Pathobiology of cervical spondylotic myelopathy

Abstract

In this narrative review, we aim to outline what is currently known about the pathophysiology of cervical spondylotic myelopathy (CSM), the most common cause of spinal cord dysfunction. In particular, we note the unique factors that distinguish it from acute spinal cord injury. Despite its common occurrence, the reasons why some patients develop severe symptomatology while others have few or no symptoms despite radiographic evidence confirming similar degrees of compression is poorly understood. Neither is there a clear understanding of why certain patients have a stable clinical myelopathy and others present with only mild myelopathy. Moreover, the precise molecular mechanisms which contribute to the pathogenesis of the disease are incompletely understood. The current treatment method is decompression of the spinal cord but a lack of clinically relevant models of CSM have hindered the understanding of the full pathophysiology which would aid the development of new therapeutic avenues of investigation. Further elucidation of the role of ischemia, currently a source of debate, as well as the complex cascade of biomolecular events as a result of the unique pathophysiology in this disease will pave the way for further neuroprotective strategies to be developed to attenuate the physiological consequences of surgical decompression and augment its benefits.

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

“…In summary, neurodegeneration in CSM, although different in causation, disease onset and progression trajectory, 3 resembles the pathophysiological processes of antero-and retrograde degeneration observed after spinal cord injury. 38,46,47 …”

“…Propriospinal circuitries 35,36 and corticospinal projections to motor neurons 37 might be indirectly perturbed by the stenosis leading to remote neurodegeneration (e.g. axonal degeneration, neuronal loss) 3,38 which cause the mean diffusivity to increase. On the contrary, in the dorsal horns, prominent atrophy in the absence of diffusivity changes was evident above the compression site.…”

“…3 Next to focal myelopathy, [4][5][6] a cascade of neurodegenerative processes is evident in the grey and white matter above the site of compression in the cervical cord [7][8][9][10] and even in the sensorimotor cortex 11,12 that can be assessed non-invasively, amongst others, by magnetic resonance spectroscopy and diffusion tensor imaging (DTI) and other advanced MRI techniques sensitive to atrophy and microstructural changes. 13 Microstructural changes can be identified by diffusivity indices (e.g.…”

Three-dimensional alteration of cervical anterior spinal artery and anterior radicular artery in rat model of chronic spinal cord compression by micro-CT

“…From the long-term observation of 3D images, we found that the vascular density of compression group had no significant different compared with that of the sham group at the 70th day. A few of studies showed that compensatory mechanisms and angiogenesis might exist in chronic compressive spinal cord injury [17,22]. These mechanisms could be useful to explain the alteration of integral vascular network at different time after spinal cord compression.…”

Magnetic Resonance Imaging Biomarker of Axon Loss Reflects Cervical Spondylotic Myelopathy Severity

“…Cervical spondylotic myelopathy(CSM) is a progressive degenerative disease that results in compression of the cervical spinal cord or nerve roots, leading to neurologic dysfunction[1-3]. It is the leading cause of progressive disability and represents a major public health importance as its prevalence increases in an aging population[4-6].…”