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BACKGROUND Decompressive hemicraniectomy (DHC) is well established as an effective life-saving intervention. Although literature documents a correlation between mortality and hemicraniectomy flap size, no literature exists demonstrating whether a larger flap may be achieved with 3-pin fixation devices versus nonfixed positioning (e.g., occipital headrest, gel donut). Therefore, positioning for DHC remains the preference of the institution and attending physician. METHODS Patients undergoing DHC during 2005-2016 were identified using Current Procedural Terminology codes. Inclusion criteria were: operative note available in the electronic medical record and postoperative head computed tomography (hCT). Exclusion criteria were: age

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Background Idiopathic spinal cord herniation (ISCH) is a rare pathology characterized by extravasation of the spinal cord through a dural defect. The optimal algorithm for choosing operative or nonoperative management is not well elucidated, partially because of the rarity of this pathology. We present the largest single-center series of ISCH and compare operative treatment to conservative management. Methods A retrospective case series of all patients evaluated for treatment of ISCH at our institution between 2010 and 2019 was conducted. Demographic variables, presenting symptoms, and imaging characteristics were assessed for all patients. For patients who underwent operative treatment, surgical approach, postoperative course, and discharge outcomes were recorded. Follow-up notes were reviewed for status of symptoms and functional capabilities, which were synthesized into Odom’s criteria score. Results Sixteen patients met the inclusion criteria for this study, 8 of whom underwent operative treatment. No significant differences were found between operative and nonoperative groups with regard to demographic variables or pathology characteristics. Odom’s criteria scores for the operative cohort were 12.5% (1 of 8) Excellent, 62.5% (5 of 8) Good, 12.5% (1 of 8) Fair, and 12.5% (1 of 8) Poor. Odom’s criteria scores for the nonoperative cohort were 16.7% (1 of 6) Excellent, 33.3% (2 of 6) Good, 16.7% (1 of 6) Fair, and 33.3% (2 of 6) Poor. There was no significant difference between Odom’s criteria score distribution between the operative and nonoperative groups at latest follow up (P = 0.715). Conclusions Conservative management of spinal cord herniation is an option that does not preclude symptomatic improvement in patients with idiopathic spinal cord herniation.

INTRODUCTION: Cervical spontaneous epidural hematoma is a serious neurosurgical pathology that often requires prompt surgical intervention. While a variety of causes may contribute, the authors present the first case in the literature of cervical disc extrusion provoking epidural hemorrhage and acute neurological deterioration. CASE PRESENTATION: A 65 year old male presented with six months of worsening signs and symptoms of cervical myelopathy. He had progressive deterioration over the course of two weeks leading to ambulatory dysfunction requiring a cane for assistance. While undergoing his medical workup in the emergency department, the patient became acutely plegic in the right lower extremity prompting emergent surgical decompression and stabilization. DISCUSSION: Based on imaging, pathology, and intraoperative findings, it was concluded that the patient had an extruded disc segment that may have precipitated venous bleeding in the epidural space and findings of acute cervical cord compression. Cervical disc extrusion may lead to venous damage, epidural hematoma, and spinal cord compression. If this unique presentation is recognized and addressed in a timely manner, patient outcomes may still be largely positive as this case demonstrates.

IMPORTANCE: Pneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness. OBJECTIVE: To evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab. DESIGN, SETTING, PARTICIPANTS: Retrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab. EXPOSURES: Confirmed COVID-19 pneumonia. MAIN OUTCOMES AND MEASURES: Outcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed. RESULTS: The average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p

Severe traumatic brain injury (TBI) remains a major cause of morbidity and mortality with mortality rates reaching 35%. Intracranial pressure (ICP) monitoring is used to prevent secondary brain injury and death. However, while the association of elevated ICP and worsened outcomes is accepted, routine ICP monitoring has been questioned after the publication of several studies including the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure trial. We examined whether severe TBI patients in the trauma system of Pennsylvania fared better with or without ICP monitoring.We conducted a statewide retrospective analysis and included all TBI patients18 years with an admission Glasgow Coma Scale (GCS)9 from January 2000 through December 2017. The primary outcome was mortality. Secondary outcomes examined were intensive care unit length of stay (LOS) and discharge functional independence measure (FIM).A total of 36,929 patients matched our inclusion criteria and were included in the analysis. Of those, 6025 (16.3%) had ICP monitor placement. Mean ICU LOS was significantly higher in ICP-monitored patients (13.1 ± 11.6 days vs. 6.0 ± 10.8 days, P0.0001). Increasing age was a significant predictor of death (P0.0001). Mean FIM scores at discharge were significantly higher in patients without an ICP monitor (16.21 ± 4.91 vs. 9.53 ± 5.07, P0.0001). When controlling for injury severity score, GCS, age, and craniotomy, ICP monitoring conferred a hazard ratio of 0.85 (χWe found that ICP-monitored patients had a lower risk of in-hospital mortality. Our findings support the use of ICP monitors in eligible patients.

The utilization of robotics has been gaining increased popularity in spine surgery. It can be used to assist in pedicle screw insertion when anatomy is complex in deformity surgery, but is also helpful in degenerative spine as it can minimize tissue dissection and fluoroscopy use.1-6 We present an operative video that demonstrates the use of a robotic system (Globus Excelsius GPS, Audubon, Pennsylvania) for thoracic instrumentation in an unstable fracture. The patient we present is a 64-yr-old male who sustained a T8-9 distraction extension fracture after falling down a flight of stairs. His computed tomography (CT) scan showed ossification of the anterior longitudinal ligament making ankylosing spondylitis the likely underlying condition.7,8 His magnetic resonance imaging showed an epidural hematoma extending from T7 to T11. Due to the unstable nature of this fracture and the presence of the hematoma, informed consent was obtained and the patient underwent thoracic pedicle screw fixation from T7 to T11 and laminectomy for hematoma evacuation. A preoperative CT was done for screw trajectory planning. Paraspinal muscle dissection was limited to the hematoma level to allow for laminectomy and evacuation. After registration of the patient to the robotic system using C-arm fluoroscopy, pilot burr holes are drilled using a rigid robotic arm and with optical tracking in real time. This reduces the degrees of freedom and allows for higher precision of screw placement. To the authors' knowledge, this video is the first one to show the utilization of robotics for thoracic instrumentation in an acute fracture.

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.]

BACKGROUND Traumatic brain injury (TBI) carries a devastatingly high rate of morbidity and mortality. OBJECTIVE To assess whether patients undergoing craniotomy/craniectomy for severe TBI fare better at level I than level II trauma centers in a mature trauma system. METHODS The data were extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients > 18 yr with severe TBI (Glasgow Coma Scale [GCS] score less than 9) undergoing craniotomy or craniectomy in the state of Pennsylvania from January 1, 2002 through September 30, 2017. RESULTS Of 3980 patients, 2568 (64.5%) were treated at level I trauma centers and 1412 (35.5%) at level II centers. Baseline characteristics were similar between the 2 groups except for significantly worse GCS scores at admission in level I centers (P = .002). The rate of in-hospital mortality was 37.6% in level I centers vs 40.4% in level II centers (P = .08). Mean Functional Independence Measure (FIM) scores at discharge were significantly higher in level I (10.9 ± 5.5) than level II centers (9.8 ± 5.3; P

Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication.To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature.Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software.Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis.Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to60 trial sites.

A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study.Randomized prospective clinical trial.Ten ICUs in the United States.One hundred nineteen severe traumatic brain injury patients.Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended.A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy.Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.

Summary Background Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. Funding National Institute of Neurological Disorders and Stroke.

Background Prior studies published in the cardiothoracic, orthopedic and gastrointestinal surgery have identified the importance of nasal (methicillin-resistant Staphylococcus aureus) MRSA screening and subsequent decolonization to reduce MRSA surgical site infection (SSI). This is the first study to date correlating nasal MRSA colonization with postoperative spinal MRSA SSI. Objective To assess the significance of nasal MRSA colonization in the setting of MRSA SSI. Methods A retrospective electronic chart review of patients from year 2011 to June 2013 was conducted for patients with both nasal MRSA colonization within 30 days prior to spinal surgery. Patients who tested positive for MRSA were put on contact isolation protocol. None of these patients received topical antibiotics for decolonization of nasal MRSA. Results A total of 519 patients were identified; 384 negative (74%), 110 MSSA-positive (21.2%), and 25 (4.8%) MRSA-positive. Culture positive surgical site infection (SSI) was identified in 27 (5.2%) cases and was higher in MRSA-positive group than in MRSA-negative and MSSA-positive groups (12% vs. 5.73% vs. 1.82%; p = 0.01). The MRSA SSI rate was 0.96% (n = 5). MRSA SSI developed in 8% of the MRSA-positive group as compared to only in 0.61% of MRSA-negative group, with a calculated odds ratio of 14.23 (p = 0.02). In the presence of SSI, nasal MRSA colonization was associated with MRSA-positive wound culture (66.67 vs. 12.5%; p Conclusion Preoperative nasal MRSA colonization is associated with postoperative spinal MRSA SSI. Preoperative screening and subsequent decolonization using topical antibiotics may help in decreasing the incidence of MRSA SSI after spine surgery. Nasal MRSA+ patients undergoing spinal surgery should be informed regarding their increased risk of developing surgical site infection.

We aimed to assess the efficacy of intraoperative vancomycin powder in intrathecal baclofen pump placement patients, a high risk population. A retrospective review was conducted using prospectively collected data at an academic tertiary care unit. The neurosurgical adult patient population was queried for all intrathecal baclofen pump implantation procedures. Patients were then reviewed for the use of intraoperative crystalline vancomycin powder. Those with a history of prior surgical site infection, chronic systemic infections or osteomyelitis were excluded. Anhydrous, crystalline vancomycin was utilized in the wound bed after completion of implantation, distributed evenly in the case of multiple incisions. Patients received 500 mg or 1000 mg of crystallized vancomycin, evenly distributed through the wound layers based on a 70 kg weight cutoff. Intraoperative institutional standards of infection prophylaxis were unchanged throughout the study period. Infection rate of baclofen pump placement prior to the use of vancomycin powder from 2001–2009 at the same institution was monitored. Wound infection rate was tracked for a 12 month postoperative period. Six patients out of 26 baclofen pump implantations (23%) in this cohort were identified to have seven infections despite vancomycin powder placement in the lumbar and catheter wounds. Prior infection rates have been investigated for intrathecal drug delivery systems from 2001 to 2009 at the same institution with an overall infection rate of 3% (8/274). The use of vancomycin powder in patients with implants in this series did not reduce infection rates compared to published historical controls, and was elevated compared to institutional controls. Further prospective study of this high risk patient population is warranted.

The reported incidence of concurrent traumatic brain (TBI) and spine or spinal cord injuries (SCI) is poorly defined, with widely variable literature rates from 16 to 74%.To define the incidence of concurrent TBI and SCI, and compare the incidence over a twenty-year time period.To define the longitudinal incidence and concurrent rate of TBI and SCI via a retrospective review of the Nationwide Inpatient Sample (NIS) database over a twenty year period.Over the study period, the incidence of TBI declined from 143 patients/100k admissions to 95 patients/100k. However, there was a concurrent increase in SCI from 61 patients/100k admissions to 75 patients/100k admissions (P0.0001). Regional variations in SCI trends were noted, with specific regions demonstrating an increasing trend. Cervical fractures had the greatest increase by nearly a three-fold rise (1988: 4562-2008: 12,418). There was an increase in the incidence of TBI among SCI admission from 3.7% (1988) to 12.5% (2008) (OR=1.067 per year; 95% CI=1.065-1.069 per year; P0.0001). Concurrently, SCI patients had an increase in TBI (9.1% (1988)-15.9% (2008) (OR=1.038 per year (95% CI 1.036-1.040; P0.001))).A retrospective review of the NIS demonstrates a rising trend in the incidence of concurrent TBI and SCI. More investigative work is necessary to examine causative factors for this trend.

Objective:To study factors associated with permanent CSF diversion and the relationship between shunting and functional outcomes in spontaneous intraventricular hemorrhage (IVH).Methods:Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III), a randomized, multicenter, double-blind, placebo-controlled trial, was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular alteplase improved outcome, in comparison to EVD plus saline. Outcome measures were predictors of shunting and blinded assessment of mortality and modified Rankin Scale at 180 days.Results:Among the 500 patients with IVH, CSF shunting was performed in 90 (18%) patients at a median of 18 (interquartile range [IQR] 13–30) days. Patient demographics and IVH characteristics were similar among patients with and without shunts. In the multivariate analysis, black race (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.18–3.34), duration of EVD (OR 1.10; CI 1.05–1.15), placement of more than one EVD (OR 1.93; CI 1.13–3.31), daily drainage CSF per 10 mL (OR 1.07; CI 1.04–1.10), and intracranial pressure >30 mm Hg (OR 1.70; CI 1.09–2.88) were associated with higher odds of permanent CSF shunting. Patients who had CSF shunts had similar odds of 180-day mortality, while survivors with shunts had increased odds of poor functional outcome, compared to survivors without shunts.Conclusions:Among patients with spontaneous IVH requiring emergency CSF diversion, those with early elevated intracranial pressure, high CSF output, and placement of more than one EVD are at increased odds of permanent ventricular shunting. Administration of intraventricular alteplase, early radiographic findings, and CSF measures were not useful predictors of permanent CSF diversion.

OBJECTIVE To determine the prevalence of status epilepticus, associated factors, and relationship with in-hospital mortality in primary admissions of septic patients in the United States. DESIGN Cross-sectional study. SETTING Primary admissions of adult patients more than 18 years old with a diagnosis of sepsis and status epilepticus from 1988 to 2008 identified through the Nationwide Inpatient Sample. PARTICIPANTS A total of 7,669,125 primary admissions of patients with sepsis. INTERVENTIONS None. RESULTS During the 21-year study period, the prevalence of status epilepticus in primary admissions of septic patients increased from 0.1% in 1988 to 0.2% in 2008 (p < 0.001). Status epilepticus was also more common among later years, younger admissions, female gender, Black race, rural hospital admissions, and in those patients with organ dysfunctions. Mortality of primary sepsis admissions decreased from 20% in 1988 to 18% in 2008 (p < 0.001). Mortality in status epilepticus during sepsis decreased from 43% in 1988 to 28% in 2008. In-hospital mortality after admissions for sepsis was associated with status epilepticus, older age, and Black and Native American/Eskimo race; patients admitted to a rural or urban private hospitals; and patients with organ dysfunctions. CONCLUSION Our analysis demonstrates that status epilepticus after admission for sepsis in the United States was rare. Despite an overall significant reduction in mortality after admission for sepsis, status epilepticus carried a higher risk of death. More aggressive electrophysiological monitoring and a high level of suspicion for the diagnosis of status epilepticus may be indicated in those patients with central nervous system organ dysfunction after sepsis.

Purpose: To determine the epidemiology of the acute respiratory distress syndrome (ARDS) and impact on in-hospital mortality in admissions of patients with acute ischemic stroke (AIS) in the United States. Methods: Retrospective cohort study of admissions with a diagnosis of AIS and ARDS from 1994 to 2008 identified through the Nationwide Inpatient Sample. Results: During the 15-year study period, we found 55 58 091 admissions of patients with AIS. The prevalence of ARDS in admissions of patients with AIS increased from 3% in 1994 to 4% in 2008 ( P < .001). The ARDS was more common among younger men, nonwhites, and associated with history of congestive heart failure, hypertension, chronic obstructive pulmonary disease, renal failure, chronic liver disease, systemic tissue plasminogen activator, craniotomy, angioplasty or stent, sepsis, and multiorgan failures. Mortality due to AIS and ARDS decreased from 8% in 1994 to 6% in 2008 ( P < .001) and 55% in 1994 to 45% in 2008 ( P < .001), respectively. The ARDS in AIS increased in-hospital mortality (odds ratio, 14; 95% confidence interval, 13.5-14.3). A significantly higher length of stay was seen in admissions of patients with AIS having ARDS. Conclusion: Our analysis demonstrates that ARDS is rare after AIS. Despite an overall significant reduction in mortality after AIS, ARDS carries a higher risk of death in this patient population.

Retrospective Nationwide Inpatient Sample (NIS) study.To determine national trends in prevalence, risk factors and mortality for vertebral column fracture (VCF) and spinal cord injury (SCI) patients with and without acute respiratory distress syndrome/acute lung injury (ARDS/ALI).United States of America, 1988 to 2008.The NIS was utilized to select 284 612 admissions for VCF with and without acute SCI from 1988 to 2008 based on ICD-9-CM. The data were stratified for in-hospital complications of ARDS/ALI.Patients with SCI were more likely to develop ARDS/ALI compared with those without (odds ratio (OR): 4.9, 95% confidence interval (CI) 4.7-5.2, P0.001). Compared with patients with lumbar fractures, those with cervical, thoracic and sacral fractures were more likely to develop ARDS/ALI (P0.001). ARDS/ALI was statistically more prevalent (P0.01) in VCF/SCI patients with epilepsy, sepsis, cardiac arrest, congestive heart failure (CHF), hypertension, chronic obstructive pulmonary disease and metabolic disorders. Patients with female gender, surgery at rural practice setting, and coronary artery disease and diabetes were less likely to develop ARDS/ALI (P0.001). VCF/SCI patients who developed ARDS/ALI were more likely to die in-hospital than those without ARDS/ALI (OR 6.5, 95% CI 6.0-7.1, P0.001). Predictors of in-hospital mortality after VCF/SCI include: older age, male sex, epilepsy, sepsis, hypertension, CHF, chronic obstructive pulmonary disease and liver disease. Patients who developed ARDS/ALI stayed a mean of 25 hospital days (30-440 days) while patients without ARDS/ALI stayed a mean of 6 days (7-868 days, P0.001).Our analysis demonstrates that SCI patients are more at risk for ARDS/ALI, which carries a significantly higher risk of mortality.

OBJECTIVES:Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS:A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging. METHODS:Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. MEASURES:Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS:Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment. CONCLUSIONS:Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI.

Background and Purpose— Intracerebral hemorrhage (ICH) is a devastating disease without a proven therapy to improve long-term outcome. Considerable controversy about the role of surgery remains. Minimally invasive endoscopic surgery for ICH offers the potential of improved neurological outcome. Methods— We tested the hypothesis that intraoperative computerized tomographic image–guided endoscopic surgery is safe and effectively removes the majority of the hematoma rapidly. A prospective randomized controlled study was performed on 20 subjects (14 surgical and 4 medical) with primary ICH of >20 mL volume within 48 hours of ICH onset. We prospectively used a contemporaneous medical control cohort (n=36) from the MISTIE trial (Minimally Invasive Surgery and r-tPA for ICH Evacuation). We evaluated surgical safety and neurological outcomes at 6 months and 1 year. Results— The intraoperative computerized tomographic image–guided endoscopic surgery procedure resulted in immediate reduction of hemorrhagic volume by 68±21.6% (interquartile range 59–84.5) within 29 hours of hemorrhage onset. Surgery was successfully completed in all cases, with a mean operative time of 1.9 hours (interquartile range 1.5–2.2 hours). One surgically related bleed occurred peri-operatively, but no patient met surgical safety stopping threshold end points for intraoperative hemorrhage, infection, or death. The surgical intervention group had a greater percentage of patients with good neurological outcome (modified Rankin scale score 0–3) at 180 and 365 days as compared with medical control subjects (42.9% versus 23.7%; P =0.19). Conclusions— Early computerized tomographic image–guided endoscopic surgery is a safe and effective method to remove acute intracerebral hematomas, with a potential to enhance neurological recovery. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00224770.

OBJECTIVE The aim in this paper was to evaluate the efficacy of long-acting liposomal bupivacaine in comparison with bupivacaine hydrochloride for lowering postoperative analgesic usage in the management of posterior cervical and lumbar decompression and fusion. METHODS A retrospective cohort-matched chart review of 531 consecutive cases over 17 months (October 2013 to February 2015) for posterior cervical and lumbar spinal surgery procedures performed by a single surgeon (J.J.) was performed. Inclusion criteria for the analysis were limited to those patients who received posterior approach decompression and fusion for cervical or lumbar spondylolisthesis and/or stenosis. Patients from October 1, 2013, through December 31, 2013, received periincisional injections of bupivacaine hydrochloride, whereas after January 1, 2014, liposomal bupivacaine was solely administered to all patients undergoing posterior approach cervical and lumbar spinal surgery through the duration of treatment. Patients were separated into 2 groups for further analysis: posterior cervical and posterior lumbar spinal surgery. RESULTS One hundred sixteen patients were identified: 52 in the cervical cohort and 64 in the lumbar cohort. For both cervical and lumbar cases, patients who received bupivacaine hydrochloride required approximately twice the adjusted morphine milligram equivalent (MME) per day in comparison with the liposomal bupivacaine groups (5.7 vs 2.7 MME, p = 0.27 [cervical] and 17.3 vs 7.1 MME, p = 0.30 [lumbar]). The amounts of intravenous rescue analgesic requirements were greater for bupivacaine hydrochloride in comparison with liposomal bupivacaine in both the cervical (1.0 vs 0.39 MME, p = 0.31) and lumbar (1.0 vs 0.37 MME, p = 0.08) cohorts as well. None of these differences was found to be statistically significant. There were also no significant differences in lengths of stay, complication rates, or infection rates. A subgroup analysis of both cohorts of opiate-naive versus opiate-dependent patients found that those patients who were naive had no difference in opiate requirements. In chronic opiate users, there was a trend toward higher opiate requirements for the bupivacaine hydrochloride group than for the liposomal bupivacaine group; however, this trend did not achieve statistical significance. CONCLUSIONS Liposomal bupivacaine did not appear to significantly decrease perioperative narcotic use or length of hospitalization, although there was a trend toward decreased narcotic use in comparison with bupivacaine hydrochloride. While the results of this study do not support the routine use of liposomal bupivacaine, there may be a benefit in the subgroup of patients who are chronic opiate users. Future prospective randomized controlled trials, ideally with dose-response parameters, must be performed to fully explore the efficacy of liposomal bupivacaine, as the prior literature suggests that clinically relevant effects require a minimum tissue concentration.

Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is a significant cause of morbidity due to poor wound healing and infection, meningitis, and pseudomeningocele formation. Many common dural closure techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and fibrin glues, are used to achieve watertight closure, although none are US Food and Drug Administration approved for this use. DuraSeal Dural Sealant System is a polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug Administration for obtaining watertight dural closure when applied after standard dural suturing. This multicenter, prospective randomized study further evaluated the safety of a PEG hydrogel compared with common dural sealing techniques.A total of 237 patients undergoing elective cranial surgery at 17 institutions were randomized to dural closure augmented with the PEG hydrogel or a control "standard of care" dural sealing technique after Valsalva maneuver demonstrated an intraoperative nonwatertight dural closure. Data were collected on complications resulting in unplanned postoperative interventions or reoperations, surgical site infections, CSF leaks, and other neurological complications within 30 days. Surgeons also provided data on the ease of use of the dural sealing techniques, as well as preparation and application times.The incidences of neurosurgical complications, surgical site infections, and CSF leaks were similar between treatment and control groups, with no statistically significant difference between the measures. In the PEG hydrogel group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7), the incidence of surgical site infections was 1.7% (n = 2), and the incidence of CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of neurosurgical complications was 7.7% (n = 9), the incidence of surgical site infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2). Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel group compared with 66.4% of controls (P

After traumatic brain injury (TBI), inflammation participates in both the secondary injury cascades and the repair of the CNS, both of which are influenced by the endocannabinoid system. This study determined the effects of repeated treatment with a cannabinoid type 2 receptor (CB(2) R) agonist on blood-brain barrier integrity, neuronal degeneration, and behavioral outcome in mice with TBI. We also looked for the presence of a prolonged treatment effect on the macrophage/microglial response to injury. C57BL/6 mice underwent controlled cortical impact (CCI) and received repeated treatments with a CB(2) R agonist, 0-1966, or vehicle. After euthanasia at 6 hr or 1, 2, 3, or 7 days postinjury, brains were removed for histochemical analysis. Blood-brain barrier permeability changes were evaluated by using sodium fluorescein (NaF). Perilesional degenerating neurons, injury volumes, and macrophage/microglia cells were quantified by stereological methods. Rota-rod and open-field testing were performed to evaluate motor function and natural exploratory behavior in mice. 0-1966 Treatment resulted in a significant reduction in NaF uptake and number of degenerating neurons compared with the vehicle-treated group. 0-1966-Treated mice demonstrated improvement on rota-rod and open-field testing compared with vehicle-treated mice. These changes in CCI mice treated with 0-1966 were associated with a prolonged reduction in macrophage/microglia cell counts. In conclusion, repeated treatments with a CB(2) R agonist, 0-1966, result in attenuated blood-brain barrier disruption and neuronal degeneration. In addition, repeated treatment with 0-1966 shows prolonged treatment effects on behavior and the macrophage/microglia cell response over several days. © 2012 Wiley Periodicals, Inc. Language: en

Objective To compare outcomes in the setting of spontaneous intracerebral hemorrhage (ICH) in patients taking aspirin (acetylsalicylic acid [ASA]) versus patients taking clopidogrel before hospitalization. Methods Patients admitted to the neurosurgical service with a spontaneous ICH while taking an antiplatelet agent were prospectively identified and retrospectively reviewed. Two groups of 28 consecutive patients taking ASA or clopidogrel on admission were ultimately evaluated. Results Patients in the clopidogrel group had a mean age of 72.6 years, and patients in the ASA group had a mean age of 65.8 years ( P = 0.04). Patients taking clopidogrel before hospitalization were significantly more likely than patients taking ASA to experience an increase in hematoma volume ( P = 0.05). Patients in the ASA group trended toward being discharged to home more frequently than other destinations ( P = 0.07). The in-hospital mortality rates in this series were 14.3% for the ASA group and 28.6% for the clopidogrel group. However, this association did not reach statistical significance ( P = 0.19). Conclusions In this study, patients taking clopidogrel showed more hematoma expansion, higher in-hospital mortality rates, and a decreased likelihood of a home discharge compared with patients taking ASA alone.

Object: Neurostimulation is widely accepted for the treatment of refractory Parkinson's disease, essential tremor, and chronic pain. The presence of a cardiovascular implantable electronic device (CIED) might be considered a contraindication for neurostimulators due to the possible interaction between the two devices. The purpose of this study is to report the feasibility and safety of concomitant use of neurostimulators and CIED, and to review surgical and clinical precautions needed to avoid possible interference between the two systems. Methods: A retrospective institutional review board approved chart review of six patients having both a neurostimulator(s) and a CIED was performed. Diagnosis included Parkinson's disease (two) and intractable pain (four). All implantable cardiac devices were set on bipolar sensing mode and bipolar stimulation was chosen for the neurostimulators. In general, both systems were implanted at sites seven inches apart. Electrocardiogram monitoring was observed throughout implantation. Patients were followed up for a mean period of 31.7 months (ranging from 14 to 67 months). An extensive chart review was done and cases from previous reports were compiled. Results: In all six patients, no acute events occurred during surgery with no interaction or interference noted during implantation of the second device. Subsequent follow-up visits continued to exhibit a lack of interference between the two systems, including normal electrocardiogram studies. Both systems were noted to function at optimal levels. An extensive literature review revealed 57 unique cases previously published reporting the simultaneous use of neurostimulators and a CIED in the same patient. A table summarizing previously cited cases from the literature is provided. Conclusion: The concomitant use of neurostimulator(s) and permanent pacemaker(s) can be safely performed. Permanent pacemaker should not be considered a general contraindication for neurostimulation therapy. Current literature lacks evidence to determine the safety of concomitant use of neurostimulator(s) and implantable cardioverter defibrillator(s).

Hypertonic saline is currently being used in the treatment of patients with post-traumatic cerebral edema and elevated intracranial pressure resulting from TBI. A limited number of studies show the cellular effects of hypertonic saline and no studies, to our knowledge, have investigated the effects on astrocytes. The role of astrocyte responses after traumatic brain injury remains unclear. There is evidence that reduced astrocyte proliferation is detrimental while increased hypertrophy and proliferation are signs of increased injury severity. Therefore, this study focused on the hypothesis that hypertonic saline-induced improvements in histological outcome are time dependent and may be associated with alterations in astrocyte hypertrophy after cortical contusion injury. Histopathological changes at 7 days after controlled cortical impact (CCI) injury were examined. Brain tissue loss determined using cresyl violet staining and astrocyte hypertrophy and proliferation were assessed using glial fibrillary acidic protein immunostaining in hypertonic saline and normal saline treated rats, and untreated, injured controls. Effects of the timing of hypertonic saline treatment administration on tissue loss were also examined. Plasma osmolarity and sodium levels were measured over 4 h and again at 24 h following hypertonic saline administration. Results show that hypertonic saline treatment reduced tissue loss that correlated with attenuated astrocyte hypertrophy characterized by reductions in astrocyte immunoreactivity without changes in the number of astrocytes after CCI injury. Delayed treatment of hypertonic saline resulted in the greatest reduction in tissue loss compared to all other treatments indicating that there is a therapeutic window for hypertonic saline use after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.

Cannabinoid CB2Receptor (CB2) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB2agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB2agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB2agonists significantly decreased cerebral infarction (30%) and improved motor function ( P < 0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles ( P < 0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB2agonists administered either at 1 h before or after MCAO ( P < 0.05). CB2activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.

Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized.Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score3. ATC was defined as INR 1.3, PTT 38 s, or platelets 100 K, determined at baseline, and during the first 7 days of hospitalization.Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS 8, compared with 11.3 % of non-ATC patients (p 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score 6), and the DRS (i.e., score 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days.ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days.

Syringomyelia is a potentially debilitating disease that involves abnormal CSF flow mechanics; its incidence after traumatic spinal cord injury (SCI) is approximately 15%. Treatment consists of restoration of CSF flow, typically via arachnoidolysis and syrinx decompression. The authors present a case of pronounced syringomyelia in a patient with concomitant severe cervical myelomalacia to demonstrate unilateral C-5 palsy as a potential complication of aggressive syrinx decompression at a remote level. A 56-year-old man with a remote history of SCI at T-11 (ASIA [American Spinal Injury Association] Grade A) presented with complaints of ascending motor and sensory weakness into the bilateral upper extremities that had progressed over 1 year. MRI demonstrated severe distortion of the spinal cord at the prior injury level of T10–11, where an old anterior column injury and prior hook-rod construct was visualized. Of note, the patient had a holocord syrinx with demonstrable myelomalacia. To restore CSF flow and decompress the spinal cord, T-2 and T-3 laminectomies, followed by arachnoidolysis and syringopleural shunt placement, were performed. Postoperatively on Day 1, with the exception of a unilateral deltoid palsy, the patient had immediate improvement in upper-extremity strength and myelopathy. He was discharged from the hospital on postoperative Day 5; however, at his 2-week follow-up visit, a persistent unilateral deltoid palsy was noted. MRI demonstrated a significant reduction in the holocord syrinx, no neural foraminal stenosis, and a significant positional shift of the ventral spinal cord. Further motor recovery was noted at the 8-month follow-up. Syringomyelia is a debilitating disease arising most often as a result of traumatic SCI. In the setting of myelomalacia with a pronounced syrinx, C-5 palsy is a potential complication of syrinx decompression.

Study design This is a retrospective study consisting of medical records review and evaluation of pertinent radiographs. Objectives In this study, complications and outcomes are reviewed in a series of HIV-positive patients undergoing spinal surgery. Surgery was performed for conditions that were unrelated to HIV infection. Methods From the period 1996 to 2000, we identified 10 seropositive patients who underwent spinal procedures for conditions that did not arise as a complication of HIV infection. A retrospective review was done, which included inpatient and out patient records. Results A total of 6 women and 5 men who were HIV-positive underwent spinal surgery during the time period reviewed. Surgery was performed for a variety of conditions, including lumbar disc herniaition, degenerative disc disease, cervical disc herniation, spinal fractures, and Arnold-Chiari malformation. The mean CD4 count was 279 cells/mm3 before surgery. All patients had at least 6 months of conservative management before surgery, except in the case of those who had spinal fractures. Two patients sustained postoperative complications: 1 patient developed a superficial wound infection, which was successfully treated with antibiotics, and 1 patient experienced prolonged fever (7 days) after surgery, which resolved without a clear diagnosis. All patients were improved after surgery (mean follow-up, 29.3 months) Conclusions Many physicians have held a nihilistic approach, when it comes to the treatment of HIV-positive persons. However, our results in this small series of patients suggest that spinal surgery may be appropriate and can be performed with acceptable outcomes in selected patients.

Study design Retrospective case series. Objective To demonstrate the microbial trends of spinal surgical site infections in patients who had previously received crystallized vancomycin in the operative bed. Summary of background data Prior large, case control series demonstrate the significant decrease in surgical site infection with the administration of vancomycin in the wound bed. Methods A single institution, electronic database search was conducted for all patients who underwent spinal surgery who had received prophylactic crystalline vancomycin powder in the wound bed. Patients with a prior history of wound infection, intrathecal pumps, or spinal stimulators were excluded. Results A total of 981 consecutive patients (494 males, 487 females; mean age, 59.4 yr; range, 16-95 yr) were identified from January 2011 to June 2013. The average dose of vancomycin powder was 1.13 g (range, 1-6 g). Sixty-six patients (6.71%) were diagnosed with a surgical site infection, of which 51 patients had positive wound cultures (5.2%). Of the 51 positive cultures, the most common organism was Staphylococcus aureus. The average dose of vancomycin was 1.3 g in the 38 cases where a gram-positive organism was cultured. A number of gram-negative infections were encountered such as Serratia marcescens, Enterobacter aerogenes, Bacteroides fragilis, Enterobacter cloacae, Citrobacter koseri, and Pseudomonas aeruginosa. The average dose of vancomycin was 1.2 g in 23 cases where a gram-negative infection was cultured. Fifteen of the 51 positive cultures (29.4%) were polymicrobial. Eight (53%) of these 15 polymicrobial cultures contained 3 or more distinct organisms. Conclusion Prophylactic intraoperative vancomycin use in the wound bed in spinal surgery may increase the incidence of gram-negative or polymicrobial spinal infections. The use of intraoperative vancomycin may correlate with postoperative seromas, due to the high incidence of nonpositive cultures. Large, randomized, prospective trials are needed to demonstrate causation and dose-response relationship.

To test the hypothesis that hyperoxia was associated with higher in-hospital mortality in ventilated stroke patients admitted to the ICU.Retrospective multicenter cohort study.Primary admissions of ventilated stroke patients with acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage who had arterial blood gases within 24 hours of admission to the ICU at 84 U.S. ICUs between 2003 and 2008. Patients were divided into three exposure groups: hyperoxia was defined as PaO2 ≥ 300 mm Hg (39.99 kPa), hypoxia as any PaO260 mm Hg (7.99 kPa) or PaO2/FiO2 ratio ≤ 300, and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital mortality.Two thousand eight hundred ninety-four patients.Patients were divided into three exposure groups: hyperoxia was defined as PaO2 more than or equal to 300 mm Hg (39.99 kPa), hypoxia as any PaO2 less than 60 mm Hg (7.99 kPa) or PaO2/FIO2 ratio less than or equal to 300, and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital mortality.Exposure to hyperoxia.Over the 5-year period, we identified 554 ventilated patients with acute ischemic stroke (19%), 936 ventilated patients with subarachnoid hemorrhage (32%), and 1,404 ventilated patients with intracerebral hemorrhage (49%) of whom 1,084 (38%) were normoxic, 1,316 (46%) were hypoxic, and 450 (16%) were hyperoxic. Mortality was higher in the hyperoxia group as compared with normoxia (crude odds ratio 1.7 [95% CI 1.3-2.1]; p0.0001) and hypoxia groups (crude odds ratio, 1.3 [95% CI, 1.1-1.7]; p0.01). In a multivariable analysis adjusted for admission diagnosis, other potential confounders, the probability of being exposed to hyperoxia, and hospital-specific effects, exposure to hyperoxia was independently associated with in-hospital mortality (adjusted odds ratio, 1.2 [95% CI, 1.04-1.5]).In ventilated stroke patients admitted to the ICU, arterial hyperoxia was independently associated with in-hospital death as compared with either normoxia or hypoxia. These data underscore the need for studies of controlled reoxygenation in ventilated critically ill stroke populations. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in ventilated stroke patients.

In this retrospective multi-centre cohort study, we tested the hypothesis that hyperoxia was not associated with higher in-hospital case fatality in ventilated traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU).Admissions of ventilated TBI patients who had arterial blood gases within 24 h of admission to the ICU at 61 US hospitals between 2003 and 2008 were identified. Hyperoxia was defined as PaO2 ≥300 mm Hg (39.99 kPa), hypoxia as any PaO260 mm Hg (7.99 kPa) or PaO2/FiO2 ratio ≤300 and normoxia, not defined as hyperoxia or hypoxia. The primary outcome was in-hospital case fatality.Over the 5-year period, we identified 1212 ventilated TBI patients, of whom 403 (33%) were normoxic, 553 (46%) were hypoxic and 256 (21%) were hyperoxic. The case-fatality was higher in the hypoxia group (224/553 [41%], crude OR 2.3, 95% CI 1.7-3.0, p.0001) followed by hyperoxia (80/256 [32%], crude OR 1.5, 95% CI 1.1-2.5, p=.01) as compared to normoxia (87/403 [23%]). In a multivariate analysis adjusted for other potential confounders, the probability of being exposed to hyperoxia and hospital-specific characteristics, exposure to hyperoxia was independently associated with higher in-hospital case fatality adjusted OR 1.5, 95% CI 1.02-2.4, p=0.04.In ventilated TBI patients admitted to the ICU, arterial hyperoxia was independently associated with higher in-hospital case fatality. In the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in critically ill ventilated TBI patients.

Objective To determine national trends for patients with subarachnoid hemorrhage (SAH) and pulmonary complications including acute respiratory distress syndrome (ARDS). Methods The Nationwide Inpatient Sample database was used to sample 193,209 admissions for SAH with and without ARDS during the period 1993–2008 using International Classification of Diseases, Ninth Revision, Clinical Modification coding. A multivariate stepwise regression analysis was performed. Results The incidence of ARDS in patients with SAH increased from 35.51% in 1993 to 37.60% in 2008. However, the overall mortality in patients with SAH and in patients with SAH and ARDS decreased in the same period, from 42.30% to 31.99% and from 75.13% to 60.76%, respectively. Multivariate analysis showed that the predictors of developing ARDS in patients with SAH include older age; larger hospital size; and comorbidities such as epilepsy, cardiac arrest, sepsis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, hematologic dysfunction, renal dysfunction, and neurologic dysfunction. Predictors of mortality in patients with SAH include age and hospital complications, such as coronary artery disease, ARDS, cancer, hematologic dysfunction, and renal dysfunction. Conclusions Patients with SAH are at increased risk of developing ARDS. The identification of certain risk factors may alert and aid practitioners in preventing worsening disease.

Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury.To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI.The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe.Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo.Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects.Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]).Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status.clinicaltrials.gov Identifier: NCT00545662.

In spite of its common occurrence, the factors predictive of the rupture of intracranial aneurysms (IAs) remain poorly defined.A retrospective analysis of patients admitted with a primary diagnosis of cerebral aneurysm in a single institution was done. The factors studied were age, sex, size, site, side, multiplicity, neck type, aspect ratio, positive family history, smoking and drinking habits, and hypertension. The morphological parameters were evaluated for a total of 5,138 aneurysms obtained from the 2,347 patients. Factors found significant on univariate analysis were further tested on a multivariate model.We found 1,088 patients (46.36%) had at least a single aneurysmal rupture. Among the morphologic factors, size greater than 10 mm, right sidedness, aspect ratio greater than 1.6, deviated neck type, and multiplicity were found to be associated with higher incidences of rupture. Aneurysms on posterior communicating and middle cerebral arteries were found to be more prone to rupture. The demographic factors that were more linked with the ruptured aneurysms were positive family history, smoking, and hypertension.Relevant cases should be started on intensive lifestyle modification, and extensive screening of those with a positive family history is highly warranted. All "at-risk" patients should be evaluated for early surgical intervention.

BACKGROUND Traumatic brain injury (TBI) is a major cause of disability, morbidity, and mortality. The effect of the acute respiratory distress syndrome and acute lung injury (ARDS/ALI) on in-hospital mortality after TBI remains controversial. OBJECTIVE To determine the epidemiology of ARDS/ALI, the prevalence of risk factors, and impact on in-hospital mortality after TBI in the United States. METHODS Retrospective cohort study of admissions of adult patients>18 years with a diagnosis of TBI and ARDS/ALI from 1988 to 2008 identified through the Nationwide Inpatient Sample. RESULTS During the 20-year study period, the prevalence of ARDS/ALI increased from 2% (95% confidence interval [CI], 2.1%-2.4%) in 1988 to 22% (95% CI, 21%-22%) in 2008 (P

Long-term disability from traumatic brain injury (TBI) is prevalent occurring in approximately 3.17 million persons on an annual basis.1 Among the long-term consequences of TBI, post-traumatic headache (PTH) disorder represents the most common chronic pain syndrome within this patient population.2–7 PTH disorders are highly prevalent across all grades of TBI severity.8 Mild and moderate TBI is more prevalent compared to severe cases of TBI; however, there is a current controversy surrounding epidemiologic reports that cite a higher incidence of PTH for mild TBI compared with moderate and severe cases. A recent prospective 12-month study of TBI patients provides compelling evidence that the prevalence of PTH is unrelated to injury severity.9 Important aspects of PTH to consider relate to the time-course of this disorder. In many patients, it resolves in 3 months; in others, it persists for much longer. Currently, PTH, as classified by the International Classification of Headache Disorders, is defined as headache secondary to head trauma that develops within 7 days after injury or regaining consciousness. TBI is a risk factor for acute episodic headache (headache occurring less than 15 days/month) persisting less than 3 months transitioning into chronic headache (≥15 days/month).10,11 Clinical evidence suggest that the persistence of PTH beyond the expected tissue-healing time-course would argue for its chronicity, as well as mechanisms of central sensitization.12–14 A recent prospective study found the onset of PTH occurred between 7 and 30 days after injury or later in nearly half of patients.15 A study by Ofek and Defrin found that patients with TBI had a mean onset of chronic pain, including head pain, just over 6 months after injury.14 Headache was reported at 3, 6, and 12 months in 41% of patients with TBI in a study by Hoffman and colleagues.9 Studies using quantitative sensory testing (eg, von Frey mechanical stimuli for allodynia [cutaneous sensitivity to mechanical stimuli that are innocuous under normal conditions]) show that 40% of patients with TBI experience chronic head and face pain after head injury.14,16 Significant reductions in pressure-pain thresholds were found at least 1 year after mild-to-moderate TBI.16 To date, investigations into the proposed mechanisms and treatments for PTH have been impeded by a lack of preclinical models. Therefore, a research initiative implemented by our laboratory is to study mechanisms of PTH and its chronification using a well-known animal model of TBI, controlled cortical impact (CCI) injury. Headache pain, whether acute or chronic, involves abnormal activation of the trigeminovascular system. Using a model of diffuse TBI, Hall and Lifshitz have characterized hypersensitivity of the whiskers to be associated with neuroplasticity in the cortical barrel circuit and thalamus.17 Peripheral axons of the trigeminal ganglion innervate the peri-orbital skin, facial whiskers, anterior scalp, meninges, and cerebral vasculature. Periorbital and facial allodynia have been well-documented in rodent migraine models following infusion of an inflammatory soup over the meninges.18–20 Afferent fibers of the trigeminal ganglia relay nociceptive information to the trigeminal nuclei in which the neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), play important roles. CGRP and SP are also important in normal physiologic and pathologic function including cerebrovascular regulation and the development of neurogenic inflammation.21–26 CGRP has been particularly well-studied for its role in primary headache disorders such as migraine.27,28 To date, preclinical studies examining allodynia and the potential role of CGRP and SP in PTH are nonexistent. This study aimed to characterize periorbital sensory changes to mechanical stimuli (allodynia) and neuroplasticity in the brainstem in a mouse model of TBI, as this has not yet been reported in any model of TBI. The present study tests the hypothesis that focal injury to the somatosensory cortex will be associated with increased neuropeptides within the brainstem trigeminal nucleus caudalis and periorbital allodynia in a mouse model of CCI injury. The time-course for macrophage/microglial and astrocyte responses in the somatosensory cortex after CCI were examined because these cell populations are a potential cellular source of mediators (eg, cytokines, nitric oxide [NO], excitatory amino acids) of nociceptor sensitization known to contribute to behavioral morbidity. The pattern of periorbital allodynia over 4 weeks in mice with CCI and those undergoing a craniotomy only was characterized, while changes in the nociceptive neuropeptides, CGRP, and SP within the brainstem were determined. The temporal relationships between periorbital sensory changes (allodynia), central nociceptive neuropeptides, and gliosis (macrophage/microglia and astrocyte activation) were examined.

Proposed therapeutic strategies for attenuating secondary traumatic brain injury (TBI) include modulation of acute neuroimmune responses. The goal of this study was to examine the acute effects of cannabinoid-2 receptor (CB(2)R) modulation on behavioral deficits, cerebral edema, perivascular substance P, and macrophage/microglial activation in a murine model of TBI. Thirty male C57BL/6 mice underwent sham surgery, or cortical contusion impact injury (CCI). CCI mice received vehicle or the CB(2)R agonist 0-1966 at 1 and 24 h after injury. Performance on the rotarod, forelimb cylinder, and open-field tests were evaluated before and at 48 h after sham or CCI surgery. Cerebral edema was evaluated using the wet-dry weight technique. Immunohistochemical analysis was used to examine changes in substance P and macrophage/microglia-specific Iba1 protein immunoreactivity. Locomotor performance and exploratory behavior were significantly improved in mice receiving 0-1966 (CB(2)R agonist) compared to vehicle-treated mice. Significant reductions were found for cerebral edema, number of perivascular areas of substance P immunoreactivity, and number of activated macrophages/microglial cells in the injured brains of 0-1966-treated mice compared to vehicle-treated mice. The findings show that the effects of the CB(2)R agonist 0-1966 on edema, substance P immunoreactivity, and macrophage/microglial activation, were associated with recovery of acute motor and exploratory deficits. This study provides evidence of acute neuroprotective effects derived from selective CB(2)R activation that may represent an avenue for further development of novel therapeutic agents in the treatment of TBI.

Background Aneurysms of the carotid-ophthalmic artery present unique challenges to cerebrovascular neurosurgeons given their proximity to vital anatomic structures. Objective To report our experience with a combined-modality treatment of unruptured carotid-ophthalmic aneurysms over a 12-year period. Methods A retrospective review of 161 patients who underwent open, endovascular, or combined treatment of 170 aneurysms from January 1997 to July 2009 was conducted. Medical records, operative reports, office notes, and follow-up angiograms were reviewed to obtain data on patient demographics, angiographic results, and clinical outcomes. Results One hundred forty-seven aneurysms were treated via endovascular techniques; 17 aneurysms (10%) were treated with microsurgical clip ligation; and 6 aneurysms (3.5%) were treated with a combined approach. Of the aneurysms treated via an endovascular approach alone, 81.6% of aneurysms had evidence of ≥ 95% occlusion on initial angiogram. There was a 1.4% rate of major complications associated with the initial procedure. Twenty-six of these aneurysms (18.9%) required further intervention on the basis of early angiographic results. Major complications occurred after 6 of 23 open microsurgical procedures (26.1%), including 2 instances of permanent visual loss. Nine clipped patients had long-term angiographic follow-up; none required further intervention. Conclusion Endovascular treatment of carotid-ophthalmic aneurysms with modern endovascular techniques can be performed safely and efficaciously in the elective setting.

Previous studies from our laboratory indicated that selective cannabinoid CB(2) agonists were able to attenuate cerebral ischemia/reperfusion (I/R) injury. The goal of current study is to further test whether this attenuation involves cerebral microcirculatory function during I/R injury. Middle cerebral artery occlusion with reperfusion (MCAO/R) was performed in male mice. A selective CB(2) agonist was administered at different dosages and different times. Cerebral infarction volume, neurological function and cerebral microcirculatory function (leukocyte/endothelial interactions, cell adhesion molecule expression and blood-brain barrier disruption) were examined in vivo and in vitro. CB(2) knockout mice were subjected to MCAO/R following same procedures. Administration of the CB(2) agonist at middle dosage exerted optimal effects in reducing cerebral infarction and improving neurological function compared with other dosage groups and control group. Treatment with the CB(2) agonist at the optimal dose was still effective when given 3 h after MCAO. Transient ischemia significantly increased leukocyte/endothelial interactions, adhesion molecules expression and blood-brain barrier disruption which were all attenuated by pre-treatment with a CB(2) agonist. CB(2) knockout mice showed larger cerebral infarction and worse neurological function compared to wide type. In conclusion, CB(2) activation contributed to protecting the brain through the attenuation of cerebral microcirculatory dysfunction during cerebral I/R injury.

The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.

Object One often overlooked aspect of spinal epidural abscesses (SEAs) is the timing of surgical management. Limited evidence is available correlating earlier intervention with outcomes. Spinal epidural abscesses, once a rare diagnosis carrying a poor prognosis, are steadily becoming more common, with one recent inpatient meta-analysis citing an approximate incidence of 1 in 10,000 admissions with a mortality approaching 16%. One key issue of contention is the benefit of rapid surgical management of SEA to maximize outcomes. Timing of surgical management is definitely one overlooked aspect of care in spinal infections. Therefore, the authors performed a retrospective analysis in which they evaluated patients who underwent early (evacuation within 24 hours) versus delayed surgical intervention (> 24 hours) from the point of diagnosis, in an attempt to test the hypothesis that earlier surgery results in improved outcomes. Methods A retrospective review of a prospectively maintained adult neurosurgical database from 2009 to 2011 was conducted for patients with the diagnostic heading: epidural abscess, infection, osteomyelitis, osteodiscitis, spondylodiscitis, and abscess. The primary end point for each patient was neurological grade, measured as an American Spinal Injury Association Impairment Scale grade using hospital inpatient records on admission and discharge. Patients were divided into early surgical (< 24 hours) and delayed surgical cohorts. Results Eighty-seven consecutive patients were identified (25 females; mean age 55.5 years, age range 18–87 years). Fifty-four patients received surgery within 24 hours of admission (mean time from admission to incision, 11.2 hours), and 33 underwent surgery longer than 24 hours (mean 59 hours) after admission. Of the 54 patients undergoing early surgery 45 (85%) had a neurological deficit, whereas in the delayed surgical group 21 (64%) of 33 patients presented with a neurological deficit (p = 0.09). Patients in the delayed surgery cohort were significantly older by 10 years (59.6 vs 51.8 years, p = 0.01). With regard to history of prior revision, body mass index, intravenous drug abuse, tobacco use, prior radiation therapy, diabetes, chronic systemic infection, and prior osteomyelitis, there were no significant differences. There was no significant difference between early and delayed surgery groups in neurological grade on presentation, discharge, or location of epidural abscess. The most common organism isolated was Staphylococcus aureus (n = 51, 59.3%). The incidence of methicillin-resistant S. aureus was 21% (18 of 87). Conclusions Evacuation within 24 hours appeared to have a relative advantage over delayed surgery with regard to discharge neurological grade. However, due to a limited, variable sample size, a significant benefit could not be shown. Further subgroup analyses with larger populations are required.

This study has explored the impact of Hunt-Hess (H-H) grade of aneurysmal subarachnoid hemorrhage (aSAH) on the glycemic status of such patients during their intensive care unit (ICU) stay and has also analyzed whether H-H grade predicts their outcome independent of their glycemic status.This was a retrospective case record review of prospectively maintained database of 1090 previously non-diabetic aSAH patients admitted to Thomas Jefferson University Hospital, Philadelphia. H-H grade of SAH, serum and CSF glucose on admission, serum glucose on the day of surgery and 14 days post-surgery, as well as the extended Glasgow Outcome Score (GOS-E score) at discharge were noted. After univariate analysis, significant variables (P0.05) were entered into a logistic regression model to identify significant associations with admission H-H grade.Although admission serum glucose was significantly higher for H-H grades 4-5 than grades 1-3 (P0.001); after postoperative day 4, the difference between the H-H grades got blurred. Admission CSF glucose was also significantly higher for H-H grades 3-4 than for grades 1-3 and 5 (P0.001). H-H grades 4-5 were related with higher incidences of both hypoglycemia (serum glucose level80 mg/dl) and hyperglycemia (serum glucose level200 mg/dl) (P0.001) during the 14-day period of ICU stay. Also, the relationship between serum and CSF glucose levels at admission increased with HH grades 1 through 4, but became negative and more tightly bound at H-H grade 5. Admission H-H grades 4-5 contributed to poor outcome compared to lower H-H grades (P0.0001).Poor admission H-H grades lead to poor immediate glycemic status as well as poor short-term outcome, and it is dependent on serum glucose but independent of CSF glucose in predicting the outcome.

Lipomas of the cerebellopontine angle are rare, although well described in the literature. A review of the literature with an emphasis on pathogenesis and management is presented.

Background Immunomodulatory therapies have been identified as interventions for secondary injury after traumatic brain injury (TBI). The cannabinoid receptor type-2 (CB2R) is proposed to play an important, endogenous role in regulating inflammation. The effects of CB2R stimulation, blockade, and deletion on the neurovascular inflammatory responses to TBI were assessed. Methods Wild-type C57BL/6 or CB2R knockout mice were randomly assigned to controlled cortical impact (CCI) injury or to craniotomy control groups. The effects of treatment with synthetic, selective CB2R agonists (0-1966 and JWH-133), a selective CB2R antagonist, or vehicle solution administered to CCI groups were assessed at 1-day after injury. Changes in TNF-α, intracellular adhesion molecule (ICAM-1), inducible nitric oxide synthase (iNOS), macrophage/microglial ionized calcium-binding adaptor molecule, and blood-brain-barrier (BBB) permeability were assessed using ELISA, quantitative RT-PCR, immunohistochemistry, and fluorometric analysis of sodium fluorescein uptake. CB2R knockouts and wild-type mice with CCI injury were treated with a CB2R agonist or vehicle treatment. Results TNF-α mRNA increased at 6 hours and 1 to 3 days after CCI; a CB2R antagonist and genetic knockout of the CB2R exacerbated TNF-α mRNA expression. Treatment with a CB2R agonist attenuated TNF-α protein levels indicating post-transcriptional mechanisms. Intracellular adhesion molecule (ICAM-1) mRNA was increased at 6 hours, and at 1 to 2 days after CCI, reduced in mice treated with a CB2R agonist, and increased in CB2R knockout mice with CCI. Sodium fluorescein uptake was increased in CB2R knockouts after CCI, with and without a CB2R agonist. iNOS mRNA expression peaked early (6 hours) and remained increased from 1 to 3 days after injury. Treatment with a CB2R agonist attenuated increases in iNOS mRNA expression, while genetic deletion of the CB2R resulted in substantial increases in iNOS expression. Double label immunohistochemistry confirmed that iNOS was expressed by macrophage/microglia in the injured cortex. Conclusion Findings demonstrate that the endogenous cannabinoid system and CB2R play an important role in regulating inflammation and neurovascular responses in the traumatically injured brain. CB2R stimulation with two agonists (0-1966 and JWH-133) dampened post-traumatic inflammation, while blockade or deletion of the CB2R worsened inflammation. Findings support previous evidence that modulating the CB2R alters infiltrating macrophages and activated resident microglia. Further investigation into the role of the CB2R on specific immune cell populations in the injured brain is warranted.