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Neuroimage Clin. 2017 Jan 24;14:269-276. doi: 10.1016/j.nicl.2017.01.024. eCollection 2017.

Longitudinal evaluation of cerebral and spinal cord damage in Amyotrophic Lateral Sclerosis.

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Department of Neurology and Neuroimaging Laboratory, School of Medical Sciences, University of Campinas - UNICAMP Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz" Campinas, SP 13083-887, Brazil.



To evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression.


Twenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software). All analyses were corrected for multiple comparisons. The standardized response mean (SRM = mean score change / standard deviation of score change) was calculated for all methods herein employed and used for comparison purposes.


There were 18 men and mean age at first examination was 51.9 years. Mean ALSFRS-R scores at baseline and follow-up were 34.0 and 29.0, respectively. There was no region with progressive cortical thinning, but there was significant brainstem volumetric reduction (p = 0.001). TBSS analyses revealed progressive increase of AD (axial diffusivity) and MD (mean diffusivity) at the corpus callosum (p < 0.05), whereas SpineSeg showed progressive cord area reduction (p = 0.002). Cervical spinal cord cross-sectional area reduction was the only MRI parameter that correlated with ALSFRS-R change (r = 0.309, p = 0.038). SRM for ALSFRS-R was 0.95, for cord area 0.95, for corpus callosum AD 0.62 and MD 0.65, and for brainstem volume 0.002.


Structural MRI is able to detect short term longitudinal changes in ALS. Cervical spinal cord morphometry is a promising neuroimaging marker to assess ALS course.


Amyotrophic Lateral Sclerosis; Cortical thickness; MRI; Spinal cord; TBSS

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