Civilian gunshot injuries of the spinal cord: a systematic review of the current literature.

BACKGROUND: The principles that guide management of spinal cord injury (SCI) derive from injury resulting from blunt trauma, not gunshot wounds. Civilian gunshot-induced spinal cord injury (CGSWSCI) is a common, potentially serious cause of neurological deficit; there is disagreement about whether the same approaches used for SCI caused by blunt-force trauma should apply to gunshot-induced SCI. QUESTIONS/PURPOSES: We reviewed the literature to answer the following questions regarding presentation and outcome of gunshot wound-induced SCI: (1) Are there differences in recovery prognosis between complete SCI and other patterns of SCI in CGSWSCI. (2) Does the use of steroids improve neurological recovery? (3) Does surgery to remove the bullet affect neurological recovery in CGSWSCI? (4) Does surgery result in an increased risk of complications of treatment? METHODS: We performed a systematic literature review of articles related to civilian gunshot injuries to the spine. Information relating to incidence, pattern of neurological injury, associated injuries, treatment, neurological outcome, and associated complications was extracted. Three independent reviewers assessed the strength of evidence present in the literature by examining quality, quantity, and consistency of results. RESULTS: A total of 15 articles met the predetermined inclusion criteria. Complete SCIs are associated with the worst functional recovery regardless of treatment. Steroids do not appear to have any added benefit in terms of restoring sensory and motor function. There appears to be some neurologic benefit to surgical decompression with intracanalicular bullet retrieval in patients with an incomplete lesion and a cauda equina syndrome. Complication rates are greater in operated patients. CONCLUSIONS: These findings should be interpreted with caution because of considerable heterogeneity among the studies in the literature on gunshot-induced SCI and because of generally poor-quality study design and a high associated risk of selection bias. Supportive management should be the primary method of care, whereas surgery should be an option in case of radiographic evidence of a static compression on the spinal cord. Future studies are necessary to develop better treatment guidelines for patients with gunshot wound-associated SCI.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Neurophysiological monitoring of spinal cord function during spinal deformity surgery: 2020 SRS neuromonitoring information statement.

The Scoliosis Research Society has developed an updated information statement on intraoperative neurophysiological monitoring of spinal cord function during spinal deformity surgery. The statement reviews the risks of spinal cord compromise associated with spinal deformity surgery; the statement then discusses the various modalities that are available to monitor the spinal cord, including somatosensory-evoked potentials, motor-evoked potentials, and electromyographic (EMG) options. Anesthesia considerations, the importance of a thoughtful team approach to successful monitoring, and the utility of checklists are also discussed. Finally, the statement expresses the opinion that utilization of intraoperative neurophysiological spinal cord monitoring in spinal deformity surgery is the standard of care when the spinal cord is at risk.

Opinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals.

We previously conducted a survey to gather the opinions and perspectives of scientific and clinical researchers on what levels of preclinical evidence were needed to justify translating a promising neuroprotective or neuroregenerative therapy in spinal cord injury (SCI) into a human clinical trial (Kwon et al., 2010 ). Here we conducted an analogous survey of individuals living with SCI in which we gathered their expectations for the levels of preclinical evidence achieved by researchers in substantiating the neuroprotective and neuroregenerative therapies being offered to them in clinical trials. In total, 214 individuals with SCI completed the survey, and their responses were compared to the responses of the 235 scientists and clinicians who completed our previous survey. SCI individuals were more likely than SCI researchers to opine that demonstrating efficacy and safety in rodent models of SCI alone is sufficient to proceed with clinical trials. However, SCI individuals also reported strong support for large animal and primate model studies, and in the case of the latter, were actually more in agreement for the need for primate studies than researchers. SCI individuals also reported strong support for independent replication studies. In general, individuals with SCI had high expectations for the levels of preclinical evidence required to justify translating novel therapies into clinical trials. These expectations should be considered in the decisions to translate specific experimental therapies for SCI.

Expectations of benefit and tolerance to risk of individuals with spinal cord injury regarding potential participation in clinical trials.

We conducted a survey of individuals living with spinal cord injury (SCI) to determine their receptivity to participating in clinical trials of drug therapies or stem cell therapies, their anticipation of therapeutic benefits, and their tolerance to risk. A 46-item questionnaire was administered to individuals with cervical or thoracic SCI identified through a provincial database. The average age was 42 years and the individuals were, on average, 5.5 years post-injury. Receptivity to neuroprotective drug trials in the acute setting was very high, but somewhat less so for stem cell trials in the subacute or chronic (current) setting. With respect to expectation of functional benefit, approximately one third of the respondents indicated that they would want a 5-25% chance of achieving some functional recovery if enrolling in a stem cell therapy clinical trial in the current, chronic injury state. Whereas the majority typically would require the risk of spinal cord damage, cancer, infection, and nerve pain from invasive cell transplantation trials to be ≤1%, 15-30% would participate regardless of the risk of these complications. The factors associated with this high risk tolerance were gender (males>females), age (elderly>young), and self-reported knowledge of SCI research (greater knowledge>less knowledge). Injury severity or chronicity did not have a significant correlation with risk tolerance. Whereas previous studies have shown that the understanding of stem cell science is limited among individuals with SCI, here we show that many still have high hopes for the possibility of neurological benefit, are anxious to participate in invasive stem cell trials, and, in many cases, have high tolerance for risk in such trials. Taken together, the data underscore the need for careful communication with individuals with SCI to avoid unrealistic expectations and therapeutic misconception in experimental trials.

Feasibility of patient recruitment into clinical trials of experimental treatments for acute spinal cord injury.

Clinical trials of experimental neuroprotective and neuroregenerative therapies for acute spinal cord injury (SCI) typically require large numbers of patients to be enrolled. An important factor in designing such trials is the number of patients that can be realistically recruited at a given institution. The total number of patients with acute SCI treated at a neurotrauma centre is typically considered when such a site becomes a recruiting centre for a clinical trial. However, only a fraction of patients may be truly eligible due to the inclusion and exclusion criteria of the trial. This study was conducted to estimate the proportion of patients with acute SCI who would theoretically satisfy basic inclusion criteria for such a hypothetical clinical trial. Using a local prospective database, we reviewed 406 patients with acute traumatic SCI admitted between 2005 and 2009. 259 of 406 patients (64%) presented within 12 hours of injury, 53 patients (13%) between 12 hours and 24 hours, and 30 patients (7%) between 24 hours and 48 hours. Patients were assessed on admission using the American Spinal Injury Association Impairment Scale: category A, 39% of patients; B, 11%; C, 17%; and D, 28%. The number of patients who presented with injuries or other conditions that would likely exclude them from enrolment was 30%. Thus, of a total of 406 patients with SCI admitted over four years, the number who would have been eligible for an acute clinical trial was disappointingly small. This study is the first to quantify this challenging aspect of conducting acute SCI clinical trials, and provides guidance for those planning such initiatives.

Inter-observer and intra-observer agreement in the radiographic diagnosis of avascular necrosis of the femoral head following slipped capital femoral epiphysis.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is a common pediatric hip disorder. Avascular necrosis (AVN) of the femoral head is a devastating complication of SCFE. The frequency of this complication reported in the literature has been variable. It was the objective of this study to estimate the inter- and intra-observer agreement between two experienced pediatric orthopaedic surgeons for the radiographic diagnosis of AVN following SCFE. METHODS: A retrospective review of all cases of SCFE treated at our center between 1995 and 2005 was performed. All cases of AVN and a random sample of 19 of the remaining cases were selected for study. The most recent anteroposterior and lateral radiographs were presented to two experienced pediatric orthopaedic surgeons in a random order. Inter-observer reliability was determined by calculating the kappa statistic to assess for clinical agreement. Each observer repeated this process two weeks after the initial review. RESULTS: There were a total of 103 cases of SCFE, of which four were diagnosed with AVN. The inter-observer agreement in the first trial was 0.79. The intra-observer agreement for the first observer was 0.9 and for the second observer, it was 0.88. CONCLUSION: The agreement, both inter- and intra-observer, for the radiographic diagnosis of AVN amongst adolescents with previous SCFE is very high. The results of this study suggest that the reported discrepancy of AVN in the literature following SCFE is not likely due to the lack of inter- and intra-observer agreement.