex
Upper Extremity
Pons
Disease Progression
Body Regions
Sex Ratio
Motor Neurons
Inositol
Glutamine
Observational Studies
Longitudinal Studies
Glutamic Acid
Brain

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{bcd6d8c1a54f4cdbad170ac3aa3aed85,
title = "Neurochemical correlates of functional decline in amyotrophic lateral sclerosis",
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.",
keywords = "7 tesla, amyotrophic lateral sclerosis, biomarker, longitudinal, motor cortex, proton MRS",
author = "Ian Cheong and Deelchand, {Dinesh K} and Eberly, {Lynn E} and Malgorzata Marjanska and Manousakis, {Georgios E} and Gaurav Guliani and David Walk and Gulin Oz",
year = "2019",
month = "3",
day = "1",
doi = "10.1136/jnnp-2018-318795",
language = "English (US)",
volume = "90",
pages = "294--301",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - Neurochemical correlates of functional decline in amyotrophic lateral sclerosis

AU - Cheong, Ian

AU - Deelchand, Dinesh K

AU - Eberly, Lynn E

AU - Marjanska, Malgorzata

AU - Manousakis, Georgios E

AU - Guliani, Gaurav

AU - Walk, David

AU - Oz, Gulin

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - 7 tesla

KW - amyotrophic lateral sclerosis

KW - biomarker

KW - longitudinal

KW - motor cortex

KW - proton MRS

UR - http://www.scopus.com/inward/record.url?scp=85057114292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057114292&partnerID=8YFLogxK

U2 - 10.1136/jnnp-2018-318795

DO - 10.1136/jnnp-2018-318795

M3 - Article

VL - 90

SP - 294

EP - 301

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 3

ER -