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Spinal Cord Parenchyma Vascular Redistribution Underlies Hemodynamic and Neurophysiological Changes at Dynamic Neck Positions in Cervical Spondylotic Myelopathy.

ABSTRACT: Cervical spondylotic myelopathy (CSM) is a degenerative condition of the spine that caused by static and dynamic compression of the spinal cord. However, the mechanisms of motor and somatosensory conduction, as well as pathophysiological changes at dynamic neck positions remain unclear. This study aims to investigate the interplay between neurophysiological and hemodynamic responses at dynamic neck positions in the CSM condition, and the pathological basis behind. We first demonstrated that CSM patients had more severe dynamic motor evoked potentials (DMEPs) deteriorations upon neck flexion than upon extension, while their dynamic somatosensory evoked potentials (DSSEPs) deteriorated to a similar degree upon extension and flexion. We therefore generated a CSM rat model which developed similar neurophysiological characteristics within a 4-week compression period. At 4 weeks-post-injury, these rats presented decreased spinal cord blood flow (SCBF) and oxygen saturation (SO₂) at the compression site, especially upon cervical flexion. The dynamic change of DMEPs was significantly correlated with the change in SCBF from neutral to flexion, suggesting they were more sensitive to ischemia compared to DSSEPs. We further demonstrated significant vascular redistribution in the spinal cord parenchyma, caused by angiogenesis mainly concentrated in the anterior part of the compressed site. In addition, the comparative ratio of vascular densities at the anterior and posterior parts of the cord was significantly correlated with the perfusion decrease at neck flexion. This exploratory study revealed that the motor and somatosensory conductive functions of the cervical cord changed differently at dynamic neck positions in CSM conditions. Compared with somatosensory conduction, the motor conductive function of the cervical cord suffered more severe deteriorations upon cervical flexion, which could partly be attributed to its higher susceptibility to spinal cord ischemia. The uneven angiogenesis and vascular distribution in the spinal cord parenchyma might underlie the transient ischemia of the cord at flexion.

SUBMITTER: Yu Z

PROVIDER: S-EPMC8650056 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:MethodsTwenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (p<0.05) were performed to assess significant differences in reflexes, proprioception and strength among patients and controls (SPSS software version 24).ResultsPatients reported higher Nurick (1.90±1.0 vs 0±0, p<0.001) and lower mJOA scores (14.3±1.9 vs 18.0±0, p<0.001) as compared to controls. Similarly, patients with CSM had increased reflexes (peak FDS EMG) (0.073±0.096 vs. 0.014±0.010, p = 0.019). Patient proprioception was significantly worse; mean angle of detection was greater than twice as high in patients (9.6± 9.43°) compared to controls (4.0± 2.3°), p = 0.022. MRI based compression ratio (CR) was a significant predictor of hyperreflexia, CR<0.44 resulted in steep increase in reflex activity. Fifteen of the 20 patients who completed follow up testing at 6 months after surgery show substantial clinical improvement in reflexes and proprioceptive angle, while repeated testing in controls were unchanged.ConclusionIn conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Project description:Study designA case-control study.ObjectiveThe aim of this study was to understand the role of magnetization transfer ratio (MTR) in identifying patients with clinically significant myelopathy and disability.Summary of background dataMTR is a quantitative measure that correlates with myelin loss and neural tissue destruction in a variety of neurological diseases. However, the usefulness of MTR in patients with cervical spondylotic myelopathy (CSM) has not been examined.MethodsWe prospectively enrolled seven CSM patients and seven age-matched controls to undergo magnetic resonance imaging (MRI) of the cervical spine. Nurick, Neck Disability Index (NDI), and modified Japanese Orthopedic Association (mJOA) scores were collected for all patients. Clinical hyperreflexia was tested at the MCP joint, using a six-axis load cell. Reflex was simulated by quickly moving the joint from maximum flexion to maximum extension (300°/second). Anterior, lateral, and posterior cord MTR measurements were compared with clinical outcomes.ResultsCompared with controls, CSM patients had lower anterior cord MTR (38.29 vs. 29.97, Δ = -8.314, P = 0.0022), and equivalent posterior cord (P = 0.2896) and lateral cord (P = 0.3062) MTR. Higher Nurick scores were associated with lower anterior cord MTR (P = 0.0205), but not lateral cord (P = 0.5446) or posterior cord MTR (P = 0.1222). Lower mJOA was associated with lower anterior cord MTR (P = 0.0090), but not lateral cord (P = 0.4864) or posterior cord MTR (P = 0.4819). There was no association between NDI and MTR of the anterior (P = 0.4351), lateral (P = 0.7557), or posterior cord (P = 0.9171). There was a linear relationship between hyperreflexia and anterior cord MTR (slope = -117.3, R = 0.6598, P = 0.0379), but not lateral cord (P = 0.1906, R = 0.4511) or posterior cord (P = 0.2577, R = 0.3957) MTR.ConclusionAnterior cord MTR correlates with clinical outcomes as measured by mJOA index, Nurick score, and quantitative hyperreflexia, and could play a role in the preoperative assessment of CSM.Level of evidence2.

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Spinal Cord Parenchyma Vascular Redistribution Underlies Hemodynamic and Neurophysiological Changes at Dynamic Neck Positions in Cervical Spondylotic Myelopathy.

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