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Kevin D. Morrow, Adam G. Podet, Casey P. Spinelli, Lindsay M. Lasseigne, Clifford L. Crutcher II, Jason D. Wilson, Gabriel C. Tender and Anthony M. DiGiorgio

OBJECTIVE

While blunt spinal trauma accounts for the majority of spine trauma, penetrating injuries affect a substantial number of patients. The goal of this study was to examine the epidemiology of penetrating spine injuries compared with blunt injuries and review the operative interventions and outcomes in the penetrating spine injury group.

METHODS

The prospectively maintained trauma database was queried for spinal fractures from 2012 to 2018. Charts from patients with penetrating spine trauma were reviewed.

RESULTS

A total of 1130 patients were evaluated for traumatic spinal fractures; 154 injuries (13.6%) were secondary to penetrating injuries. Patients with penetrating injuries were significantly younger (29.2 years vs 44.1 years, p < 0.001), more likely male (87.7% vs 69.2%, p < 0.001), and more commonly African American (80.5% vs 33.3%, p < 0.05). When comparing primary insurers, the penetrating group had a significantly higher percentage of patients covered by Medicaid (60.4% vs 32.6%, p < 0.05) or prison (3.9% vs 0.1%, p < 0.05) or being uninsured (17.5% vs 10.3%, p < 0.05). The penetrating group had a higher Injury Severity Score on admission (20.2 vs 15.6, p < 0.001) and longer hospital length of stay (20.1 days vs 10.3 days, p < 0.001) and were less likely to be discharged home (51.3% vs 65.1%, p < 0.05). Of the penetrating injuries, 142 (92.2%) were due to firearms. Sixty-three patients (40.9%) with penetrating injuries had a concomitant spinal cord or cauda equina injury. Of those, 44 (69.8%) had an American Spinal Injury Association Impairment Scale (AIS) grade of A. Ten patients (15.9%) improved at least 1 AIS grade, while 2 patients (3.2%) declined at least 1 AIS grade. Nine patients with penetrating injuries underwent neurosurgical intervention: 5 for spinal instability, 4 for compressive lesions with declining neurological examination results, and 2 for infectious concerns, with some patients having multiple indications. Patients undergoing neurosurgical intervention did not show a significantly greater change in AIS grade than those who did not. No patient experienced a complication directly related to neurosurgical intervention.

CONCLUSIONS

Penetrating spinal trauma affects a younger, more publicly funded cohort than blunt spinal trauma. These patients utilize more healthcare resources and are more severely injured. Surgery is undertaken for limiting progression of neurological deficit, stabilization, or infection control.

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Ian F. Pollack, Sameer Agnihotri and Alberto Broniscer

Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. While tumors such as medulloblastomas have been historically grouped into standard- and high-risk categories, it is now recognized that these tumors encompass four or more molecular subsets with distinct clinical and molecular characteristics. Likewise, high-grade glioma, which for decades was considered a single high-risk entity, is now known to comprise multiple subsets of tumors that differ in terms of patient age, tumor location, and prognosis. The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. Accordingly, the present era is one in which treatment is evolving from the historical standard of radiation and conventional chemotherapy to a more nuanced approach in which these modalities are applied in a risk-adapted framework and molecularly targeted therapies are implemented to augment or, in some cases, replace conventional therapy. Herein, the authors review advances in the categorization and treatment of several of the more common pediatric brain tumors and discuss current and future directions in tumor management that hold significant promise for patients with these challenging tumors.

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Saman Shabani, Mayank Kaushal, Matthew Budde and Shekar N. Kurpad

OBJECTIVE

Conventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.

METHODS

A prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1–2, following which C1–2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.

RESULTS

Correlation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1–2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).

CONCLUSIONS

In patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1–2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.

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Shanmukha Srinivas, Arvin R. Wali and Martin H. Pham

OBJECTIVE

Riluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.

METHODS

The PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.

RESULTS

A total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.

CONCLUSIONS

SCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

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Joshua D. Burks, Katie L. Gant, James D. Guest, Aria G. Jamshidi, Efrem M. Cox, Kim D. Anderson, W. Dalton Dietrich, Mary Bartlett Bunge, Barth A. Green, Aisha Khan, Damien D. Pearse, Efrat Saraf-Lavi and Allan D. Levi

OBJECTIVE

In cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors’ institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.

METHODS

The authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.

RESULTS

Imaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).

CONCLUSIONS

While screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

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Joseph P. Antonios, Ghassan J. Farah, Daniel R. Cleary, Joel R. Martin, Joseph D. Ciacci and Martin H. Pham

Spinal cord injury (SCI) has been associated with a dismal prognosis—recovery is not expected, and the most standard interventions have been temporizing measures that do little to mitigate the extent of damage. While advances in surgical and medical techniques have certainly improved this outlook, limitations in functional recovery continue to impede clinically significant improvements. These limitations are dependent on evolving immunological mechanisms that shape the cellular environment at the site of SCI. In this review, we examine these mechanisms, identify relevant cellular components, and discuss emerging treatments in stem cell grafts and adjuvant immunosuppressants that target these pathways. As the field advances, we expect that stem cell grafts and these adjuvant treatments will significantly shift therapeutic approaches to acute SCI with the potential for more promising outcomes.

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Sanjay S. Dhall, Shekar N. Kurpad, R. John Hurlbert and Praveen V. Mummaneni