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Introduction Indocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. Methods In this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. Results This patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes – not consistent with spinal cord tumor or germinoma. Conclusion Second Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

Background A limitation of diffusion tensor imaging (DTI)-based tractography is peritumoral edema that confounds traditional diffusion-based magnetic resonance metrics. Objective To augment fiber-tracking through peritumoral regions by performing novel edema correction on clinically feasible DTI acquisitions and assess the accuracy of the fiber-tracks using intraoperative stimulation mapping (ISM), task-based functional magnetic resonance imaging (fMRI) activation maps, and postoperative follow-up as reference standards. Methods Edema correction, using our bi-compartment free water modeling algorithm (FERNET), was performed on clinically acquired DTI data from a cohort of 10 patients presenting with suspected high-grade glioma and peritumoral edema in proximity to and/or infiltrating language or motor pathways. Deterministic fiber-tracking was then performed on the corrected and uncorrected DTI to identify tracts pertaining to the eloquent region involved (language or motor). Tracking results were compared visually and quantitatively using mean fiber count, voxel count, and mean fiber length. The tracts through the edematous region were verified based on overlay with the corresponding motor or language task-based fMRI activation maps and intraoperative ISM points, as well as at time points after surgery when peritumoral edema had subsided. Results Volume and number of fibers increased with application of edema correction; concordantly, mean fractional anisotropy decreased. Overlay with functional activation maps and ISM-verified eloquence of the increased fibers. Comparison with postsurgical follow-up scans with lower edema further confirmed the accuracy of the tracts. Conclusion This method of edema correction can be applied to standard clinical DTI to improve visualization of motor and language tracts in patients with glioma-associated peritumoral edema.

Although prescription opioid abuse is a serious concern, patients are commonly prescribed opioids for postoperative pain management. This study sought to evaluate the efficacy of low-dose steroids to reduce postoperative pain and opioid use after lumbar laminectomy and/or discectomy. In the 10-day period postdischarge, patients prescribed a low-dose steroid reported decreased pain scores compared with those who were not prescribed a low-dose steroid; however, there was no associated significant difference in opioid consumption. Outcomes data suggest that postoperative oral steroid may reduce postoperative pain but does not necessarily decrease short-term opioid use after lumbar laminectomy and/or discectomy.

Background Multimodality monitoring is used frequently to guide care of patients with severe acute brain injury. The aim of this study was to examine the safety and reliability of multimodality monitoring. Methods From a prospective observational database at a Level I trauma center, 501 patients, including 300 men and 201 women (mean age 58 ± 39 years) were identified retrospectively. Each patient received a triple-lumen bolt and 3 monitors: intracranial pressure, brain temperature, and brain oxygen. Intensive care unit and hospital records were examined to identify complications, reasons for device replacement, malfunction and infection. Head computed tomography (CT) scans performed before and after the monitors were inserted were examined for evidence of monitor-related adverse effects. Results A total of 696 triple-lumen bolts were placed. Median duration of monitoring was 78.88 hours (interquartile range, 33.0–133.2 hours). Bilateral monitors were inserted in 22 (3.16%) patients. Ten (1.43%) monitors were replaced to allow magnetic resonance imaging, and 40 (5.74%) monitors were replaced to facilitate additional cranial surgery. Of 35 (5.02%) monitors that were replaced because they were thought to not be functioning properly, 19 (54.29%) were subsequently found to be functioning normally. Follow-up CT scans were compared with CT scans obtained before insertion of monitors; 9 (2.13%) small contusions and 10 (2.36%) extra-axial hematomas associated with the devices were identified. Based on the CT findings, the hematomas were thought to be associated with the insertion technique rather than the device; 4 hematomas required treatment. Twenty-two (3.16%) devices were incorrectly placed (e.g., the probe was in an infarct or an already existing contusion). Only 1 associated infection was identified. Conclusions Placement of intracranial monitors for multimodality neuromonitoring using a triple-lumen bolt appears to be safe. The complication rate is similar to published complication rates for single-lumen bolts and single monitors.

BACKGROUND Patients with an external ventricular drain (EVD) may not be readily mobilized because of concerns of catheter dislodgment and/or inappropriate cerebrospinal fluid drainage. Delayed mobilization may result in longer hospital stays and an increased risk for complications related to immobility. We aimed to determine the safety, feasibility, and outcome of an EVD mobilization protocol in patients with subarachnoid hemorrhage (SAH). METHODS A multidisciplinary group developed a formal algorithm for the mobilization of patients with SAH with EVDs. Outcome measures included intensive care unit (ICU) length of stay (LOS), day to first mobilization, and discharge disposition. Patients were prospectively enrolled during a 12-month period and compared with a historical control group of patients with SAH for the preceding 12-month period. RESULTS Thirty-nine of 45 (86.7%) patients were women. Mean age did not differ significantly between the preintervention (n = 19) and postintervention (n = 26) groups (59.6 vs 55.7). Number of EVD device days did not differ significantly between groups (16.3 vs 15, P = .422]. Of 101 attempted postintervention mobilization sessions, six were aborted for increased lethargy (1), pain (1), elevated intracranial pressure (1), drain malfunction (1), and hypotension (2). Twenty-four sessions were attempted but never initiated because of worsening neurologic examination (10), pulmonary instability (2), hemodynamic instability (2), medical instability (3), and provider request (1). No patient experienced catheter dislodgment. Mean ICU LOS was not different between groups (20.7 vs 18.2, P = .262). The day of first mobilization was significantly earlier in the postintervention group (18.7 vs 6.5, P < .0001). The percentage of patients discharged home or to acute rehabilitation was higher in the postintervention group (63.2% vs 88.5%, P = .018], when accounting for Hunt and Hess grade. CONCLUSIONS The mobilization of patients with EVDs is safe and feasible; it may be associated with earlier mobilization, reduced ICU LOS, and better discharge disposition. No major complications were attributable to early mobilization.

BACKGROUND This study builds on the results of the University of Pennsylvania sponsored phase I study of a single peripheral infusion of chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor variant III (EGFRvIII) in recurrent glioblastoma (GBM) (NCT02209376). A dose of 5x108 CART-EGFRvIII cells was safe, and the cells were able to expand in the host and reach the GBM tumor in the brain. In addition, there was no cross-reactivity of CART-EGFRvIII cells with wild-type EGFR normally expressed by human tissues. Some patients required tumor resection after CAR T cell infusion. In situ evaluation of the tumor microenvironment demonstrated increased and robust expression of inhibitory molecules, such as programmed death-ligand 1 (PD-L1), compared to pre–CART-EGFRvIII tumor specimens. Therefore, we hypothesized that using a combination of CART-EGFRvIII cells and a PD-1 inhibitor would improve the outcome of the treatment. METHODS This single-center study (NCT03726515) has a single-arm, open-label, phase 1 design and will enroll 7 patients with newly diagnosed, O6-methylguanine-methyltransferase (MGMT)-unmethylated, EGFRvIII+ GBM. Following maximal safe tumor resection, patients receive a short course of adjuvant radiation with a total dose of 40 Gy administered in 15 fractions. Peripheral IV infusions of 2x108 CART-EGFRvIII cells and 200mg pembrolizumab begin 2–3 weeks after completing radiation therapy. Thereafter, subjects receive CART-EGFRvIII cells + pembrolizumab in 3-week cycles for up to 3 infusions of CART-EGFRvIII cells and 4 infusions of pembrolizumab. The primary endpoint of the study is the safety and tolerability of administering multiple infusions of CART-EGFRvIII cells in combination with pembrolizumab, as measured by the occurrence of study-related adverse events. Secondary endpoints include overall survival, progression-free survival, and objective response rate. PROGRESS: At 5 June 2019, 2 patients have been enrolled and treated on study.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Objective Hypercoagulability after subarachnoid hemorrhage (SAH) is well described and may be platelet mediated. Thromboelastography (TEG) provides a global assessment of coagulation. We sought to determine whether the maximum amplitude (MA) parameter of TEG, a measure of platelet strength and function, is associated with outcome after SAH. Methods One hundred ten TEG analyses were performed for patients with moderate-to-severe SAH and compared with 6 healthy age- and sex-matched controls. TEG indices included MA, G value (G), alpha angle, and thrombus generation and were correlated to functional outcomes and laboratory tests including complete blood count, erythrocyte sedimentation rate, high sensitivity C-reactive protein, fibrinogen, and d-dimer, obtained on post-bleed days (PBDs) 1, 3, 5, 7, and 10. Results MA was significantly elevated compared with controls on PBD 3 (70.0 mm ± 4.5 mm vs. 64.1 mm ± 6.5 mm; P = 0.02), PBD 5 (72.6 mm ± 5.3 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), PBD 7 (73.0 mm ± 5.4 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), and PBD 10 (73.4 mm ± 6.0 mm vs. 64.1 mm ± 6.5 mm; P = 0.005). G was significantly elevated compared with controls on PBD 3 ( P = 0.03), PBD 5 ( P = 0.01), PBD 7 ( P = 0.01), and PBD 10 ( P = 0.02). The only biomarker associated with poor outcome was CRP. Multivariate logistic regression demonstrated an association between elevated MA and outcome (odds ratio 39.1, P = 0.006) independent of CRP, age, Hunt Hess grade, and transfusion. Conclusions TEG indices are associated with poor outcome after SAH and may identify a platelet-mediated hypercoagulable state. The association between MA and outcome was stronger than that between traditional biomarkers and was independent of age and Hunt Hess grade.

Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). In this retrospective single-center cohort of aSAH patients (October 2009–September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. Of 179 patients, 27 % had a high Hunt–Hess grade (IV–V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07–6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30–7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt–Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04–629], p = 0.040). RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry. Analysis of CMD analytes as part of a multimodal approach may help inform clinical decision making, guide medical treatments, and aid in prognostication of patient outcome. Its use is most frequently documented in traumatic brain injury and subarachnoid hemorrhage. Incorporating CMD into clinical practice is a multidisciplinary effort.

Traumatic microvascular injury (tMVI) is a universal endophenotype of traumatic brain injury (TBI) that is responsible for significant neurological morbidity and mortality. The mechanism underlying tMVI is not fully understood. The present study aims to determine plasma levels of von Willebrand factor (VWF), a disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS) 13 activity, and human neutrophil peptides (HNP) 1-3 and to correlate these biomarkers with functional outcomes after moderate-severe TBI. Thirty-one consecutive TBI patients (Glasgow Coma Scale [GCS] range, 3-12) were enrolled into the study between February 2010 and November 2014. Blood samples were collected on 0, 1, 2, 3, and 5 days after admission and analyzed for plasma levels of VWF antigen (VWFAg), collagen-binding activity (VWFAc), ADAMTS13 activity, and HNP1-3 proteins. Mean values of plasma VWFAg, VWFAc, and HNP1-3 were significantly increased in TBI patients compared to those in healthy controls (n = 30). Conversely, mean plasma values of ADAMTS13 activity in TBI patients were significantly decreased during the first 2 days after admission. This resulted in a dramatic reduction in the ratio of ADAMTS13 activity to VWFAg or ADAMTS13 to VWFAc in all 5 post-TBI days. Cluster analysis demonstrated that high median plasma levels of VWFAg and HNP1-3 were observed in the cluster with a high mortality rate. These results demonstrate that a relative deficiency of plasma ADAMTS13 activity, resulting from activation of neutrophils and endothelium, may contribute to the formation of microvascular thrombosis and mortality after moderate-severe TBI.

Background: Despite the known benefits of early postsurgical mobility, there are no clear recommendations on early mobility among uncomplicated postoperative neurosurgical spine patients.The purpose of this quality improvement initiative was to establish an NP-led early mobility protocol to reduce uncomplicated postsurgical spine patients' length of stay (LOS) in the hospital and eliminate the variability of postsurgical care. A secondary objective was to educate and empower nursing staff to initiate the early mobility protocol independently and incorporate it in their practice to improve patient care.Two neurosurgery NPs led an interprofessional team to develop the early mobility protocol. Team members provided preadmission preoperative education to communicate the necessity for early mobility and provide information about the protocol. New nursing guidelines called for patient mobility on the day of surgery, within six hours of arrival on the medical-surgical unit. Nurses were empowered to get patients out of bed independently, without a physical therapy consultation; they also removed urinary catheters and discontinued IV opioids when patients' status permitted.Over a one-year period, implementation of the protocol resulted in a nine-hour reduction in LOS per hospitalization in neurosurgical spine patients who underwent lumbar laminectomies. The protocol also allowed nurses more autonomy in patient care and was a catalyst for patient involvement in their postoperative mobility. Given the success of the protocol, it is being replicated by other surgical services throughout the organization.This low-cost, high-reward initiative aligns with the strategic plan of the organization and ensures that high-quality, patient-centered care remains the priority. NPs in other institutions can modify this protocol to promote postoperative mobility in their organizations.

The red cell distribution width (RDW) is a biomarker strongly associated with poor outcome in inflammatory and thrombotic diseases. Subarachnoid hemorrhage (SAH) is both an inflammatory and thrombotic state in which many biomarkers have been studied. In this exploratory pilot study, we sought to determine whether RDW predicts poor outcome in patients with SAH.Patients with moderate-to-severe SAH were prospectively enrolled in an observational study of biomarkers and outcome. CBC, ESR, high sensitivity CRP, D-dimer, and fibrinogen were obtained on post-bleed days (PBD) 1, 3, 5, 7, and 10. Poor outcome was defined as a modified Rankin score of 3-6 at 90-days.Of 40 patients, 5 (12.5%) died and 19 (47.5%) had a poor outcome. RDW (p = 0.046) when measured serially over the study period, was significantly higher among patients with poor outcome. Maximum RDW (OR 2.3 95% CI 1.2-3.6; p = 0.014) and maximum WBC count (OR 1.29 95% CI 1.04-1.60; p = 0.018) were associated with poor outcome. Stepwise addition of maximum ESR, CRP, D-dimer, and fibrinogen yielded a model with RDW (OR 2.54 95% CI 1.21-5.35; p = 0.014) and fibrinogen (OR 1.01 95% CI 1.002-1.01; p = 0.004) predicting outcome. With addition of age and Hunt and Hess grade, RDW, fibrinogen, and high-grade status remained significantly associated with poor outcome. Use of PBD1 RDW in lieu of maximum RDW, resulted in a similar model.An elevated RDW is associated with poor outcome in SAH patients. RDW may be a useful predictor of outcomes after SAH.

BACKGROUND: The efficacy and safety of cervical laminoforaminotomy (FOR) in the treatment of cervical radiculopathy has been demonstrated in several series with follow-up less than a decade. However, there is little data analyzing the relative effectiveness of FOR for radiculopathy due to soft disc versus osteophyte disease. In the present study, we review our experience with FOR in a single-center cohort, with long-term follow-up. METHODS: We examined the charts of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these patients participated in a telephone interview designed to assess improvement in symptoms and function. RESULTS: A total of 338 interviews were completed with a mean follow-up of 10 years. Approximately 90% of interviewees reported improved pain, weakness, or function following FOR. Ninety-three percent of patients were able to return to work after FOR. The overall complication rate was 3.3%, and the rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes compared to osteophyte disease by operative report were associated with improved symptoms (P < 0.05). The operative report of these pathologic subtypes was associated with the preoperative magnetic resonance imaging (MRI) interpretation (P < 0.001). CONCLUSIONS: These results suggest that FOR is a highly effective surgical treatment for cervical radiculopathy with a low incidence of complications. Radiculopathy due to soft disc subtypes may be associated with a better prognosis compared to osteophyte disease, although osteophyte disease remains an excellent indication for FOR.

BACKGROUND Oligodendroglioma is a rare primary brain tumor characterized by mutation in the IDH1/IDH2 genes and codeletion of chromosomes 1p and 19q. Although median overall survival extends beyond 10 years for patients with oligodendroglioma who receive adjuvant radiation and alkylating chemotherapy, the disease uniformly relapses and has no other effective treatments. The CIC gene, which encodes a high-mobility group box transcriptional repressor, is mutated in about 70% of oligodendrogliomas and is associated with worse prognosis and overexpression of cyclin D1 (CCND1). Cyclin D1 assembles with the cyclin-dependent kinases CDK4 and CDK6 to cause phosphorylation of Rb protein and subsequent cell cycle progression from the G1 to S phase. Therapeutic inhibition of CDK4/6 activity, which leads to Rb dephosphorylation and cell cycle arrest, has revolutionized the care of breast cancer. The current phase 2 study will investigate the efficacy and safety of abemaciclib, a selective and potent small molecule inhibitor of CDK4 and CDK6 with significant brain-brain barrier penetration, in patients with 1p/19q codeleted oligodendroglioma that has recurred after standard radiation and alkylating chemotherapy. METHODS This protocol (NCT03969706) has a single-arm, open-label, single-stage phase 2 design. Subjects will be treated with abemaciclib 200mg tablet twice daily on 28-day cycles until disease progression or unacceptable toxicity. Tumor response will be assessed according to modified Response Assessment in Neuro-Oncology (mRANO) criteria. The primary objective of the study is to determine the efficacy of abemaciclib for recurrent oligodendroglioma. The primary endpoint is the progression-free survival status of the subject at 6 months after enrollment (PFS-6). The alternative hypothesis is that the proportion of subjects without an event at 6 months will be ³85%. We will test this hypothesis against a null hypothesis of PFS-6 = 50%. With enrollment of 10 planned subjects, the power to detect this difference is 82% (one-sided alpha = 0.05).

Object Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. Methods On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. Results When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)−, CD66b+(neutrophil)−, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])–associated MPs and CD146+(endothelial cell)–associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. Conclusions Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)–associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Despite more than 30 years of clinical use, questions remain about the safety of xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular, xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined. Our objective was to assess the effect of a 4.5-min inhalation of 28 % stable xenon on several physiologic variables, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma Scale [GCS] ≤ 8). Thirty-seven comatose patients who underwent 73 XeCTCBF studies were identified retrospectively from a prospective observational database. Changes in MAP, HR, SaO2, EtCO2, ICP, CPP, and PbtO2 measured at the start of xenon administration and every minute for 5 min thereafter were assessed. The maximum change in each variable also was determined for each scan to tabulate clinically relevant changes. Statistically, but not clinically significant changes in MAP, HR, and EtCO2 were seen. Xenon had no effect on ICP, and a small, but clinically insignificant decrease in CPP and PbtO2, was observed. There was a varied response to xenon in most measured variables. Clinically significant changes in each were infrequent, and readily reversed with the cessation of the gas. We conclude that xenon does not appear to have a clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to evaluate cerebral blood flow in comatose patients.

To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome.This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11;11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2)20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3).We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p0.001). Anemia with simultaneous PbtO(2)20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score.In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

Brain hypoxia (BH) can aggravate outcome after severe traumatic brain injury (TBI). Whether BH or reduced brain oxygen (Pbto(2)) is an independent outcome predictor or a marker of disease severity is not fully elucidated.To analyze the relationship between Pbto(2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) and to examine whether BH correlates with worse outcome independently of ICP and CPP.We studied 103 patients monitored with ICP and Pbto(2) for24 hours. Durations of BH (Pbto(2)15 mm Hg), ICP20 mm Hg, and CPP60 mm Hg were calculated with linear interpolation, and their associations with outcome within 30 days were analyzed.Duration of BH was longer in patients with unfavorable (Glasgow Outcome Scale score, 1-3) than in those with favorable (Glasgow Outcome Scale, 4-5) outcome (8.3 ± 15.9 vs 1.7 ± 3.7 hours; P.01). In patients with intracranial hypertension, those with BH had fewer favorable outcomes (46%) than those without (81%; P.01); similarly, patients with low CPP and BH were less likely to have favorable outcome than those with low CPP but normal Pbto(2) (39% vs 83%; P.01). After ICP, CPP, age, Glasgow Coma Scale score, Marshall computed tomography grade, and Acute Physiology and Chronic Health Evaluation II score were controlled for, BH was independently associated with poor prognosis (adjusted odds ratio for favorable outcome, 0.89 per hour of BH; 95% confidence interval, 0.79-0.99; P = .04).Brain hypoxia is associated with poor short-term outcome after severe traumatic brain injury independently of elevated ICP, low CPP, and injury severity. Pbto(2) may be an important therapeutic target after severe traumatic brain injury.

Observational clinical studies demonstrate that brain hypoxia is associated with poor outcome after severe traumatic brain injury (TBI). In this study, available medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)-based therapy is associated with improved patient outcome after severe TBI. Clinical studies published between 1993 and 2010 that compared PbtO2-based therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)-based therapy to ICP/CPP-based therapy alone were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. For analysis, each selected paper had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs) of outcome described by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2- to ICP/CPP-based therapy were identified. There were no randomized studies and no comparison studies in children. Four studies, published in 2003, 2009, and 2010 that included 491 evaluable patients were used in the final analysis. Among patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191 (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome. Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI 1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy is associated with better outcome after severe TBI than ICP/CPP-based therapy alone. Cross-organizational practice variances cannot be controlled for in this type of review and so we cannot answer whether PbtO2-based therapy improves outcome. However, the potentially large incremental value of PbtO2-based therapy provides justification for a randomized clinical trial.

Background Obesity has been associated with compromised tissue oxygenation and reduced organ perfusion. The brain is critically dependent on oxygen delivery, and reduced brain tissue oxygen tension (PbtO2) may result in poor outcome after brain injury. We tested the hypothesis that obesity is associated with compromised PbtO2 after severe brain injury. Methods Patients with severe brain injury (GCS score ≤ 8) who underwent continuous PbtO2 monitoring were retrospectively identified from a prospective single-center database. Patients, were classified by body mass index (BMI = weight (kg)/m2) and were included if they were obese (BMI ≥ 30) or non-obese (BMI =

Object Follow-up head CT scans are important in neurocritical care but involve intrahospital transport that may be associated with potential hazards including a deleterious effect on brain tissue oxygen pressure (PbtO2). Portable head CT (pHCT) scans offer an alternative imaging technique without a need for patient transport. In this study, the investigators examined the effects of pHCT scans on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in patients with severe brain injury. Methods Fifty-seven pHCT scans were obtained in 34 patients (mean age of 42 ± 15 years) who underwent continuous ICP, CPP, and PbtO2 monitoring in the neuro intensive care unit at a university-based Level I trauma center. Patient ICU records were retrospectively reviewed and physiological data obtained during the 3 hours before and after pHCT scans were examined. Results Before pHCT, the mean ICP and CPP were 14.3 ± 7.4 and 78.9 ± 20.2 mm Hg, respectively. Portable HCT had little effect on ICP (mean ICP 14.1 ± 6.6 mm Hg, p = 0.84) and CPP (mean CPP 81.0 ± 19.8 mm Hg, p = 0.59). The mean PbtO2 was similar before and after pHCT (33.2 ± 17.0 mm Hg and 31.6 ± 15.9 mm Hg, respectively; p = 0.6). Ten episodes of brain hypoxia (PbtO2 < 15 mm Hg) were observed before pHCT; these episodes prompted scans. Brain hypoxia persisted in 5 patients after pHCT despite treatment. No new episodes of brain hypoxia were observed during or after pHCT. Conclusions These data suggest that pHCT scans do not have a detectable effect on a critically ill patient's ICP, CPP, or PbtO2.

Brain tissue oxygen (PbtO(2)) monitoring is used in severe traumatic brain injury (TBI) patients. How brain reduced PbtO(2) should be treated and its response to treatment is not clearly defined. We examined which medical therapies restore normal PbtO(2) in TBI patients.Forty-nine (mean age 40 ± 19 years) patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) admitted to a University-affiliated, Level I trauma center who had at least one episode of compromised brain oxygen (PbtO(2)25 mmHg for10 min), were retrospectively identified from a prospective observational cohort study. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) were monitored continuously. Episodes of compromised PbtO(2) and brain hypoxia (PbtO(2)15 mmHg for10 min) and the medical interventions that improved PbtO(2) were identified.Five hundred and sixty-four episodes of compromised PbtO2 were identified from 260 days of PbtO2 monitoring. Medical management used in a "cause-directed" manner successfully reversed 72% of the episodes of compromised PbtO(2), defined as restoration of a "normal" PbtO(2) (i.e. ≥ 25 mmHg). Ventilator manipulation, CPP augmentation, and sedation were the most frequent interventions. Increasing FiO(2) restored PbtO(2) 80% of the time. CPP augmentation and sedation were effective in 73 and 66% of episodes of compromised brain oxygen, respectively. ICP reduction using mannitol was effective in 73% of treated episodes, though was used only when PbtO(2) was compromised in the setting of elevated ICP. Successful medical treatment of brain hypoxia was associated with decreased mortality. Survivors (n = 38) had a 71% rate of response to treatment and non-survivors (n = 11) had a 44% rate of response (P = 0.01).Reduced PbtO(2) may occur in TBI patients despite efforts to maintain CPP. Medical interventions other than those to treat ICP and CPP can improve PbtO(2). This may increase the number of therapies for severe TBI in the ICU.

Brain tissue oxygenation (PbtO2)-guided management facilitates treatment of reduced PbtO2 episodes potentially conferring survival and outcome advantages in severe traumatic brain injury (TBI). To date, the nature and effectiveness of commonly used interventions in correcting compromised PbtO2 in TBI remains unclear. We sought to identify the most common interventions used in episodes of compromised PbtO2 and to analyze which were effective.A retrospective 7-year review of consecutive severe TBI patients with a PbtO2 monitor was conducted in a Level I trauma center's intensive care unit or neurosurgical registry. Episodes of compromised PbtO2 (defined as20 mm Hg for 0.25-4 hours) were identified, and clinical interventions conducted during these episodes were analyzed. Response to treatment was gauged on how rapidly (ΔT) PbtO2 normalized (20 mm Hg) and how great the PbtO2 increase was (ΔPbtO2). Intracranial pressure (ΔICP) and cerebral perfusion pressure (ΔCPP) also were examined for these episodes.Six hundred twenty-five episodes of reduced PbtO2 were identified in 92 patients. Patient characteristics were: age 41.2 years, 77.2% men, and Injury Severity Score and head or neck Abbreviated Injury Scale score of 34.0 ± 9.2 and 4.9 ± 0.4, respectively. Five interventions: narcotics or sedation, pressors, repositioning, FIO2/PEEP increases, and combined sedation or narcotics + pressors were the most commonly used strategies. Increasing the number of interventions resulted in worsening the time to PbtO2 correction. Triple combinations resulted in the lowest ΔICP and dual combinations in the highest ΔCPP (p0.05).Clinicians use a limited number of interventions when correcting compromised PbtO2. Using strategies employing many interventions administered closely together may be less effective in correcting PbO2, ICP, and CPP deficits. Some PbtO2 deficits may be self-limited.

How body position influences brain tissue oxygen (PbtO2) and intracranial pressure (ICP) in critically ill neurosurgical patients remains poorly defined. In a prospective observational repeated measures study, we examined the effects of 12 different body positions on neurodynamic and hemodynamic outcomes. Thirty-three consecutive patients (mean +/- SD, age = 48.3 +/- 16.6 years; 22 men), admitted after traumatic brain injury, subarachnoid hemorrhage, or craniotomy for tumor, were evaluated in a neurocritical care unit at a level 1 academic trauma center. Patients were eligible if the admission score in the Glasgow Coma Scale was < or =8 and they had a Licox CMP Monitoring System (Integra Neurosciences, Plainsboro, NJ). Patients were exposed to all 12 positions in random order. Changes from baseline to the 15-minute postposition assessment mean change scores showed a downward trend for PbtO2 for all positions with statistically significant decreases observed for supine head of bed (HOB) elevated 30 degrees and 45 degrees (p < .01) and right and left lateral positioning HOB 30 degrees (p < .05). ICP decreased with supine HOB 45 degrees (p < .01) and knee elevation, HOB 30 degrees and 45 degrees (p < .05), and increased (p < .05) with right and left lateral HOB 15 degrees. Hemodynamic parameters were similar in the various positions. Positioning practices can positively or negatively affect PbtO2 and ICP and fluctuate with considerable variability among patients. Nurses must consider potential effects of turning, evaluate changes with positioning on the basis of monitoring feedback from multimodality devices, and make independent clinical judgments about optimal positions to maintain or improve cerebral oxygenation.

Object The object of this study was to determine whether brain tissue oxygen (PbtO2)–based therapy or intracranial pressure (ICP)/cerebral perfusion pressure (CPP)–based therapy is associated with improved patient outcome after severe traumatic brain injury (TBI). Methods Seventy patients with severe TBI (postresuscitation GCS score ≤ 8), admitted to a neurosurgical intensive care unit at a university-based Level I trauma center and tertiary care hospital and managed with an ICP and PbtO2 monitor (mean age 40 ± 19 years [SD]) were compared with 53 historical controls who received only an ICP monitor (mean age 43 ± 18 years). Therapy for both patient groups was aimed to maintain ICP < 20 mm Hg and CPP > 60 mm Hg. Patients with PbtO2 monitors also had therapy to maintain PbtO2 > 20 mm Hg. Results Data were obtained from 12,148 hours of continuous ICP monitoring and 6,816 hours of continuous PbtO2 monitoring. The mean daily ICP and CPP and the frequency of elevated ICP (> 20 mm Hg) or suboptimal CPP (< 60 mm Hg) episodes were similar in each group. The mortality rate was significantly lower in patients who received PbtO2-directed care (25.7%) than in those who received conventional ICP and CPP–based therapy (45.3%, p < 0.05). Overall, 40% of patients receiving ICP/CPP–guided management and 64.3% of those receiving PbtO2–guided management had a favorable short-term outcome (p = 0.01). Among patients who received PbtO2-directed therapy, mortality was associated with lower mean daily PbtO2 (p < 0.05), longer durations of compromised brain oxygen (PbtO2 < 20 mm Hg, p = 0.013) and brain hypoxia (PbtO2 < 15 mm Hg, p = 0.001), more episodes and a longer cumulative duration of compromised PbtO2 (p < 0.001), and less successful treatment of compromised PbtO2 (p = 0.03). Conclusions These results suggest that PbtO2-based therapy, particularly when compromised PbtO2 can be corrected, may be associated with reduced patient mortality and improved patient outcome after severe TBI.

Pulmonary complications are frequently observed after severe traumatic brain injury (TBI), but little is known about the consequences of lung injury on brain tissue oxygenation and metabolism.We examined the association between lung function and brain tissue oxygen tension (PbtO2) in patients with severe TBI.We analyzed data from 78 patients with severe, nonpenetrating TBI who underwent continuous PbtO2 and intracranial pressure monitoring. Acute lung injury was defined by the presence of pulmonary infiltrates with a PaO2/FiO2 (PF) ratio less than 300 and the absence of left ventricular failure. A total of 587 simultaneous measurements of PbtO2 and PF ratio were examined using longitudinal data analysis.PbtO2 correlated strongly with PaO2 and PF ratio (P.05) independent of PaCO2, brain temperature, cerebral perfusion pressure, and hemoglobin. Acute lung injury was associated with lower PbtO2 (34.6 +/- 13.8 mm Hg at PF ratio300 vs 30.2 +/- 10.8 mm Hg [PF ratio 200-300], 28.9 +/- 9.8 mm Hg [PF ratio 100-199], and 21.1 +/- 7.4 mm Hg [PF ratio100], all P values.01). After adjusting for intracranial pressure, Marshall computed tomography score, and APACHE II (Acute Physiology and Chronic Health Evaluation) score, acute lung injury was an independent risk factor for compromised PbtO2 (PbtO220 mm Hg; adjusted odds ratio: 2.13, 95% confidence interval: 1.21-3.77; P.01).After severe TBI, PbtO2 correlates with PF ratio. Acute lung injury is associated with an increased risk of compromised PbtO2, independent from intracerebral and systemic injuries. Our findings support the use of lung-protective strategies to prevent brain hypoxia in TBI patients.

Transport of critically ill intensive care unit (ICU) patients may be hazardous. In this study, we examined the use of a portable head CT scanner (CereTom) in the ICU to assess its feasibility, safety, and radiological quality. Two hundred and twenty-five portable head CT scans were obtained from 114 patients (mean age = 57 +/- 18 years) treated in a neurosurgical intensive care unit at a university-based Level I trauma center. Patient radiological and ICU records were retrospectively reviewed. The vast majority of portable CT scans were performed after an intracranial procedure (24%) due to neurological deterioration (16%) or in routine follow-up (16%). Diagnostic quality was judged to be adequate, and no scans needed to be repeated because of poor quality. No scans were complicated by accidental disconnection of an intravenous line. In ventilated patients, there were no interruptions in mechanical ventilation and no inadvertent extubations. In addition, continuous intracranial monitoring, when in use, remained connected. The average total time to perform a portable head CT scan was 19.5 +/- 3.5 min. The actual scan time was 2.5 +/- 0.7 min. These results suggest that the portable CT scanner (CereTom) is feasible, easy to use, and safe and provides adequate radiological quality for diagnostic decisions.

Secondary neuronal injury is implicated in poor outcome after acute neurological insults. Outcome can be improved with protocol-driven therapy. These therapies have largely been based on monitoring and control of intracranial pressure and the maintenance of an adequate cerebral perfusion pressure. In recent years, brain tissue oxygen partial pressure (PbtO2) monitoring has emerged as a clinically useful modality and a complement to intracranial pressure monitors. This review examines the physiology of PbtO2 monitors and practical aspects of their use.

We analyzed the impact of shivering on brain tissue oxygenation (PbtO(2)) during induced normothermia in patients with severe brain injury.We studied patients with severe brain injury who developed shivering during induced normothermia. Induced normothermia was applied to treat refractory fever (body temperature [BT]or =38.3 degrees C, refractory to conventional treatment) using a surface cooling device with computerized adjustment of patient BT target to 37 +/- 0.5 degrees C. PbtO(2), intracranial pressure, mean arterial pressure, cerebral perfusion pressure, and BT were monitored continuously. Circulating water temperature of the device system was measured to assess the intensity of cooling.Fifteen patients (10 with severe traumatic brain injury, 5 with aneurysmal subarachnoid hemorrhage) were treated with induced normothermia for an average of 5 +/- 2 days. Shivering caused a significant decrease in PbtO(2) levels both in SAH and TBI patients. Compared to baseline, shivering was associated with an overall reduction of PbtO(2) from 34.1 +/- 7.3 to 24.4 +/- 5.5 mmHg (P0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P0.001).In patients with severe brain injury treated with induced normothermia, shivering was associated with a significant decrease of PbtO(2), which correlated with the intensity of cooling. Monitoring of therapeutic cooling with computerized thermoregulatory systems may help prevent shivering and optimize the management of induced normothermia. The clinical significance of shivering-induced decrease in brain tissue oxygenation remains to be determined.

Background: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO 2 ) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. Methods: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO 2 monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO 2 , ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. Results: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO 2 (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p 2 (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. Conclusions: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Hypertonic saline (HTS) may decrease intracranial pressure (ICP) in severe traumatic brain injury (STBI) and effectively resuscitates hypotensive patients. No data exist on institutional standardization of HTS for hypotensive patients with STBI. It remains unclear how HTS affects brain tissue oxygenation (PbtO2) in STBI. We hypothesized HTS could be safely standardized in patients with STBI and would lower ICP while improving cerebral perfusion pressure (CPP) and PbtO2. Under institutional guidelines in a Level I trauma center, 12 hypotensive STBI intensive care unit subjects received HTS. Inclusion criteria included mean arterial pressure (MAP) ≤ 90 mmHg, Glasgow Coma Scale (GCS) ≤ 8, ICP ≥ 20 mmHg, and serum [Na+] < 155 mEq/L. All patients underwent ICP monitoring. Hemodynamics, CPP, ICP, and PbtO2 data were collected before and hourly for 6 hours after HTS infusion. Guideline criteria compliance was greater than 95 per cent. No major complications occurred. Mean ICP levels dropped by 45 per cent (P < 0.01) and this drop persisted for 6 hours. CPP levels increased by 20 per cent (P < 0.05). PbtO2 remained persistently elevated for all time points after HTS infusion. Institutional use of HTS in STBI can be safely implemented in a center caring for neurotrauma patients. HTS infusion in hypotensive STBI reduces ICP and raises CPP. Brain tissue oxygenation tends to improve after HTS infusion.

Object Although neuron transplantation to repair the nervous system has shown promise in animal models, there are few practical sources of viable neurons for clinical application and insufficient approaches to bridge extensive nerve damage in patients. Therefore, the authors sought a clinically relevant source of neurons that could be engineered into transplantable nervous tissue constructs. The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture. Methods Cervical DRGs were harvested from 16 live patients following elective ganglionectomies, and thoracic DRGs were harvested from 4 organ donor patients. Following harvest, the DRGs were digested in a dispase–collagenase treatment to dissociate neurons for culture. In addition, dissociated human DRG neurons were placed in a specially designed axon expansion chamber that induces continuous mechanical tension on axon fascicles spanning 2 populations of neurons originally plated ∼ 100 μm apart. Results The adult human DRG neurons, positively identified by neuronal markers, survived at least 3 months in culture while maintaining the ability to generate action potentials. Stretch-growth of axon fascicles in the expansion chamber occurred at the rate of 1 mm/day to a length of 1 cm, creating the first engineered living human nervous tissue constructs. Conclusions These data demonstrate the promise of adult human DRG neurons as an alternative transplant material due to their availability, viability, and capacity to be engineered. Also, these data show the feasibility of harvesting DRGs from living patients as a source of neurons for autologous transplant as well as from organ donors to serve as an allograft source of neurons.

Brain death is a clinical diagnosis often confirmed with supplementary tests. In this study, we examined the relationship between brain death and the partial pressure of brain tissue oxygen (PbtO(2)). We hypothesized that a sustained PbtO(2) of 0 is associated with brain death.One hundred and twenty-six patients (Glasgow coma scaleor = 8, median age: 50 years) who underwent PbtO(2) monitoring were studied prospectively during a 2 year period in the neurointensive care unit at a university-based level I trauma center. PbtO(2), intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain temperature (BT) were compared before and after the diagnosis of brain death.Six patients (median age: 52 years) experienced brain death. In these patients, PbtO(2) decreased toward 0 mmHg as ICP increased and CPP decreased. PbtO(2) reached 0 only when there was clinical evidence for brain death. During the subsequent 12 hours until the second brain death examination, PbtO(2) remained 0 mmHg and did not respond to oxygen challenge. In addition, TCD examination demonstrated a 'to and fro' pattern consistent with brain death and cerebral circulatory arrest. PbtO(2) of 0 mmHg was observed in five non-brain dead patients. These episodes were transient (30 minutes) and responded to an oxygen challenge, directed treatment or catheter replacement.A sustained (30 minutes) brain PbtO(2) of 0 is consistent with brain death. We suggest that a sustained 'zero' PbtO(2) may be used to determine when a brain death examination is appropriate in the pharmacologically suppressed patient.

Object Control of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is the foundation of traumatic brain injury (TBI) management. In this study, the authors examined whether conventional ICP- and CPP-guided neurocritical care ensures adequate brain tissue O2 in the first 6 hours after resuscitation. Methods Resuscitated patients with severe TBI (Glasgow Coma Scale score ≤ 8 and Injury Severity Scale score ≥ 16) who were admitted to a Level I trauma center and who underwent brain tissue O2 monitoring within 6 hours of injury were evaluated as part of a prospective observational database. Therapy was directed to maintain an ICP of 25 mm Hg or less and a CPP of 60 mm Hg or higher. Data from a group of 25 patients that included 19 men and six women (mean age 39 ± 20 years) were examined. After resuscitation, ICP was 25 mm Hg or less in 84% and CPP was 60 mm Hg or greater in 88% of the patients. Brain O2 probes were allowed to stabilize; the initial brain tissue O2 level was 25 mm Hg or less in 68% of the patients, 20 mm Hg or less in 56%, and 10 mm Hg or less in 36%. Nearly one third (29%) of patients with ICP readings of 25 mm Hg or less and 27% with CPP levels of 60 mm Hg or greater had severe cerebral hypoxia (brain tissue O2 ≤10 mm Hg). Nineteen patients had both optimal ICP (≤25 mm Hg) and CPP (> 60 mm Hg); brain tissue O2 was 20 mm Hg or less in 47% and 10 mm Hg or less in 21% of these patients. The mortality rate was higher in patients with reduced brain tissue O2. Conclusions Brain resuscitation based on current neurocritical care standards (that is, control of ICP and CPP) does not prevent cerebral hypoxia in some patients. This finding may help explain why secondary neuronal injury occurs in some patients with adequate CPP and suggests that the definition of adequate brain resuscitation after TBI may need to be reconsidered.

Objectives: Previous reports indicate that elevated intracranial pressure (ICP) may cause spontaneous cerebrospinal fluid (CSF) leaks. In this study we examined the clinical diagnosis of benign intracranial hypertension (BIH) in this population using the modified Dandy criteria. Methods: We performed a retrospective review of clinical data and measurements of ICPs after surgical repair. Results: Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. In 11 patients with CSF pressure measurements, strict adherence to the modified Dandy criteria definitively confirmed a diagnosis of BIH in 8 patients (72%) and a likely diagnosis in the 3 remaining patients. The mean ICP was 31.1 cm H2O (range, 17.3 to 52 cm H2O), and 81% of the patients were obese middle-aged women. Clinically, all patients had signs and/or symptoms of elevated ICP, such as headache (91%), pulsatile tinnitus (45%), hypertension (45%), balance problems (27%), and visual complaints (18%). Surgical repair was 100% successful in leak cessation over a mean follow-up of 14.1 months. Conclusions: Most patients with spontaneous CSF leaks fulfill the modified Dandy criteria; thus, this disorder appears to be a variant of BIH. Further investigation is needed to determine the exact cause of elevated CSF pressures in this group and whether medical or surgical treatments to correct the intracranial hypertension are warranted.

Intra-arterial papaverine (IAP) is used to treat symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). IAP, however, can increase intracranial pressure (ICP). In this study we examined whether IAP alters brain oxygen (BtO2). Poor clinical grade (Hunt & Hess IV or V) SAH patients who underwent continuous ICP and BtO2 monitoring during IAP infusion for symptomatic cerebral vasospasm were evaluated as part of a prospective observational study. Data are available for five patients (median age 58) who received IAP for cerebral vasospasm 4 to 7 days after SAH. In each patient, angiographic vasospasm was improved on postinfusion angiogram. Mean ICP before IAP was 23.04±1.18 mmHg; it increased immediately after IAP infusion and remained elevated (29.89±1.18 mmHg; p

Object. An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. Methods. Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 ± 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 ± 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). Conclusions. The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.

When a new technology is introduced it is important to empower the bedside practitioner with a resource tool that outlines the purpose, placement procedure, technology application guidelines, and interventions associated with that new technology. This promotes product and patient safety and successful implementation of the new technology. Continued evaluation of bedside clinical practice and the technology used in the care and treatment of the severe brain injured patient can lead to improvements in management and in technology design. Future clinical research initiatives exploring the impact of new technology will enable us to discover cost-effective treatments and interventions that will improve the outcome for a person with traumatic brain injury, a condition that devastates hundreds of thousands of Americans each year.

Background Spontaneous cerebrospinal fluid (CSF) leak is a condition that previously has been considered idiopathic and classified as having “normal” intracranial pressure (ICP). We present clinical and radiographic evidence that indicates elevated ICP in this group. In addition, we review the pathophysiology and unique management issues in caring for patients with spontaneous CSF leak. Methods We present a retrospective review of medical records, imaging studies, ICP measurements, and surgical treatment of patients with spontaneous CSF leaks. Results Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. Ten patients underwent postoperative lumbar puncture with CSF pressure measurement during clinically indicated computed tomography cisternograms. Intracranial pressures were elevated in all 10 patients, with a mean of 26.5 cm H2O and a range of 17.3–34 cm H2O, (normal, 0–15 cm H2O). Demographically, 13/16 patients were women, all were middle-aged with a mean age of 49.6 years, and 15/16 patients were obese with a mean body mass index of 35.9 kg/m2. Radiographically, 15 patients had imaging of the sella turcica, 10 patients had completely empty sellas, and 5 patients had partially empty sellas. Surgical repair was 100% successful in leak cessation with a mean follow-up of 14.1 months. Conclusion Although the precise cause and mechanism of spontaneous CSF leaks is not fully understood, this study sheds light on important factors to consider. Patients with this condition have similar physical and radiographic findings such as middle-aged, female gender, obesity, and empty sella. Additional investigation is needed to determine the exact cause of the condition, its relationship to elevated ICPs, and if further medical or surgical treatments to correct the intracranial hypertension are warranted.

Traumatic brain injury (TBI) is associated with a hypercoagulable state, the mechanism and duration of which remain unclear. We sought to determine whether thromboelastography (TEG) analysis could identify the hypercoagulable state after TBI, as defined by elevations in maximal amplitude (MA), thrombus generation (TG), G value (G), and alpha angle (αA).Patients with moderate-severe TBI, defined primarily as a GCS12, admitted between 1/2012 and 8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and 96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was defined as48 h.Twenty five patients (80 % men) and 7 age- and sex-matched control subjects were studied. Median age was 38 years (range 18-85). Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p = 0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min (791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G [11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG (p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p ≤ 0.001), and G value by 1.3 d/cm(2) (p ≤ 0.001) when clustered by pairs in regression analysis. Lower MA values trended toward home discharge (p = 0.08).The data suggest a progressive and delayed hypercoagulable state observed days after initial TBI. The hypercoagulable state may reflect excess platelet activity.

BACKGROUND: Our objective was to determine whether there is variability in the foundational literature and across centers in how mean arterial blood pressure is measured to calculate cerebral perfusion pressure. METHODS: We reviewed foundational literature and sent an e-mail survey to members of the Neurocritical Care Society. RESULTS: Of 32 articles reporting cerebral perfusion pressure data, the reference point for mean arterial blood pressure was identified in 16: 10 heart and 6 midbrain. The overall survey response rate was 14.3%. Responses from 31 of 34 (91%) United Council for Neurologic Subspecialties fellowship-accredited Neurointensive Care Units indicated the reference point was most often the heart (74%), followed by the midbrain (16%). Conflicting answers were received from 10%. CONCLUSIONS: There is substantive heterogeneity in both research reports and clinical practice in how mean arterial blood pressure is measured to determine cerebral perfusion pressure.

Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH.On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden.When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH.Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Background and Purpose— Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Methods— Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO 2 ) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO 2 and CMD pyruvate and categorized as hypoxic (PbtO 2 119 μmol/L) versus nonhyperglycolytic. Results— Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%–80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%–98%) than brain hypoxia (11%; interquartile range, 4%–75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%–95%] in nonsurvivors versus 9% [interquartile range 3%–17%] in survivors; P =0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%–87%] versus 88% [interquartile range, 27%–99%]; P =0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0–3 1.49; CI, 1.08–2.05; P =0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59–1.03; P =0.08). Conclusions— Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

Follow-up head CT scans are important in neurocritical care but involve intrahospital transport that may be associated with potential hazards including a deleterious effect on brain tissue oxygen pressure (PbtO(2)). Portable head CT (pHCT) scans offer an alternative imaging technique without a need for patient transport. In this study, the investigators examined the effects of pHCT scans on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) in patients with severe brain injury.Fifty-seven pHCT scans were obtained in 34 patients (mean age of 42 ± 15 years) who underwent continuous ICP, CPP, and PbtO(2) monitoring in the neuro intensive care unit at a university-based Level I trauma center. Patient ICU records were retrospectively reviewed and physiological data obtained during the 3 hours before and after pHCT scans were examined.Before pHCT, the mean ICP and CPP were 14.3 ± 7.4 and 78.9 ± 20.2 mm Hg, respectively. Portable HCT had little effect on ICP (mean ICP 14.1 ± 6.6 mm Hg, p = 0.84) and CPP (mean CPP 81.0 ± 19.8 mm Hg, p = 0.59). The mean PbtO(2) was similar before and after pHCT (33.2 ± 17.0 mm Hg and 31.6 ± 15.9 mm Hg, respectively; p = 0.6). Ten episodes of brain hypoxia (PbtO(2)15 mm Hg) were observed before pHCT; these episodes prompted scans. Brain hypoxia persisted in 5 patients after pHCT despite treatment. No new episodes of brain hypoxia were observed during or after pHCT.These data suggest that pHCT scans do not have a detectable effect on a critically ill patient's ICP, CPP, or PbtO(2).

The purpose of this multicenter observational clinical study was to evaluate the performance of a near-infrared (NIR)-based, non-invasive, portable device to screen for traumatic intracranial hematomas. Five trauma centers collected data using the portable NIR device at the time a computed tomography (CT) scan was performed to evaluate a suspected traumatic brain injury (TBI). The CT scans were read by an independent neuroradiologist who was blinded to the NIR measurements. Of 431 patients enrolled, 365 patients were included in the per-protocol population analyzed. Of the 365 patients, 96 were determined by CT scan to have intracranial hemorrhages of various sizes, depths, and anatomical locations. The NIR device demonstrated sensitivity of 88% (95% confidence interval [CI] 74.9,95.0%), and specificity of 90.7% (95% CI 86.4,93.7%), in detecting the 50 intracranial hematomas that were large enough to be clinically important (larger than 3.5 mL in volume), and that were less than 2.5 cm from the surface of the brain. For all 96 cases with intracranial hemorrhage, regardless of size and type of hemorrhage, the sensitivity was 68.7% (CI 58.3,77.6%), and specificity was 90.7% (CI 86.4,93.7%). These results confirm the results of previous studies that indicate that a NIR-based portable device can reliably screen for intracranial hematomas that are superficial and of a size likely to be of clinical importance. The NIR device cannot replace CT scanning in the diagnosis of TBI, but the device might be useful to supplement clinical information used to triage TBI patients, and in situations in which CT scanning is not readily available.