Spasticity Predicts Motor Recovery for Patients with Subacute Motor Complete Spinal Cord Injury.

OBJECTIVE: A motor complete spinal cord injury (SCI) results in the loss of voluntary motor control below the point of injury. Some of these patients can regain partial motor function through inpatient rehabilitation; however, there is currently no biomarker to easily identify which patients have this potential. Evidence indicates that spasticity could be that marker. Patients with motor complete SCI who exhibit spasticity show preservation of descending motor pathways, the pathways necessary for motor signals to be carried from the brain to the target muscle. We hypothesized that the presence of spasticity predicts motor recovery after subacute motor complete SCI. METHODS: Spasticity (Modified Ashworth Scale and pendulum test) and descending connectivity (motor evoked potentials) were tested in the rectus femoris muscle in patients with subacute motor complete (n = 36) and motor incomplete (n = 30) SCI. Motor recovery was assessed by using the International Standards for Neurological Classification of Spinal Cord Injury and the American Spinal Injury Association Impairment Scale (AIS). All measurements were taken at admission and discharge from inpatient rehabilitation. RESULTS: We found that motor complete SCI patients with spasticity improved in motor scores and showed AIS conversion to either motor or sensory incomplete. Conversely, patients without spasticity showed no changes in motor scores and AIS conversion. In incomplete SCI patients, motor scores improved and AIS conversion occurred regardless of spasticity. INTERPRETATION: These findings suggest that spasticity represents an easy-to-use clinical outcome that might help to predict motor recovery after severe SCI. This knowledge can improve inpatient rehabilitation effectiveness for motor complete SCI patients. ANN NEUROL 2023.

Hypotension During Vasopressor Infusion Occurs in Predictable Clusters: A Multicenter Analysis.

Background: Published evidence indicates that mean arterial pressure (MAP) below a goal range (hypotension) is associated with worse outcomes, though MAP management failures are common. We sought to characterize hypotension occurrences in ICUs and consider the implications for MAP management. Methods: Retrospective analysis of 3 hospitals' cohorts of adult ICU patients during continuous vasopressor infusion. Two cohorts were general, mixed ICU patients and one was exclusively acute spinal cord injury patients. "Hypotension-clusters" were defined where there were ≥10 min of cumulative hypotension over a 60-min period and "constant hypotension" was ≥10 continuous minutes. Trend analysis was performed (predicting future MAP using 14 min of preceding MAP data) to understand which hypotension-clusters could likely have been predicted by clinician awareness of MAP trends. Results: In cohorts of 155, 66, and 16 ICU stays, respectively, the majority of hypotension occurred within the hypotension-clusters. Failures to keep MAP above the hypotension threshold were notable in the bottom quartiles of each cohort, with hypotension durations of 436, 167, and 468 min, respectively, occurring within hypotension-clusters per day. Mean arterial pressure trend analysis identified most hypotension-clusters before any constant hypotension occurred (81.2%-93.6% sensitivity, range). The positive predictive value of hypotension predictions ranged from 51.4% to 72.9%. Conclusions: Across 3 cohorts, most hypotension occurred in temporal clusters of hypotension that were usually predictable from extrapolation of MAP trends.

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships.

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships. METHODS: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation. RESULTS: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds. CONCLUSIONS: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Factors contributing to a longer length of stay in adults admitted to a quaternary spinal care center.

BACKGROUND: Longer hospital length of stay (LOS) has been associated with worse outcomes and increased resource utilization. However, diagnostic and patient-level factors associated with LOS have not been well studied on a large scale. The goal was to identify patient, surgical and organizational factors associated with longer patient LOS for adult patients at a high-volume quaternary spinal care center. METHODS: We performed a retrospective analysis of 13,493 admissions from January 2006 to December 2019. Factors analyzed included age, sex, admission status (emergent vs scheduled), ASIA grade, operative vs non-operative management, mean blood loss, operative time, and adverse events. Specific adverse events included surgical site infection (SSI), other infection (systemic or UTI), neuropathic pain, delirium, dural tear, pneumonia, and dysphagia. Diagnostic categories included trauma, oncology, deformity, degenerative, and "other". A multivariable linear regression model was fit to log-transformed LOS to determine independent factors associated with patient LOS, with effects expressed as multipliers on mean LOS. RESULTS: Mean LOS for the population (SD) was 15.8 (34.0) days. Factors significantly (p < 0.05) associated with longer LOS were advanced patient age [multiplier on mean LOS 1.011/year (95% CI: 1.007-1.015)], emergency admission [multiplier on mean LOS 1.615 (95% CI: 1.337-1.951)], ASIA grade [multiplier on mean LOS 1.125/grade (95% CI: 1.051-1.205)], operative management [multiplier on mean LOS 1.211 (95% CI: 1.006-1.459)], and the occurrence of one or more AEs [multiplier on mean LOS 2.613 (95% CI: 2.188-3.121)]. Significant AEs included postoperative SSI [multiplier on mean LOS 1.749 (95% CI: 1.250-2.449)], other infections (systemic infections and UTI combined) [multiplier on mean LOS 1.650 (95% CI: 1.359-2.004)], delirium [multiplier on mean LOS 1.404 (95% CI: 1.103-1.787)], and pneumonia [multiplier on mean LOS 1.883 (95% CI: 1.447-2.451)]. Among the diagnostic categories explored, degenerative patients experienced significantly shorter LOS [multiplier on mean LOS 0.672 (95%CI: 0.535-0.844), p < 0.001] compared to non-degenerative categories. CONCLUSION: This large-scale study taking into account diagnostic categories identified several factors associated with patient LOS. Future interventions should target modifiable factors to minimize LOS and guide hospital resource allocation thereby improving patient outcomes and quality of care and decreasing healthcare-associated costs.

Degenerative spinal conditions requiring emergency surgery: an evolving crisis in a publicly funded health care system.

BACKGROUND: Surgery for degenerative spine pathologies is typically performed on a scheduled basis; however, worsening symptoms may warrant emergency surgery. An increasing number of patients requiring emergency surgery has been observed (22.6% in 2006 to 34.8% in 2019). We sought to compare the outcomes of patients who received scheduled surgery and those who required emergency surgery. METHODS: All patients treated between Jan. 1, 2006, and Dec. 31, 2019, were included. Retrospective comparisons were made between patients who were scheduled (elective) for surgery and those requiring emergency surgery, patients who were scheduled for surgery and those who decompensated while on the surgical waitlist and patients who presented as de novo emergencies and those who decompensated while on the surgical waitlist. RESULTS: Among the 6217 patients with degenerative pathologies, 4654 (74.9%) patients were scheduled (elective) for surgery and 1563 (25.1%) were patients requiring emergency surgery. Compared with patients who were scheduled, patients requiring emergency surgery had a longer length of stay (LOS) in hospital (5.1 d, interquartile range [IQR] 2.7-11.2 v. 3.6 d, IQR 1.3-6.4, p < 0.001) and lower rate of home discharge (78.6% v. 94.2%, p < 0.001). Patients requiring emergency surgery were 1.34 times more likely to have any adverse events (95% confidence interval [CI] 1.06-1.68, p = 0.01). When compared with patients who were scheduled for surgery, those who decompensated while on the surgical waitlist had longer LOS (7.0 d, IQR 3.3-15.0 v. 3.6 d, IQR 1.3-6.4, p < 0.001), less home discharge (77.6% v. 94.2%, p < 0.001) and were 2.5 times more likely to have any adverse events (95% CI 1.5-4.1, p < 0.001). Patients who decompensated had a 2.1 times higher risk of having any adverse events than patients who presented as de novo emergencies (95% CI 1.2-3.6, p < 0.001). CONCLUSION: We observed worse perioperative outcomes for patients requiring emergency surgery for degenerative spinal conditions than for patients who were scheduled for surgery. Patients who decompensated while on the surgical waitlist had the worst outcomes.

Effectiveness of prophylactic intranasal photodynamic disinfection therapy and chlorhexidine gluconate body wipes for surgical site infection prophylaxis in adult spine surgery.

BACKGROUND: Current measures to prevent spinal surgical site infection (SSI) lack compliance and lead to antimicrobial resistance. We aimed to examine the effectiveness of bundled preoperative intranasal photodynamic disinfection therapy (nPDT) and chlorhexidine gluconate (CHG) body wipes in the prophylaxis of spine SSIs in adults, as well as determine our institutional savings attributable to the use of this strategy and identify adverse events reported with nPDT-CHG. METHODS: We performed a 14-year prospective observational interrupted time-series study in adult (age > 18 yr) patients undergoing emergent or elective spine surgery with 3 time-specific cohorts: before rollout of our institution's nPDT-CHG program (2006-2010), during rollout (2011-2014) and after rollout (2015-2019). We used unadjusted bivariate analysis to test for temporal changes across patient and surgical variables, and segmented regression to estimate the effect of nPDT-CHG on the annual SSI incidence rates per period. We used 2 models to estimate the cost of nPDT-CHG to prevent 1 additional SSI per year and the annual cumulative cost savings through SSI prevention. RESULTS: Over the study period, 13 493 patients (mean 964 per year) underwent elective or emergent spine surgery. From 2006 to 2019, the mean age, mean Charlson Comorbidity Index (CCI) score and mean Spine Surgical Invasiveness Index (SSII) score increased from 48.4 to 58.1 years, from 1.7 to 2.6, and from 15.4 to 20.5, respectively (p < 0.001). Unadjusted analysis confirmed a significant decrease in the annual number (74.6 to 26.8) and incidence (7.98% to 2.67%) of SSIs with nPDT-CHG (p < 0.001). After adjustment for mean age, mean CCI score and mean SSII score, segmented regression showed an absolute reduction in the annual SSI incidence rate of 3.36% per year (p < 0.001). The estimated annual cost to prevent 1 additional SSI per year was about $1350-$1650, and the estimated annual cumulative cost savings were $2 484 856-$2 495 016. No adverse events were reported with nPDT-CHG. CONCLUSION: Preoperative nPDT-CHG administration is an effective prophylactic strategy for spinal SSIs, with significant cost savings. Given its rapid action, minimal risk of antimicrobial resistance, broad-spectrum activity and high compliance rate, preoperative nPDT-CHG decolonization should be the standard of care for all patients undergoing emergent or elective spine surgery.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular (LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

All over the MAP: describing pressure variability in acute spinal cord injury.

STUDY DESIGN: Observational study. OBJECTIVES: To examine the feasibility of meeting the current clinical guidelines for the hemodynamic management of acute spinal cord injury (SCI) which recommend maintaining mean arterial pressure (MAP) at 85-90 mmHg in the days following injury. METHODS: This study examined data collected minute-by-minute to describe the pressure profile in the first 5 days following SCI in 16 patients admitted to the Intensive Care Unit at Vancouver General Hospital (40 ± 19 years, 13 M/3 F, C4-T11). MAP and intrathecal pressure (ITP) were monitored at 100 Hz by arterial and lumbar intrathecal catheters, respectively, and reported as the average of each minute. Spinal cord perfusion pressure was calculated as the difference between MAP and ITP. The minute-to-minute difference (MMdiff) of each pressure variable was calculated as the absolute difference between consecutive minutes. RESULTS: Only 24 ± 7% of MAP recordings were between 85 and 90 mmHg. Average MAP MMdiff was ~3 mmHg. The percentage of MAP recordings within target range was negatively correlated with the degree of variability (i.e. MMdiff; r = -0.64, p < 0.008) whereas higher mean MAP was correlated with greater variability (r = 0.57, p = 0.021). CONCLUSIONS: Our findings point to the 'real life' challenges in maintaining MAP in acute SCI patients. Given MAP fluctuated ~3 mmHg minute-to-minute, maintaining MAP within a 5 mmHg range with conventional volume replacement and vasopressors presents an almost impossible task for clinicians and warrants reconsideration of current management guidelines.

Characterization of the gut microbiome in a porcine model of thoracic spinal cord injury.

BACKGROUND: The gut microbiome is a diverse network of bacteria which inhabit our digestive tract and is crucial for efficient cellular metabolism, nutrient absorption, and immune system development. Spinal cord injury (SCI) disrupts autonomic function below the level of injury and can alter the composition of the gut microbiome. Studies in rodent models have shown that SCI-induced bacterial imbalances in the gut can exacerbate the spinal cord damage and impair recovery. In this study we, for the first time, characterized the composition of the gut microbiome in a Yucatan minipig SCI model. We compared the relative abundance of the most dominant bacterial phyla in control samples to those collected from animals who underwent a contusion-compression SCI at the 2nd or 10th Thoracic level. RESULTS: We identify specific bacterial fluctuations that are unique to SCI animals, which were not found in uninjured animals given the same dietary regimen or antibiotic administration. Further, we identified a specific time-frame, "SCI-acute stage", during which many of these bacterial fluctuations occur before returning to "baseline" levels. CONCLUSION: This work presents a dynamic view of the microbiome changes that accompany SCI, establishes a resource for future studies and to understand the changes that occur to gut microbiota after spinal cord injury and may point to a potential therapeutic target for future treatment.

Patient perspective: diagnosis and prognosis of acute spinal cord injuries.

STUDY DESIGN: Qualitative study. OBJECTIVES: The purpose of this study is to understand the patient perspective after diagnosis of an acute traumatic spinal cord injury (tSCI). Discussing the diagnosis and prognosis of a tSCI with a patient can be a challenging experience for both the patient and the physician. As such, this paper attempts to better understand the patient experience to improve communication when discussing this life-altering injury. SETTING: Vancouver General Hospital, Vancouver, British Columbia, Canada. METHODS: This study is a qualitative study utilizing grounded theory and semi-structured interviews. The interview transcripts were manually coded using manifest and latent content analysis. Major and minor codes were identified and discussed. RESULTS: In total, 17 interviews were conducted, fifteen individuals with tSCI who received acute care at Vancouver General Hospital (VGH) and eleven family members were interviewed. Patient participants were interviewed individually or in a paired interview with a participating family member. Patient participants had varying spinal cord injuries from AIS A-D. Two major themes were identified from the interviews. The first major theme was physician demeanor (general approach and attitude towards patients) and the second major theme was delivery of information (content, timing, and source). CONCLUSIONS: This study summarizes the preferences of patients who sustained a tSCI discussions regarding their diagnosis and prognosis in the acute care setting. The goal of this study is to help guide physician interactions at this difficult and vulnerable time for patients with hopes to improve patient care through effective communication.

A porcine model for studying the cardiovascular consequences of high-thoracic spinal cord injury.

KEY POINTS: We have developed a novel porcine model of high-thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level. We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post-SCI. We demonstrate that the high-thoracic SCI model, but not a low-thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II. We additionally conducted a proof-of-concept long-term (12 weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long-term drug studies prior to translation to the clinic. ABSTRACT: Cardiovascular disease is a leading cause of morbidity and mortality in the spinal cord injury (SCI) population, especially in those with high-thoracic or cervical SCI. With this in mind, we aimed to develop a large animal (porcine) model of high-thoracic (T2 level) contusion SCI and compare the haemodynamic and neurohormonal responses of this injury against a low-thoracic (T10 level) model. Ten Yorkshire pigs were randomly subjected to 20 cm weight drop contusion SCI at either the T2 or the T10 spinal level. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored until 4 h post-SCI. Plasma noradrenaline (NA), aldosterone and angiotensin II (ANGII) were measured pre-SCI and at 30, 60, 120 and 240 min post-SCI. Additionally, two Yucatan pigs were subjected to T2-SCI and survived up to 12 weeks post-injury to demonstrate the efficacy of this model for long-term survival studies. Immediately after T2-SCI, SBP, MAP and HR increased (P < 0.0001). Between decompression (5 min post-SCI) and 30 min post-decompression in T2-SCI, SBP and MAP were lower than pre-SCI (P < 0.038). At 3 and 4 h after T2-SCI, SBP remained lower than pre-SCI (P = 0.048). After T10-SCI, haemodynamic indices remained largely unaffected. Plasma NA was lower in T2- vs. T10-SCI post-SCI, whilst aldosterone and ANGII were higher. Both chronically injured pigs demonstrated a vast reduction in SBP at 12 weeks post-SCI. Our model of T2-SCI causes a rapid and sustained alteration in neurohormonal control and cardiovascular function, which does not occur in the T10 model.

Correction: The influence of neurological examination timing within hours after acute traumatic spinal cord injuries: an observational study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The influence of neurological examination timing within hours after acute traumatic spinal cord injuries: an observational study.

STUDY DESIGN: Cohort study. OBJECTIVES: It is widely accepted that the prediction of long-term neurologic outcome after traumatic spinal cord injury (SCI) can be done more accurately with neurological examinations conducted days to weeks post injury. However, modern clinical trials of neuroprotective interventions often require patients be examined and enrolled within hours. Our objective was to determine whether variability in timing of neurological examinations within 48 h after SCI is associated with differences in observations of follow-up neurologic recovery. SETTING: Level I trauma hospital. METHODS: An observational analysis testing for differences in AIS conversion rates and changes in total motor scores by neurological examination timing, controlling for potential confounders with multivariate stepwise regression. RESULTS: We included 85 patients, whose mean times from injury to baseline and follow-up examinations were 11.8 h (SD 9.8) and 208.2 days (SD 75.2), respectively. AIS conversion by 1+ grade was significantly more likely in patients examined at ≤4 h in comparison with later examination (78% versus 47%, RR = 1.66, p = 0.04), even after controlling for timing of surgery, age, and sex (OR 5.0, 95% CI 1.1-10, p = 0.04). We failed to identify any statistically significant associations for total motor score recovery in unadjusted or adjusted analyses. CONCLUSIONS: AIS grade conversion was significantly more likely in those examined ≤4 h of injury; the effect of timing on motor scores remains uncertain. Variability in neurological examination timing within hours after acute traumatic SCI may influence observations of long-term neurological recovery, which could introduce bias or lead to errors in interpretation of studies of therapeutic interventions.

Pseudarthrosis in adult and pediatric spinal deformity surgery: a systematic review of the literature and meta-analysis of incidence, characteristics, and risk factors.

We conducted a systematic review with meta-analysis and qualitative synthesis. This study aims to characterize pseudarthrosis after long-segment fusion in spinal deformity by identifying incidence rates by etiology, risk factors for its development, and common features. Pseudarthrosis can be a painful and debilitating complication of spinal fusion that may require reoperation. It is poorly characterized in the setting of spinal deformity. The MEDLINE, EMBASE, and Cochrane databases were searched for clinical research including spinal deformity patients treated with long-segment fusions reporting pseudarthrosis as a complication. Meta-analysis was performed on etiologic subsets of the studies to calculate incidence rates for pseudarthrosis. Qualitative synthesis was performed to identify characteristics of and risk factors for pseudarthrosis. The review found 162 articles reporting outcomes for 16,938 patients which met inclusion criteria. In general, the included studies were of medium to low quality according to recommended reporting standards and study design. Meta-analysis calculated an incidence of 1.4% (95% CI 0.9-1.8%) for pseudarthrosis in adolescent idiopathic scoliosis, 2.2% (95% CI 1.3-3.2%) in neuromuscular scoliosis, and 6.3% (95% CI 4.3-8.2%) in adult spinal deformity. Risk factors for pseudarthrosis include age over 55, construct length greater than 12 segments, smoking, thoracolumbar kyphosis greater than 20°, and fusion to the sacrum. Choice of graft material, pre-operative coronal alignment, post-operative analgesics, and sex have no significant impact on fusion rates. Older patients with greater deformity requiring more extensive instrumentation are at higher risk for pseudarthrosis. Overall incidence of pseudarthrosis requiring reoperation is low in adult populations and very low in adolescent populations.

Monitoring spinal cord hemodynamics and tissue oxygenation: a review of the literature with special focus on the near-infrared spectroscopy technique.

STUDY DESIGN: Review. OBJECTIVES: Clinical studies have shown that the hemodynamic management of patients following acute spinal cord injury (SCI) is an important aspect of their treatment for maintaining spinal cord (SC) perfusion and minimizing ischemic secondary injury to the SC. While this highlights the importance of ensuring adequate perfusion and oxygenation to the injured cord, a method for the real-time monitoring of these hemodynamic measures within the SC is lacking. The purpose of this review is to discuss current and potential methods for SC hemodynamic monitoring with special focus on applications using near-infrared spectroscopy (NIRS). METHODS: A literature search using the PubMed database. All peer-reviewed articles on NIRS monitoring of SC published from inception to May 2019 were reviewed. RESULTS: Among 125 papers related to SC hemodynamics monitoring, 26 focused on direct/indirect NIRS monitoring of the SC. DISCUSSION: Current options for continuous, non-invasive, and real-time monitoring of SC hemodynamics are challenging and limited in scope. As a relatively new technique, NIRS has been successfully used for monitoring human cerebral hemodynamics, and has shown promising results in intraoperative assessment of SC hemodynamics in both human and animal models. Although utilizing NIRS to monitor the SC has been validated, applying NIRS clinically following SCI requires further development and investigation. CONCLUSIONS: NIRS is a promising non-invasive technique with the potential to provide real-time monitoring of relevant parameters in the SC. Currently, in its first developmental stages, further clinical and experimental studies are mandatory to ensure the validity and safety of NIRS techniques.

Neurochemical biomarkers in spinal cord injury.

STUDY DESIGN: This is a narrative review of the literature on neurochemical biomarkers in spinal cord injury (SCI). OBJECTIVES: The objective was to summarize the literature on neurochemical biomarkers in SCI and describe their use in facilitating clinical trials for SCI. Clinical trials in spinal cord injury (SCI) have been notoriously difficult to conduct, as exemplified by the paucity of definitive prospective randomized trials that have been completed, to date. This is related to the relatively low incidence and the complexity and heterogeneity of the human SCI condition. Given the increasing number of promising approaches that are emerging from the laboratory which are vying for clinical evaluation, novel strategies to help facilitate clinical trials are needed. METHODS: A literature review was conducted, with a focus on neurochemical biomarkers that have been described in human neurotrauma. RESULTS: We describe advances in our understanding of neurochemical biomarkers as they pertain to human SCI. The application of biomarkers from serum and cerebrospinal fluid (CSF) has been led by efforts in the human traumatic brain injury (TBI) literature. A number of promising biomarkers have been described in human SCI whereby they may assist in stratifying injury severity and predicting outcome. CONCLUSIONS: Several time-specific biomarkers have been described for acute SCI and for chronic SCI. These appear promising for stratifying injury severity and potentially predicting outcome. The subsequent application within a clinical trial will help to demonstrate their utility in facilitating the study of novel approaches for SCI.

The challenge of recruitment for neurotherapeutic clinical trials in spinal cord injury.

STUDY DESIGN: Narrative review by individuals experienced in the recruitment of participants to neurotherapeutic clinical trials in spinal cord injury (SCI). OBJECTIVES: To identify key problems of recruitment and explore potential approaches to overcoming them. METHODS: Published quantitative experience with recruitment of large-scale, experimental neurotherapeutic clinical studies targeting central nervous system and using primary outcome assessments validated for SCI over the last 3 decades was summarized. Based on this experience, potential approaches to improving recruitment were elicited from the authors. RESULTS: The rate of recruitment has varied between studies, depending on protocol design and other factors, but particularly inclusion/exclusion criteria. The recruitment rate also ranged over an order of magnitude between individual centers in a given study. In older multicenter studies, average recruitment rate was approximately one person per study center per month. More recent trials experienced lower rates of recruitment and potential reasons for this trend were examined. The current roles and potential of various stakeholder organizations in addressing problems of recruitment were explored. In addition, recent developments in methodology may help reduce the number of subjects required for well-powered studies. CONCLUSIONS: Several approaches are emerging to improve clinical trial design, efficacy outcome measures, and quantifiable surrogate markers, all of which should reduce the number of participants required for adequate statistical power. There is a growing sense of cooperation between various stakeholders but more should be done to bring together consumer and provider groups to improve recruitment and the effectiveness and relevance of neurotherapeutic clinical trials.

Intra-rater and inter-rater reliability of the Penn Spasm Frequency Scale in People with chronic traumatic spinal cord injury.

STUDY DESIGN: Psychometric study. OBJECTIVES: Evaluate the intra-rater and inter-rater reliability of the Penn Spasm Frequency Scale (PSFS) in people with chronic traumatic spinal cord injury (SCI). SETTING: Community setting. METHODS: Participants with chronic traumatic SCI were administered the PSFS, a self-reported spasticity measure in which the individual documents the frequency (Part 1) and severity (Part 2) of their muscle spasms. One rater administered the PSFS at baseline, 5 to 10 days, and 4 to 6 weeks after baseline. The second rater administered the PSFS within 3 days of the first rater. RESULTS: Reliability was assessed using weighted-kappa (95% confidence interval) statistics. In 61 participants, the intra-rater reliability between 5 to 10 days and 4 to 6 weeks after baseline was 0.822 (0.709, 0.935) and 0.734 (0.586, 0.883), respectively, for PSFS Part 1. With the addition of Part 2, the intra-rater reliabilities were 0.812 (0.705, 0.919) and 0.729 (0.586, 0.872) for 5 to 10 days and 4 to 6 weeks, respectively. The PSFS inter-rater reliability within a 3-day time interval was 0.862 (0.759, 0.965) for Part 1 and 0.857 (0.762, 0.952) with the addition of Part 2. CONCLUSIONS: PSFS Part 1 intra-rater and inter-rater reliability weighted-kappa statistics are in the "almost perfect" category, with lower confidence bounds in the "substantial" range. By adding Part 2 the reliability decreases, but the kappa statistics remain "substantial," with a lower confidence bound in the "moderate" range. The PSFS is probably a reliable outcome measure to assess self-reported spasticity after chronic traumatic SCI.