Lindsay Tetreault

BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration. Over the subsequent hours, release of proinflammatory cytokines and cytotoxic debris (DNA, ATP, reactive oxygen species) cyclically adds to the harsh postinjury microenvironment. As the lesions mature into the chronic phase, regeneration is severely impeded by the development of an astroglial-fibrous scar surrounding coalesced cystic cavities. Addressing these challenges forms the basis of current and upcoming treatments for SCI. MANAGEMENT: This paper discusses the evidence-based management of a patient with SCI while emphasizing the importance of early definitive care. Key neuroprotective therapies are summarized including surgical decompression, methylprednisolone, and blood pressure augmentation. We then review exciting neuroprotective interventions on the cusp of translation such as Riluzole, Minocycline, magnesium, therapeutic hypothermia, and CSF drainage. We also explore the most promising neuroregenerative strategies in trial today including Cethrin™, anti-NOGO antibody, cell-based approaches, and bioengineered biomaterials. Each section provides a working knowledge of the key preclinical and patient trials relevant to clinicians while highlighting the pathophysiologic rationale for the therapies. CONCLUSION: We conclude with our perspectives on the future of treatment and research in this rapidly evolving field.

STUDY DESIGN: Prospective, multicenter international cohort. OBJECTIVE: To evaluate outcomes of surgical decompression for cervical spondylotic myelopathy (CSM) at a global level. SUMMARY OF BACKGROUND DATA: CSM is a degenerative spine disease and the most common cause of spinal cord dysfunction worldwide. Surgery is increasingly recommended as the preferred treatment strategy for CSM to improve neurological and functional status and quality of life. The outcomes of surgical intervention for CSM have never been evaluated at an international level. METHODS: Between October 2007 and January 2011, 479 symptomatic patients with image evidence of CSM were enrolled in the prospective, multicenter AOSpine CSM-International study from 16 global sites. Preoperative and postoperative clinical status, functional impairment, and quality of life were evaluated using the modified Japanese Orthopaedic Assessment Scale, Nurick Scale, Neck Disability Index, and Short-Form-36v2. Preoperative and 12- and 24-month postoperative outcomes were compared using mixed-model analysis of covariance for repeated measurements. RESULTS: The study cohort consisted of 310 males and 169 females, with a mean age of 56.37 ± 11.91 years. There were significant differences in age, etiology, and surgical approaches between the regions. At 24 months postoperatively, the mean modified Japanese Orthopaedic Assessment Scale score improved from 12.50 (95% confidence interval [CI], 12.24-12.76) to 14.90 (95% CI, 14.64-15.16); the Neck Disability Index improved from 36.38 (95% CI, 34.33-38.43) to 23.20 (95% CI, 21.24-25.15); and the SF36v2 Physical Component Score and Mental Composite Score improved from 34.28 (95% CI, 33.46-35.10) to 40.76 (95% CI, 39.71-41.81) and 39.45 (95% CI, 38.25-40.64) to 46.24 (95% CI, 44.94-47.55), respectively. The rate of neurological complications was 3.13%. CONCLUSION: 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 sociocultural determinants of health. LEVEL OF EVIDENCE: 3.

BACKGROUND: Surgeons often choose between 2 different approaches (anterior and posterior) for surgical treatment of degenerative cervical myelopathy on the basis of imaging features of spinal cord compression, the number of levels affected, and the spinal alignment. However, there is a lack of consensus on which approach is preferable. The objective of the present study was to use magnetic resonance imaging (MRI)-based propensity-score-matched analysis to compare postoperative outcomes between the anterior and posterior surgical approaches for degenerative cervical myelopathy. METHODS: A total of 757 patients were enrolled in 2 prospective multicenter AOSpine studies, which involved 26 international sites. Preoperative MRIs were reviewed to characterize the causes of the cord compression, including single-level disc disease, multilevel disc disease, ossification of the posterior longitudinal ligament, enlargement of the ligamentum flavum, vertebral subluxation/spondylolisthesis, congenital fusion, number of compressed levels, or kyphosis. The propensity to choose anterior decompression was calculated using demographic data, preoperative MRI findings, and the modified Japanese Orthopaedic Association (mJOA) scores in a logistic regression model. We then performed 1-to-1 matching of patients who had received anterior decompression with those who had the same propensity score but had received posterior decompression to compare 2-year postoperative outcomes and 30-day perioperative complication rates between the 2 groups after adjustment for background characteristics. RESULTS: A total of 435 cases were included in the propensity score calculation, and 1-to-1 matching resulted in 80 pairs of anterior and posterior surgical cases; 99% of these matched patients had multilevel compression. The anterior and posterior groups did not differ significantly in terms of the postoperative mJOA score (15.1 versus 15.3, p = 0.53), Neck Disability Index (20.5 versus 24.1, p = 0.44), or Short Form-36 (SF-36) Physical Component Summary (PCS) score (41.9 versus 40.9, p = 0.30). The overall rates of perioperative complications were similar between the 2 groups (16% versus 11%, p = 0.48); however, dysphagia/dysphonia was reported only in the anterior group whereas surgical site infection and C5 radiculopathy were reported only in the posterior group. CONCLUSIONS: Anterior and posterior decompression for degenerative cervical myelopathy resulted in similar postoperative outcomes and rates of complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVES: Degenerative cervical myelopathy (DCM) involves extrinsic spinal cord compression causing tissue injury and neurological dysfunction. Asymptomatic spinal cord compression (ASCC) is more common, but its significance is poorly defined. This study investigates if: (1) ASCC can be automatically diagnosed using spinal cord shape analysis; (2) multiparametric quantitative MRI can detect similar spinal cord tissue injury as previously observed in DCM. DESIGN: Prospective observational longitudinal cohort study. SETTING: Single centre, tertiary care and research institution. PARTICIPANTS: 40 neurologically intact subjects (19 female, 21 male) divided into groups with and without ASCC. INTERVENTIONS: None. OUTCOME MEASURES: Clinical assessments: modified Japanese Orthopaedic Association score and physical examination. 3T MRI assessments: automated morphometric analysis compared with consensus ratings of spinal cord compression, and measures of tissue injury: cross-sectional area, diffusion fractional anisotropy, magnetisation transfer ratio and T2*-weighted imaging white to grey matter signal intensity ratio (T2*WI WM/GM) extracted from rostral (C1-3), caudal (C6-7) and maximally compressed levels. RESULTS: ASCC was present in 20/40 subjects. Diagnosis with automated shape analysis showed area under the curve >97%. Five MRI metrics showed differences suggestive of tissue injury in ASCC compared with uncompressed subjects (p<0.05), while a composite of all 10 measures (average of z scores) showed highly significant differences (p=0.002). At follow-up (median 21 months), two ASCC subjects developed DCM. CONCLUSIONS: ASCC appears to be common and can be accurately and objectively diagnosed with automated morphometric analysis. Quantitative MRI appears to detect subclinical tissue injury in ASCC prior to the onset of neurological symptoms and signs. These findings require further validation, but offer the intriguing possibility of presymptomatic diagnosis and treatment of DCM and other spinal pathologies.

BACKGROUND: Preoperative duration of symptoms may significantly impact outcomes in patients treated surgically for degenerative cervical myelopathy (DCM). OBJECTIVE: To (i) analyze whether duration of symptoms is associated with preoperative functional impairment, disability, and quality of life and (ii) determine the optimal timing for decompressive surgery. METHODS: Patients with DCM were prospectively enrolled in either the AOSpine North American or International study at 26 global sites (n = 757). Postoperative functional impairment was evaluated at 1-yr using the modified Japanese Orthopaedic Association (mJOA) score. Change scores between baseline and 1-yr were computed for the mJOA. Duration of symptoms was dichotomized into a "short" and "long" group at several cut-offs. Analysis of covariance was used to evaluate differences in change scores on the mJOA between duration of symptoms groups in 4-mo increments. RESULTS: Our cohort consisted of 424 men and 255 women, with a mean duration of symptoms of 26.1 ± 36.4 mo (0.25-252 mo). Duration of symptoms was not correlated with preoperative mJOA, Nurick, Neck Disability Index, or Short-Form (SF)-36 Physical and Mental Component Scores. Patients with a duration of symptoms shorter than 4 mo had significantly better functional outcomes on the mJOA than patients with a longer duration of symptoms (>4 mo). Thirty-two months was also a significant cut-off. CONCLUSION: Patients who are operated on within 4 mo of symptom presentation have better mJOA outcomes than those treated after 4 mo. It is recommended that patients with DCM are diagnosed in a timely fashion and managed appropriately.