Patrick Freund, University Hospital Balgrist, Zurich, Switzerland

Tracking progressive neurodegenerative processes after spinal cord injury: 5 year follow-up

Funded in: 2017, 2018, 2019


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Problem: The neurodegenerative process and the correlation with the clinical outcome and functional recovery are not well understood

Target: Visualization of time profiles of cervical cord and brain changes as well as correlations between the extent of lesion, level and outcome

Goal: assessment of the correlations of structural CNS changes and predictive potentials for a long-term clinical recovery/impairment.

 

Traumatic spinal cord injury (SCI) is a devastating and life-changing incidence that leads instantaneously to permanent paralysis and loss of sensory input. SCI results in the disruption of ascending and descending pathways mediating sensory and motor information between the brain, spinal cord, and periphery. Currently there is no “cure” for paralysis. However, recent discoveries have increased our understanding of central nervous system regeneration and functional recovery in animal models.

In the interest of advancing translational SCI research and to better understand the neuronal mechanisms underlying neuro-functional recovery in patients suffering from both acute and chronic SCI, more refined diagnostic tools are required. A method to assess the severity of the SCI is employing non-invasive Magnetic Resonance Imaging (MRI) to assess the volumetric and microstructural changes above the lesion epicentre. This strategy overcomes problems caused by implants induced artefacts with simply focusing on implant free zones within the spinal cord above the site of trauma in the high cervical cord. Crucially, we demonstrated important relationships between structural volume changes (i.e. atrophy) and clinical impairment in SCI patients within the first year after injury.

In 2010, we started to enrol a longitudinal study in which we applied optimized quantitative brain MRI sequences – which covered also portions of the upper cervical cord (C1-C3 level) – in acute SCI. This study enabled us to track trajectories of atrophy within the high cervical cord and brain over the first two years following the acute trauma. Importantly, while cord atrophy showed first signs of decelerations after two years, the brain atrophy trajectories showed sustained declines.

The current research proposal therefore aims to expand this study to 5 years using the same MRI protocol. The rich longitudinal data set collected over the past years following patients with acute SCI has already provided new insights into early degenerative changes across the neuroaxis and promises further insights into long-term progressive morphometric and microstructural changes in the spinal cord and brain far above the level of injury. These insights will enable us to understand the time course of basic disease mechanisms underpinning degeneration, demyelination, iron accumulation, and neuronal damage. We hypothesize that traumatic injury to the spinal cord results in progressive lesion-level dependant tissue loss with different trajectories in brain (motor and sensory) areas over 5 years after injury; the magnitude of these changes relate to clinical impairment.

We therefore aim for the first time to

(1) track the temporal and regional evolution of remote MRI based structural cord and brain changes over 5 years using an established and comprehensive longitudinal toolbox based on structural brain mapping,

(2) assess correlations of structural CNS changes and

(3) predictive potentials for a long term clinical recovery/impairment.