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The neurological sequelae of Bacillus anthracis infection include a rapidly progressive fulminant meningoencephalitis frequently associated with intracranial hemorrhage, including subarachnoid and intracerebral hemorrhage. Higher mortality than other forms of bacterial meningitis suggests that antimicrobials and cardiopulmonary support alone may be insufficient and that strategies targeting the hemorrhage might improve outcomes. In this review, we describe the toxic role of intracranial hemorrhage in anthrax meningoencephalitis. We first examine the high incidence of intracranial hemorrhage in patients with anthrax meningoencephalitis. We then review common diseases that present with intracranial hemorrhage, including aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, postulating applicability of established and potential neurointensive treatments to the multimodal management of hemorrhagic anthrax meningoencephalitis. Finally, we examine the therapeutic potential of minocycline, an antimicrobial that is effective against B. anthracis and that has been shown in preclinical studies to have neuroprotective properties, which thus might be repurposed for this historically fatal disease.

Unruptured cerebral aneurysms are increasingly identified in elderly patients as the global life expectancy continues to rise and non-invasive vascular imaging becomes more prevalent. The optimal management of unruptured aneurysms in elderly patients remains controversial. Variability in life expectancy, comorbidities and rupture risk coupled with heterogenous endovascular and surgical treatments contribute to a paucity of clear guidelines, and current management is highly individualized. Elderly patients present unique considerations including frailty, cognitive dysfunction, vasculopathy, reduced life expectancy and overall worse prognosis in case of rupture which shape the risks and likelihood of success of endovascular and microsurgical treatment. In this review, we provide a comprehensive overview of unruptured cerebral aneurysms in the elderly, with a particular focus on the natural history, key challenges associated with advanced age, management and future innovations to further refine treatment.Key MessagesThe management of unruptured cerebral aneurysms in elderly patients remains controversial.Key challenges including frailty, cognitive dysfunction, reduced life expectancy, vasculopathy and poor prognosis with aneurysm rupture add complexity to endovascular and surgical decision making not encountered with younger demographics.A thorough understanding of available treatment options, likelihood of treatment success and associated risks weighed against the risk of aneurysm rupture informs patient discussion and management.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12–24 h), and 15 underwent decompressive surgery late (> 24–138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862–0.957; p

The development of cerebral edema following traumatic brain injury is one of the most significant predictors of outcome and is associated with high rates of morbidity and mortality. A prominent focus of neurosurgical and neurocritical care is the evaluation and aggressive management of cerebral edema and subsequent intracranial hypertension. Despite numerous advances and capabilities in neurocritical care, treatments remain primarily reactive and are instituted only after secondary pathophysiological pathways have culminated in an intracranial pressure crisis. Recent reviews have focused on several key molecular contributors to post-traumatic cerebral edema and on several potential anti-edema therapeutic targets. The present article provides a contemporary overview of post-traumatic cerebral edema by reviewing important historical concepts, fundamental pathophysiological mechanisms, various causes and key contributors specific to traumatic brain injury, and established treatments of downstream intracranial hypertension.

BackgroundHigh levels of platelet inhibition have been associated with hemorrhagic complications following Pipeline embolization of intracranial aneurysms. We therefore titrate clopidogrel dosing to maintain a moderate level of platelet inhibition using the VerifyNow P2Y12 assay. However, many patients demonstrate dramatic increases in platelet inhibition following treatment despite being on a consistent antiplatelet regimen. We therefore elected to explore the incidence of this phenomenon and possible predisposing factors.MethodsAll successful Pipeline aneurysm treatments performed at our institution from 2011 to 2019 with moderate procedure-day platelet inhibition levels as indicated by a VerifyNow PRU of 60–235 were included. Patients who received glycoprotein IIb/IIIa inhibitors and those treated for ruptured/symptomatic lesions were excluded. The incidence of excessive platelet inhibition defined by a PRUResultsSome 190 treatments were performed in 178 qualifying patients. A post-procedure PRU ConclusionElevations in platelet inhibition were frequently observed following flow diversion with Pipeline.

Objective Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied. Methods A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months. Results A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm2. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87–0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99–1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination. Conclusion The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

Background Context Complex sacral fractures with vertical and anterior pelvic ring instability treated with traditional fixation methods are associated with high rates of failure and poor clinical outcomes. Supplemental lumbopelvic fixation (LPF) has been applied for additional stability to help with fracture union. Purpose The study aimed to determine whether minimally invasive LPF provides reliable fracture stability and acceptable complication rates in cases of complex sacral fractures. Study Design/Setting This is a retrospective cohort study at a single level I trauma center. Patient Sample The sample includes 24 patients who underwent minimally invasive LPF for complex sacral fracture with or without associated pelvic ring injury. Outcome Measures Reoperation for all causes, loss of fixation, surgical time, transfusion requirements, length of hospital stay, postoperative day at mobilization, and mortality were evaluated. Methods Patient charts from 2008 to 2014 were reviewed. Of the 32 patients who underwent minimally invasive LPF for complex sacral fractures, 24 (12 male, 12 female) met all inclusion and exclusion criteria. Outcome measures were assessed with a retrospective chart review and radiographic review. The authors did not receive external funding for this study. Results Acute reoperation was 12%, and elective reoperation was 29%. Two (8%) patients returned to the operating room for infection, one (4.2%) required revision for instrumentation malposition, and seven (29%) underwent elective removal of instrumentation. No patient experienced failure of instrumentation or loss of correction. Average surgical time was 3.6 hours, blood loss was 180 mL, transfusion requirement was 2.1 units of packed red blood cells, and postoperative mobilization was on postoperative day 5. No mortalities occurred as a result of the minimally invasive LPF procedure. Conclusions Compared with historic reports of open LPF, our results demonstrate reliable maintenance of reduction and acceptable complication rates with minimally invasive LPF for complexsacral fractures. The benefits of minimally invasive LPF may be offset with increased elective reoperations for removal of instrumentation.

Study design A retrospective review (2001-2014) was conducted using prospectively collected data at a level I trauma center. Objective We sought to determine the incidence and characteristics of complications occurring secondary to therapeutic anticoagulation in adult spine trauma patients. Summary of background data Numerous studies have assessed prophylactic anticoagulation after spine surgery, but none has investigated the risks of therapeutic doses of anticoagulation for treatment of postoperative thromboembolic events. Methods Patients were included if they sustained a postoperative thromboembolic event (deep venous thrombosis, pulmonary embolism, or myocardial infarction). Patients were excluded if anticoagulation was subtherapeutic. Of 1712 patients, 62 who received therapeutic anticoagulation and 174 propensity-matched control patients who did not receive therapeutic anticoagulation were included in the study. Results Initial anticoagulation was obtained by heparin infusion (51%), low-molecular-weight heparin (LMWH, 46%), and warfarin (3%). Complications requiring unplanned reoperation occurred in 18% of anticoagulated patients and 10% of nonanticoagulated patients (P = 0.17). The reoperation rate after heparin infusion was 31% and after LMWH was 6.5% (P = 0.02). Epidural hematoma occurred in 3% and 1% of anticoagulated and nonanticoagulated patients, respectively. Multivariate logistic regression analysis of the two groups showed a trend toward increased risk of reoperation in the anticoagulation group. Analysis of the heparin infusion subgroup separate from the LMWH subgroup compared with the control group showed an increased risk of reoperation for any complication (odds ratio, 3.57; P = 0.01) and for bleeding complications (odds ratio, 43.1; P = 0.01). Conclusion This is the first study to quantify complications secondary to postoperative therapeutic anticoagulation in spine patients. Postoperative spine trauma patients who underwent therapeutic anticoagulation experienced an unplanned reoperation rate of 18%, including a 3% incidence of spinal epidural hematoma. Therapeutic anticoagulation using heparin infusion seems to drive the overall rate of reoperation (31%) compared with LMWH. Level of evidence 3.

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial KATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

OBJECTIVE Optimal strategies for fixation in the osteoporotic lumbar spine remain a clinical issue. Classic transpedicular fixation in the osteoporotic spine is frequently plagued with construct instability, often due to inadequate cortical screw–bone purchase. A cortical bone trajectory maximizes bony purchase and has been reported to provide increased screw pullout strength. The aim of the current investigation was to evaluate the biomechanical efficacy of cortical spinal fixation as a surgical alternative to transpedicular fixation in the osteoporotic lumbar spine under physiological loading. METHODS Eight fresh-frozen human spinopelvic specimens with low mean bone mineral densities (T score less than or equal to –2.5) underwent initial destabilization, consisting of laminectomy and bilateral facetectomies (L2–3 and L4–5), followed by pedicle or cortical reconstructions randomized between levels. The surgical constructs then underwent fatigue testing followed by tensile load to failure pullout testing to quantify screw pullout force. RESULTS When stratifying the pullout data with fixation technique and operative vertebral level, cortical screw fixation exhibited a marked increase in mean load at failure in the lower vertebral segments (p = 0.188, 625.6 ± 233.4 N vs 450.7 ± 204.3 N at L-4 and p = 0.219, 640.9 ± 207.4 N vs 519.3 ± 132.1 N at L-5) while transpedicular screw fixation demonstrated higher failure loads in the superior vertebral elements (p = 0.024, 783.0 ± 516.1 N vs 338.4 ± 168.2 N at L-2 and p = 0.220, 723.0 ± 492.9 N vs 469.8 ± 252.0 N at L-3). Although smaller in diameter and length, cortical fixation resulted in failures that were not significantly different from larger pedicle screws (p > 0.05, 449.4 ± 265.3 N and 541.2 ± 135.1 N vs 616.0 ± 384.5 N and 484.0 ± 137.1 N, respectively). CONCLUSIONS Cortical screw fixation exhibits a marked increase in mean load at failure in the lower vertebral segments and may offer a viable alternative to traditional pedicle screw fixation, particularly for stabilization of lower lumbar vertebral elements with definitive osteoporosis.

First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.