Our study showed that age and flexors were potentialrisk factors for patients with DCM. Cervical curvature, endplate degeneration, and disc degeneration were not associated with pain, limb numbness, pathological signs, concomitant symptoms, or muscle strength. Given that delayed diagnosis of DCM could lead to irreversible and serious consequences, we needed to recognize the importance of accurate diagnosis for the prevention, treatment, and rehabilitation of DCM. While there are numerous diagnostic methods and assessment modalities for DCM, it is essential to fully understand the diagnostic difficulty of DCM and the advantages and disadvantages of each evaluation element.
What are the difficulties in diagnosingDCM
Accurate detection of DCM can be challenging, especially in the early stage, in partly because of the poorly understood of epidemiology, lack of awareness of DCM, subtle and Non-specific early features that overlap with other neurological disorders[1].Incomplete neurological assessment by professionals with insufficient knowledge of the disease further contributes to delays.General conditions, symptoms, and examinations are the most important diagnostic elements for diagnosingDCM[1],butthe first two are too subjective, and the latter lacks of objective evaluation indicators. MRI may be the best investigation for all types of DCM, especially in urgent patients with disease progression or symptoms that seriously impact limb function. However, the degree of spinal cord compression and signal changes in cervical spinal cord on MRI images do not correlate well with symptom severity sometimes, which means mild compression can account for serious illness[12].Adequate knowledge of the imaging characteristics of the various neck anatomical structures involved in DCM can help in the diagnosis of DCM.
The diagnostic value of imaging assessment in DCM
Cervical curvature
Cervical curvature is one of the most important indicators for clinicians to evaluate the sagittal balance of the cervical spinein DCM. Normal cervical curvature allows cervical spine to play the biomechanical roles in protecting the spinal cord, supporting the skull, and allowing maximum range of motion[13]. Studies have shown that cervical curvature imbalance may be related to the onset andprogressof DCM. Harrison et al. found that the normal cervical curvature was lordotic (16.5-66 degrees), and beyond that was pathological and associated to DCM[3].Smith et al. clarified that normal cervical curvature was an important guarantee for stability of cervical spine and sagittal imbalance of cervical spine could breakdown the cervical anatomy and result in DCM[14].Weng et al. studied many parameters of cervical sagittal balance of DCM and found that the more outside the normal Cobb's angle range, the more severe symptoms of DCM[15].Mohantyet al. reported that increasing sagittal vertical axis has been associated with worse myelopathy, neck disability, and physical health scores in DCM patients[16]. The data we provided showed that the sagittal imbalance status of cervical spine was not associated with clinical severity of DCM.Most of the cervical curvature of the patients were on the normal sagittal balance status, whereas the symptoms of the patients were severity, which was in accordance with the finding in a previous report that normal cervical lordosis often found inDCM[13]. This can also be interpreted that the cervical Cobb's angle reflected changes in the overall sequence of the cervical spine and did not reflect conditions such as spinal cord compression caused by a localized disc of a particular stage. Therefore, there was no consensus on whether lordosis should be considered the only normal alignment, and degeneration of cervical curvature may secondary to degeneration of other cervical anatomy.
Cervical endplate degeneration
The cervical endplate,which main function is to prevent the nucleus pulposus tissue of the intervertebral disc from being embedded in the vertebral body and balanced stress, is composed of approximately 1mm thick concave-shaped structures with the cartilage endplate and the bony endplate[17].Modic change (MC),which was first proposed by Assheuer and established a grading system by Modic et al.[18], is subchondral vertebral endplate changes available on MRI and widely used to assess endplate degeneration. Three original studies elucidated in detail how MC were displayed and characterized on MRI and their value to clinicians.De Roos et al. concluded that bone marrow signal changes of spine under the endplate were common and should not be confused with related diseases such as infections or tumors and their signal abnormalities.Modic et al. noted Three types of signal strength variations (MC-1 ,MC-2 , MC-3), and highlighted the clinical importance of these findings on disc degeneration to clinicians. However, Subsequent studies have reached inconsistent conclusions about the clinical significance ofMCin patients with DCM, although most of the studies referred to the details of the description and classification of MCin the original studies[19, 20]. The present study showed MC of cervical spine was not associated with clinical severity of DCM and cervical disc degeneration. This may be due to the fact that the endplate was far from the spinal cord and was not directly involved in the motor function units of the cervical spine.
Cervical disc degeneration
Cervical disc is an avascular complex anatomical structure that composed of peripheral annulus fibrosus, central nucleus pulposus and the cartilaginous endplate,essential for performing complex movements in all directions of the cervical spine, and also considered the primary structure of cervical spine degeneration[21]. Degeneration of cervical discs occurs throughout life with progressive morphological and cellular changes.Proteoglycan degeneration begins in childhood, and all the proteoglycan and water molecules of the intervertebral disc decreases with age[22].
As MRI continues to improve and becomes more widely used, clinicians and researchers are better able to understand the importance of MRI examinations in the evaluation of patients with DCM[21]. MRI provides a non-invasive assessment method of theintervertebral disc degeneration with Pfirrmann classification system[23],which has been widely accepted and used for decades. Matsumoto et al. found that intervertebral disc degeneration occurred in males and females in their 20s, 17% and 12% respectively and Boden et al.found that intervertebral disc degeneration occurred in 8% of patients with DCM youngerthan 40 years[1]. However, drawbacks exist inherently at detecting biochemical changes within the disc with the Pfirrmann classification system.Intervertebral disc degeneration is common in asymptomatic adults. Hiroaki Nakashima et al. found that almost all of the healthy adults (98%) in their 20s showed early disc degeneration but these changes werecommonanomalies in people aged between 40 and 50 years[24]. Boden et al.also reported that nearly 1/5 of MR scans showed dis degenerative changes in the cervical spine in 63 asymptomatic population.These drawbacks are also seen in the lumbar spine. Seong et al. reported the sensitivity and specificity of the Pfirrmann classification system was insufficient to diagnosis of discogenic pain and has proof insufficient effectiveness in fully confirming sources of discogenic pain in degenerative disease of the lumbar spine[9].This means that despite similar disc degeneration on MRI, pathological disc degeneration can cause severe discogenic pain, whereas aging disc degeneration can't cause discogenic pain.Our study found that disc degeneration valued by Pfirrmann classification system was inconsistent with the severity of DCM. We speculated that this would be due to the fact that the Pfirrmann classification system only reflected signal changes in disc degeneration and does not reflectthe degree of disc herniation and spinal cord compression, on the other hand, it would be due to the relatively small sample size and the subjective interference of the assessor.
Cervical paraspinal muscles degeneration
The neck muscle groups have a complex anatomy of flexors and extensors that work together to help complete complex movements of the head and neck[25].Morphological differences in cervical paraspinal muscles lead todifferential effects on cervical spine biomechanics. The basic parameters used to evaluate cervical paraspinal muscles include fat infiltration rate (fatty degeneration) and cross-sectional area (muscle morphometry). Fat infiltration rate is a qualitative assessment that represents the rate at which muscle is replaced by fat.Cross-sectional area (CSA) is a quantitative assessment used to measure muscle volume on MRI[10]. In present study, we used the ratio of paraspinal muscleCSA, which was defined as a value of the CSA of cervical paraspinal muscle/ CSA of cervical vertebrae on the same cross-sectional slice, rather than the paraspinal muscle CSA itself to assess morphological changes in the paraspinal muscles. This helps eliminate the confounding effects of the patient's age and size, since there is an accepted notion that sarcopenia gets worse with age[26].
Several aspects of cervical paraspinal muscle morphology and fatty degeneration have been studiedpreviouslyand demonstrated the important association between cervical paraspinal muscles and cervical clinical presentation,cervical instability, cervical disc degeneration,cervical disc endplate degeneration.However, the diagnostic value of paraspinal muscle CSA in DCM remains unclear.
Great relevance between cervical paraspinal muscles and cervical dysfunction has been illuminated. Gu et al. reported that the degeneration of cervical paraspinal muscleswas inversely correlated with the effectiveness of cervical traction in patients with DCM poorly controlled by NSAIDs[27]. Iqbal et al. found that specific training of the deep neck flexors helped improve neck pain and dysfunction in teachers with DCM[28].Thakar et al. found significant atrophy in both cervical paraspinal flexors and extensors in all patients with severe DCM[25].Fortin et al. detected significant increase in fat infiltration rates of paraspinal musclesbelow the spine compression segment was observed in DCM patients, suggesting DCM may contribute to muscle steatosis[29].Taotao Lin et al. demonstrated that the severity of cervical paraspinal muscle degeneration at the corresponding level in DCM was associated with the cervical sagittal parameters, neck pain, but Without paresthesia, limb weakness, gait disturbance, neurological dysfunction, bladder/intestinal dysfunction[30]. Our study is consistent with Jull 's findings since we found that cervical flexor muscle groups were related with DCM.However, we also found that a particular flexor muscle alone may not be associated with DCM.This may be due to the fact that the neck flexor groups are performing the various movements of the neck as a whole, while it is difficult for a single muscle to complete complex movements of the neck independently, or even cervical paraspinal muscle may be involved in multiple directions of neck movement at the same time.
Due to differences in the function of the neck flexors and extensors, their clinical presentations with DCM also differ, meaning that some muscles may not be associated with DCM. Elliott et al. reported that patients with occult neck pain and DCM were not association with symptom duration,NDI score, and relative fatty infiltration of cervicalextensor muscles.Despite differences in muscle function in the cervical and lumbar spine, the same findings were also found in the lumbar, and they showed that CSA of lumbar extensor muscles was not related with degenerative spine disease or low back pain[31].
Cervical paraspinal muscle and cervical instability is closely related.Yoon et al. found that cervical flexors and extensors weakness was closely related to the loss of cervical lordosis, and cervical extensor training was more important for the rehabilitation of DCM[32]. Koji et al. found that cervical paraspinal muscles at the fourth cervical vertebra of DCM was closely associated to cervical degeneration evaluated by sagittal parameters[7]. Xiao Fei Hou et al. showed that the interaction between cervical paraspinal muscle degeneration and the onset and progression of DCM was complex and even forms a vicious cycle[33]. That was to say, the degeneration of the cervical paraspinal muscles broken the sagittal balance of the cervical spine, which in turn accelerated the occurrence and progression of DCM.Fortin et al. showed that injury to cervical paraspinal muscles and continuous stretching could lead to muscle necrosis and denervation, further compromising the stability of the cervical spine and causing poor postoperative outcomes of DCM. These changes resulted in clinicians who might have to prioritize an anterior approach to maintain neck musculature integrity and function, although sometimes anterior approach was not the optimal approach[29]. In summary, the diagnostic value of the cervical paraspinal muscles and cervical curvature may be comparable, but the paraspinal muscles, as the power system of cervical motion and innervated by nerve endings, can detect cervical abnormalities and the onset and progression of DCM earlier.
Few studies have investigated the association between cervical paraspinal muscles and cervical endplate degeneration. Andrew et al. reported that fatty infiltration ofthe paraspinal muscles was closely associated with endplate degeneration evaluated with MC[31]. However, Tamai et al. showed no correlation between degeneration in cervical paraspinal muscles and endplate[26].This may be because the endplate is neither the connecting structure of the neck motor unit nor the power system of the neck movement.
Paraspinal muscle was of greater value than cervical disc degeneration for diagnosing DCM. Okada et al.found no significant association between cervical disc degeneration and cervical extensor muscle CSA in DCM, suggesting a weak association between cervical extensors and cervical degeneration[34]. Another studies found similar results as they found that cervical paraspinal muscle CSA was not associated with the degree of disc degeneration in DCM, but they did confirm that cervical paraspinal muscle CSA ratios correlated with the severity of lower segment cervical disc degeneration[26].Abiomechanical study showed that cervical paraspinal muscles dysfunction had a more pronounced impact on cervical spinal stability than disc degeneration[29].This may be because the intervertebral disc, as the connecting structure of the cervical spine, cannot actively generate movement, and is not innervated by nerve fibers. Although the intervertebral disc is considered to be the first element of the onset of DCM, due to limited evaluation methods, better, earlier, and more accurate detection of DCM cannot be achieved. As the dynamic system of neck movement, cervical paraspinal muscles participate in the maintenance of all dynamic and static postures of the neck, and can better and more timely reflect the occurrence and development of DCM.
Age and DCM
As there is a well-established concept of increasing sarcopenia as we age, studies about association between age and DCM have been investigated and shown significant correlation. Age has an important diagnostic value for DCM. One study reported that age was not associated with fatty infiltration of the cervical paraspinal muscles in patients with DCM, but does affect paraspinal muscle CSA, another study reported that age was associated with fatty infiltration of the paraspinal muscles on the right side of the cervical spine, and the others reported that age was associated with all paraspinal muscles[35]. Grodzinskiet al. found that age was a significant predictor of clinical presentation, course and outcome of DCM[6]. Tamai et al. showed a significant correlation between paraspinal muscles and age in the patients with DCM[26],and they also found patient’s age was an essential factor in muscle degeneration in another literature[10]. Ray Tanget al.found significant associations between age and many cervical sagittal balance parameters in DCM[36]. Few studies found no significantcorrelation between age and muscle degeneration in DCM.Lin et al. found that in patients under the age of 50, age was inversely associated with symptom severity, but in patients older than 60 years, age was positively associated with symptom severity, meaning that older age was associated with more severe symptoms[30]. Older patients were more likely to be poorer functional disease scores which were essential in diagnosis DCM[5].
How is DCM diagnosed?
Detecting early DCM can be challenging, partly due to widespread difficulties of diagnosis and inconsistent scoring criteria for ancillary examinations.Comprehensive clinical examination and imaging scan of the cervical spine are advised. Although many measurement techniques have been well recognized and are widely used to diagnose DCM, the techniques have been reported only infrequently in the literature, not clinical practice[21]. Confirmation of the diagnostic tools for DCM is controversial and confusing even to medical experts in the relevant professions, lead to delay the diagnosis and develop to tetraplegia and wheelchair dependence[1, 30]. We assessed the ability of age and flexors in diagnosing DCM alone and in combination using ROC curve method and showed that the combination of the two indicators had the best diagnostic effect. Comparison of the present diagnostic model and other diagnostic tools showed that the present diagnostic model performed better (sensitivity 66.7%, specificity 81.3%, accuracy 72.5%), Kappa value 0.363, p=0.011.)
Limitations of the Study
First, this study is limited by its retrospective nature; caution should be taken when interpreting the results, as only associations were identified and causal relationships could not be confirmed. Prospective studies are needed to further confirm and extend our results.
Second, this study was based on people who diagnosed with DCM and had a small sample size. Further extension to cervical degenerative related diseases and expansion of the sample size would be beneficial to further validate the diagnostic value.
Third, we do not record BMI value, but just BMI was positively associated with thigh, but not paraspinal, fat fraction.
Despite these limitations, this is the only study combining age and cervical flexors to diagnose DCM. We believe that this study effectively reduces confounding factors, and these results will further clarify the significance of age and cervical flexors in the pathogenesis of DCM. Future studies should explore combining more cervical degenerative factors for the diagnosis of DCM.