Our objective was to demonstrate that ALS patients have sensory pathway involvement and that local cord atrophy reflects segmental lower motor neuron involvement. Twenty-nine ALS patients with spinal onset and twenty-one healthy controls were recruited. Diffusion tensor imaging (DTI), magnetization transfer and atrophy index were measured in the spinal cord, complemented with transcranial magnetic stimulations. Metrics were quantified within the lateral corticospinal and the dorsal segments of the cervical cord. Significant differences were detected between patients and controls for DTI and magnetization transfer metrics in the lateral and dorsal segments of the spinal cord. Fractional anisotropy correlated with ALSFRS-R (p = 0.04) and motor threshold (p = 0.02). Stepwise linear regression detected local spinal cord atrophy associated with weakness in the corresponding muscle territory, i.e. C4 level for deltoid and C7 level for hand muscles. In conclusion, impairment of spinal sensory pathways was detected at an early stage of the disease. Our data also demonstrate an association between muscle deficits and local spinal cord atrophy, suggesting that atrophy is a sensitive biomarker for lower motor neurons degeneration.

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.