Cervical Cord Neurodegeneration in Traumatic and Non-Traumatic Spinal Cord Injury.

Maryam Seif,Armin Curt,Gergely David,Kevin Vallotton,Eveline Huber,Patrick Freund

doi:10.1089/neu.2019.6694

Abstract

This study aimed to compare macrostructural and microstructural neurodegenerative changes remote from a cervical spinal cord injury in traumatic spinal cord injury (tSCI) and degenerative cervical myelopathy (DCM) patients using quantitative magnetic resonance imaging (MRI). Twenty-nine tSCI patients, 20 mild/moderate DCM patients, and 22 healthy controls underwent a high-resolution MRI protocol at the cervical cord (C2/C3). High-resolution T2*-weighted and diffusion-weighted scans provided data to calculate tissue-specific cross-sectional areas of the spinal cord and tract-specific diffusion indices of cord white matter, respectively. Regression analysis determined associations between neurodegeneration and clinical impairment. tSCI patients showed more impairment in upper limb strength and manual dexterity when compared with DCM patients. While macrostructural MRI measures revealed a similar extent of remote cord atrophy at cervical level, microstructural measures (diffusion indices) were able to distinguish more pronounced tract-specific neurodegeneration in tSCI patients when compared with DCM patients. Tract-specific neurodegeneration was associated with upper limb impairment. Despite clinical differences between severely impaired tSCI compared with mildly affected DCM patient, extensive cord atrophy is present remotely from the focal spinal cord injury. Diffusion indices revealed greater tract-specific alterations in tSCI patients. Therefore, diffusion indices are more sensitive than macrostructural MRI measures as these are able to distinguish between traumatic and non-traumatic spinal cord injury. Neuroimaging biomarkers of cervical cord integrity hold potential as predictors of recovery and might be suitable biomarkers for interventional trials both in traumatic and non-traumatic SCI.

Highlights

Such advanced clinical assessment allows quantifying the degree of impairment, it cannot disclose the underlying pathophysiology that occurs at the microstructural level
Comparing traumatic spinal cord injury (tSCI) with degenerative cervical myelopathy (DCM) patients, we found that in tSCI patients, axial diffusivity (AD) was lower in the dorsal columns (AIS A&B = -14.4%; p = 0.005, localization: x = -0.1, y = -21.9, z = 15; Z-score = 3.39; cluster extent = 157) and AIS C&D = -12.6%, p < 0.001, and in the lateral corticospinal tract (AIS C&D = -11.1%, p = 0.041; localization: x = 1.5, y = -22.6, z = 26; Z-score = 4.33; cluster extent = 467)
Our findings suggest that measures of cord atrophy are insensitive to reveal disease-specific changes while advanced Quantitative magnetic resonance imaging (qMRI) measures are sensitive to the underlying disease process, as it can detect tract-specific changes

Summary

Introduction

T raumatic spinal cord injury (tSCI) and non-traumatic degenerative cervical myelopathy (DCM) are conditions that arise from focal cervical damage.[1,2] The most obvious difference between a traumatic and non-traumatic cervical myelopathy lies in the time profile of neural changes (acute onset in tSCI vs. slowly developing symptoms in DCM).[3,4,5,6] Due to progressive impairment of gait and the increasing risk of falls, DCM patients can develop a central cord syndrome, which per definition is a tSCI.[7]Experimental evidence suggests that tSCI and DCM share several aspects of myelopathy with a combination of alpha-motoneuron damage (lesion of the central gray),[8] demyelination,[9,10,11,12] and axonal damage of long projecting spinal nerve fiber tracts (white matter damage),[13,14] as well as edema and ischemic changes.[11,15]Both etiologies present with varying degrees of upper limb impairment[16,17,18] that can be assessed by comprehensive clinical protocols sensitive to sensorimotor functions (e.g., Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP]).[19,20] such advanced clinical assessment allows quantifying the degree of impairment, it cannot disclose the underlying pathophysiology that occurs at the microstructural level. Experimental evidence suggests that tSCI and DCM share several aspects of myelopathy with a combination of alpha-motoneuron damage (lesion of the central gray),[8] demyelination,[9,10,11,12] and axonal damage of long projecting spinal nerve fiber tracts (white matter damage),[13,14] as well as edema and ischemic changes.[11,15] Both etiologies present with varying degrees of upper limb impairment[16,17,18] that can be assessed by comprehensive clinical protocols sensitive to sensorimotor functions (e.g., Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP]).[19,20] such advanced clinical assessment allows quantifying the degree of impairment, it cannot disclose the underlying pathophysiology that occurs at the microstructural level

Objectives

Methods

Results

Discussion

Conclusion