Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

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.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis

“…SCCSA also reflected clinical disability as previously shown, 3 though with lower sensitivity than GMCSA. A previous study 7 established a strong link between SCCSA and lower motor neuron degeneration by relating motorevoked potential amplitude of the adductor digiti minimi and deltoid, respectively, with cord atrophy at spinal levels C8 and C5 (here, it was not possible to study the C8 spinal level; see "Limitations" section).…”

“…3 More interestingly, GMCSA showed larger differences between the 2 groups (P ϭ .004 for GMCSA versus .02 for SCCSA at the C4 -C6 vertebral levels), suggesting that GMCSA is a more sensitive marker of atrophy in ALS and that cord atrophy in ALS is predominantly driven by lower motor neuron degeneration. Although WM is expected to degenerate as a secondary effect of upper motor neuron degeneration, gliosis and myelin debris forming in the SC WM might somewhat lower the sensitivity of global cord atrophy.…”

“…3,4 Common clinical manifestations include muscle weakness or clumsiness, atrophy, cramps, fasciculations, dysphagia, dysarthria, and respiratory symptoms such as dyspnea, orthopnea, and respiratory failure.…”

“…6 In particular, imaging biomarkers of the spinal cord (SC) can potentially provide a relevant measure of the degeneration of lower motor neurons. 3,4 A recent study showed that spinal cord cross-sectional area (SCCSA) measured with MR imaging improves prediction of the arm-revised ALS Functional Rating Scale (ALSFRS-R) subscore at 1 year. 3 Another study 7 established a strong link between SCCSA and the degeneration of lower motor neurons.…”

“…3,4 A recent study showed that spinal cord cross-sectional area (SCCSA) measured with MR imaging improves prediction of the arm-revised ALS Functional Rating Scale (ALSFRS-R) subscore at 1 year. 3 Another study 7 established a strong link between SCCSA and the degeneration of lower motor neurons. The main limita-tion of these studies is that they looked at cord atrophy, hindering the separation of the specific contribution of GM and WM atrophy.…”