The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

Thomas Wimmer,Jörn Kaufmann,Nathalie Hensiek,Peter J Nestor,Judith Machts,Stefanie Schreiber,Susanne Petri,Stefan Vielhaber,Johannes Prudlo,Frank Schreiber,Susanne Vogt,Cornelia Garz,Reinhard Dengler,Hans-Jochen Heinze

doi:10.1038/s41598-020-58687-z

Abstract

The upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1–C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients. Compared to controls, in ALS there was a significant mean spinal cord atrophy (63.8 mm² vs. 60.8 mm², p = 0.001) which showed a trend towards worsening over time (mean spinal cord CSA decrease from 61.4 mm² to 60.6 mm² after 6 months, p = 0.06). Findings were most pronounced in the caudal segments of the upper cervical spinal cord and in limb-onset ALS. Baseline CSA was related to the revised ALS functional rating scale, disease duration, precentral gyrus thickness and total brain gray matter volume. In conclusion, spinal cord atrophy as assessed in brain MRIs in ALS patients mirrors the extent of overall neurodegeneration and parallels disease severity.

Highlights

In-vivo studies applying magnetic resonance imaging (MRI) correspondingly display a reduction of the spinal cord cross-sectional area (CSA) in amyotrophic lateral sclerosis (ALS), i.e. showing spinal cord atrophy together with pyramidal tract integrity loss in diffusion tensor imaging (DTI)[5,6,7]
Only a few ALS studies far took advantage of the capability of spinal cord in-vivo MRI to monitor CSA evolution over time[5,12,13]. In consideration of these uncertainties, we conducted a retrospective analysis of the upper cervical spinal cord within brain MRIs that were acquired during a large cross-sectional (N = 158) and longitudinal (N = 103) multicenter study to understand how in-vivo spinal cord atrophy relates to clinical features, other biomarkers, and, how it evolves over time in ALS
Considering the whole cohort, mean CSA was related to baseline age (r = −0.2, p = 0.003) in that older age was associated with a smaller spinal cord CSA (Fig. 3a)

Summary

Introduction

In-vivo studies applying magnetic resonance imaging (MRI) correspondingly display a reduction of the spinal cord cross-sectional area (CSA) in ALS, i.e. showing spinal cord atrophy together with pyramidal tract integrity loss in diffusion tensor imaging (DTI)[5,6,7]. Only a few ALS studies far took advantage of the capability of spinal cord in-vivo MRI to monitor CSA evolution over time[5,12,13]. In consideration of these uncertainties, we conducted a retrospective analysis of the upper cervical spinal cord within brain MRIs that were acquired during a large cross-sectional (N = 158) and longitudinal (N = 103) multicenter study to understand how in-vivo spinal cord atrophy relates to clinical features, other biomarkers, and, how it evolves over time in ALS

Methods

Results

Discussion

Conclusion