Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. METHODS: We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods. RESULTS: The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. CONCLUSION: DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

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.

Functional Outcomes After Treatment of Posterior Inferior Cerebellar Artery Aneurysms.

Objective Aneurysms of the posterior inferior cerebellar artery (PICA) are a rare cause of subarachnoid hemorrhage. Treatment for this type of aneurysm may be microsurgical clipping or endovascular. This decision is based on patient characteristics, aneurysm location and dimensions, along with surgeon and institutional experience. In this study we aim to assess the outcomes of surgical and endovascular treatment of PICA aneurysms. Methods We retrospectively reviewed the charts of 52 patients who were admitted to Vancouver General Hospital for ruptured or symptomatic PICA aneurysms between 2005 and 2015. Modified Rankin scores were assigned at the time of discharge and at two subsequent follow-up time points. The mean short-term follow-up period post-operatively was 11.1 months and the mean long-term follow-up period was 19.3 months. Clinical and radiological characteristics were collected for all patients. Results Of the 52 patients, two died prior to obtaining treatment. Of the 50 patients who were treated for their PICA aneurysm, 39 presented with subarachnoid hemorrhage while 11 had symptomatic unruptured PICA aneurysms. Overall, 11 patients had endovascular treatment (coil embolization) while 39 patients underwent microsurgical clipping/trapping of the aneurysm. At the time of hospital discharge, patients in the microsurgical group trended towards a better the modified Rankin Scale score (2.3) compared to the endovascular group, though this did not reach significance (3.0) (p=0.20). The long-term score in the endovascular group (1.6) was also comparable to the microsurgical group (1.9) (p=0.55). Conclusion While the early outcomes in patients treated endovascularly appear better, there is no statistically significant difference in outcomes between the microsurgical and endovascular treatment groups at short- and long-term follow-up.

Evaluation of a virtual reality head mounted display as a tool for posture assessment in digital human modelling software.

The purpose of this work was to assess the feasibility of using a head mounted display with a motion capture system to simulate real world occupational tasks. Participants performed a pointing task under 3 conditions: (1) real environment (REA), (2) virtual environment with auditory stimulus (VEA) and (3) virtual environment with visual stimulus (VEV). End point error, movement time and peak fingertip velocity were calculated for each discrete point event. Upper extremity joint angles were calculated at the end-state for each point and did not significantly differ between real and virtual conditions. There was significantly greater target error in virtual conditions, compared to the real condition. Peak pointing velocity was slower and movement time was longer during virtual conditions. The similarity of joint angles between real and virtual conditions suggests future use of posture-based ergonomic assessments for use with virtual reality task simulations using Oculus Rift and Siemens Jack.

MicroRNA Biomarkers in Cerebrospinal Fluid and Serum Reflect Injury Severity in Human Acute Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment after SCI is measured and classified by a widely accepted standard neurological examination. In the very acute stages post-injury, however, this examination is extremely challenging (and often impossible) to conduct and has modest prognostic value in terms of neurological recovery. The lack of objective tools to classify injury severity and predict outcome is a barrier for clinical trials and thwarts development of therapies for those with SCI. Biological markers (biomarkers) represent a promising, complementary approach to these challenges because they represent an unbiased approach to classify injury severity and predict neurological outcome. Identification of a suitable panel of molecular biomarkers would comprise a fundamental shift in how patients with acute SCI are evaluated, stratified, and treated in clinical trials. MicroRNA are attractive biomarker candidates in neurological disorders for several reasons, including their stability in biological fluids, their conservation between humans and model mammals, and their tissue specificity. In this study, we used next-generation sequencing to identify microRNA associated with injury severity within the cerebrospinal fluid (CSF) and serum of human patients with acute SCI. The CSF and serum samples were obtained 1-5 days post-injury from 39 patients with acute SCI (24 American Spinal Injury Association Impairment Scale [AIS] A, 8 AIS B, 7 AIS C) and from five non-SCI controls. We identified a severity-dependent pattern of change in microRNA expression in CSF and identified a set of microRNA that are diagnostic of baseline AIS classification and prognostic of neurological outcome six months post-injury. The data presented here provide a comprehensive description of the CSF and serum microRNA expression changes that occur after acute human SCI. This data set reveals microRNA candidates that warrant further evaluation as biomarkers of injury severity after SCI and as key regulators in other neurological disorders.

Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury.

Therapeutic development for spinal cord injury is hindered by the difficulty in conducting clinical trials, which to date have relied solely on functional outcome measures for patient enrollment, stratification, and evaluation. Biological biomarkers that accurately classify injury severity and predict neurologic outcome would represent a paradigm shift in the way spinal cord injury clinical trials could be conducted. MicroRNAs have emerged as attractive biomarker candidates due to their stability in biological fluids, their phylogenetic similarities, and their tissue specificity. Here we characterized a porcine model of spinal cord injury using a combined behavioural, histological, and molecular approach. We performed next-generation sequencing on microRNAs in serum samples collected before injury and then at 1, 3, and 5 days post injury. We identified 58, 21, 9, and 7 altered miRNA after severe, moderate, and mild spinal cord injury, and SHAM surgery, respectively. These data were combined with behavioural and histological analysis. Overall miRNA expression at 1 and 3 days post injury strongly correlates with outcome measures at 12 weeks post injury. The data presented here indicate that serum miRNAs are promising candidates as biomarkers for the evaluation of injury severity for spinal cord injury or other forms of traumatic, acute, neurologic injury.