Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.

Mohamed-Mounir El Mendili,Régine Morizot-Koutlidis,Stéphane Lehericy,Serge Rossignol,Rose Katz,Habib Benali,Pierre-François Pradat,Julien Cohen-Adad,Sina Sangari,Véronique Marchand-Pauvert,Caroline Iglesias,Mélanie Pelegrini-Issac

doi:10.1371/journal.pone.0095516

Abstract

ObjectiveTo evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients.Materials and MethodsAfter a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score.ResultsAt MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change.ConclusionAtrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

Highlights

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease characterized by degeneration of both upper and lower motor neurons
Cord Cross-sectional area (CSA) was the only significant predictor associated with the arm subscore of ALSFRS-R (P = 0.049) and manual muscle testing (MMT) (P = 0.019 for arm and 0.04 for leg) scales
Fractional anisotropy (FA) measure in the lateral segment of the spinal cord was the only predictor of leg subscore (P = 3.1024) and total score (P = 0.039) of the ALSFRS-R

Summary

Introduction

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease characterized by degeneration of both upper and lower motor neurons. Disease progression is characterized by worsening of weakness and physical disability with a median survival ranging from 2.5 to 3 years [1,2]. There is an unmet need for biomarkers in amyotrophic lateral sclerosis, for better diagnosis and to assess disease progression and the effect of disease-modifying drugs in clinical trials (surrogate markers) [4,5,6]. Spinal cord MRI has the advantage of investigating the two motor system components that are involved in ALS, i.e the lower motor neuron (via gray matter atrophy) and upper motor neuron (via degeneration of corticospinal tract).

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