Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Varan Govind,Kristopher L Arheart,Sulaiman Sheriff,Khema R Sharma,Gaurav Saigal,Andrew A Maudsley,Jean-Claude Baron

doi:10.1371/journal.pone.0035607

Varan Govind, Kristopher L Arheart + Show 5 more

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https://doi.org/10.1371/journal.pone.0035607

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Journal: PloS one	Publication Date: Apr 23, 2012
Citations: 42	License type: CC BY 4.0

Affiliation: University of Miami

Abstract

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of both upper motor neurons (UMN) in the primary motor cortex (PMC) and lower motor neurons (LMN) in the brain stem and spinal cord anterior horns
For the purpose of finer analysis of metabolite alterations, the intracranial corticospinal tracts (CST) was divided into 5 anatomically distinct segments
Data analysis was performed at the volume levels of the entire intracranial CST and its segments bilaterally

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of both upper motor neurons (UMN) in the primary motor cortex (PMC) and lower motor neurons (LMN) in the brain stem and spinal cord anterior horns. Neurochemicals indicative of metabolic processes responsible for degeneration of the motor neurons and CST in patients with ALS can be accessed from the disease onset stage using proton MR spectroscopic (MRS) methods. Several previous cross-sectional and longitudinal studies have demonstrated the value of proton MRS for evaluation of metabolite alterations in the PMC [6,7,8,9,10,11,12,13,14,15,16] and CST [11,17] of patients with ALS using single voxel (SVS) and 2D MR spectroscopic imaging [11,17,18,19] (MRSI) methods.

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