Browsing by Author "Harrop, James S"
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Item Open Access A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.(Journal of neurotrauma, 2012-09) Wilson, Jefferson R; Grossman, Robert G; Frankowski, Ralph F; Kiss, Alexander; Davis, Aileen M; Kulkarni, Abhaya V; Harrop, James S; Aarabi, Bizhan; Vaccaro, Alexander; Tator, Charles H; Dvorak, Marcel; Shaffrey, Christopher I; Harkema, Susan; Guest, James D; Fehlings, Michael GTo improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score >50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families.Item Open Access A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group.(Spine, 2010-10) Fisher, Charles G; DiPaola, Christian P; Ryken, Timothy C; Bilsky, Mark H; Shaffrey, Christopher I; Berven, Sigurd H; Harrop, James S; Fehlings, Michael G; Boriani, Stefano; Chou, Dean; Schmidt, Meic H; Polly, David W; Biagini, Roberto; Burch, Shane; Dekutoski, Mark B; Ganju, Aruna; Gerszten, Peter C; Gokaslan, Ziya L; Groff, Michael W; Liebsch, Norbert J; Mendel, Ehud; Okuno, Scott H; Patel, Shreyaskumar; Rhines, Laurence D; Rose, Peter S; Sciubba, Daniel M; Sundaresan, Narayan; Tomita, Katsuro; Varga, Peter P; Vialle, Luiz R; Vrionis, Frank D; Yamada, Yoshiya; Fourney, Daryl RStudy design
Systematic review and modified Delphi technique.Objective
To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability.Summary of background data
Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors.Methods
We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability.Results
A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus.Conclusion
The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.Item Open Access A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury.(Journal of neurotrauma, 2014-02) Grossman, Robert G; Fehlings, Michael G; Frankowski, Ralph F; Burau, Keith D; Chow, Diana SL; Tator, Charles; Teng, Angela; Toups, Elizabeth G; Harrop, James S; Aarabi, Bizhan; Shaffrey, Christopher I; Johnson, Michele M; Harkema, Susan J; Boakye, Maxwell; Guest, James D; Wilson, Jefferson RA prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.Item Open Access Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury.(Critical care medicine, 2019-11) Jiang, Fan; Jaja, Blessing NR; Kurpad, Shekar N; Badhiwala, Jetan H; Aarabi, Bizhan; Grossman, Robert G; Harrop, James S; Guest, Jim D; Schär, Ralph T; Shaffrey, Chris I; Boakye, Max; Toups, Elizabeth G; Wilson, Jefferson R; Fehlings, Michael G; North American Clinical Trials Network CollaboratorsObjectives
There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome.Design
Multicenter prospective registry.Setting
Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network.Patients
Eight-hundred one spinal cord injury patients enrolled by participating centers.Interventions
Appropriate spinal cord injury treatment at individual centers.Measurements and main results
A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores.Conclusions
Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury.Item Open Access Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury.(Journal of neurotrauma, 2019-11) Jaja, Blessing NR; Jiang, Fan; Badhiwala, Jetan H; Schär, Ralph; Kurpad, Shekar; Grossman, Robert G; Harrop, James S; Guest, Jim D; Toups, Elizabeth G; Shaffrey, Chris I; Aarabi, Bizhan; Boakye, Max; Fehlings, Michael G; Wilson, Jefferson RPneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.Item Open Access Brief History of Spinal Neurosurgical Societies in the United States: Part 1.(Neurospine, 2019-12) Vaziri, Sasha; Resnick, Daniel K; Ames, Christopher P; Harrop, James S; Shaffrey, Christopher I; Singh, Kern; Smith, Justin S; Hoh, Daniel JItem Open Access Degenerative Spinal Deformity.(Neurosurgery, 2015-10) Ailon, Tamir; Smith, Justin S; Shaffrey, Christopher I; Lenke, Lawrence G; Brodke, Darrel; Harrop, James S; Fehlings, Michael; Ames, Christopher PDegenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22°, and lumbopelvic mismatch <±9°; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes.Item Open Access Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS).(PloS one, 2012-01) Fehlings, Michael G; Vaccaro, Alexander; Wilson, Jefferson R; Singh, Anoushka; W Cadotte, David; Harrop, James S; Aarabi, Bizhan; Shaffrey, Christopher; Dvorak, Marcel; Fisher, Charles; Arnold, Paul; Massicotte, Eric M; Lewis, Stephen; Rampersaud, RajaBACKGROUND:There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI. METHODS:We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality. FINDINGS:A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(± 5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(± 29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥ 2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21). CONCLUSION:Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up.Item Open Access Effect of type II odontoid fracture nonunion on outcome among elderly patients treated without surgery: based on the AOSpine North America geriatric odontoid fracture study.(Spine, 2013-12) Smith, Justin S; Kepler, Christopher K; Kopjar, Branko; Harrop, James S; Arnold, Paul; Chapman, Jens R; Fehlings, Michael G; Vaccaro, Alexander R; Shaffrey, Christopher IStudy design
Subgroup analysis of a prospective multicenter study.Objective
Outcome analysis of nonoperatively treated elderly patients with type II odontoid fractures, including assessment of consequence of a fracture nonunion.Summary of background data
Odontoid fractures are among the most common fractures in the elderly, and controversy exists regarding treatment.Methods
Subgroup analysis of a prospective multicenter study of elderly patients (≥65 yr) with type II odontoid fracture. Neck Disability Index and Short-Form 36 (SF-36) version 2 were collected at baseline and 6 and 12 months. Fifty-eight (36.5%) of the 159 patients were treated nonoperatively.Results
Of the 58 patients initially treated nonoperatively, 8 died within 90 days and were excluded. Of the remaining 50 patients, 11 (22.0%) developed nonunion, with 7 (63.6%) requiring surgery. Four of the 39 (10.3%) patients classified as having "successful union" required surgery due to late fracture displacement. Thus, 15 (30.0%) patients developed primary or secondary nonunion and 11 (22.0%) required surgery. The overall 12-month mortality was 14.0% (nonunion = 2, union = 5; P= 0.6407). For union and nonunion groups, Neck Disability Index and SF-36 version 2 declined significantly at 12 months compared with preinjury values (P< 0.05), except for SF-36 version 2 Physical Functioning (P= 0.1370). There were no significant differences in outcome parameters based on union status at 12 months (P> 0.05); however, it is important to emphasize that the 12-month outcomes for the nonunion patients reflect the status of the patient after delayed surgical treatment in the majority of these cases.Conclusion
Nonoperative treatment for type II odontoid fracture in the elderly has high rates of nonunion and mortality. Patients with nonunion did not report worse outcomes compared with those who achieved union at 12 months; however, the majority of patients with nonunion required delayed surgical treatment. These findings may prove useful for patients who are not surgical candidates or elect for nonoperative treatment.Level of evidence
2.Item Open Access Frequency and Acceptability of Adverse Events After Anterior Cervical Discectomy and Fusion: A Survey Study From the Cervical Spine Research Society.(Clinical spine surgery, 2018-06) Wilson, Jefferson R; Radcliff, Kris; Schroeder, Gregory; Booth, Madison; Lucasti, Christopher; Fehlings, Michael; Ahmad, Nassr; Vaccaro, Alexander; Arnold, Paul; Sciubba, Daniel; Ching, Alex; Smith, Justin; Shaffrey, Christopher; Singh, Kern; Darden, Bruce; Daffner, Scott; Cheng, Ivan; Ghogawala, Zoher; Ludwig, Steven; Buchowski, Jacob; Brodke, Darrel; Wang, Jeffrey; Lehman, Ronald A; Hilibrand, Alan; Yoon, Tim; Grauer, Jonathan; Dailey, Andrew; Steinmetz, Michael; Harrop, James SPURPOSE:Anterior cervical discectomy and fusion has a low but well-established profile of adverse events. The goal of this study was to gauge surgeon opinion regarding the frequency and acceptability of these events. METHODS:A 2-page survey was distributed to attendees at the 2015 Cervical Spine Research Society (CSRS) meeting. Respondents were asked to categorize 18 anterior cervical discectomy and fusion-related adverse events as either: "common and acceptable," "uncommon and acceptable," "uncommon and sometimes acceptable," or "uncommon and unacceptable." Results were compiled to generate the relative frequency of these responses for each complication. Responses for each complication event were also compared between respondents based on practice location (US vs. non-US), primary specialty (orthopedics vs. neurosurgery) and years in practice. RESULTS:Of 150 surveys distributed, 115 responses were received (76.7% response rate), with the majority of respondents found to be US-based (71.3%) orthopedic surgeons (82.6%). Wrong level surgery, esophageal injury, retained drain, and spinal cord injury were considered by most to be unacceptable and uncommon complications. Dysphagia and adjacent segment disease occurred most often, but were deemed acceptable complications. Although surgeon experience and primary specialty had little impact on responses, practice location was found to significantly influence responses for 12 of 18 complications, with non-US surgeons found to categorize events more toward the uncommon and unacceptable end of the spectrum as compared with US surgeons. CONCLUSIONS:These results serve to aid communication and transparency within the field of spine surgery, and will help to inform future quality improvement and best practice initiatives.Item Open Access History and Accomplishments of the North American Clinical Trials Network (NACTN) for Spinal Cord Injury, 2004 to 2022.(Journal of neurotrauma, 2022-12) Tator, Charles H; Guest, James D; Neal, Chris J; Howley, Susan P; Toups, Elizabeth G; Harrop, James S; Aarabi, Bizhan; Shaffrey, Christopher I; Fehlings, Michael GThis is a historical account of the origin and accomplishments of the North American Clinical Trials Network (NACTN) for traumatic spinal cord injury (SCI), which was established in 2004 by Christopher Reeve and Dr. Robert Grossman. Christopher Reeve was an actor who became quadriplegic and started the Christopher and Dana Reeve Foundation, while Robert Grossman was a neurosurgeon experienced in neurotrauma and a university professor in Houston. NACTN has member investigators at university and military centers in North America and has contributed greatly to the improvement of care, primarily acute care, of patients sustaining traumatic SCI. Its accomplishments are a clinical registry database of more than 1000 acute SCI patients documenting the care pathways, including complications. NACTN determined the effectiveness of treatment, including pharmacotherapy and the role and timing of surgery, and barriers to early surgery with a focus on neurological recovery. NACTN has assessed the effectiveness of treatment, including pharmacotherapy and the role and timing of surgery, and has also identified barriers to early surgery. The principal focus has been on improving neurological recovery. It has trained many SCI practitioners and has collaborated with many other SCI networks and organizations internationally to promote the care of SCI patients.Item Open Access Incidence and severity of acute complications after spinal cord injury.(Journal of neurosurgery. Spine, 2012-09) Grossman, Robert G; Frankowski, Ralph F; Burau, Keith D; Toups, Elizabeth G; Crommett, John W; Johnson, Michele M; Fehlings, Michael G; Tator, Charles H; Shaffrey, Christopher I; Harkema, Susan J; Hodes, Jonathan E; Aarabi, Bizhan; Rosner, Michael K; Guest, James D; Harrop, James SObject
The aim of this multicenter, prospective study was to determine the spectrum, incidence, and severity of complications during the initial hospitalization of patients with spinal cord injury.Methods
The study was conducted at 9 university-affiliated hospitals that comprise the clinical centers of the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The study population comprised 315 patients admitted to NACTN clinical centers between June 25, 2005, and November 2, 2010, who had American Spinal Injury Association (ASIA) Impairment Scale grades of A-D and were 18 years of age or older. Patients were managed according to a standardized protocol.Results
The study population was 79% male with a median age of 44 years. The leading causes of injury were falls (37%) and motor vehicle accidents (28%). The distribution of initial ASIA grades were A (40%), B (16%), C (15%), and D (29%). Fifty-eight percent of patients sustained 1 or more severe, moderate, or mild complications. Complications were associated with more severe ASIA grade: 84% of patients with Grade A and 25% of patients with Grade D had at least 1 complication. Seventy-eight percent of complications occurred within 14 days of injury. The most frequent types of severe and moderate complications were respiratory failure, pneumonia, pleural effusion, anemia, cardiac dysrhythmia, and severe bradycardia. The mortality rate was 3.5% and was associated with increased age and preexisting morbidity.Conclusions
Knowledge of the type, frequency, time of occurrence, and severity of specific complications that occur after spinal cord injury can aid in their early detection, treatment, and prevention. The data are of importance in evaluating and selecting therapy for clinical trials.Item Open Access Interhospital Transfer delays care for spinal cord injury patients: A Report from the North American Clinical Trials Network for Spinal Cord Injury.(Journal of neurotrauma, 2023-04) Kelly-Hedrick, Margot; Ugiliweneza, Beatrice; Toups, Elizabeth G; Jimsheleishvili, George; Kurpad, Shekar N; Aarabi, Bizhan; Harrop, James S; Foster, Norah; Goodwin, Rory C; Shaffrey, Christopher I; Fehlings, Michael G; Tator, Charles H; Guest, James D; Neal, Chris J; Abd-El-Barr, Muhammad M; Williamson, TheresaThe North America Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that has maintained a prospective SCI registry since 2004, and has espoused that early surgical intervention is associated with improved outcome. It has previously been shown that initial presentation to a lower acuity center and necessity of transfer to a higher acuity center reduce rates of early surgery. The NACTN database was evaluated to examine the association between interhospital transfer (IHT), early surgery, and outcome, taking into account distance traveled and site of origin for the patient. Data from a 15-year period of the NACTN SCI Registry were analyzed (years 2005-2019). Patients were stratified into transfers directly from the scene to a level I trauma center (NACTN site) versus IHT from a level II or III trauma facility. The main outcome was surgery within 24 hours of injury (yes/no) while secondary outcomes were length of stay, death, discharge disposition, and 6-month AIS grade conversion. For the IHT patients, distance traveled for transfer was calculated by measuring the shortest distance between origin and NACTN hospital. Analysis was performed with Brown-Mood test and chi-square tests. Of 724 patients with transfer data, 295 (40%) underwent IHT and 429 (60%) were admitted directly from the scene of accident. Patients who underwent IHT were more likely to have a less severe SCI (AIS D) (p=.002), have a central cord injury (p=.004), and have a fall as their mechanism of injury (p<.0001) than those directly admitted to a NACTN center. Of the 634 patients who had surgery, direct admission to a NACTN site was more likely to result in surgery within 24 hours compared to IHT patients (52% vs. 38%) (p< .0003). Median IHT distance was 28 miles (interquartile range=13-62 miles). There was no significant difference in death, length of stay, discharge to a rehab facility versus home, or 6-month AIS grade conversion rates between the two groups. Patients who underwent IHT to a NACTN site were less likely to have surgery within 24 hours of injury, compared to those directly admitted to the level I trauma facility. While there was no difference in mortality rates, length of stay, or 6-month AIS conversion between groups, patients with IHT were more likely be older with a less severe level of injury (AIS D). This work suggests there are barriers to timely recognition of SCI in the field, appropriate admission to a higher level of care after recognition, and challenges related to the management of individuals with less severe SCI.Item Open Access Lateral mass screw fixation in the cervical spine.(Journal of neurosurgery. Spine, 2014-05) Coe, Jeffrey D; Vaccaro, Alexander R; Dailey, Andrew T; Sasso, Rick C; Ludwig, Steven C; Harrop, James S; Dettori, Joseph R; Shaffrey, Christopher I; Emery, Sanford E; Fehlings, Michael GItem Open Access Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.(Journal of clinical pharmacology, 2021-09) Nguyen, Ashley; Chow, Diana S-L; Wu, Lei; Teng, Yang Angela; Sarkar, Mahua; Toups, Elizabeth G; Harrop, James S; Schmitt, Karl M; Johnson, Michele M; Guest, James D; Aarabi, Bizhan; Shaffrey, Christopher I; Boakye, Maxwell; Frankowski, Ralph F; Fehlings, Michael G; Grossman, Robert GRiluzole, a benzothiazole sodium channel blocker that received US Food and Drug Administration approval to attenuate neurodegeneration in amyotrophic lateral sclerosis in 1995, was found to be safe and potentially efficacious in a spinal cord injury (SCI) population, as evident in a phase I clinical trial. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes can alter the pharmacokinetics of therapeutics. A 1-compartment with first-order elimination population pharmacokinetic model for riluzole incorporating time-dependent clearance and volume of distribution was developed from combined data of the phase 1 and the ongoing phase 2/3 trials. This change in therapeutic exposure may lead to a biased estimate of the exposure-response relationship when evaluating therapeutic effects. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification that preserves the required therapeutic exposure of riluzole.Item Open Access Natural History, Predictors of Outcome, and Effects of Treatment in Thoracic Spinal Cord Injury: A Multi-Center Cohort Study from the North American Clinical Trials Network.(Journal of neurotrauma, 2018-11) Wilson, Jefferson R; Jaja, Blessing NR; Kwon, Brian K; Guest, James D; Harrop, James S; Aarabi, Bizhan; Shaffrey, Christopher I; Badhiwala, Jetan H; Toups, Elizabeth G; Grossman, Robert G; Fehlings, Michael GThe course, treatment response, and recovery potential after acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. There are limited data focused on thoracic-level injuries, however. A cohort of 86 patients from the prospectively maintained North American Clinical Trials Network SCI registry were identified and studied to characterize the patterns of neurological recovery and to determine rates of acute hospital death and pulmonary complications. Regression analyses were used to examine the relationship between timing of surgery and administration of methylprednisolone on neurologic and clinical outcomes. Neurological conversion (≥1 American Spinal Injury Association Impairment Scale [AIS] grade improvement) was poorest for AIS grade A patients; 14.3% converted at last available follow-up (mean eight months). While rates of conversion were more optimistic for AIS-B patients (54.5%) and AIS C injuries (77.8%) at the same time point, none of the AIS grade D patients converted to AIS E. At last available follow-up (mean eight months), the magnitudes of lower motor extremity score (LEMS) change were highest for AIS C injuries (21.9 points), then AIS B (17.7 points), AIS D (16.4 points), and finally AIS A (2.5 points) (p < 0.05). Early surgical intervention (<24 h post-injury) was independently associated with an additional seven points in motor recovery and a 60% decreased incidence of pulmonary events (p < 0.05). Methylprednisolone administration was not an independent predictor of neurological outcome or pulmonary complications. Evaluation of this cohort obtained from a modern multi-center SCI registry provides an update on the natural history, acute death, and incidence of pulmonary complications after traumatic thoracic SCI. Although small sample size limited the extent of analyses possible, early surgical treatment was associated with significantly larger motor recovery and lower rates of pulmonary complications.Item Open Access Pharmacology of riluzole in acute spinal cord injury.(Journal of neurosurgery. Spine, 2012-09) Chow, Diana SL; Teng, Yang; Toups, Elizabeth G; Aarabi, Bizhan; Harrop, James S; Shaffrey, Christopher I; Johnson, Michele M; Boakye, Maxwell; Frankowski, Ralph F; Fehlings, Michael G; Grossman, Robert GObject
The aim of this paper was to characterize individual and population pharmacokinetics of enterally administered riluzole in a Phase 1 clinical trial of riluzole as a neuroprotective agent in adults 18-70 years old with acute spinal cord injury (SCI).Methods
Thirty-five individuals with acute SCI, American Spinal Injury Association Impairment Scale Grades A-C, neurological levels from C-4 to T-12, who were enrolled in the Phase 1 clinical trial sponsored by the North American Clinical Trials Network for Treatment of Spinal Cord Injury, received 50 mg riluzole twice daily for 28 doses. The first dose was administered at a mean of 8.7 ± 2.2 hours postinjury. Trough plasma samples were collected within 1 hour predose, and peak plasma samples were collected 2 hours postdose on Days 3 and 14 of treatment. Riluzole concentrations were quantified by high-performance liquid chromatography assay. The data were analyzed for individual and population pharmacokinetics using basic structural and covariate models. The pharmacokinetic measures studied were the peak concentration (C(max)), trough concentration (C(min)), systemic exposure (AUC(0-12)), clearance (CL/F), and volume of distribution (V_F) normalized by the bioavailability (F).Results
The C(max) and AUC(0-12) achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher CL and larger V. The pharmacokinetics of riluzole (C(max), C(min), AUC(0-12), CL, and V) changed during the acute and subacute phases of SCI during the 14 days of therapy. It was consistently observed in patients at all clinical sites that C(max), C(min), and AUC(0-12) (128.9 ng/ml, 45.6 ng/ml, and 982.0 ng × hr/ml, respectively) were significantly higher on Day 3 than on Day 14 (76.5 ng/ml, 19.1 ng/ml, and 521.0 ng × hr/ml, respectively). These changes resulted from lower CL (49.5 vs 106.2 L/hour) and smaller V (557.1 vs 1297.9/L) on Day 3. No fluid imbalance or cytochrome P 1A2 induction due to concomitant medications was identified during the treatment course to account for such increases in V and CL, respectively. Possible mechanisms underlying these changes are discussed.Conclusions
This is the first report of clinical pharmacokinetics of riluzole in patients with SCI. The C(max) and AUC(0-12) achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher clearance and larger volume of distribution in SCI patients. The finding in SCI patients of an increase in the clearance and distribution of riluzole between the 3rd and 14th days after SCI, with a lower plasma concentration of riluzole on the 14th day, stresses the importance of monitoring changes in drug metabolism after SCI in interpreting the safety and efficacy of therapeutic drugs that are used in clinical trials in SCI. Clinical trial registration no.: NCT00876889.Item Open Access Postoperative C5 Palsy after Anterior or Posterior Decompression for Degenerative Cervical Myelopathy: A Subgroup Analysis of the Multicenter, Prospective, Randomized, Phase III, CSM-Protect Clinical Trial.(Spine, 2024-10) Bak, Alex B; Moghaddamjou, Ali; Alvi, Mohammed; Ahn, Henry; Farhadi, H Francis; Shaffrey, Christopher I; Nassr, Ahmad; Mummaneni, Praveen; Arnold, Paul M; Jacobs, W Bradley; Riew, K Daniel; Kelly, Michael; Brodke, Darrel S; Vaccaro, Alexander R; Hilibrand, Alan S; Wilson, Jason; Harrop, James S; Yoon, S Tim; Kim, Kee D; Fourney, Daryl R; Santaguida, Carlo; Massicotte, Eric M; Kopjar, Branko; Fehlings, Michael GStudy design
Retrospective cohort study of prospectively accrued data.Objective
To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach.Summary of background data
The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data.Methods
Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy.Results
A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches.Conclusion
The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM.Level of evidence
Therapeutic Level-II.Item Open Access Predictors of pulmonary complications in blunt traumatic spinal cord injury.(Journal of neurosurgery. Spine, 2012-09) Aarabi, Bizhan; Harrop, James S; Tator, Charles H; Alexander, Melvin; Dettori, Joseph R; Grossman, Robert G; Fehlings, Michael G; Mirvis, Stuart E; Shanmuganathan, Kathirkamanathan; Zacherl, Katie M; Burau, Keith D; Frankowski, Ralph F; Toups, Elizabeth; Shaffrey, Christopher I; Guest, James D; Harkema, Susan J; Habashi, Nader M; Andrews, Penny; Johnson, Michele M; Rosner, Michael KObject
Pulmonary complications are the most common acute systemic adverse events following spinal cord injury (SCI), and contribute to morbidity, mortality, and increased length of hospital stay (LOS). Identification of factors associated with pulmonary complications would be of value in prevention and acute care management. Predictors of pulmonary complications after SCI and their effect on neurological recovery were prospectively studied between 2005 and 2009 at the 9 hospitals in the North American Clinical Trials Network (NACTN).Methods
The authors sought to address 2 specific aims: 1) define and analyze the predictors of moderate and severe pulmonary complications following SCI; and 2) investigate whether pulmonary complications negatively affected the American Spinal Injury Association (ASIA) Impairment Scale conversion rate of patients with SCI. The NACTN registry of the demographic data, neurological findings, imaging studies, and acute hospitalization duration of patients with SCI was used to analyze the incidence and severity of pulmonary complications in 109 patients with early MR imaging and long-term follow-up (mean 9.5 months). Univariate and Bayesian logistic regression analyses were used to analyze the data.Results
In this study, 86 patients were male, and the mean age was 43 years. The causes of injury were motor vehicle accidents and falls in 80 patients. The SCI segmental level was in the cervical, thoracic, and conus medullaris regions in 87, 14, and 8 patients, respectively. Sixty-four patients were neurologically motor complete at the time of admission. The authors encountered 87 complications in 51 patients: ventilator-dependent respiratory failure (26); pneumonia (25); pleural effusion (17); acute lung injury (6); lobar collapse (4); pneumothorax (4); pulmonary embolism (2); hemothorax (2), and mucus plug (1). Univariate analysis indicated associations between pulmonary complications and younger age, sports injuries, ASIA Impairment Scale grade, ascending neurological level, and lesion length on the MRI studies at admission. Bayesian logistic regression indicated a significant relationship between pulmonary complications and ASIA Impairment Scale Grades A (p = 0.0002) and B (p = 0.04) at admission. Pulmonary complications did not affect long-term conversion of ASIA Impairment Scale grades.Conclusions
The ASIA Impairment Scale grade was the fundamental clinical entity predicting pulmonary complications. Although pulmonary complications significantly increased LOS, they did not increase mortality rates and did not adversely affect the rate of conversion to a better ASIA Impairment Scale grade in patients with SCI. Maximum canal compromise, maximum spinal cord compression, and Acute Physiology and Chronic Health Evaluation-II score had no relationship to pulmonary complications.Item Open Access Progressive Spinal Kyphosis in the Aging Population.(Neurosurgery, 2015-10) Ailon, Tamir; Shaffrey, Christopher I; Lenke, Lawrence G; Harrop, James S; Smith, Justin SThoracic kyphosis tends to increase with age. Hyperkyphosis is defined as excessive curvature of the thoracic spine and may be associated with adverse health effects. Hyperkyphosis in isolation or as a component of degenerative kyphoscoliosis has important implications for the surgical management of adult spinal deformity. Our objective was to review the literature on the epidemiology, etiology, natural history, management, and outcomes of thoracic hyperkyphosis. We performed a narrative review of literature on thoracic hyperkyphosis and its implications for adult spinal deformity surgery. Hyperkyphosis has a prevalence of 20% to 40% and is more common in the geriatric population. The cause is multifactorial and involves an interaction between degenerative changes, vertebral compression fractures, muscular weakness, and altered biomechanics. It may be associated with adverse health consequences including impaired physical function, pain and disability, impaired pulmonary function, and increased mortality. Nonoperative management may slow the progression of kyphosis and improve function. Surgery is rarely performed for isolated hyperkyphosis in the elderly due to the associated risk, but is an option when kyphosis occurs in the context of significant deformity. In this scenario, increased thoracic kyphosis influences selection of fusion levels and overall surgical planning. Kyphosis is common in older individuals and is associated with adverse health effects and increased mortality. Current evidence suggests a role for nonoperative therapies in reducing kyphosis and delaying its progression. Isolated hyperkyphosis in the elderly is rarely treated surgically; however, increased thoracic kyphosis as a component of global spinal deformity has important implications for patient selection and operative planning.