Claire F. Jones, Jae H. T. Lee, Brian K. Kwon and Peter A. Cripton
Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may “cushion” the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.
A custom weight-drop device was used to apply thoracic contusion SCI to 17 Yucatan miniature pigs. Impact load and velocity were measured. Using fiber optic pressure transducers implanted in the thecal sac, CSF pressures resulting from 2 injury severities (caused by 50-g and 100-g weights released from a 50-cm height) were measured.
The median peak impact loads were 54 N and 132 N for the 50-g and 100-g injuries, respectively. At a nominal 100 mm from the injury epicenter, the authors observed a small negative pressure peak (median −4.6 mm Hg [cranial] and −5.8 mm Hg [caudal] for 50 g; −27.6 mm Hg [cranial] and −27.2 mm Hg [caudal] for 100 g) followed by a larger positive pressure peak (median 110.5 mm Hg [cranial] and 77.1 mm Hg [caudal] for 50 g; 88.4 mm Hg [cranial] and 67.2 mm Hg [caudal] for 100 g) relative to the preinjury pressure. There were no significant differences in peak pressure between the 2 injury severities or the caudal and cranial transducer locations.
A new model of contusion SCI was developed to measure spinal CSF pressures during the SCI event. The results suggest that the Yucatan miniature pig is an appropriate model for studying CSF, spinal cord, and dura interactions during injury. With further development and characterization it may be an appropriate in vivo largeanimal model of SCI to answer questions regarding pathological changes, therapeutic safety, or treatment efficacy, particularly where humanlike dimensions and physiology are important.
Marcel F. Dvorak, Michael G. Johnson, Michael Boyd, Garth Johnson, Brian K. Kwon and Charles G. Fisher
Object. The primary goal of this study was to describe the long-term health-related quality of life (HRQOL) outcomes in patients who have suffered Jefferson-type fractures. These outcomes were compared with matched normative HRQOL data and with the patient's perceptions of their HRQOL prior to the injury. Variables that potentially influence these HRQOL outcomes were analyzed.
No standardized outcome assessments have been published for patients who suffer these fractures; their outcomes have long thought to be excellent following treatment. Determining the optimal surrogate measure to represent preinjury HRQOL in trauma patients is difficult.
Methods. A retrospective review, radiographic analysis, and cross-sectional outcome assessment were performed. The Short Form (SF)—36 and the American Academy of Orthopaedic Surgeons/North American Spine Society (AAOS/NASS) outcome instruments were filled out by patients at final follow-up examination (follow-up period 75 months, range 19–198 months) to represent their current status as well as their perceptions of preinjury status.
In 34 patients, the SF-36 physical component score and the AAOS/NASS pain values were significantly lower than normative values. There was no significant difference between normative and preinjury values. Spence criteria greater than 7 mm and the presence of associated injuries predicted poorer outcome scores during the follow-up period.
Conclusions. Long-term follow-up examination of patients with Jefferson fractures indicated that patients' status does not return to the level of their perceived preinjury health status or that of normative population controls. Those with other injuries and significant osseous displacement (≥ 7 mm total) may experience poorer long-term outcomes. Limitations of the study included a relatively low (60%) response rate and the difficulties of identifying an appropriate baseline outcome in a trauma population with which the follow-up outcomes can be compared.
Kenneth C. Thomas, Christopher S. Bailey, Marcel F. Dvorak, Brian Kwon and Charles Fisher
Despite extensive published research on thoracolumbar burst fractures, controversy still surrounds which is the most appropriate treatment. The objective of this study was to evaluate the scientific literature on operative and nonoperative treatment of patients with thoracolumbar burst fractures and no neurological deficit.
In their search of the literature, the authors identified all possible relevant studies concerning thoracolumbar burst fracture without neurological deficit. Two independent observers performed study selection, methodological quality assessment, and data extraction in a blinded and objective manner for all papers identified during the search. In a synthesis of the literature, the authors obtained evidence for both operative and nonoperative treatments.
There is a lack of evidence demonstrating the superiority of one approach over the other as measured using generic and disease-specific health-related quality of life scales. There is no scientific evidence linking posttraumatic kyphosis to clinical outcomes. The authors found that there is a strong need for improved clinical research methodology to be applied to this patient population.
Gregory W. J. Hawryluk, James Rowland, Brian K. Kwon and Michael G. Fehlings
Over the past 2 decades, advances in understanding the pathophysiology of spinal cord injury (SCI) have stimulated the recent emergence of several therapeutic strategies that are being examined in Phase I/II clinical trials. Ten randomized controlled trials examining methylprednisolone sodium succinate, tirilizad mesylate, monosialotetrahexosylganglioside, thyrotropin releasing hormone, gacyclidine, naloxone, and nimodipine have been completed. Although the primary outcomes in these trials were laregely negative, a secondary analysis of the North American Spinal Cord Injury Study II demonstrated that when administered within 8 hours of injury, methylprednisolone sodium succinate was associated with modest clinical benefits, which need to be weighed against potential complications. Thyrotropin releasing hormone (Phase II trial) and monosialotetrahexosylganglioside (Phase II and III trials) also showed some promise, but we are unaware of plans for future trials with these agents. These studies have, however, yielded many insights into the conduct of clinical trials for SCI. Several current or planned clinical trials are exploring interventions such as early surgical decompression (Surgical Treatment of Acute Spinal Cord Injury Study) and electrical field stimulation, neuroprotective strategies such as riluzole and minocycline, the inactivation of myelin inhibition by blocking Nogo and Rho, and the transplantation of various cellular substrates into the injured cord. Unfortunately, some experimental and poorly characterized SCI therapies are being offered outside a formal investigational structure, which will yield findings of limited scientific value and risk harm to patients with SCI who are understandably desperate for any intervention that might improve their function. Taken together, recent advances suggest that optimism for patients and clinicians alike is justified, as there is real hope that several safe and effective therapies for SCI may become available over the next decade.
James W. Rowland, Gregory W. J. Hawryluk, Brian Kwon and Michael G. Fehlings
This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho–associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.
Charles Fisher, Sandeep Singh, Michael Boyd, Stephen Kingwell, Brian Kwon, Meng Jun Li and Marcel Dvorak
The use of pedicle screws (PSs) for stabilization of unstable thoracolumbar fractures has become the standard of care, but PS efficacy has not been reported in the upper thoracic spine. The primary outcome of this study was to determine the efficacy of PS fixation to achieve and maintain reduction of unstable upper thoracic spine fractures (T1–5). Secondary outcomes included scores on a 1-year postoperative generic health-related quality of life (QOL) questionnaire and postoperative complications.
This study was a retrospective analysis and cross-sectional outcome assessment of cases prospectively entered into a spine database from 1997 to 2004. All patients with a traumatic, unstable upper thoracic spine (T1–5) fracture who underwent PS fixation were included. Preoperative CT scans with sagittal plane reformatted images were used to determine kyphotic deformity and compared with immediate postoperative and latest follow-up radiographs or CT scans. Patient charts, operative notes, and the results of postoperative follow-up examinations were reviewed. Patients were mailed the Short Form-36v2 (SF-36 version 2) by an independent study coordinator.
Cases involving 27 patients (23 male, 4 female) were evaluated. The patients' mean age was 39.9 years (range 16–73 years). In all, 251 PSs were passed between T-1 and T-8. The mean true kyphotic deformity was 18.2° preoperatively, 8.7° (p < 0.0005) initially postoperatively, and 10.1° at final follow-up (mean 2.3 years postoperatively). The mean SF-36 physical component summary score was 35.89 while the mental component summary score was 56.43 at a minimum of 1-year postoperatively (mean 3.2 years). There were no intraoperative vascular or neural complications.
In the hands of fellowship-trained spinal surgeons, PS fixation for reduction and stabilization of upper thoracic spine fractures is a safe and efficacious technique. Health-related QOL outcome data are deficient for spine trauma patients and should be an essential component of quantifying treatment outcomes.
John M. Beiner, Jonathan Grauer, Brian K. Kwon and Alexander R. Vaccaro
Postoperative spinal wound infections occur in 1 to 12% of patients. The rate of infection is related to the type and duration of the procedure, comorbidities, nutritional status, and various other risk factors. Antibiotic prophylactic therapy has been clearly shown to decrease the rate of infection dramatically after lumbar surgery. These infections typically manifest with signs and symptoms of wound swelling, erythema, and drainage. Laboratory-detected values such as the erythrocyte sedimentation rate and C-reactive protein can be elevated beyond what is normal for the uncomplicated postoperative course following lumbar surgery, and combined with the clinical symptoms should alert the physician to the possibility of infection. When detected, these infections should be managed aggressively with operative debridment and irrigation, including the deep subfascial layer in all cases except those with clearly demarcated superficial infection. The choice of one versus multiple debridments can be made based on the appearance of the wound, patient factors, and nutritional status. Hardware and incorporated bone graft can be left in place in the majority of cases, adding to stability. Outcomes following aggressive treatment of this complication can be excellent, with no long-term loss of function and complete eradication of the infection.
Brian K. Kwon, Charles G. Fisher, Michael C. Boyd, John Cobb, Hilary Jebson, Vanessa Noonan, Peter Wing and Marcel F. Dvorak
Unilateral facet injuries can be treated with either anterior or posterior fixation techniques with reportedly good outcomes. The two approaches have not been directly compared, however, and consensus is lacking as to which is the optimal method. The primary objective of this study was to determine whether acute postoperative morbidity differed between anteriorly and posteriorly treated patients with unilateral facet injuries.
Forty-two patients were prospectively randomized to undergo either anterior cervical discectomy and fusion or posterior fixation. The primary outcome measure was the postoperative time required to achieve a predefined set of discharge criteria. Secondary outcome measures included postoperative pain, wound infections, radiographically demonstrated fusion and alignment, and patient-reported outcome measures.
The median time to achieve the discharge criteria was 2.75 and 3.5 days for anterior and posterior groups, respectively, a difference that did not reach statistical significance (p = 0.096). Compared with those treated using posterior fixation, anteriorly treated patients exhibited somewhat less postoperative pain, a lower rate of wound infection, a higher rate of radiographically demonstrated union, and better radiographically proven alignment. Nonetheless, the anterior approach was accompanied by a risk of swallowing difficulty in the early postoperative period. Patient-reported outcome measures did not reveal a difference between anterior and posterior fixation procedures.
This prospective randomized controlled trial provided level 1 evidence that both the anterior and posterior fixation approaches appear to be valid treatment options. Although statistical significance was not reached in the primary outcome measure, some secondary outcome measures favored anterior fixation and others favored posterior treatment for unilateral facet injuries.
Brian P. Walcott, Churl-Su Kwon, Sameer A. Sheth, Corey R. Fehnel, Robert M. Koffie, Wael F. Asaad, Brian V. Nahed and Jean-Valery Coumans
Decompressive craniectomy mandates subsequent cranioplasty. Complications of cranioplasty may be independent of the initial craniectomy, or they may be contingent upon the craniectomy. Authors of this study aimed to identify surgery- and patient-specific risk factors related to the development of surgical site infection and other complications following cranioplasty.
A consecutive cohort of patients of all ages and both sexes who had undergone cranioplasty following craniectomy for stroke or trauma at a single institution in the period from May 2004 to May 2012 was retrospectively established. Patients who had undergone craniectomy for infectious lesions or neoplasia were excluded. A logistic regression analysis was performed to model and predict determinants related to infection following cranioplasty.
Two hundred thirty-nine patients met the study criteria. The overall rate of complication following cranioplasty was 23.85% (57 patients). Complications included, predominantly, surgical site infection, hydrocephalus, and new-onset seizures. Logistic regression analysis identified previous reoperation (OR 3.25, 95% CI 1.30–8.11, p = 0.01) and therapeutic indication for stroke (OR 2.45, 95% CI 1.11–5.39, p = 0.03) as significantly associated with the development of cranioplasty infection. Patient age, location of cranioplasty, presence of an intracranial device, bone flap preservation method, cranioplasty material, booking method, and time interval > 90 days between initial craniectomy and cranioplasty were not predictive of the development of cranioplasty infection.
Cranioplasty complications are common. Cranioplasty infection rates are predicted by reoperation following craniectomy and therapeutic indication (stroke). These variables may be associated with patient-centered risk factors that increase cranioplasty infection risk.