Tracking the neurodegenerative gradient after spinal cord injury.

Maryam Seif,Sreenath Kyathanahally,Armin Curt,Michela Azzarito,Patrick Freund

doi:10.1016/j.nicl.2020.102221

Abstract

To quantify neurodegenerative changes along the cervical spinal cord rostral to a spinal cord injury (SCI) by means of quantitative MRI (qMRI) and to determine its relationship with clinical impairment. Thirty chronic SCI patients (15 tetraplegics and 15 paraplegics) and 23 healthy controls underwent a high-resolution T1-weighted and myelin-sensitive magnetization transfer (MT) MRI. We assessed macro- and microstructural changes along the cervical cord from levels C1 to C4, calculating cross-sectional spinal cord area, its anterior-posterior and left-right width and myelin content (i.e. MT). Regression analysis determined associations between qMRI parameters and clinical impairment. In SCI patients, cord area decreased by 2.67mm2 (p=0.004) and left-right width decreased by 0.35mm (p=0.002) per cervical cord level in the caudal direction when compared to the healthy controls. This gradient of neurodegeneration was greater in tetraplegic than paraplegics in the cross-sectional cervical cord area (by 3.28mm2, p=0.011), left-right width (by 0.36mm, p=0.03), and mean cord MT (by 0.13%, p=0.04), but independant of lesion severity (p>0.05). Higher lesion level was associated with greater magnitudes of neurodegeneration. Greater loss in myelin content in the dorsal columns and spinothalamic tract was associated with worse light touch (p=0.016) and pin prick score (p=0.024), respectively. A gradient of neurodegeneration is evident in the cervical cord remote from a SCI. Tract-specific associations with appropriate clinical outcomes highlight that remote neurodegenerative changes are clinically eloquent. Monitoring the neurodegenerative gradient could be used to track treatment effects of regenerative and neuroprotective agents, both in trials targeting cervical and thoracic SCI patients.

Highlights

Traumatic spinal cord injury (SCI) leads most often to paralysis below the level of injury and functional recovery is limited (Ahuja et al., 2017)
This gradient of neurodegeneration was greater in tetraplegic than paraplegics in the cross-sectional cervical cord area, left-right width, and mean cord magnetization transfer (MT), but independant of lesion severity (p > 0.05)
Tract-specific associations with appropriate clinical outcomes highlight that remote neurodegenerative changes are clinically eloquent

Summary

Introduction

Traumatic spinal cord injury (SCI) leads most often to paralysis below the level of injury and functional recovery is limited (Ahuja et al., 2017). In human SCI, tissuespecific neurodegenerative changes have been quantified in the spinal cord either at the C2/C3 level (Freund et al, 2013, 2011; Huber et al., 2018; Lundell et al, 2011; Seif et al, 2018) or at the lumbar enlargement (David et al, 2019), but not along the cervical spinal cord It Corresponding author at: Spinal Cord Injury Center, Balgrist University Hospital, Forchstrasse 340, Zurich 8008, Switzerland. Is unknown whether a tract-specific neurodegenerative gradient exists (Bresnahan, 1978; Bresnahan et al, 1976; Kalil and Schneider, 1975; Kerschensteiner et al, 2005) that could be quantified in-vivo. A potential gradient of neurodegeneration could be influenced by the level of injury and the anatomical characteristics of the spinal level being affected by a lesion

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