Aria Nouri

Global prevalence and incidence of traumatic spinal cord injury.

Background Spinal cord injury (SCI) is a traumatic event that impacts a patient’s physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. Methods A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. Results The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidences were in Fiji (10.0 per million) and Spain (8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population. Conclusion This review demonstrates that the incidence, prevalence, and causation of SCI differs between developing and developed countries and suggests that management and preventative strategies need to be tailored to regional trends. The rising aging population in westernized countries also indicates that traumatic SCI secondary to falls may become an increasing public health challenge and that incidence among the elderly may rise with increasing life expectancy.

Degenerative Cervical Myelopathy: Epidemiology, Genetics, and Pathogenesis.

Study Design. Review. Objective. To formally introduce “degenerative cervical myelopathy” (DCM) as the overarching term to describe the various degenerative conditions of the cervical spine that cause myelopathy. Herein, the epidemiology, pathogenesis, and genetics of conditions falling under this hypernym are carefully described. Summary of Background Data. Nontraumatic, degenerative forms of cervical myelopathy represent the commonest cause of spinal cord impairment in adults and include cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and degenerative disc disease. Unfortunately, there is neither a specific term nor a specific diagnostic International Classification of Diseases, Tenth Revision code to describe this collection of clinical entities. This has resulted in the inconsistent use of diagnostic terms when referring to patients with myelopathy due to degenerative disease of the cervical spine. Methods. Narrative review. Results. The incidence and prevalence of myelopathy due to degeneration of the spine are estimated at a minimum of 41 and 605 per million in North America, respectively. Incidence of cervical spondylotic myelopathy–related hospitalizations has been estimated at 4.04/100,000 person-years, and surgical rates seem to be rising. Pathophysiologically, myelopathy results from static compression, spinal malalignment leading to altered cord tension and vascular supply, and dynamic injury mechanisms. Occupational hazards, including transportation of goods by weight bearing on top of the head, and other risk factors may accelerate DCM development. Potential genetic factors include those related to MMP-2 and collagen IX for degenerative disc disease, and collagen VI and XI for ossification of the posterior longitudinal ligament. In addition, congenital anomalies including spinal stenosis, Down syndrome, and Klippel-Feil syndrome may predispose to the development of DCM. Conclusion. Although DCMs can present as separate diagnostic entities, they are highly interrelated, frequently manifest concomitantly, present similarly from a clinical standpoint, and seem to be in part a response to compensate and improve stability due to progressive age and wear of the cervical spine. The use of the term “degenerative cervical myelopathy” is advocated. Level of Evidence: 5

Systematic review of magnetic resonance imaging characteristics that affect treatment decision making and predict clinical outcome in patients with cervical spondylotic myelopathy.

Study Design. Systematic review. Objective. To determine whether there are magnetic resonance imaging (MRI) characteristics in patients with cervical spondylotic myelopathy that affect treatment decisions or predict postsurgical outcomes or adverse events. Summary of Background Data. Although the role of MRI in confirming the clinical diagnosis of cervical spondylotic myelopathy and directing surgical management is well established, its potential value as a prognostic tool is largely unknown. Methods. A systematic search was conducted using PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 20, 2012. The overall body of evidence with respect to each clinical question was determined on the basis of precepts outlined by the Grading of Recommendation Assessment, Development and Evaluation Working Group and recommendations made by the Agency for Healthcare Research and Quality. Results. The initial search yielded 268 citations. Twenty publications met all inclusion criteria and were included in the review. Three of these assessed MRI predictors of clinical deterioration in the case of conservative treatment and 17 evaluated MRI anatomic or cord characteristics that could predict surgical outcome or adverse events. There is low evidence suggesting that a high signal intensity (SI) grade on T2WI is not associated with patient deterioration during conservative treatment. High SI grade on T2WI, along with compression ratio and canal diameter, was not an important predictor of outcome. There is low evidence identifying number of high SI segments on T2WI, low SI segments on T1WI, combined T1/T2 SI, and SI ratio as important negative predictors of surgical outcome. Conclusion. On the basis of this review and on low-quality evidence, we have identified 3 important negative predictors of surgical outcome: number of high SI segments on T2WI, combined T1/T2 signal change, and SI ratio. Evidence-Based Clinical Recommendations. Recommendation 1. We suggest that when clinically feasible, surgeons rely on MRI to confirm the diagnosis of CSM and rely on clinical history and examination to determine progression and severity of disease. Overall Strength of Evidence. Low Strength of Recommendation. Weak Recommendation 2. T2 signal may be a useful prognostic indicator when used in combination with low SI change on T1WI, or as a ratio comparing compressed with noncompressed segments, or as a ratio of T2 compared with T1WI. We suggest that if surgeons use MRI signal intensity to estimate the risk of a poor outcome after surgery, they use high SI change on T2WI in combination with other signal intensity parameters, and not in isolation. Overall Strength of Evidence: Low Strength of Recommendation: Weak

Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review 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.Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review 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.

Role of magnetic resonance imaging in predicting surgical outcome in patients with cervical spondylotic myelopathy.

Study Design. Ambispective, retrospective cohort study from prospectively collected data. Summary of Background Data. Cervical spondylotic myelopathy is the commonest cause of spinal cord impairment in the elderly population worldwide. Although magnetic resonance imaging (MRI) is the primary imaging modality for confirming the diagnosis, its role in predicting surgical outcome remains unclear. Methods. Two hundred seventy-eight patients with 1 or more clinical signs of myelopathy were enrolled; and they underwent decompression surgery. Complete baseline clinical and MRI data were available for 102 patients. MRI parameters measured included presence/absence of signal change on T1 and T2, T2 signal quantitative factors, and anatomical measurements. A dichotomized postoperative modified Japanese Orthopedic Association (mJOA) score at 6 months was used to characterize patients with mild myelopathy (≥16) and those with substantial residual neurological impairment (<16). Univariate analysis assessed the relationship between baseline parameters and outcome. Multivariate logistic regression was conducted after a conceptual division of variables into 3 groups: T1 signal analysis, T2 signal analysis, and anatomical measurements. Results. Baseline mJOA (P < 0.001; odds ratio [OR] = 1.644, 95% confidence interval [95% CI]: 1.326–2.037), maximum canal compromise (MCC) (P = 0.0322; OR = 0.965, 95% CI: 0.934–0.997), T2 hyperintensity region of interest area (P = 0.0422; OR = 0.67; 95% CI: 0.456–0.986), and sagittal extent (P = 0.026; OR = 0.673; 95% CI: 0.475–0.954) were significantly associated with outcome univariately. The final model was comprised of T1 hypointensity (P = 0.029; OR = 0.242; CI: 0.068–0.866), MCC (P = 0.005; OR = 0.940; CI: 0.90–0.982) and baseline mJOA (P < 0.001; OR = 1.743; CI: 1.353–2.245), yielding an area under the receiver operating characteristic curve (AUC) of 0.845. Conclusion. Baseline mJOA is a strong predictor of postsurgical outcome in cervical spondylotic myelopathy at 6 months. However, a model inclusive of MCC and T1 hypointensity assessment provides superior predictive capacity. This suggests that MRI analysis has a significant role in predicting surgical outcome. Level of Evidence: 3

The Minimum Clinically Important Difference of the Modified Japanese Orthopaedic Association Scale in Patients with Degenerative Cervical Myelopathy.

Study Design. Analysis of the prospective AOSpine CSM-International and North America datasets and survey of AO Spine International. Objective. This study aims to define the minimum clinically important difference (MCID) of the modified Japanese Orthopaedic Association (mJOA) in patients with degenerative cervical myelopathy (DCM). Summary of Background Data. The mJOA is the most frequently used clinician-administered tool to assess functional status in patients with DCM. By defining its MCID, clinicians can better evaluate treatment outcomes for this condition. Methods. Three methods were used to determine the MCID of the mJOA: (1) distribution-based, (2) anchor-based and receiver operating characteristic (ROC) analysis, and (3) professional opinion. Distribution-based methods were used to estimate the MCID by computing the half standard deviation and standard error of measurement. Using anchor-based methods, mJOA at 12 months after surgery was compared between patients who were “slightly improved” on the Neck Disability Index (NDI) and those who were “unchanged.” ROC analysis was performed to compute a discrete integer value for the MCID that yielded the smallest difference between sensitivity and specificity. We repeated anchor-based methods for patients with mild (mJOA: 15–17), moderate (mJOA: 12–14), and severe disease (mJOA <12). Results. The half standard deviation of the baseline mJOA was 1.36 and the standard error of measurement was 1.21. The difference in mJOA between patients who “slightly improved” on the NDI and “unchanged” patients was 1.11. ROC analysis yielded a value of 2 for the MCID. The survey of 416 spine professionals confirmed these estimates: the mean response was 1.65 ± 0.66. The MCID significantly varied depending on myelopathy severity: ROC analysis yielded a threshold of 1 for mild, 2 for moderate, and 3 for severe patients. Conclusion. The MCID of the mJOA is estimated to be between 1 and 2 points and varies with myelopathy severity. This knowledge will enable clinicians to identify meaningful functional improvements in DCM patients. Level of Evidence: N/A

Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques

Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy.

Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients

Background In general, older patients with degenerative cervical myelopathy (DCM) are felt to have lower recovery potential following surgery due to increased degenerative pathology, comorbidities, reduced physiological reserves and age-related changes to the spinal cord. This study aims to determine whether age truly is an independent predictor of surgical outcome and to provide evidence to guide practice and decision-making. Methods A total of 479 patients with DCM were prospectively enrolled in the CSM-International study at 16 centres. Our sample was divided into a younger group (<65 years) and an elderly (≥65 years) group. A mixed model analytic approach was used to evaluate differences in the modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36) and Neck Disability Index (NDI) scores between groups. We first created an unadjusted model between age and surgical outcome and then developed two adjusted models that accounted for variations in (1) baseline characteristics and (2) both baseline and surgical factors. Results Of the 479 patients, 360 (75.16%) were <65 years and 119 (24.84%) were ≥65 years. Elderly patients had a worse preoperative health status (p<0.0001) and were functionally more severe (p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery, whereas the preferred approach in the elderly group was posterior (58.62%, p<0.0001). Elderly patients had a greater number of decompressed levels than younger patients (p<0.0001). At 24 months after surgery, younger patients achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score (p<0.0001) than elderly patients. After adjustments for patient and surgical characteristics, these differences in postoperative outcome scores decreased but remained significant. Conclusions Older age is an independent predictor of functional status in patients with DCM. However, patients over 65 with DCM still achieve functionally significant improvement after surgical decompression.

Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability

Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies. BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy. MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1–C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression. RESULTS: The maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10−13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10−7; maximally compressed level: P = 1 × 10−11; caudal: P = 1 × 10−4), correlations (modified Japanese Orthopedic Association score; rostral: −0.52; maximally compressed level: −0.59; caudal: −0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (−0.45) and sensory (−0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10−13; area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.