Spinal cord compression is associated with brain plasticity in degenerative cervical myelopathy.
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ABSTRACT:
SUBMITTER: Cronin AE
PROVIDER: S-EPMC8361426 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction Degenerative Cervical Myelopathy [DCM] is a slow-motion spinal cord injury. Compression and dynamic compression have been considered disease hallmarks. However, this is likely an oversimplification, as compression is more commonly incidental and has only modest correlation to disease severity. MRI studies have recently suggested spinal cord oscillation could play a role. Research question To determine if spinal cord oscillation could contribute to spinal cord injury in degenerative cervical myelopathy. Material and methods A computational model of an oscillating spinal cord was developed from imaging of a healthy volunteer. Using finite element analysis, the observed implications of stress and strain, were measured in the context of a simulated disc herniation. The significance was bench marked by comparison to a more recognised dynamic injury mechanism; a flexion extension model of dynamic compression. Results Spinal cord oscillation altered both compressive and shear strain on the spinal cord. Following initial compression, compressive strain moves from within the spinal cord to the spinal cord surface, whilst shear strain is magnified by 0.1–0.2, depending on the amplitude of oscillation. These orders of magnitude are equivalent to a dynamic compression model. Discussion and conclusion Spinal cord oscillation could significantly contribute to spinal cord damage across DCM. Its repeated occurrence with every heartbeat, draws parallels to the concept of fatigue damage, which could reconcile differing theories on the origins of DCM. This remains hypothetical at this stage, and further investigations are required. Highlights • Aetiology of Degenerative Cervical Myelopathy is poorly understood• Paradigm based purely on ‘compression’ could be an oversimplification• Analysis of a computational model based on an MRI cervical spine• Loading from cord oscillation was equivalent to that from dynamic compression• Proposes a cause of ‘repetitive microtrauma’ warranting further investigation
| S-EPMC10293319 | biostudies-literature
Project description:BackgroundAdvanced imaging modalities have helped elucidate the cerebral alterations associated with neurological impairment caused by degenerative cervical myelopathy (DCM), but it remains unknown how brain functional network changes at different stages of myelopathy severity in DCM patients, and if patterns in network connectivity can be used to predict transition to more myelopathic stages of DCM.MethodsThis pilot cross-sectional study, which involves the collection of resting-state functional MRI (rs-fMRI) images and the modified Japanese Orthopedic Association (mJOA) score, enrolled 116 participants (99 patients and 17 healthy controls) from 2016 to 2021. The patient cohort included 21patients with asymptomatic spinal cord compression, 48 mild DCM patients, and 20 moderate or severe DCM patients. Functional connectivity networks were quantified for all participants, and the transition matrices were quantified to determine the differences in network connectivity through increasingly myelopathic stages of DCM. Additionally, a link prediction model was used to determine whether more severe stages of DCM can be predicted from less symptomatic stages using the transition matrices.FindingsResults indicated interruptions in most connections within the sensorimotor network in conjunction with spinal cord compression, while compensatory connectivity was observed within and between primary and secondary sensorimotor regions, subcortical regions, visuospatial regions including the cuneus, as well as the brainstem and cerebellum. A link prediction model achieved an excellent predictive performance in estimating connectivity of more severe myelopathic stages of DCM, with the highest area under the receiver operator curve (AUC) of 0.927 for predicting mild DCM from patients with asymptomatic spinal cord compression.InterpretationA series of predictable changes in functional connectivity occur throughout the stages of DCM pathogenesis. The brainstem and cerebellum appear highly influential in optimizing sensorimotor function during worsening myelopathy. The link predication model can inclusively estimate brain alterations associated with myelopathy severity.FundingNIH/NINDS grants (1R01NS078494-01A1, and 2R01NS078494).
| S-EPMC9483733 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a prevalent condition in which spinal degeneration causes cord compression and neurological dysfunction. The spinal cord is anatomically complex and operates in conjunction with the brain, the musculoskeletal system, and numerous organs to control numerous functions, including simple and coordinated movement, sensation, and autonomic functions. As a result, accurate and comprehensive measurement of spinal cord function in patients with DCM and other spinal pathologies is challenging. This project aimed to summarize the neurological, functional, and quality of life (QoL) outcome measures currently in use to quantify impairment in DCM. A systematic review of the literature was performed to identify prospective studies with at least 100 DCM subjects that utilized one or more quantitative neurological, functional, or QoL outcome measures. A total of 148 studies were identified. The most commonly used instruments were subjective functional scales including the Japanese Orthopedic Association (JOA) (71 studies), modified JOA (mJOA) (66 studies), Neck Disability Index (NDI) (54 studies), and Nurick (39 studies), in addition to the QoL measure Short-Form-36 (SF-36, 52 studies). A total of 92% (320/349) of all outcome measures were questionnaires, whereas objective physical testing of neurological function (strength, gait, balance, dexterity, or sensation) made up 8% (29/349). Studies utilized an average of 2.36 outcomes measures, while 58 studies (39%) utilized only a single outcome measure. No studies were identified that specifically assessed the dorsal column sensory pathway or respiratory, bowel, or sexual function. In the past five years, there were no significant differences in the number of total, functional, or QoL outcome measures used, but physical testing of neurological function has increased (p = 0.005). Prior to 2017, cervical spondylotic myelopathy (CSM) was the most frequently used term to describe the study population, whereas in the last five years, DCM has become the preferred terminology. In conclusion, clinical studies of DCM typically utilize limited data to characterize impairment, often relying on subjective, simplistic, and non-specific measures that do not reflect the complexity of the spinal cord. Although accurate measurement of impairment in DCM is challenging, it is necessary for early diagnosis, monitoring for deterioration, and quantifying recovery after therapeutic interventions. Clinical decision-making and future clinical studies in DCM should employ a combination of subjective and objective assessments to capture the multitude of spinal cord functions to improve clinical management and inform practice guidelines.
| S-EPMC8910882 | biostudies-literature
Project description:OBJECTIVE:Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS:To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS:High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION:EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.
| S-EPMC6903714 | biostudies-literature
Project description:Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.
| S-EPMC8917902 | biostudies-literature
Project description:Background and purposeAlthough current radiologic evaluation of degenerative cervical myelopathy by conventional MR imaging accurately demonstrates spondylosis or degenerative disc disease causing spinal cord dysfunction, conventional MR imaging still fails to provide satisfactory anatomic and clinical correlations. In this context, we assessed the potential value of quantitative cervical spinal cord T1 mapping regarding the evaluation of patients with degenerative cervical myelopathy.Materials and methodsTwenty patients diagnosed with mild and moderate-to-severe degenerative cervical myelopathy and 10 healthy subjects were enrolled in a multiparametric MR imaging protocol. Cervical spinal cord T1 mapping was performed with the MP2RAGE sequence procedure. Retrieved data were processed and analyzed regarding the global spinal cord and white and anterior gray matter on the basis of the clinical severity and the spinal canal stenosis grading.ResultsNoncompressed levels in healthy controls demonstrated significantly lower T1 values than noncompressed, mild, moderate, and severe stenotic levels in patients. Concerning the entire spinal cord T1 mapping, patients with moderate-to-severe degenerative cervical myelopathy had higher T1 values compared with healthy controls. Regarding the specific levels, patients with moderate-to-severe degenerative cervical myelopathy demonstrated a T1 value increase at C1, C7, and the level of maximal compression compared with healthy controls. Patients with mild degenerative cervical myelopathy had lower T1 values than those with moderate-to-severe degenerative cervical myelopathy at the level of maximal compression. Analyses of white and anterior gray matter confirmed similar results. Strong negative correlations between individual modified Japanese Orthopaedic Association scores and T1 values were also observed.ConclusionsIn this preliminary study, 3D-MP2RAGE T1 mapping demonstrated increased T1 values in the pathology tissue samples, with diffuse medullary alterations in all patients with degenerative cervical myelopathy, especially relevant at C1 (nonstenotic level) and at the maximal compression level. Encouraging correlations observed with the modified Japanese Orthopaedic Association score make this novel approach a potential quantitative biomarker related to clinical severity in degenerative cervical myelopathy. Nevertheless, patients with mild degenerative cervical myelopathy demonstrated nonsignificant results compared with healthy controls and should now be studied in multicenter studies with larger patient populations.
| S-EPMC8324281 | biostudies-literature
Project description:In degenerative cervical myelopathy (DCM), focally increased spinal cord motion has been observed for C5/C6, but whether stenoses at other cervical segments lead to similar pathodynamics and how severity of stenosis, age, and gender affect them is still unclear. We report a prospective matched-pair controlled trial on 65 DCM patients. A high-resolution 3D T2 sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) and a phase-contrast magnetic resonance imaging (MRI) sequence were performed and automatically segmented. Anatomical and spinal cord motion data were assessed per segment from C2/C3 to C7/T1. Spinal cord motion was focally increased at a level of stenosis among patients with stenosis at C4/C5 (n = 14), C5/C6 (n = 33), and C6/C7 (n = 10) (p < 0.033). Patients with stenosis at C2/C3 (n = 2) and C3/C4 (n = 6) presented a similar pattern, not reaching significance. Gender was a significant predictor of higher spinal cord dynamics among men with stenosis at C5/C6 (p = 0.048) and C6/C7 (p = 0.033). Age and severity of stenosis did not relate to spinal cord motion. Thus, the data demonstrates focally increased spinal cord motion depending on the specific level of stenosis. Gender-related effects lead to dynamic alterations among men with stenosis at C5/C6 and C6/C7. The missing relation of motion to severity of stenosis underlines a possible additive diagnostic value of spinal cord motion analysis in DCM.
| S-EPMC8432264 | biostudies-literature
Project description:BackgroundDegenerative cervical spinal cord compression is becoming increasingly prevalent, yet the MRI criteria that define compression are vague, and vary between studies. This contribution addresses the detection of compression by means of the Spinal Cord Toolbox (SCT) and assesses the variability of the morphometric parameters extracted with it.MethodsProspective cross-sectional study. Two types of MRI examination, 3 and 1.5 T, were performed on 66 healthy controls and 118 participants with cervical spinal cord compression. Morphometric parameters from 3T MRI obtained by Spinal Cord Toolbox (cross-sectional area, solidity, compressive ratio, torsion) were combined in multivariate logistic regression models with the outcome (binary dependent variable) being the presence of compression determined by two radiologists. Inter-trial (between 3 and 1.5 T) and inter-rater (three expert raters and SCT) variability of morphometric parameters were assessed in a subset of 35 controls and 30 participants with compression.ResultsThe logistic model combining compressive ratio, cross-sectional area, solidity, torsion and one binary indicator, whether or not the compression was set at level C6/7, demonstrated outstanding compression detection (area under curve =0.947). The single best cut-off for predicted probability calculated using a multiple regression equation was 0.451, with a sensitivity of 87.3% and a specificity of 90.2%. The inter-trial variability was better in Spinal Cord Toolbox (intraclass correlation coefficient was 0.858 for compressive ratio and 0.735 for cross-sectional area) compared to expert raters (mean coefficient for three expert raters was 0.722 for compressive ratio and 0.486 for cross-sectional area). The analysis of inter-rater variability demonstrated general agreement between SCT and three expert raters, as the correlations between SCT and raters were generally similar to those of the raters between one another.ConclusionsThis study demonstrates successful semi-automated compression detection based on four parameters. The inter-trial variability of parameters established through two MRI examinations was conclusively better for Spinal Cord Toolbox compared with that of three experts' manual ratings.
| S-EPMC8923862 | biostudies-literature
Project description:The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.
| S-EPMC4488354 | biostudies-literature
Project description:Study designSystematic review.BackgroundAlthough degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models.MethodsMEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14).ResultsThe search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models.ConclusionFew human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach.
| S-EPMC10140111 | biostudies-literature