Pathogenesis Of Cervical Spondylotic Myelopathy Research Articles

Current Concepts and Management Strategies in Cervical Spondylotic Myelopathy

Abstract Early diagnosis and treatment of cervical spondylotic myelopathy (CSM) are critical to achieve satisfactory results and successful functional outcomes for the patients. Usually, such patients present late, resulting in unsatisfactory treatment outcomes. It is not uncommon to see clinicians failing to recognize the early symptoms there by resulting in delayed referrals to spine surgeons. The objective of this review is to highlight the salient clinical features, pathogenesis, and management options for CSM. The epidemiology, applied anatomy, and pathogenesis of CSM are discussed, along with a review of current literature regarding the management of CSM. A thorough evaluation needs to be done to rule out medical causes for myelopathy and other neurological conditions which mimic CSM. Those with mild CSM with minimal symptoms need to be observed carefully at regular intervals. Early intervention in patients with moderate-to-severe CSM is superior to conservative treatment. Surgical strategies include anterior, posterior, or combined approaches. A thorough decompression of the spinal cord and roots and restoration of cervical lordosis should be the primary goal of the operating surgeon. Needless to mention high quality postoperative rehabilitation and exercise programs go a long way in achieving satisfactory results after surgery.

Ultrastructural destruction of neurovascular unit in experimental cervical spondylotic myelopathy.

The pathogenesis of cervical spondylotic myelopathy (CSM) remains unclear. This study aimed to explore the ultrastructural pathology of neurovascular unit (NVU) during natural development of CSM. A total of 24 rats were randomly allocated to the control group and the CSM group. Basso-Beattie-Bresnahan (BBB) scoring and somatosensory evoked potentials (SEP) were used as functional assessments. Hematoxylin-eosin (HE), toluidine blue (TB), and Luxol fast blue (LFB) stains were used for general structure observation. Transmission electron microscopy (TEM) was applied for investigating ultrastructural characteristics. The evident compression caused significant neurological dysfunction, which was confirmed by the decrease in BBB score and SEP amplitude, as well as the prolongation of SEP latency (P < 0.05). The histopathological findings verified a significant decrease in the amount of Nissl body and myelin area and an increase in vacuolation compared with the control group (P < 0.05). The TEM results revealed ultrastructural destruction of NVU in several forms, including: neuronal degeneration and apoptosis; disruption of axonal cytoskeleton (neurofilaments) and myelin sheath and dystrophy of axonal terminal with dysfunction mitochondria; degenerative oligodendrocyte, astrocyte, and microglial cell inclusions with degenerating axon and dystrophic dendrite; swollen microvascular endothelium and loss of tight junction integrity; corroded basement membrane and collapsed microvascular wall; and proliferated pericyte and perivascular astrocytic endfeet. In the CSM group, reduction was observed in the amount of mitochondria with normal appearance and the number of cristae per mitochondria (P < 0.05), while no substantial drop of synaptic vesicle number was seen (P > 0.05). Significant narrowing of microvascular lumen size was also observed, accompanied by growth in the vascular wall area, endothelial area, basement membrane thickness, astrocytic endfeet area, and pericyte coverage area (rate) (P < 0.05). Altogether, the findings of this study demonstrated ultrastructural destruction of NVU in an experimental CSM model with dorsal-lateral compression, revealing one of the crucial pathophysiological mechanisms of CSM.

TXNIP Participated in NLRP3-Mediated Inflammation in a Rat Model of Cervical Spondylotic Myelopathy

BackgroundCervical spondylotic myelopathy (CSM) is a spinal cord disease caused by cervical disc degeneration and related pathological changes. Cervical spondylotic myelopathy may result from inflammation responses and neuronal damage. Thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling promotes inflammation. However, the effects of TXNIP/NLRP3 on the pathogenesis of CSM have not been reported.MethodsA rat model of chronic cervical cord compression was established to observe changes in the levels of of TNXIP/NeuN and NLRP3/NeuN expression in the damaged anterior horn of the spinal cord following progression of CSM. Rats were injected with TXNIP small interfering RNA (siRNA) and scrambled control to determine the effects of TXNIP inhibition on NLRP3-mediated inflammation in rats with CSM. Behaviors effects and the expression of NLRP3 and pro-caspase-1 in the damaged spinal cord were evaluated.ResultsThe expression levels of TXNIP and NLRP3 were significantly increased in the damaged anterior horn of the spinal cord following CSM. Injection of TXNIP siRNA significantly improved behavioral measures and decreased apoptosis in the damaged anterior horn of spinal cord. Furthermore, the levels of NLRP3 and pro-caspase-1 in the lesioned area were reduced by the TXNIP siRNA injection.ConclusionThioredoxin-interacting protein participated in NLRP3 mediated inflammation in a rat model of CSM, which indicated that TXNIP may be a potential therapeutic target in improving CSM.

Construction of three-dimensional finite element model and biomechanical study on patient with with cervical spondylotic myelopathy

To establish a three-dimensional finite element model (FEM) of the neck, to analyze the differences in neck biomechanics between patient with cervical spondylotic myelopathy (CSM) and healthy subject and to provide biomechanics basis for the pathogenesis of CSM. Methods: A patient with CSM was enrolled in a mechanical simulation experiment. Three-dimensional CT scan was performed, and three-dimensional FEM of the neck was constructed. A heathy subject was selected as a control according to the patient's age, gender, height, and weight. Three-dimensional FEM was used to compare the stress differences in the vertebral body, intervertebral disc, ligament and spinal cord under the normal stress of the cervical spine and the maximum stress of the posterior reclining motion. Results: Successfully constructed FEM model of CSM patient and control, and performed mechanical analysis, the most obvious difference in cervical vertebral body force was at C5-C6 segment in CSM patients. The maximum stress site of control and patient was at the anterior edge of the vertebral body. The maximum stress of the vertebral body in the CSM patient was less than that of the control. The stress distribution of the intervertebral disc was irregular in the CSM patient, and the maximum stress was concentrated on both sides of the posterior edge of the intervertebral disc. The stress distribution of the ligaments of the CSM patient was uneven. The maximum stress was in the posterior longitudinal ligament. The range of neck movement in extension of the CSM patient was restricted. Conclusion: Compared with the healthy subject, the balance of the vertebral body, intervertebral disc, ligament and limited range of motion of the CSM patient has been changed, which may be related to the mechanical pathogenesis of cervical spondylotic myelopathy.

Natural history, prevalence, and pathophysiology of cervical spondylotic myelopathy

This study is a narrative review performed to summarize the current knowledge about the epidemiology, natural history and pathogenesis of cervical spondylotic myelopathy (CSM). A comprehensive search was undertaken to look at all available articles between January 1, 1956 to May 1, 2018, on PubMed and the Cochrane Collaboration Library. The natural history of CSM is variable. The main determinants of the clinical course of CSM are the extent of neurological impairment, age, cervical instability, abnormalities of cord conduction, canal diameter, congenitally stenotic spinal canal and the extent of involvement and tract disruption on diffusion tensor imaging (DTI) imaging. There is little data on the true incidence and prevalence of CSM across the globe and none from India. The pathoanatomic basis of CSM is cord compression, either dynamic or static. The biological events that are thought to play a significant role in the development of CSM are ischemia, derangement of the blood-spinal cord barrier, chronic neuronal inflammation, and apoptosis. Emerging knowledge about the molecular biology holds promise for potential intervention, both for prevention and for cure, of this common and debilitating condition.

Spondylotic cervical myelopathy : Indication of surgical treatment

The pathogenesis of cervical spondylotic myelopathy (CSM) is often multifactorial. Hence, the treatment of this disease requires adifferentiated surgical approach in order to adequately address the underlying pathology. The aim of this review is to identify factors that influence the choice of treatment strategy and to summarize them in an algorithm that serves as adecision aid in choosing the optimal indication for surgical treatment. An attempt is made to define the threshold values for the indication of surgical treatment and to discuss the ideal timing for performing surgery. On the basis of the published data, the influencing factors on the prognosis of CSM, as well as surgical approaches are discussed. Circumferential spinal cord compression, asharply defined myelopathy signal in the T2-weighted MRI sequence, and segmental instability at the level of the myelopathy signal mean an unfavorable prognosis for the worsening of CSM. The most important factors that influence the choice of the surgical access point are the sagittal profile of the cervical spine, the extent of myelopathy, the extent of stenosis, and the location of the myelopathy-inducing pathology. Previously existing neck pain and prior cervical surgery must also be considered. On the basis of the research carried out, we developed an algorithm that could serve as an aid in choosing the right treatment in the setting of cervical spondylotic myelopathy.

Preoperative cervical sagittal alignment parameters and their impacts on myelopathy in patients with cervical spondylotic myelopathy: a retrospective study.

BackgroundCervical sagittal alignment plays an important role in the pathogenesis of cervical spondylotic myelopathy (CSM), but there are limited studies on the cervical sagittal parameters in CSM patients and their correlations with myelopathy. The aim of this study is to investigate the correlations among the preoperative cervical sagittal alignment parameters and their correlations with the development of myelopathy in patients with CSM.MethodsWe retrospectively collected 212 patients with CSM who underwent surgical interventions. Gender, age, modified Japanese Orthopedic Association score (mJOA), cervical lordosis (CL), C2–C7 sagittal vertical axis (C2–C7 SVA), T1 slope (T1S), neck tilt (NT) and thoracic inlet angle (TIA) were collected before operation. Interobserver and intraobserver reliability were calculated for all measurements (intraclass correlation coefficient, ICC). Data were analyzed with Pearson and Spearman correlation tests and multiple linear regression analysis.ResultsA total of 212 patients with CSM were included in this study (male: 136, female: 76) with an average age of 54.5 ± 10.1 years old. Intraobserver and interobserver reliability for all included radiographic parameters presented good to excellent agreement (ICC > 0.7). No significant differences in demographic and radiological parameters have been observed between males and females (P > 0.05). We found statistically significant correlations among the following parameters: age with CL (r = 0.135, P = 0.049), age with T1S (r = 0.222, P = 0.001), CL with T1S (r = 0.291, P < 0.001), CL with C2-C7 SVA (r = − 0.395, P < 0.001), mJOA with age (r = − 0.274, P < 0.001), mJOA with C2–C7 SVA (r = − 0.219, P < 0.001) and mJOA with T1S(r = − 0.171, p = 0.013). Linear regression analysis showed that C2–C7 SVA was the predictor of CL (adjusted R2 = 0.152, P < 0.001) and multiple linear regression showed that age combined with C2–C7 SVA was a sensitive predictor of mJOA (adjusted R2 = 0.106, P < 0.001).DiscussionThere were significant correlations among certain preoperative cervical sagittal parameters in CSM patients. CL was the only predictor of C2–C7 SVA. Age combined with C2–C7 SVA could predict the severity of myelopathy.

Dynamic Evaluation of the Cervical Spine and the Spinal Cord of Symptomatic Patients Using a Kinetic Magnetic Resonance Imaging Technique.

The purpose of this study was to examine the movement of the spinal cord and its relationship to the spinal canal in patients with mild spondylosis using kinetic magnetic resonance imaging (kMRI). Weight-bearing, multiposition kMRI was performed on symptomatic patients through a full range of flexion-extension. A total of 52 study patients were selected based on the C2-C7 Cobb angle of sagittal alignment: lordotic (from 30 to 45 degrees). We evaluated dynamic changes in different parameters from flexion-extension: spinal canal diameter (CD), spinal cord diameter (SCD), space available for the cord, anterior space available for the cord (ASAC), posterior space available for the cord (PSAC), average distance between the anterior canal and the cord (d-value), and global angle for the spinal canal and cord. The CD tended to decrease from flexion to extension from C3/C4 to C6/C7, however, there were no significant differences at the proximal and distal levels, C2/C3 and C7/T1. There were no significant differences of SCD between different postures. The SCD tended to decrease from C2/C3 to C7/T1. The ASAC followed the same pattern as CD-values. The ASAC was narrowest at C4/C5 and C5/C6. The PSAC tended to increase from C2/C3 to C7/T1. The spinal cord shifted anteriorly with extension and posteriorly with flexion. In addition, the spinal cord maintained its curve with the movement. The kinematics of spinal cord motion may be associated with the pathogenesis of cervical spondylotic myelopathy. However, the spinal cord maintains its curve with position changes. Consequently, different motions of the cervical spine may affect spinal cord migration and cause changes in ASAC and PSAC.

Advances in MR imaging for cervical spondylotic myelopathy

To outline the pathogenesis of cervical spondylotic myelopathy (CSM), the correlative abnormalities observed on standard magnetic resonance imaging (MRI), the biological implications and current status of diffusion tensor imaging (DTI), and MR spectroscopy (MRS) as clinical tools, and future directions of MR technology in the management of CSM patients. A systematic review of the pathogenesis and current state-of-the-art in MR imaging technology for CSM was performed. CSM is caused by progressive, degenerative, vertebral column abnormalities that result in spinal cord damage related to both primary mechanical and secondary biological injuries. The T2 signal change on conventional MRI is most commonly associated with neurological deficits, but tends not to be a sensitive predictor of recovery of function. DTI and MRS show altered microstructure and biochemistry that reflect patient-specific pathogenesis. Advanced imaging techniques, including DTI and MRS, show higher sensitivity to microstructural and biochemical changes within the cord, and may aid in management of CSM patients.

Cervical spondylotic myelopathy with vitamin B12 deficiency: Two case reports

Although it has been observed that a vitamin B12 (VB12) deficiency may lead to defects in the nervous system, there is a lack of studies elucidating whether VB12 has a role in the pathogenesis of cervical spondylotic myelopathy (CSM). The present study describes two cases of CSM observed in the clinic, where the patients presented with common characteristics of the typical clinical symptoms; however, T2-weighted magnetic resonance imaging examinations revealed that although the degree of spinal cord compression was not serious, the spinal cord exhibited significant high signal changes. At the same time, the serum VB12 levels of the two patients were lower compared with those of normal controls. The symptoms of the patients improved following anterior cervical decompression surgery and VB12 replacement therapy. The incidence of CSM in the two patients may have been correlated with a lack of VB12. Therefore, it is recommended that the serum VB12 levels are checked in cases of CSM where the standard imaging and clinical manifestations do not fully match.

Dynamic somatosensory evoked potentials to determine electrophysiological effects on the spinal cord during cervical spine extension

The goal of this prospective study was to investigate somatosensory evoked potentials (SSEPs) during dynamic motion of the cervical spine and to evaluate the efficacy of analyzing dynamic SSEPs for predicting dynamic effects on the spinal cord in patients with cervical spondylotic myelopathy (CSM). In total, 40 human subjects (20 CSM patients and 20 healthy volunteers as a control group) were examined prospectively using dynamic SSEPs with median nerve stimulation. The CSM patients showed cervical myelopathy due to cervical cord compression at the C4-5 segment. The SSEPs were examined with the cervical spine in a neutral position and at a 20° extension for 10 and 20 minutes. Changes in the N20 latency and amplitude were determined and analyzed. The authors defined the changes in the N20 latency and N20 amplitude between the neutral and extension positions of the cervical spine as percent latency and amplitude, respectively. In the CSM patients, SSEPs tended to deteriorate after cervical spine extension, and a statistically significant deterioration of the N20 amplitude after the extension was observed. Moreover, the percent latency and amplitude progressively increased during cervical spine extension in these patients. In the healthy controls, SSEPs tended to deteriorate with cervical spine extension, but these changes did not result in statistically significant differences. Moreover, in this group the percent latency and amplitude were almost identical during the extension. When the CSM patients and the healthy controls were compared, a significant difference in the percent amplitude was observed between the 2 groups during the cervical spine extension. This study suggests the potential of dynamic SSEPs as a useful neurophysiological technique to detect the effect of dynamic factors on the pathogenesis of CSM.

Dietary therapy to promote neuroprotection in chronic spinal cord injury

The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission. An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period. At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane. Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.

Effect of IL-6 and TNF-a in the Cervical Spondylotic Myelopathy

Objective To measure the levels of interleukin-6 (IL-6) and tumor necrosis factor-a( TNF-a) in the cervical intervertebral disk of patients with cervical spondylotic myelopathy ( CSM) ,study the role of IL-6 and TNF-a in the pathogenesis of CSM.Methods 40 degenerative cervical vertebral disk tissues were collected from CSM cases;20 normal tissues of vertebral disk were taken as control.The contents of IL-6 and TNF-a were detected by ELISA.Results The contents of IL-6 and TNF-a in disk of CSM sufferers increased significantly compared with the control group (P<0.01).Conclusion The results of the present study indicated that IL-6 and TNF-a may be involved in the pathogenesis of CSM. Key words: Cervical spondylotic myelopathy; IL-6; TNF-a

Management of cervical spondylotic myelopathy with insights from metabolic imaging of the spinal cord and brain

Cervical spondylotic myelopathy (CSM) is a potentially debilitating disorder primarily related to spinal cord injury caused by degenerative changes of the spine. As the population continues to age and live longer, it is likely that this disorder will be encountered with increasing frequency. Surgical management continues to be a mainstay of treatment of CSM patients, but some studies have indicated that nonoperative treatment may be equivalent to surgical management in some patients. Recent advances in neuroimaging of the spinal cord and brain have provided novel information regarding the pathogenesis of CSM, as well as compensatory mechanisms to preserve neurological function. CSM is a complex disorder whose incidence is likely to increase in coming years. Prospective, randomized studies are required to help establish the optimal treatment paradigm. Recent advances such as novel neuroimaging techniques and the continued development of neural repair strategies to treat the secondary biological injury associated with this disorder are likely to play key roles in the future management of CSM.

Stretch-associated Injury in Cervical Spondylotic Myelopathy: New Concept and Review

The simple pathoanatomic concept that a narrowed spinal canal causes compression of the enclosed cord, leading to local tissue ischemia, injury, and neurological impairment, fails to explain the entire spectrum of clinical findings observed in cervical spondylotic myelopathy. A growing body of evidence indicates that spondylotic narrowing of the spinal canal and abnormal or excessive motion of the cervical spine results in increased strain and shear forces that cause localized axonal injury within the spinal cord. During normal motion, significant axial strains occur in the cervical spinal cord. At the cervicothoracic junction, where flexion is greatest, the spinal cord stretches 24% of its length. This causes local spinal cord strain. In the presence of pathological displacement, strain can exceed the material properties of the spinal cord and cause transient or permanent neurological injury. Stretch-associated injury is now widely accepted as the principal etiological factor of myelopathy in experimental models of neural injury, tethered cord syndrome, and diffuse axonal injury. Axonal injury reproducibly occurs at sites of maximal tensile loading in a well-defined sequence of intracellular events: myelin stretch injury, altered axolemmal permeability, calcium entry, cytoskeletal collapse, compaction of neurofilaments and microtubules, disruption of anterograde axonal transport, accumulation of organelles, axon retraction bulb formation, and secondary axotomy. Stretch and shear forces generated within the spinal cord seem to be important factors in the pathogenesis of cervical spondylotic myelopathy.

Cervical spondylotic myelopathy: functional and radiographic long-term outcome after laminectomy and posterior fusion.

To evaluate the long-term efficacy of cervical laminectomy with posterior lateral mass fusion/fixation in the treatment of patients with cervical spondylotic myelopathy (CSM). Twenty-five patients treated for CSM by laminectomy and lateral mass fusion at the Division of Neurosurgery at The Ohio State University between 1989 and 1994 were studied retrospectively. Only patients with longer than 2-year postoperative follow-up durations were included. At follow-up examination, each patient completed an SF36 questionnaire, underwent a physical examination, underwent plain radiography showing the spinal curvature with plate and screw position, and underwent magnetic resonance imaging of the cervical spine, which evaluated dural sac decompression and spinal cord abnormalities. Patient-generated data were used for outcome measurements. The mean follow-up duration was 47.5 months. Good outcome was defined by the presence of three criteria: ability to walk unassisted (Grade IIIA or better), ability to write unassisted, and ability to manage buttons and/or zippers unassisted. The inability to meet these criteria was defined as a poor outcome. Two patients (8%) experienced complications that resulted from the surgery. There was no instability or progression to significant kyphosis. Lesions that were hyperintense on magnetic resonance images did not correlate with outcome. Eighty percent of the patients achieved good outcomes, and 76% had improved myelopathy scores. None of the patients had late neurological deterioration. Patients with better neurological statuses at the time of surgery (Grade IIIA or better) were more likely to improve (P < 0.0001); the likelihood of a change in status for those starting with poorer grades (IIIB or worse) was not statistically significant (P < 0.08). Cervical laminectomy with posterior fusion/fixation proved useful in the treatment of patients with CSM with straight or lordotic spines and multilevel compression. This therapy addresses the dynamic and compressive forces that are important in the pathogenesis of CSM, resulting in minimal complications and possible improvement in long-term outcomes.

Dynamic changes of the spinal canal in patients with cervical spondylosis at flexion and extension using magnetic resonance imaging.

The authors determine the dynamic changes of the spinal canal during flexion and extension in patients with cervical spondylosis. Forty-six patients were studied inside a whole-body magnetic resonance (MR) scanner with between 50 degrees of flexion and 30 degrees of extension, using a positioning device. At neutral position (0 degree) and maximum flexion and extension sagittal T2-weighted turbo spin echo sequences were acquired. A significant (P < or = 0.05) increase of spinal stenosis was found at extension (48%, 22 of 46 patients) when compared with flexion (24%, 11 of 46). Cervical cord compression was diagnosed at flexion in 5 patients (11%) and at extension in 9 patients (20%). Concerning the number of patients with cervical cord compression at flexion and extension, significant differences (P < or = 0.05) were found in patients with degenerative changes at four segments compared with patients with one segment involvement. Magnetic resonance imaging identified a significant percentage of increased spinal stenosis at flexion and, especially, at extension, which was not observed at neutral position (0 degree). Flexion and extension MR imaging demonstrates additional information using a noninvasive technique concerning the dynamic factors in the pathogenesis of cervical spondylotic myelopathy.

Pathogenesis of cervical spondylotic myelopathy.

OBJECTIVE: To determine whether either of two mechanical theories predicts the topographic pattern of neuropathology in cervical spondylotic myelopathy (CSM). The compression theory states that the spinal cord is compressed...

The Role of Ischemia in the Pathogenesis of Cervical Spondylotic Myelopathy

The Role of Ischemia in the Pathogenesis of Cervical Spondylotic Myelopathy

Studies on pathogenesis of cervical spondylotic myelopathy: sagittal diameter of the spinal canal and cerebrospinal fluid characteristics in cervical spondylosis.

Studies on pathogenesis of cervical spondylotic myelopathy: sagittal diameter of the spinal canal and cerebrospinal fluid characteristics in cervical spondylosis.