A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients
To define the temporal evolution of intrinsic tissue damage and atrophy in the cervical cord and the brain portion of the corticospinal tracts (CST) from patients with amyotrophic lateral sclerosis (ALS).
Conventional and diffusion tensor (DT) magnetic resonance imaging (MRI) of the cervical cord and brain were obtained from 17 ALS patients and 20 controls, at baseline and after a mean follow-up of 9 months. The following measurements were assessed: (a) cervical cord cross-sectional area, average mean diffusivity (MD) and average fractional anisotropy (FA); and (b) CST T2-visible hyperintensities, average MD and FA.
During the follow-up, ALS patients showed a significant decrease in cord area (p = 0.003) and cord average FA (p = 0.01), and a significant increase in cord average MD (p = 0.01). In ALS patients, longitudinal changes of diffusivity measurements were not associated with cord area changes. At baseline, brain CST average MD was significantly higher in ALS patients compared with controls (p = 0.001). Brain CST diffusivity measurements remained stable over time in ALS patients and did not correlate with cord damage.
This study shows that progressive tissue loss and injury to the remaining tissue occur in the cervical cord of ALS patients and that these two features of ALS-related pathology are not strictly interrelated. Cord pathology in ALS patients is likely to be independent of brain changes, indicating that imaging the cervical cord may be a useful adjunctive tool to monitor ALS evolution.
Available from: Patrizia Longone
- "Rather, we believe ALS to be a complex pathology affecting central and peripheral nervous system areas with different degrees of penetration. Upper and lower MNs could very well degenerate independently of each other (Terao et al., 1999; Attarian et al., 2008; Agosta et al., 2009), although the reports that have especially looked at the cortical area, the minority in the ALS field, suggest the they have an unquestionable role in the disease path (Fig. 1). In 2006, Browne et al. reported that in the SOD1G93A mouse model the degeneration of spinal cord MNs is secondary to the appearance of bioenergetics abnormalities (glucose utilization and cortical ATP depletion) within the CNS motor pathways (the primary motor cortex, corticospinal tract and bulbospinal pathways). "
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ABSTRACT: Amyotrophic lateral sclerosis (ALS) is now recognized as a multisystem disorder, in which the primary pathology is the degeneration of motor neurons, with cognitive and/or behavioral dysfunctions that constitutes the non-motor manifestations of ALS. The combination of clinical, neuroimaging, and neuropathological data, and detailed genetic studies suggest that ALS and frontotemporal dementia (FTD) might form part of a disease continuum, with pure ALS and pure FTD at the two extremes. Mutations in the superoxide dismutase 1 (SOD1) gene were the first genetic mutations linked to the insurgence of ALS. Since that discovery numerous animal models carrying SOD1 mutations have been created. Despite their limitations these animal models, particularly the mice, have broaden our knowledge on the system alterations occurring in the ALS spectrum of disorders. The present review aims at providing an overview of the data obtained with the SOD1 animal models first and foremost on the cortical and subcortical regions, the cortico-striatal and hippocampal synaptic plasticity, dendritic branching and glutamate receptors function.
Available from: Pierre-François Pradat
- "Significant decrease in cord area in ALS patients followed longitudinally was previously reported , although no correlation with the ALSFRS score was found. Several factors may explain this lack of correlation in the study of Agosta et al. "
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ABSTRACT: To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients.
After 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.
At 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.
Atrophy 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.
Available from: Maria Piotrkiewicz
- "However, if ALS pathology indeed began in axons, then the lower and upper MNs could degenerate independently of each other. This possibility was recently suggested by several authors (Terao et al., 1999; Attarian et al., 2008; Agosta et al., 2009). "
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ABSTRACT: This is an opinion article, which presents an unusual single motor unit (MU) from an ALS patient. This unit, in contrast to 124 other MUs recorded for our recently published ALS study, exhibited an exceptional variability of potential shape and extremely irregular firing pattern. We hypothesize that this MU is controlled by a motoneuron, which is loosing its synaptic contacts with muscle fibres. The evidence in favor of this view is presented.
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