Neurosurgery Service, Alicante University General Hospital, Alicante, Spain.
The assessment, diagnosis, operative and nonoperative management of degenerative cervical myelopathy (DCM) have evolved rapidly over the last 20 years. A clearer understanding of the pathobiology of DCM has led to attempts to develop objective measurements of the severity of myelopathy, including technology such as multiparametric magnetic resonance imaging, biomarkers, and ancillary clinical testing. New pharmacological treatments have the potential to alter the course of surgical outcomes, and greater innovation in surgical techniques have made surgery safer, more effective and less invasive. Future developments for the treatment of DCM will seek to improve the diagnostic accuracy of imaging, improve the objectivity of clinical assessment, and increase the use of surgical techniques to ensure the best outcome is achieved for each individual patient 1).
Goel was troubled by the fact that his several PubMed and MEDLINE indexed articles on the subject published in leading journals dedicated to the study of the spine have not found any place in the huge reference list of 137 articles 2)
A review of Tetreault et al. summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies 3).
Histological findings
MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in the human cadaveric spinal cordtissue. Data were extracted using a piloted proforma. The 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).
The search yielded 4127 unique records. After the 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 hematoxylin 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.
Few 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 underutilized but complementary approach 4).
A National Institutes of Health-funded (1R13AR065834-01) investigator meeting was held before the initiation of the trial to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths of, limitations of, and concerns about the study. The final protocol was approved for funding by the Patient-Centered Outcomes Research Institute (CE-1304-6173). The trial began enrollment on April 1, 2014 6).
Wilson JRF, Badhiwala JH, Moghaddamjou A, Martin AR, Fehlings MG. Degenerative Cervical Myelopathy; A Review of the Latest Advances and Future Directions in Management. Neurospine. 2019 Sep;16(3):494-505. doi: 10.14245/ns.1938314.157. Epub 2019 Aug 26. PubMed PMID: 31476852; PubMed Central PMCID: PMC6790745.
Dohle E, Beardall S, Chang A, Mena KPC, Jovanović L, Nath U, Lee KS, Smith AH, Thirunavukarasu AJ, Touzet AY, Norton EJ, Mowforth OD, Kotter MRN, Davies BM. Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies. Acta Neurochir (Wien). 2023 Feb 23. doi: 10.1007/s00701-023-05526-5. Epub ahead of print. PMID: 36820887.
Augusto MT, Diniz JM, Rolemberg Dantas FL, Fernandes de Oliveira M, Rotta JM, Botelho RV. Development of the Portuguese version of the modified Japanese Orthopaedic Association Score: cross-cultural adaptation, reliability, validity and responsiveness. World Neurosurg. 2018 Jun 1. pii: S1878-8750(18)31127-6. doi: 10.1016/j.wneu.2018.05.173. [Epub ahead of print] PubMed PMID: 29864576.
Indications and optimal timing for surgical treatment of degenerative cervical myelopathy (DCM) remain unclear, and data from daily clinical practice are warranted.
Gulati et al. investigated clinical outcomes following decompressive surgery for DCM.
They included 905 patients operated between January 2012 and June 2018. There were significant improvements in all Patient-reported outcome measures (PROMs) including NDI (mean -10.0, 95% CI -11.5 to -8.4, P < .001), EMS (mean 1.0, 95% CI 0.8-1.1, P < .001), EQ-5D index score (mean 0.16, 95% CI 0.13-0.19, P < .001), EQ-5D visual analogue scale (mean 13.8, 95% CI 11.7-15.9, P < .001), headache NRS (mean -1.1, 95% CI -1.4 to -0.8, P < .001), neck pain NRS (mean -1.8, 95% CI -2.0 to -1.5, P < .001), and arm pain NRS (mean -1.7, 95% CI -1.9 to -1.4, P < .001). According to GPE scale assessments, 229/513 patients (44.6%) experienced “complete recovery” or felt “much better” at 1 yr. There were significant improvements in all PROMs for both mild and moderate-to-severe DCM. A total of 251 patients (27.7%) experienced adverse effects within 3 mo.
Surgery for DCM is associated with significant and clinically meaningful improvement across a wide range of PROMs 1).
Objective scoring of the post-operative neurological function did not correlate with patient-perceived outcomes in Degenerative cervical myelopathy outcome (DCM). Traditional testing of motor and sensory function as part of the neurological assessment may not be sensitive enough to assess the scope of neurological changes experienced by Degenerative cervical myelopathy patients 2).
This retrospective observational study was conducted on twenty-five patients with degenerative cervical disc prolapse associated with MRI T2WI hyperintense cord signal, at the Department of Neurosurgery, Qena University Hospital, South Valley University from August 2014 to December 2016. A complete clinical and radiological evaluation of the patients was done. Anterior cervical discectomy and fusion was done for all patients. Patients were clinically assessed preoperatively and postoperatively at 3, 6, and 12 months using Modified Japanese Orthopaedic Association scale (MJOA). Radiographic assessment was done by preoperative and postoperative T2WI MRI. The statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software (version 22.0).
There were 25 patients included in the study; 16 (64%) females and 9 (36%) males. The mean age was 46.89 ± 7.52 standard deviation (SD) years with range from 26 to 64 years, 3 (12%) patients had worsened in the form of postoperative motor power deterioration, and 14 (56%) patients has no improvement and remain as preoperative condition. The remaining 8 (32%) patients had a reported postoperative improvement of symptoms and signs according to MJOA score. The mean follow-up period (in months) was 11 ± 2.34 (SD). Conclusion:
The presence of T2W hyperintense signal on preoperative MRI predicts a poor surgical outcome in patients with cervical disc prolapse. The regression of T2W ISI postoperatively correlates with better functional outcomes 3).
Whilst decompressive surgery can halt disease progression, existing spinal cord damage is often permanent, leaving patients with lifelong disability.
Early surgery improves the likelihood of recovery, yet the average time from onset of symptoms to correct diagnosis is over 2 years. The majority of delays occur initially, before and within primary care, mainly due to a lack of recognition. Symptom checkers are widely used by patients before medical consultation and can be useful for preliminary triage and diagnosis. Lack of recognition of Degenerative Cervical Myelopathy (DCM) by symptom checkers may contribute to the delay in diagnosis.
The impact of the changes in myelopathic signs following cervical decompression surgery and their relationship to functional outcome measures remains unclear.
Surgery is associated with a significant quality of life improvement. The intervention is cost effective and, from the perspective of the hospital payer, should be supported 4).
Surgical decompression for CSM is safe and results in improved functional status and quality of life in patients around the world, irrespective of differences in medical systems and socio-cultural determinants of health 5).
The successful management of CSM depends upon an early and accurate diagnosis, an objective assessment of impairment and disability, and an ability to predict outcome. In this field, quantitative measures are increasingly used by clinicians to grade functional and neurological status and to provide decision-making support 6).
In addition, objective assessment tools allow clinicians to quantify myelopathy severity, predict outcome, and evaluate surgical benefits by tracking improvements throughout follow-up 7)8)9).
Several outcome measures assess functional impairment and quality of life in patients with cervical myelopathy 10)11)12)13)14).
A validated “gold standard,” however, has not been established, preventing the development of quantitative guidelines for CSM management 15).
Some studies have found that resolution of T2 hyperintensity in subjects with CSM who undergo ventral decompressive surgery correlates with improved functional outcomes. Other studies have found little correlation with postoperative outcome 16)17).
Machine learning for degenerative cervical myelopathy
1) Gulati S, Vangen-Lønne V, Nygaard ØP, Gulati AM, Hammer TA, Johansen TO, Peul WC, Salvesen ØO, Solberg TK. Surgery for Degenerative Cervical Myelopathy: A Nationwide Registry-Based Observational Study With Patient-Reported Outcomes. Neurosurgery. 2021 Jul 29:nyab259. doi: 10.1093/neuros/nyab259. Epub ahead of print. PMID: 34325471.2) McGregor SM, Detombe S, Goncalves S, Doyle-Pettypiece P, Bartha R, Duggal N. Does the Neurological Exam Correlate with Patient Perceived Outcomes in Degenerative Cervical Myelopathy? World Neurosurg. 2019 Aug 2. pii: S1878-8750(19)32111-4. doi: 10.1016/j.wneu.2019.07.195. [Epub ahead of print] PubMed PMID: 31382071.3) Hamdan ARK. The Relation between Cord Signal and Clinical Outcome after Anterior Cervical Discectomy in Patients with Degenerative Cervical Disc Herniation. Asian J Neurosurg. 2019 Jan-Mar;14(1):106-110. doi: 10.4103/ajns.AJNS_262_17. PubMed PMID: 30937019; PubMed Central PMCID: PMC6417293.4) Witiw CD, Tetreault LA, Smieliauskas F, Kopjar B, Massicotte EM, Fehlings MG. Surgery for degenerative cervical myelopathy: a patient centered quality of life and health economic evaluation. Spine J. 2016 Oct 25. pii: S1529-9430(16)31022-1. doi: 10.1016/j.spinee.2016.10.015. [Epub ahead of print] PubMed PMID: 27793760.5) Fehlings MG, Ibrahim A, Tetreault L, Albanese V, Alvarado M, Arnold P, Barbagallo G, Bartels R, Bolger C, Defino H, Kale S, Massicotte E, Moraes O, Scerrati M, Tan G, Tanaka M, Toyone T, Yukawa Y, Zhou Q, Zileli M, Kopjar B. A Global Perspective on the Outcomes of Surgical Decompression in Patients with Cervical Spondylotic Myelopathy: Results from the Prospective Multicenter AOSpine International Study on 479 patients. Spine (Phila Pa 1976). 2015 May 27. [Epub ahead of print] PubMed PMID: 26020847.6) , 15) Singh A, Tetreault L, Casey A, et al. A summary of assessment tools for patients suffering from cervical spondylotic myelopathy: a systematic review on validity, reliability, and responsiveness [published online ahead of print September 5, 2013]. Eur Spine J. doi:10.1007/s00586-013-2935-x.7) Laing RJ. Measuring outcome in neurosurgery. Br J Neurosurg 2000;14:181–4.8) Holly LT, Matz PG, Anderson PA, et al. Clinical prognostic indicators of surgical outcome in cervical spondylotic myelopathy. J Neurosurg Spine 2009;11:112–8.9) Kalsi-Ryan S, Singh A, Massicotte EM, et al. Ancillary outcome measures for assessment of individuals with cervical spondylotic myelopathy. Spine (Phila Pa 1976) 2013;38:S111–22.10) Singh A, Crockard HA. Quantitative assessment of cervical spondylotic myelopathy by a simple walking test. Lancet 1999;354:370–3.11) Nurick S. The natural history and the results of surgical treatment of the spinal cord disorder associated with cervical spondylosis. Brain 1972;95:101–8.12) Olindo S, Signate A, Richech A, et al. Quantitative assessment of hand disability by the nine-hole-peg test (9-HPT) in cervical spondylotic myelopathy. J Neurol Neurosurg Psychiatry 2008;79:965–7.13) Hosono N, Sakaura H, Mukai Y, et al. A simple performance test for quantifying the severity of cervical myelopathy [erratum in: J Bone Joint Surg Br 2008;90:1534]. J Bone Joint Surg Br 2008;90:1210–3.14) Casey AT, Bland JM, Crockard HA. Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy. Ann Rheum Dis 1996;55:901–6.16) Sarkar S, Turel MK, Jacob KS, Chacko AG. The evolution of T2-weighted intramedullary signal changes following ventral decompressive surgery for cervical spondylotic myelopathy. J Neurosurg Spine. 2014;21(4):538-546.17) Vedantam A, Rajshekhar V. Change in morphology of intramedullary T2- weighted increased signal intensity after anterior decompressive surgery for cervical spondylotic myelopathy. Spine (Phila Pa 1976). 2014;39(18):1458-1462.
According to preoperative CTM, 20 levels of maximum and 16 levels of relevant additional stenosis were defined and decompressed. Preoperative FA and particularly ADC showed a significant correlation with the CTM Naganawa score but also with the ISI grade. Furthermore, both FA and ADC facilitated a good discrimination between stenotic and nonstenotic levels with cutoff values < 0.49 for FA and > 1.15 × 10-9 m2/s for ADC. FA and especially ADC revealed a considerably higher sensitivity (79% and 82%, respectively) in discriminating levels requiring decompression surgery compared with ISI (55%). EMS and VAS-N/R were significantly improved at 14 months compared with preoperative values.
DTI parameters are highly sensitive at distinguishing surgical from nonsurgical levels in CSM patients and might therefore represent a less invasive alternative to CTM for surgical planning 1).
A study population included 50 patients with symptoms of cervical myelopathy. The patients were evaluated based on symptoms using the European myelopathy scoring system and were divided into: Grade 1, including patients with mild symptoms; Grade 2, referring to patients with moderate symptoms and Grade 3, which included patients revealing severe symptoms. All the patients were investigated with a 1.5 T MRI unit acquiring DWI and DTI sequences. FA and ADC values from each spinal segment were analyzed in terms of Frequency, Percentage, Mean, Standard Deviation and Confidence Intervals. The comparison of values was done by ANOVA and post hoc analysis by bonferroni test. Comparison of accuracy of FA, ADC and T2WI in recognizing myelopathic changes was done by t-test. Receiver Operating Characteristics (ROC) analysis was performed to obtain a cut off value of FA and ADC for each spinal level to identify myelopathic change in the spinal cord.
The study revealed a significant difference in the mean FA and ADC value of stenotic and Non-stenotic segments. T2WI was highly significant (p = 0.000) in recognizing myelopathy changes in patients falling under Grade 2(moderate) and Grade 3(severe) according to European Myelopathy scoring system. Regarding patients under Grade 1 (mild) FA and ADC values showed significant difference compared to T2WI. The collective sensitivity in the identification of myelopathic changes was highest with FA (79%) as compared to ADC (71%) and T2WI (50%). ROC analysis was done to determine the cut off values of FA and ADC at each cervical spine segments. The proposed cut off, for FA and ADC at the level of C1-C2 is 0.68 and 0.92, C2-C3 is 0.65 and 1.03, C3-C4 is 0.63 and 1.01, C4-C5 0.61 and 0.98, At C5-C6 0.57 and 1.04, At C6-C7 0.56 and 0.96 respectively.
FA and ADC values enhance the efficacy and accuracy of MRI in the diagnosis of cervical spondylotic myelopathy. Hence diffusion tensor imaging can be used as a non-invasive modality to recognize spondylotic myelopathy changes even in the early stages, which can be helpful in deciding on appropriate timing of decompression surgery before the irreversible chronic changes set in 2).
A meta-analysis was conducted to assess alterations in measures of diffusion tensor imaging (DTI) in the patients of cervical spondylotic myelopathy (CSM), exploring the potential role of DTI as a diagnosis biomarker. A systematic search of all related studies written in English was conducted using PubMed, Web of Science, EMBASE, CINAHL, and Cochrane comparing CSM patients with healthy controls. Key details for each study regarding participants, imaging techniques, and results were extracted. DTI measurements, such as fractional anisotropy (FA), apparent diffusion coefficient (ADC), and mean diffusivity (MD) were pooled to calculate the effect size (ES) by fixed or random effects meta-analysis. 14 studies involving 479 CSM patients and 278 controls were identified. Meta-analysis of the most compressed levels (MCL) of CSM patients demonstrated that FA was significantly reduced (ES -1.52, 95% CI -1.87 to -1.16, P < 0.001) and ADC was significantly increased (ES 1.09, 95% CI 0.89 to 1.28, P < 0.001). In addition, a notable ES was found for lowered FA at C2-C3 for CSM vs. controls (ES -0.83, 95% CI -1.09 to -0.570, P < 0.001). Meta-regression analysis revealed that male ratio of CSM patients had a significant effect on reduction of FA at MCL (P = 0.03). The meta-analysis of DTI studies of CSM patients clearly demonstrated a significant FA reduction and ADC increase compared with healthy subjects. This result supports the use of DTI parameters in differentiating CSM patients from health subjects. Future researches are required to investigate the diagnosis performance of DTI in cervical spondylotic myelopathy 3).
The measurement of DTI indexes within the spinal cord provides a quantitative assessment of neural damage in various spinal cord pathologies. DTI studies in animal models of spinal cord injury indicate that DTI is a reliable imaging technique with important histological and functional correlates.
DTI is a noninvasive marker of microstructural change within the spinal cord. In human studies, spinal cord DTI shows definite changes in subjects with acute and chronic spinal cord injury, as well as cervical spondylotic myelopathy. Interestingly, changes in DTI indexes are visualized in regions of the cord, which appear normal on conventional magnetic resonance imaging and are remote from the site of cord compression. Spinal cord DTI provides data that can help us understand underlying microstructural changes within the cord and assist in prognostication and planning of therapies 4).
Vedantam A, Jirjis MB, Schmit BD, Wang MC, Ulmer JL, Kurpad SN. Diffusion tensor imaging of the spinal cord: insights from animal and human studies. Neurosurgery. 2014 Jan;74(1):1-8. doi: 10.1227/NEU.0000000000000171. PubMed PMID: 24064483.
OSAM has to be considered according to the Monro-Kellie hypothesis and is affected by an engorgement of the cervical epidural venous plexus, which can produce cervical myelopathy. Since it can be treated simply by increasing the shunt resistance, surgeons should be aware of the rarely detected overdrainage complication 4).
Classically, patients present with positional headache, but less common symptoms include neck pain and cranial nerve palsies.
A 45-year-old-patient with shunt-dependent, congenital hydrocephalus presented with an 8-year history of progressive tetraparesis and gait disorder in the Department of Neurosurgery, University of Tübingen, Germany. The patient was wheelchair-dependent. A new MRI scan of the head revealed slit ventricle syndrome and dural enhancement due to shunt overdrainage. An MRI and a CT-Phlebography of the cervical spine revealed engorgement of the epidural venous plexus with secondary compression of the spinal cord and myelomalacia. Surgery was performed during which we implanted a shunt valve. The patient recovered from surgery without any new deficits. The tetraparesis improved during the inpatient hospital stay. CT-Phlebography was performed 5 days after surgery and showed that the epidural venous plexus anterior to the cervical spinal cord had returned to nearly normal size. On follow-up examination 3 month after surgery, the patient´s strength had improved, and he was able to walk short distances with assistance and with ankle foot orthosis on the right side.
OSAM has to be considered according to the Monro-Kellie doctrine and is affected by an engorgement of the epidural cervical venous plexus, which can produce cervical myelopathy. Since it can be treated simply by increasing the shunt resistance, surgeons should be aware of the rarely detected overdrainage complication 5).
Ho et al., presented 2 cases of cervical myelopathy produced by engorged vertebral veins due to overshunting. Overshunting-associated myelopathy is a rare complication of CSF shunting. Coexisting cervical degenerative disc disease may further increase the difficulty of diagnosing the condition. Neurosurgeons and others who routinely evaluate patients with intracranial shunts should be familiar with this rare but possible diagnosis 6).
A 26-year-old woman with shunt-dependent, congenital hydrocephalus, presented with rapidly progressive cervical myelopathy following ventriculoperitoneal shunt revision. Imaging revealed engorgement of the cervical epidural venous plexus and mass effect on the cervical spinal cord. “Over-shunting associated myelopathy” is a rare complication of CSF diversion that should be familiar to physicians who routinely evaluate patients with intracranial shunts 7).
Adib SD, Hauser TK, Engel DC, Tatagiba M, Skardelly M, Ramina K. Over-shunting associated myelopathy (OSAM) in a patient with bilateral jugular vein occlusion. World Neurosurg. 2018 Jun 1. pii: S1878-8750(18)31129-X. doi: 10.1016/j.wneu.2018.05.175. [Epub ahead of print] PubMed PMID: 29864573.
