A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients

Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 11/2008; 80(1):53-5. DOI: 10.1136/jnnp.2008.154252
Source: PubMed

ABSTRACT 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.

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    • "Significant decrease in cord area in ALS patients followed longitudinally was previously reported [20], 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.
    PLoS ONE 04/2014; 9(4):e95516. DOI:10.1371/journal.pone.0095516 · 3.23 Impact Factor
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    • "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.
    Frontiers in Aging Neuroscience 03/2013; 5:7. DOI:10.3389/fnagi.2013.00007 · 4.00 Impact Factor
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    • "Based on previous DTI studies in ALS, such a severe impairment in microstructural integrity is unlikely to occur. FA alterations along the corticospinal and corpus callosal tracts - being the most extensively affected white matter tracts in ALS – appear to be rather modest (approximately 10%), despite profound motor disability among studied patients [4], [5], [47], [67]. As a result this will likely not have a strong effect on the tracing procedure; the FA value along the tracts in patients will still exceed the stopping criteria of ∼0.1, resulting in normal reconstructed tracts. "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI), the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without--a priori selected--regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing). This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule), including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum) as well as high-order hub regions (right posterior cingulate and precuneus). In addition, we found a significant reduction in overall efficiency (p = 0.0095) and clustering (p = 0.0415). From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome.
    PLoS ONE 09/2011; 6(9):e24239. DOI:10.1371/journal.pone.0024239 · 3.23 Impact Factor
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