The study first uncovered the dynamic neurophysiological changes behind MRI and dynamic X-ray findings in CSM patients. Patients with lower Compression_Ratio, Central_Ratio and 1/4-Lateral_Compression_Ratio in MRI and cervical segmental instability in dynamic X-ray showed more severe neurological dysfunction at extensions and flexions. Patients with diffuse intramedullary T2 hyperintensity with obscure and faint borders in MRI (Ax-CCM type 1) had their electro-neurophysiology most severely impacted at extension. While patients with focal intermedullary T2 hyperintensity and faint borders (Ax-CCM type 2) had their DSSEP changed most greatly at flexion. Our findings suggested that the compressive degree evaluated by the three mentioned MRI measurements and segmental instability evaluated by dynamic X-rays were associated with the extent of the dynamic neural deficit of the chronic compressive spinal cord. Patients' different MRI intermedullary T2 hyperintensity patterns may suggest different modes of transient dynamic spinal cord injuries and distinct pathophysiology. These radiographic findings might have good potentials in aiding the diagnosis and prognostication of CSM clinically.
Our previous study has already proven the diagnostic effect of DSSEP N13 amplitude ratios[15]. Transient or reversible cervical cord dysfunction resulting from dynamic cervical cord compression may lead to the deterioration of some electrophysiological parameters, making DSSEP more sensitive and effective in diagnosing CSM than traditional static SSEP.[15] The DSSEP N13 wave is a non-cephalic reference which mainly reflects signal transmittance through the cervical spinal cord to lower brainstem levels, while the N20's receivers are placed on the scalp and can be easily interfered by brain waves.[20] This explains why N13 amplitude is a more suitable parameter over N20 amplitude. In this study, we used the DSSEP N13 amplitude ratios (N13_E and N13_F) to reflect transient cord dysfunction during motion in CSM patients. A lower value corresponded to a greater neurological change and a value of 0 indicated that the SSEP wave was absent. In other words, a smaller value may indicate either a serious, repetitive, or active microinjury to the spinal cord during motion, or permanent damage to the cervical cord. On the contrary, a high value corresponded to less change in neurological function during motion, and suggested either a good neurological condition or a chronic and stable condition of the spinal cord. Both the N13_E and N13_F showed good correlations with our baseline clinical assessments and postoperative outcomes.
Compression of the spinal cord does not always cause clinical symptoms and it is difficult to infer the degree of dysfunction of the spinal cord from MRI findings. In this study, we used N13 DSSEP amplitude ratios as a tool for assessing the dynamic neurological deficit of CSM, and compared them with MRI measurements. We found both the N13_E and N13_F positively correlated with the Compression_Ratio, Central_Ratio and 1/4-Lateral_Compression_Ratio measured in MR axial images. Our results suggested that the extent of dynamic neural dysfunction of the cord were associated with the degree of spinal cord deformity caused by central canal stenosis as well as lateral compression. The Compression_Ratio and Central_Ratio are sensitive markers for myelopathy[21] which have been used regularly in the management of CSM. The 1/4-Lateral_Compression_Ratio has been proved to reflect the extent of dysfunction of the corticospinal tracts[22]. However, there was no correlation between the DSSEP results and the spinal cord sagittal diameter, area, or Cord/Canal Area Ratio. An explanation for it was that the spinal cord's absolute sagittal diameter and cross-sectional area depend on several factors including height, cervical segmental level (greatest at C4), and age (greatest at the 3rd decade of life),[23–25] which vary substantially between individuals. The Cord/Canal Area Ratio failed to reflect the dynamic neural impact because it could not reflect the compression degree in some cases. For some patients with severe compression, the spinal cord and subarachnoid space may be flattened, with the spinal cord area and Cord/Canal Area Ratio remaining unchanged.
Intramedullary T2WI hyperintensity has been proved to be a sensitive marker for severe myelopathy and poor prognosis by many studies,[26–28] and is thought to reflect a broad spectrum of pathologic changes from reversible edema and inflammation to irreversible vascular ischemia and cystic necrosis.[29, 30] However, not all T2WI signal changes are the same, and the changes appear in 2 broad forms depending on the degree of intensity deviation and the patterns of the signal change.[31, 32] The Ax-CCM grading system is based on the morphology and area of intramedullary hyper-intensity on axial T2WI and has been proved to correlate well with clinical pictures[8]. In this study, we used the Ax-CCM grading system to evaluate the CSM patients, and found both the N13_E and N13_F varied statistically (ANOVA, p < 0.05) among different Ax-CCM groups. The N13_E and N13_F in the Ax-CCM Type 1 and 2 groups were lower than that in the other two groups, suggested spinal cords in these groups were more vulnerable during motion. Interestingly, we found patients in Ax-CCM Type 1 group were most severely affected at extension, while the patients in Ax-CCM Type 2 group were at flexion. According to You et al, the type 1 pattern seems to indicate an acute, transient, and recuperative cord injury with relatively good circulation[8], making the spinal cord more vulnerable at extension because of the "pincer effect", but relatively less affected at extension. The Ax-CCM type 2 pattern, or the so called "snake-eye appearance" in MRI, however, may indicate the occlusion of anterior radiculomedullary arteries and poorer spinal cord circulation in a previous CT angiography study[33]. The vasculature of the spinal cord is organized as such that its ventral aspect and grey matter is supplied centrifugally by the central artery and the anterior part of the vasocorona, both of which arise from the anterior spinal artery. As a result, patients in the Ax-CCM type 2 group tended to suffer greater neurological deterioration in the flexion position when their spinal cords are compressed from the ventral aspect where their anterior spinal arteries are compressed. The exact pathophysiology of the cervical cords with different patterns of intramedullary T2 hyperintensity during motion still needs to be further studied.
We also found the N13_F were significantly lower among patients with cervical segmental instability, while the N13_E did not show significant difference. We assume it was because patients with cervical segmental instability suffered greater subluxation and (or) rotation instability during flexion movements. During extension, the relative movements between the adjacent vertebrae of the unstable segment are generally milder, because the superior and inferior articular processes from adjacent vertebrae can help stabilize the cervical segment. Therefore, for CSM patients with segmental instability, cervical canal stenosis and neurological deteriorations mainly occurred at the flexion position.
Finally, we compared the radiographic data with baseline mJOA scores, Nurick grades and 2-year postoperative recovery rates. Compression_Ratio, Central_Ratio, 1/4-Lateral_Compression_Ratio, Ax-CCM types and cervical segmental instability in radiographs were statistically related to recovery rates. Apart from the 1/4-Lateral_Compression_Ratio, all these parameters also correlated with preoperative clinical assessments. These findings further testified the clinical utility of these radiographic parameters.
Our study had several limitations. First, this was a single-center retrospective study, which is limited in depth, a prospectively designed study with dynamic SSEPs is warranted to address this problem. Second, not all patients received uniformed treatment, therefore we could not rule out other factors that different surgical methods may have on patient outcomes. Lastly, the sample size of the study was relatively small, limiting statistical power; in the future, we plan to expand the sample size to confirm the efficacy of our method.