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Neurochemical correlates of functional decline in amyotrophic lateral sclerosis.

ABSTRACT: 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.

SUBMITTER: Cheong I

PROVIDER: S-EPMC6467050 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Neurochemical correlates of functional decline in amyotrophic lateral sclerosis.

Cheong Ian I Deelchand Dinesh K DK Eberly Lynn E LE Marjańska Małgorzata M Manousakis Georgios G Guliani Gaurav G Walk David D Öz Gülin G

Journal of neurology, neurosurgery, and psychiatry 20181122 3

<h4>Objective</h4>To determine whether proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) can detect neurochemical changes in amyotrophic lateral sclerosis (ALS) associated with heterogeneous functional decline.<h4>Methods</h4>Nineteen participants with early-stage ALS and 18 age-matched and sex ratio-matched controls underwent ultra-high field <sup>1</sup>H-MRS scans of the upper limb motor cortex and pons, ALS Functional Rating Scale-Revised (ALSFRS-R total, upper limb and bulbar) and ...[more]

PMID: 30467209

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Project description:Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.

Dataset Information

Neurochemical correlates of functional decline in amyotrophic lateral sclerosis.

Publications

Neurochemical correlates of functional decline in amyotrophic lateral sclerosis.

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