Deterioration After Surgery for Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

STUDY DESIGN: A Prospective cohort study. OBJECTIVE: To investigate the incidence, etiology, and outcomes of patients who experience neurological deterioration after surgery for Degenerative Cervical Myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Postoperative neurological deterioration is one of the most undesirable complications that can occur after surgery for DCM. METHODS: We analyzed data from the Canadian Spine Outcomes and Research Network DCM prospective cohort study. We defined postoperative neurological deterioration as any decrease in modified Japanese Orthopaedic Association (mJOA) score by at least one point from baseline to three months after surgery. Adverse events were collected using the Spinal Adverse Events Severity protocol. Secondary outcomes included patient-reported pain, disability, and health-related quality of life. RESULTS: Among a study cohort of 428 patients, 50 (12%) deteriorated by at least one mJOA point after surgery for DCM (21 by one point, 15 by two points, and 14 by three points or more). Significant risk factors included older age, female sex, and milder disease. Among those who deteriorated, 13 experienced contributing intraoperative or postoperative adverse events, six had alternative non-DCM diagnoses, and 31 did not have an identifiable reason for deterioration. Patients who deteriorated had significantly lower mJOA scores at one year after surgery [13.5 (SD 2.7) vs. 15.2 (SD 2.2), P <0.01 and those with larger deteriorations were less likely to recover their mJOA to at least their preoperative baseline, but most secondary measures of pain, disability, and health-related quality of life were unaffected. CONCLUSIONS: The incidence of deterioration of mJOA scores after surgery for DCM was approximately one in 10, but some deteriorations were unrelated to actual spinal cord impairment and most secondary outcomes were unaffected. These findings can inform patient and surgeon expectations during shared decision-making, and they demonstrate that the interpretation of mJOA scores without clinical context can sometimes be misleading.

Treatment of Mild Cervical Myelopathy: Factors Associated With Decision for Surgical Intervention.

STUDY DESIGN: Prospective Cohort OBJECTIVE.: The aim of this study was to evaluate which demographic, clinical, or radiographic factors are associated with selection for surgical intervention in patients with mild cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Surgery has not been shown superior to best conservative management in mild CSM comparative studies; trials of conservative management represent an acceptable alternative to surgical decompression. It is unknown what patients benefit from surgery. METHODS: This is a prospective study of patients with mild CSM, defined as modified Japanese Orthopaedic Association Score (mJOA) ≥15. Patients were recruited from seven sites contributing to the Canadian Spine Outcomes Research Network. Demographic, clinical, radiographic and health related quality of life data were collected on all patients at baseline. Multivariate logistic regression modeling was used to identify factors associated with surgical intervention. RESULTS: There were 122 patients enrolled, 105 (86.0%) were treated surgically, and 17 (14.0%) were treated nonoperatively. Overall mean age was 54.8 years (SD 12.6) with 80 (65.5%) males. Bivariate analysis revealed no statistically significant differences between surgical and nonoperative groups with respect to age, sex, BMI, smoking status, number of comorbidities and duration of symptoms; mJOA scores were significantly higher in the nonoperative group (16.8 [SD 0.99] vs. 15.9 [SD 0.89], P < 0.001). There was a statistically significant difference in Neck Disability Index, SF12 Physical Component, SF12 Mental Component Score, EQ5D, and PHQ-9 scores between groups; those treated surgically had worse baseline questionnaire scores (P < 0.05). There was no difference in radiographic parameters between groups. Multivariable analysis revealed that lower quality of life scores on EQ5D were associated with selection for surgical management (P < 0.018). CONCLUSION: Patients treated surgically for mild cervical myelopathy did not differ from those treated nonoperatively with respect to baseline demographic or radiographic parameters. Patients with worse EQ5D scores had higher odds of surgical intervention. LEVEL OF EVIDENCE: 3.

Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI.

BACKGROUND: A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established. METHODS: A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent. CONCLUSIONS: State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.

Spinal cord clinical trials and the role for bioengineering.

There is considerable need for bringing effective therapies for spinal cord injury (SCI) to the clinic. Excellent medical and surgical management has mitigated poor prognoses after SCI; however, few advances have been made to return lost function. Bioengineering approaches have shown great promise in preclinical rodent models, yet there remains a large translational gap to carry these forward in human trials. Herein, we provide a framework of human clinical trials, an overview of past trials for SCI, as well as bioengineered approaches that include: directly applied pharmacologics, cellular transplantation, biomaterials and functional neurorehabilitation. Success of novel therapies will require the correct application of comprehensive preclinical studies with well-designed and expertly conducted human clinical trials. While biologics and bioengineered strategies are widely considered to represent the high potential benefits for those who have sustained a spinal injury, few such therapies have been thoroughly tested with appreciable efficacy for use in human SCI. With these considerations, we propose that bioengineered strategies are poised to enter clinical trials.

Spinal cord injury: a systematic review of current treatment options.

BACKGROUND: Spinal cord injury (SCI) is a devastating event often resulting in permanent neurologic deficit. Research has revealed an understanding of mechanisms that occur after the primary injury and contribute to functional loss. By targeting these secondary mechanisms of injury, clinicians may be able to offer improved recovery after SCI. QUESTIONS/PURPOSES: In this review, we highlight advances in the field of SCI by framing three questions: (1) What is the preclinical evidence for the neuroprotective agent riluzole that has allowed this agent to move into clinical trials? (2) What is the preclinical evidence for Rho antagonists that have allowed this group of compounds to move into clinical trials? (3) What is the evidence for early surgical decompression after SCI? METHODS: We conducted a systematic review of MEDLINE and EMBASE-cited articles related to SCI to address these questions. RESULTS: As a result of an improved understanding of the secondary mechanisms of SCI, specific clinical strategies have been established. We highlight three strategies that have made their way from bench to bedside: the sodium-glutamate antagonist riluzole, the Rho inhibitor Cethrin, and early surgical decompression. Each of these modalities is under clinical investigation. We highlight the fundamental science that led to this development. CONCLUSIONS: As our understanding of the fundamental mechanisms of SCI improves, we must keep abreast of these discoveries to translate them into therapies that will hopefully benefit patients. We summarize this process of bench to bedside with regard to SCI.