Beyond fractional anisotropy in amyotrophic lateral sclerosis: the value of mean, axial, and radial diffusivity and its correlation with electrophysiological conductivity changes
This paper aims to analyze the contribution of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in the detection of microstructural abnormalities in amyotrophic lateral sclerosis (ALS) and to evaluate the degree of agreement between structural and functional changes through concomitant diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), and clinical assessment.
Fourteen patients with ALS and 11 healthy, age- and gender-matched controls were included. All participants underwent magnetic resonance imaging including DTI. TMS was additionally performed in ALS patients. Differences in the distribution of DTI-derived measures were assessed using tract-based spatial statistical (TBSS) and volume of interest (VOI) analyses. Correlations between clinical, imaging, and neurophysiological findings were also assessed through TBSS.
ALS patients showed a significant increase in AD and MD involving the corticospinal tract (CST) and the pre-frontal white matter in the right posterior limb of the internal capsule (p < 0.05) when compared to the control group using TBSS, confirmed by VOI analyses. VOI analyses also showed increased AD in the corpus callosum (p < 0.05) in ALS patients. Fractional anisotropy (FA) in the right CST correlated significantly with upper motor neuron (UMN) score (r = − 0.79, p < 0.05), and right abductor digiti minimi central motor conduction time was highly correlated with RD in the left posterior internal capsule (r = − 0.81, p < 0.05). No other significant correlation was found.
MD, AD, and RD, besides FA, are able to further detect and characterize neurodegeneration in ALS. Furthermore, TMS and DTI appear to have a role as complementary diagnostic biomarkers of UMN dysfunction.
KeywordsAmyotrophic lateral sclerosis Diffusion tensor imaging Magnetic resonance imaging Motor neuron disease Transcranial magnetic stimulation
Abductor digiti minimi
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis functional rate scale revisited
Compound motor action potentials
Central motor conduction time
Cortical silent period
Diffusion tensor imaging
Lower motor neuron
Motor evoked potential
Magnetic resonance imaging
Tract-based spatial statistical
Transcranial magnetic stimulation
Upper motor neuron
Volume of interest
Compliance with ethical standards
No funding was received for this study.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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