Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs.

BACKGROUND: Low back pain is a global health problem directly related to intervertebral disc (IVD) degeneration. Senolytic drugs (RG-7112 and o-Vanillin) target and remove senescent cells from IVDs in vitro, improving tissue homeostasis. One drawback of using a single senolytic agent is the failure to target multiple senescent antiapoptotic pathways. This study aimed to determine if combining the two senolytic drugs, o-Vanillin and RG-7112, could more efficiently remove senescent cells and reduce the release of inflammatory factors and pain mediators in cells from degenerating human IVDs than either drug alone. METHODS: Preliminary data evaluating multiple concentrations of o-Vanillin and RG-7112 led to the selection of four treatment groups. Monolayer and pellet cultures of cells from painful degenerate IVDs were exposed to TLR-2/6 agonist. They were then treated with the senolytics o-Vanillin and RG7112 alone or combined. p16ink4a, Ki-67, caspase-3, inflammatory mediators, and neuronal sprouting were assessed. RESULTS: Compared to the single treatments, the combination of o-Vanillin and RG-7112 significantly reduced the amount of senescent IVD cells, proinflammatory cytokines, and neurotrophic factors. Moreover, both single and combination treatments significantly reduced neuronal sprouting in rat adrenal pheochromocytoma (PC-12 cells). CONCLUSIONS: Combining o-Vanillin and RG-7112 greatly enhanced the effect of either senolytic alone. Together, these results support the potential of senolytics as a promising treatment for IVD-related low back pain.

o-Vanillin Modulates Cell Phenotype and Extracellular Vesicles of Human Mesenchymal Stem Cells and Intervertebral Disc Cells.

Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory environment negatively affecting tissue homeostasis. Reducing senescence could therefore improve regenerative approaches. Ortho-Vanillin (o-Vanillin) has senolytic activity and anti-inflammatory properties and could be a valuable supplement to MSC and EV therapy. Here, we used direct co-culture experiments to evaluate proteoglycan synthesis, inflammatory mediators, and senescent cells in the presence or absence of o-Vanillin. EV release and transfer between hMSCs and intervertebral disc cells (DCs) was examined, and the effect on hMSC differentiation and DC phenotype was evaluated in the presence and absence of o-Vanillin. This study demonstrates that o-Vanillin affects cell communication, enhances hMSC differentiation and improves DC phenotype. Co-cultures of DCs and hMSCs resulted in increased proteoglycan synthesis, a decreased number of senescent cells and decreased release of the cytokines IL6 and 8. Effects that were further enhanced by o-Vanillin. o-Vanillin profoundly increased EV release and/or uptake by hMSCs and DCs. DC markers were significantly upregulated in both cell types in response to conditioned media of o-Vanillin treated donor cells. Collectively, this study demonstrates that o-Vanillin affects hMSC and DC crosstalk and suggests that combining hMSCs and senolytic compounds may improve the outcome of cell supplementation and EV therapy for LBP.

Pseudotumor after total disc replacement in the lumbar spine: A case report and review of the literature.

Background: Total disc replacement as a treatment for degenerative disc disease is gaining increased popularity. There is limited data in the literature about formation of a pseudotumor as a complication following this procedure. We report a very rare case of a pseudotumor after a lumbar total disc replacement with a review of the literature. Methods: A case study of a 49-year-old lady, who underwent L4-L5 total disc replacement and presented one year later with progressive back pain radiating to both lower extremities. Imaging revealed a soft tissue mass around the prosthesis. A review of the literature for similar cases has been done and reviewed. Results: Imaging revealed a soft tissue mass around the prosthesis and left hydronephrosis. CT venogram for leg swelling showed total occlusion of the left common iliac vein. CT myelogram showed compression of the cauda from the pseudotumor. The prosthesis was removed and replaced by an allograft fusion cage and plate. Intraoperatively both extremities became pulseless and bilateral common iliac arteries thrombectomy was carried out. This occurred again after closure immediately and bilaterally femoral artery exploration and thrombectomy was carried out. Histopathology showed a soft tissue with fibrinous necrosis and lymphohistiocytic inflammation. Conclusion: Soft tissue reaction and pseudotumor formation can be induced by Metal-on-Metal total disc replacement prostheses. Neurologic, vascular, and visceral complications may occur. In this case implant removal can stopped progression of the soft tissue reaction. Most patients in the literature benefit from implant removal followed by spinal fusion.

National adverse event profile after lumbar spine surgery for lumbar degenerative disorders and comparison of complication rates between hospitals: a CSORN registry study.

OBJECTIVE: Previous works investigating rates of adverse events (AEs) in spine surgery have been retrospective, with data collection from administrative databases, and often from single centers. To date, there have been no prospective reports capturing AEs in spine surgery on a national level, with comparison among centers. METHODS: The Spine Adverse Events Severity system was used to define the incidence and severity of AEs after spine surgery by using data from the Canadian Spine Outcomes and Research Network (CSORN) prospective registry. Patient data were collected prospectively and during hospital admission for those undergoing elective spine surgery for degenerative conditions. The Spine Adverse Events Severity system defined minor and major AEs as grades 1-2 and 3-6, respectively. RESULTS: There were 3533 patients enrolled in this cohort. There were 85 (2.4%) individual patients with at least one major AE and 680 (19.2%) individual patients with at least one minor AE. There were 25 individual patients with 28 major intraoperative AEs and 260 patients with 275 minor intraoperative AEs. Postoperatively there were 61 patients with a total of 80 major AEs. Of the 487 patients with minor AEs postoperatively there were 698 total AEs. The average enrollment was 321 patients (range 47-1237 patients) per site. The rate of major AEs was consistent among sites (mean 2.9% ± 2.4%, range 0%-9.1%). However, the rate of minor AEs varied widely among sites-from 7.9% to 42.5%, with a mean of 18.8% ± 9.7%. The rate of minor AEs varied depending on how they were reported, with surgeon reporting associated with the lowest rates (p < 0.01). CONCLUSIONS: The rate of major AEs after lumbar spine surgery is consistent among different sites but the rate of minor AEs appears to vary substantially. The method by which AEs are reported impacts the rate of minor AEs. These data have implications for the detection and reporting of AEs and the design of strategies aimed at mitigating complications.

Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin.

BACKGROUND: There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. METHODS: Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). RESULTS: An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. CONCLUSIONS: Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

Preoperative Factors Predict Postoperative Trajectories of Pain and Disability Following Surgery for Degenerative Lumbar Spinal Stenosis.

STUDY DESIGN: Longitudinal analysis of prospectively collected data. OBJECTIVE: Investigate potential predictors of poor outcome following surgery for degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is the most common reason for an older person to undergo spinal surgery, yet little information is available to inform patient selection. METHODS: We recruited LSS surgical candidates from 13 orthopedic and neurological surgery centers. Potential outcome predictors included demographic, health, clinical, and surgery-related variables. Outcome measures were leg and back numeric pain rating scales and Oswestry disability index scores obtained before surgery and after 3, 12, and 24 postoperative months. We classified surgical outcomes based on trajectories of leg pain and a composite measure of overall outcome (leg pain, back pain, and disability). RESULTS: Data from 529 patients (mean [SD] age = 66.5 [9.1] yrs; 46% female) were included. In total, 36.1% and 27.6% of patients were classified as experiencing a poor leg pain outcome and overall outcome, respectively. For both outcomes, patients receiving compensation or with depression/depression risk were more likely, and patients participating in regular exercise were less likely to have poor outcomes. Lower health-related quality of life, previous spine surgery, and preoperative anticonvulsant medication use were associated with poor leg pain outcome. Patients with ASA scores more than two, greater preoperative disability, and longer pain duration or surgical waits were more likely to have a poor overall outcome. Patients who received preoperative chiropractic or physiotherapy treatment were less likely to report a poor overall outcome. Multivariable models demonstrated poor-to acceptable (leg pain) and excellent (overall outcome) discrimination. CONCLUSION: Approximately one in three patients with LSS experience a poor clinical outcome consistent with surgical non-response. Demographic, health, and clinical factors were more predictive of clinical outcome than surgery-related factors. These predictors may assist surgeons with patient selection and inform shared decision-making for patients with symptomatic LSS. LEVEL OF EVIDENCE: 2.

Opioid use trends in patients undergoing elective thoracic and lumbar spine surgery.

Background: Opioid use in North America has increased rapidly in recent years. Preoperative opioid use is associated with several negative outcomes. Our objectives were to assess patterns of opioid use over time in Canadian patients who undergo spine surgery and to determine the effect of spine surgery on 1-year postoperative opioid use. Methods: A retrospective analysis was performed on prospectively collected data from the Canadian Spine Outcomes and Research Network for patients undergoing elective thoracic and lumbar surgery. Self-reported opioid use at baseline, before surgery and at 1 year after surgery was compared. Baseline opioid use was compared by age, sex, radiologic diagnosis and presenting complaint. All patients meeting eligibility criteria from 2008 to 2017 were included. Results: A total of 3134 patients provided baseline opioid use data. No significant change in the proportion of patients taking daily (range 32.3%-38.2%) or intermittent (range 13.7%-22.5%) opioids was found from pre-2014 to 2017. Among patients who waited more than 6 weeks for surgery, the frequency of opioid use did not differ significantly between the baseline and preoperative time points. Significantly more patients using opioids had a chief complaint of back pain or radiculopathy than neurogenic claudication (p < 0.001), and significantly more were under 65 years of age than aged 65 years or older (p < 0.001). Approximately 41% of patients on daily opioids at baseline remained so at 1 year after surgery. Conclusion: These data suggest that additional opioid reduction strategies are needed in the population of patients undergoing elective thoracic and lumbar spine surgery. Spine surgeons can be involved in identifying patients taking opioids preoperatively, emphasizing the risks of continued opioid use and referring patients to appropriate evidence-based treatment programs.

Contexte: En Amérique du Nord, l'utilisation d'opioïdes a augmenté rapidement dans les dernières années. La prise d'opioïdes en période préopératoire est associée à plusieurs issues négatives. Cette étude visait à évaluer l'évolution des tendances dans l'utilisation d'opioïdes des patients canadiens ayant subi une chirurgie spinale, et de déterminer les effets de la chirurgie sur leur utilisation 1 an après l'opération. Méthodes: Une analyse rétrospective a été réalisée à partir de données recueillies de manière prospective par le Canadian Spine Outcomes and Research Network pour les patients ayant subi une chirurgie thoracique ou une chirurgie spinale élective. On a comparé l'utilisation autodéclarée d'opioïdes au début du suivi, avant la chirurgie et 1 an après la chirurgie. L'utilisation d'opioïdes au départ a été comparée selon le sexe, l'âge, le diagnostic radiologique et le motif de consultation. Entre 2008 et 2017, tous les patients satisfaisant aux critères d'admissibilités ont été inclus dans l'étude. Résultats: Au total, 3134 patients ont fourni des données sur leur prise d'opioïdes au début du suivi. Il n'y avait pas de changement significatif dans la proportion de patients utilisant quotidiennement (32,3 % à 38,2 %) ou occasionnellement (13,7 % à 22,5 %) des opioïdes entre les patients à l'étude avant 2014 et ceux à l'étude de 2014 à 2017. Parmi les patients qui ont attendu plus de 6 semaines avant la chirurgie, la fréquence de la prise d'opioïdes n'a pas changé de manière significative entre le début du suivi et la rencontre préopératoire. Une proportion significativement plus grande de patients qui utilisaient des opioïdes consultaient principalement pour des douleurs au dos ou une radiculopathie que pour une claudication neurogène (p < 0,001), et il y avait une proportion significativement plus grande de patients de moins de 65 ans qui utilisaient des opioïdes que de patients de 65 ans ou plus (p < 0,001). Environ 41 % des patients qui prenaient quotidiennement des opioïdes au départ le faisaient aussi 1 an après la chirurgie. Conclusion: Ces données suggèrent que des stratégies supplémentaires de réduction de l'utilisation d'opioïdes sont nécessaires pour les patients qui subissent une chirurgie thoracique ou une chirurgie spinale élective. Il est possible de demander aux chirurgiens spécialisés dans ce domaine de repérer les patients qui prennent des opioïdes avant l'opération, puisque l'utilisation prolongée comporte des risques, et de les aiguiller vers un programme de traitement adéquat et fondé sur des données probantes.

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis.

OBJECTIVE: Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes. METHODS: We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery. RESULTS: Data from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p < .001). CONCLUSION: Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis.

Effect of preoperative symptom duration on outcome in lumbar spinal stenosis: a Canadian Spine Outcomes and Research Network registry study.

BACKGROUND CONTEXT: Lumbar degenerative stenosis is one of the most common spine pathologies for which surgical intervention is indicated. There is some evidence that a prolonged duration of neurological compression could lead to a failure of surgery to alleviate symptoms. PURPOSE: Determination of whether longer symptom duration was associated with worse postoperative disability outcomes after decompressive surgery for lumbar degenerative stenosis. STUDY DESIGN/SETTING: The Canadian Spine Outcomes and Research Network (CSORN) prospective database includes pre- and postoperative data from 18 tertiary care hospitals. PATIENT SAMPLE: The CSORN database was queried for all cases of degenerative lumbar stenosis receiving surgical decompression for neurogenic claudication or radiculopathy. Patients with tumor, infection, fracture, or previous surgery were excluded. Patients were divided into groups based on symptom duration (<6 weeks, 6-12 weeks, 3-6 months, 6-12 months, 1-2 years, and >2 years). OUTCOME MEASURES: Change between preoperative and 12-month postoperative Oswestry Disability Index (ODI) was compared between symptom duration groups. Secondary outcomes included SF12 physical component score (PCS), and numeric rating scales for leg and back pain. Outcomes were also assessed at 3 months and 24 months postoperatively. METHODS: Change in ODI, and secondary outcome measures, were compared between different symptom duration groups. Multiple regression analysis was used to identify factors interacting with symptom duration to predict change in ODI. RESULTS: Four hundred and seventy-eight cases of lumbar stenosis with 12-month postoperative data were identified. Longer symptom duration correlated with less improvement in ODI (p<.001). Patients with >1 year of symptoms were less likely to achieve a Minimal Clinically Significant Difference in ODI (54.4% vs. 66.1%; p=.03) and were more likely to experience no improvement or worse disability, postoperatively (22.1% vs. 11.3%; p=.008). Similar results were found at 3- and 24-month timepoints. Smaller postoperative improvements in SF12 PCS and leg pain scales were also correlated with longer symptom duration (p<.05). CONCLUSIONS: Multicenter registry data provides important real-world evidence to guide consent, surgical planning, and health resource management. Longer symptom duration was found to correlate with less improvement in pain and disability after lumbar stenosis surgery suggesting that these patients may benefit from earlier treatment.

Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro.

Curcumin and o-Vanillin cleared senescent intervertebral disc (IVD) cells and reduced the senescence-associated secretory phenotype (SASP) associated with inflammation and back pain. Cells from degenerate and non-mildly-degenerate human IVD were obtained from organ donors and from patients undergoing surgery for low back pain. Gene expression of senescence and SASP markers was evaluated by RT-qPCR in isolated cells, and protein expression of senescence, proliferation, and apoptotic markers was evaluated by immunocytochemistry (ICC). The expression levels of SASP factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Matrix synthesis was verified with safranin-O staining and the Dimethyl-Methylene Blue Assay for proteoglycan content. Western blotting and ICC were used to determine the molecular pathways targeted by the drugs. We found a 40% higher level of senescent cells in degenerate compared to non-mildly-degenerate discs from unrelated individuals and a 10% higher level in degenerate compared to non-mildly-degenerate discs from the same individual. Higher levels of senescence were associated with increased SASP. Both drugs cleared senescent cells, and treatment increased the number of proliferating as well as apoptotic cells in cultures from degenerate IVDs. The expression of SASP factors was decreased, and matrix synthesis increased following treatment. These effects were mediated through the Nrf2 and NFkB pathways.

Spontaneous Spinal Epidural Hematoma: Correlation of Timing of Surgical Decompression and MRI Findings with Functional Neurological Outcome.

OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is a rare and morbid entity, with the prognosis affected by delayed diagnosis and surgical intervention. The correlation between the timing of the intervention and neurological recovery has not been clearly reported. We present a retrospective study of SSEH to determine the correlation between the timing of surgical intervention and changes in the spinal cord signal on magnetic resonance imaging (MRI) with the neurological outcome. METHODS: The records of 14 patients who had undergone surgical decompression of SSEHs during a 10-year duration were reviewed. The diagnosis was established from the MRI, intraoperative, and histopathological examination findings. RESULTS: We identified 14 patients from both centers, 6 of whom were male. Their mean age was 54.1 years. The onset was spontaneous, and 2 patients were receiving anticoagulant therapy. The most common presentation was paraplegia (n = 8), followed by paraparesis (n = 3) and quadriparesis (n = 2). Spinal cord signal changes were demonstrated on all T2-weighted MRI studies. The response to surgery was favorable for 13 of our patients at the 6-month follow-up examination. The spinal cord changes had persisted in 5 patients on the 6-month postoperative MRI scan. All 14 patients, except for 1, had a favorable neurological outcome at the last follow-up examination. CONCLUSIONS: Significant neurological recovery after surgical decompression of SSEHs can be achieved, despite the significant preoperative neurological deficits, spinal cord changes on MRI, and delayed timing of intervention.

A Systematic Review of the Utility of the Hoffmann Sign for the Diagnosis of Degenerative Cervical Myelopathy.

STUDY DESIGN: Systematic review. OBJECTIVE: To determine the validity of the Hoffmann sign for the detection of degenerative cervical myelopathy (DCM) for patients presenting with cervical complaints. SUMMARY OF BACKGROUND DATA: While physical examination maneuvers are often used to diagnose DCM, no previous review has synthesized diagnostic accuracy data. METHODS: Medline, Embase, and HealthStar were searched for articles from January 1, 1947 to March 1, 2017 using the following terms: Spinal Cord Diseases, Spinal Cord Compression, Cervical Vertebrae, Signs and Symptoms, Physical Examination, Epidemiologic studies, Epidemiologic Research Design, Predictive Value of Tests, and Myelopathy. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist was applied to determine the level of evidence. Articles included were published in English or French language, rated as QUADAS level 3 or higher with a minimum 10 patients presenting with cervical complaints having undergone the Hoffman sign. Excluded studies recruited patients with a nondegenerative type of cervical myelopathy, and/or no evaluation with magnetic resonance imaging. RESULTS: A total of 589 articles were selected for review. Following the application of inclusion and exclusion criteria, 45 articles were analyzed using the QUADAS checklist. Only of three articles were of QUADAS quality 3 or higher. Analysis of combined data from 2/3 studies indicated that the Hoffman sign has a positive likelihood ratio of 2.2 (95% CI 1.5-3.3) and a negative likelihood ratio of 0.63 (95% CI 0.5-0.8). CONCLUSION: A positive Hoffman alone is unlikely to lead to more than a small change in estimated probability of DCM as compared with the gold standard test (magnetic resonance imaging). Variability in results across individual studies may result from differences in study design. There are insufficient data to support use of the Hoffman sign alone to confirm or refute a diagnosis of DCM. LEVEL OF EVIDENCE: 1.

Postoperative Assessment of Pedicle Screws and Management of Breaches: A Survey among Canadian Spine Surgeons and a New Scoring System.

STUDY DESIGN: This study was designed as a survey amongst Canadian spine surgeon to determine a scoring system to standardize pedicle screw placement assessment. PURPOSE: This study aimed to obtain and analyze the opinions of spine surgeons regarding the assessment of pedicle screw accuracy, with the goal of establishing clinical guidelines for interventions for malpositioned pedicle screws. OVERVIEW OF LITERATURE: Accurate placement of pedicle screws is challenging, and misalignment can lead to various complications. To date, there is no recognized gold standard for assessing pedicle screw placement accuracy. The literature is lacking studies attempting to standardize pedicle screw placement accuracy assessment. METHODS: A survey of the clinical methods and imaging criteria that are used for assessing pedicle screw placement accuracy was designed and sent to orthopedic and neurosurgery spine surgeons from the Canadian Spine Society for their anonymous participation. RESULTS: Thirty-five surgeons completed the questionnaire. The most commonly used modalities for assessing pedicle screw position postoperatively were plain X-rays (97%) and computed tomography (CT, 97%). In both symptomatic and asymptomatic patients, the most and least worrisome breaches were medial and anterior breaches, respectively. The majority of surgeons tended not to re-operate on asymptomatic breaches. More than 60% of surgeons would re-operate on patients with new-onset pain and a ≤4-mm medial or inferior breach in both thoracic and lumbar regions. If a patient experienced sensory loss and a breach on CT, in either the thoracic or lumbar levels, 90% and 70% of the surgeons would re-operate for a medial breach and an inferior breach, respectively. CONCLUSIONS: Postoperative clinical presentation and imaging findings are crucial for interpreting aberrant pedicle screw placement. This study presents a preliminary scoring system for standardizing the classification of pedicle screws.

Quantitative Magnetic Resonance Imaging Analysis of the Cervical Spine Extensor Muscles: Intrarater and Interrater Reliability of a Novice and an Experienced Rater.

STUDY DESIGN: Reliability study. PURPOSE: To examine the reliability of novice and experienced raters for measurements of the size and composition of the cervical extensor muscles using a thresholding technique. OVERVIEW OF LITERATURE: Although some authors have reported on the dependability of magnetic resonance imaging (MRI) measurements of the cervical muscles, there remains some variability regarding intrarater and interrater reliabilities, and few studies have examined the associated measurement error. Whether the rater's experience noticeably influences the reliability and precision of such measurements has also not been examined. METHODS: A sample of 10 patients with cervical pathologies was selected. Muscle cross-sectional area (CSA), functional cross-sectional area (FCSA), and signal intensity of the cervical extensor muscles were acquired from axial T2-weighted MRIs by a novice and an experienced rater. All measurements were obtained twice, at least 5 days apart, while the raters were blinded to all earlier measurements. RESULTS: Interrater reliability estimates (intraclass correlation coefficients) varied between 0.84 and 0.99 for the novice rater and between 0.94 and 0.99 for the experienced rater, indicating excellent reliability. The standard error of measurement for the novice rater was, however, noticeably higher for all cervical muscle measurements. Most of the interrater estimates showed excellent agreement with the exception of CSA measurement of the semispinalis cervicis at C4-C7 and FCSA measurement of the multifidus and semispinalis cervicis at C4-C7, which showed poor interrater reliability. CONCLUSIONS: The proposed method of investigating cervical muscle measurements was highly reliable; however, novice raters should receive adequate training before using this method for diagnostic, research, and clinical purposes.

Antibiotics in the treatment of patients with lower back pain associated with Modic changes: a case series.

PURPOSE: To determine the clinical effect of antibiotic treatment for patients with low back pain and Modic 1 changes. METHODS: This is a retrospective case series of patients treated at the Canadian Forces Health Services Centre in Ottawa and the McGill University Health Centre. Where available, pain, functional, and imaging outcomes in 11 patients treated between 2013 and 2015 were analyzed to determine effect of antibiotic treatment for patients with low back pain and associated Modic 1 changes on magnetic resonance imaging. RESULTS: Conservatively, only 3 of 11 patients met the criteria for improvement for pain and/or function. While a larger proportion improved in the long term, outcomes were not thought to be temporally attributable to antibiotic treatment, as in most cases, ongoing therapy, medications, and/or injections were required. There did not appear to be a correlation between clinical improvement and associated end plate volume involvement for Modic changes. CONCLUSION: Antibiotics for the treatment of low back pain in the context of Modic changes on MRI did not generally provide significant improvement in pain and function for patients in this small cohort. Despite early excitement regarding this treatment, further research is required.

Factors Associated With Clinical Outcomes After Lumbar Interbody Fusion With a Porous Nitinol Implant.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study is to assess the association of demographic and perioperative factors with clinical outcomes of lumbar interbody fusion with a porous nitinol (TiNi) implant for degenerative disc disease. METHODS: Forty-one patients with degenerative lumbar disease were prospectively followed for a mean of 4.8 years. All patients were instrumented with porous TiNi interbody fusion devices. The Oswestry Disability Index (ODI) and return to work were used to assess clinical outcomes. Factors including age, body mass index, smoking status, insurance status, number of comorbidities, duration of surgery, estimated blood loss, number of levels fused, time since surgery, and preoperative ODI score were assessed. A multiple linear regression analysis was performed to look for demographic and perioperative factors associated with clinical outcome. RESULTS: All patients except one (98%) showed complete fusion on radiography at 1 year. Estimated blood loss and duration of surgery were significantly associated with higher postoperative ODI scores (P = .002 and P = .019, respectively). Smoking status, salary insurance status, age, body mass index, number of comorbidities, number of levels fused, time since surgery, and preoperative ODI score were not significantly associated with outcome. CONCLUSIONS: Porous nitinol permitted fusion rates similar to those reported in the literature for alternative fusion cages. Poor functional outcome of patients was strongly associated with intraoperative blood loss and duration of surgery. We believe that estimated blood loss should be carefully evaluated in studies of postoperative outcome, as it may affect midterm outcomes. LEVEL OF EVIDENCE: Level 3.

Prevalence and Complications of Postoperative Transfusion for Cervical Fusion Procedures in Spine Surgery: An Analysis of 11,588 Patients from the American College of Surgeons National Surgical Quality Improvement Program Database.

STUDY DESIGN: Retrospective cohort study. PURPOSE: The purpose of this study was to assess the rate of blood transfusion after cervical fusion surgery, and its effect on complication rates. OVERVIEW OF LITERATURE: Cervical spine fusions have gained interest in the literature since these procedures are now ever more frequently being performed in an outpatient setting with few complications. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients that underwent cervical fusion from 2010 to 2013. Multivariate regression analysis was used to determine postoperative complications associated with transfusion and cervical fusion. RESULTS: We identified 11,588 patients who had cervical fusion between 2010 and 2013. The rate of blood transfusion following cervical fusion found to be 1.47%. All transfused patients were found to have increased risk of venous thromboembolism (TBE) (odds ratio [OR], 3.19; 95% confidence interval [95% CI], 1.16-8.77), myocardial infarction (MI) (OR, 9.12; 95% CI, 2.53-32.8), increased length of stay (LOS) (OR, 28.03; 95% CI, 14.28-55.01) and mortality (OR, 4.14; 95% CI, 1.44-11.93). Single level fusion had increased risk of TBE (OR, 3.37; 95% CI, 1.01-11.33), MI (OR, 10.5; 95% CI, 1.88-59.89), and LOS (OR, 14.79; 95% CI, 8.2-26.67). Multilevel fusion had increased risk of TBE (OR, 5.64; 95% CI, 1.15-27.6), surgical site infection (OR, 16.29; 95% CI, 3.34-79.49), MI (OR, 10.84; 95% CI, 2.01-58.55), LOS (OR, 26.56; 95% CI, 11.8-59.78), and mortality (OR, 10.24; 95% CI, 2.45-42.71). Patients who had anterior cervical discectomy and fusion surgery and received a transfusion had an increased risk of TBE (OR, 4.87; 95% CI, 1.04-22.82), surgical site infection (OR, 9.73; 95% CI, 2.14-44.1), MI (OR, 9.88; 95% CI, 1.87-52.2), increased LOS of more than 2 days (OR, 28.34; 95% CI, 13.79-58.21) and increase in mortality (OR, 6.3; 95% CI, 1.76-22.48). While, transfused patients who had posterior fusion surgery had increased risk of MI (OR, 10.45; 95% CI, 1.42-77.12) and increased LOS of more than 6 days (OR, 4.42; 95% CI, 2.68-7.29). CONCLUSIONS: Our results demonstrate that although cervical fusions can be done as outpatient procedures special precautions and investigations should be done for patients who receive transfusion after cervical fusion. These patients are demonstrated to have higher rate of MI, TBE, wound infection and mortality when compared to those who do not receive transfusion.

Utility and costs of radiologist interpretation of perioperative imaging in patients with traumatic single-level thoracolumbar fractures.

OBJECTIVE The cost of spine management is rising. As diagnostic imaging accounts for approximately 10% of total patient care spending, there is interest in determining if economies could be made with regard to the routine consultation of radiology for image interpretation. In the context of spine trauma, both the spine surgeon and the radiologist interpret perioperative imaging. Authors of the present study investigated the impact of radiologist interpretation of perioperative imaging from patients with traumatic single-level thoracolumbar fractures given that spine surgeons are expected to be comfortable interpreting pathologies of the musculoskeletal system. METHODS The authors conducted a retrospective review of all patients presenting with a single-level thoracolumbar fracture treated at the McGill University Health Centre in the period from January 2003 to December 2010. The time between image capture and radiologist interpretation as well as the number of extraskeletal and/or incidental findings was extracted from the radiology reports on all perioperative images including radiographic, fluoroscopic, and CT images. The cost of interpretation was obtained from the provincial health insurance entity of Quebec. RESULTS Eighty-two patients met the study inclusion criteria. Radiologists took a median of 1 day (IQR 0-5.5 days) to interpret preoperative radiographs. Intraoperative fluoroscopic images and postoperative radiographs were read by the radiologist a median of 19 days (IQR 4-56.75 days) and 34 days (IQR 1-137.5 days) after capture, respectively (p < 0.05). Preoperative radiologist dictations reported extraskeletal and/or incidental findings for 8.1% of radiographs; there were no intraoperative or postoperative extraskeletal findings beyond those previously reported on the preoperative radiographs. Radiologists took a median of 1 day (IQR 0-1 day) to read both preoperative and postoperative CT scans; extraskeletal and/or incidental findings were present in 46.2% of preoperative reports and 4.5% of postoperative reports. There were no intraoperative or postoperative radiological findings that provoked reoperation. A total of 66 intraoperative fluoroscopy images and 225 postoperative radiographs were read for a cost of $1399.20 and $1867.50 (Canadian dollars), respectively, for radiologist interpretation. This cost amounted to 40.3% of all perioperative image interpretation spending. CONCLUSIONS In the management of single-level thoracolumbar fractures, radiologists add information to the diagnostic picture when interpreting preoperative radiographs and perioperative CT scans; however, the interpretation of intraoperative fluoroscopic images and postoperative radiographs comes with significant delay, does not add additional information, and represents an area of potential cost and professional-resource reduction.

Experimental study on pressure response to graded spinal canal compromise in an in vitro burst fracture mode.

BACKGROUND: Spinal cord compression is a known cause of spinal cord injury. The purpose of this study is to measure pressure response during graded spinal cord compression. This information will be important in evaluating the amount of canal compromise that can be tolerated before risking neurological injury secondary to cord compression. To date, there is no published study that has evaluated pressure response to graded canal compromise in the thoracic and lumbar spine. MATERIALS AND METHODS: A comparative biomechanical investigation using an in vitro burst fracture model of graded spinal canal compromise was performed. Four porcine spines, sectioned into four thoracics and four lumbar segments, were harvested from 30 kg pigs. Graded spinal canal compromise (0.75 mm/30 s) was achieved using a modified 12.7 mm dynamic hip screw. The real-time ventral epidural pressure was measured at each 0.75 mm of canal compromise. RESULTS: A significant increase in spinal cord pressure was recorded during graded spinal cord compression (P < 0.0001), and there were no statistical differences between the increase in pressure measured in the thoracic and lumbar spinal segments (P = 0.83). The pressure to degree of canal compromise curve exhibited an initial rapid rise in pressure followed by incrementally smaller increases in pressure as canal compromise increased. CONCLUSIONS: Spinal cord pressure increased with any degree of canal compromise, the most important rise occurring with initial compression. Future studies will evaluate the usefulness of laminectomy in vivo to completely restore ventral epidural pressure in the thoracic and lumbar spine.