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Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Background and Purpose: Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes., Methods: We determined prevalence of infections in a multicenter, triethnic study of ICH. We performed univariate and multivariate analyses to determine the association of infection with admission characteristics and hospital complications. We performed logistic regression on association of infection with outcomes after controlling for known determinants of prognosis after ICH (volume, age, infratentorial location, intraventricular hemorrhage, and Glasgow Coma Scale)., Results: Among 800 patients, infections occurred in 245 (31%). Admission characteristics associated with infection in multivariable models were ICH volume (odds ratio [OR], 1.02/mL; 95% confidence interval [CI], 1.01-1.03), lower Glasgow Coma Scale (OR, 0.91 per point; 95% CI, 0.87-0.95), deep location (reference lobar: OR, 1.90; 95% CI, 1.28-2.88), and black race (reference white: OR, 1.53; 95% CI, 1.01-2.32). In a logistic regression of admission and hospital factors, infections were associated with intubation (OR, 3.1; 95% CI, 2.1-4.5), dysphagia (with percutaneous endoscopic gastrostomy: OR, 3.19; 95% CI, 2.03-5.05 and without percutaneous endoscopic gastrostomy: OR, 2.11; 95% CI, 1.04-4.23), pulmonary edema (OR, 3.71; 95% CI, 1.29-12.33), and deep vein thrombosis (OR, 5.6; 95% CI, 1.86-21.02), but not ICH volume or Glasgow Coma Scale. Infected patients had higher discharge mortality (16% versus 8%; P=0.001) and worse 3-month outcomes (modified Rankin Scale ≥3; 80% versus 51%; P<0.001). Infection was an independent predictor of poor 3-month outcome (OR, 2.6; 95% CI, 1.8-3.9)., Conclusions: There are identifiable risk factors for infection after ICH, and infections predict poor outcomes., (© 2014 American Heart Association, Inc.)

Introduction: Fibrocartilaginous embolism (FCE) is an uncommon cause of myelopathy that should be considered after more common causes have been ruled out., Objective: This article presents a case report of a 50-year-old man with acute myelopathy attributed to FCE and summarizes the clinical features of the disease by analyzing all of the published evidence., Data Sources and Extraction: Two computerized literature searches (MEDLINE-Pubmed, EMBASE, the Cochrane Library) were performed. The search term used was "Fibrocartilaginous embolism." No language restrictions were applied. All articles were evaluated and key data were extracted according to predefined criteria: patient's age, year of publication, localization of the embolism and type of vascular syndrome, clinical outcome, and time to death in the fatal cases., Results: Fifty-two cases (39 biopsy proven and 13 clinically diagnosed) were found in the literature. Median age at presentation was 37 years (interquartile range, 19-53) and 56% were women. Median progression of symptoms was 6 hours (interquartile range, 5-60 h), predominantly affecting the cervical spine (48%) by an arterial embolic source (56%)., Conclusions: FCE is an unusual cause of spinal cord and cerebral ischemia with unknown incidence. Implementation of diagnostic imaging techniques and initial management of acute spinal disorders care in intensive care units might increase the incidence of disease antemortem. FCE should be considered in the differential diagnosis of ischemic spinal cord injury when no other causes can be identified and especially when the onset is progressive over several hours.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

Neurotrauma continues to be a significant cause of morbidity and mortality. Prevention of primary neurologic injury is a critical public health concern. Early and thorough assessment of the patient with neurotrauma with high index of suspicion of traumatic spinal cord injuries and traumatic vascular injuries requires a multidisciplinary approach involving prehospital providers, emergency physicians, neurosurgeons, and neurointensivists. Critical care management of the patient with neurotrauma is focused on the prevention of secondary injuries. Much research is still needed for potential neuroprotection therapies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes., Methods: We performed a retrospective case-control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score., Results: Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %)., Conclusions: Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.

Introduction: Cerebral glucose metabolism and energy production are affected by serum glucose levels. Systemic glucose variability has been shown to be associated with poor outcome in critically ill patients. The objective of this study was to assess whether glucose variability is associated with cerebral metabolic distress and outcome after subarachnoid hemorrhage., Methods: A total of 28 consecutive comatose patients with subarachnoid hemorrhage, who underwent cerebral microdialysis and intracranial pressure monitoring, were studied. Metabolic distress was defined as lactate/pyruvate ratio (LPR) >40. The relationship between daily glucose variability, the development of cerebral metabolic distress and hospital outcome was analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes., Results: Daily serum glucose variability was expressed as the standard deviation (SD) of all serum glucose measurements. General linear models were used to relate this predictor variable to cerebral metabolic distress and mortality at hospital discharge. A total of 3,139 neuromonitoring hours and 181 days were analyzed. After adjustment for Glasgow Coma Scale (GCS) scores and brain glucose, SD was independently associated with higher risk of cerebral metabolic distress (adjusted odds ratio = 1.5 (1.1 to 2.1), P = 0.02). Increased variability was also independently associated with in hospital mortality after adjusting for age, Hunt Hess, daily GCS and symptomatic vasospasm (P = 0.03)., Conclusions: Increased systemic glucose variability is associated with cerebral metabolic distress and increased hospital mortality. Therapeutic approaches that reduce glucose variability may impact on brain metabolism and outcome after subarachnoid hemorrhage.

Objective: Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures., Methods: In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships., Results: Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz., Interpretation: In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz., (© 2014 American Neurological Association.)

Background: The objective of this study was to investigate the relationship between cardiac index (CI) response to a fluid challenge and changes in brain tissue oxygen pressure (PbtO(2)) in patients with subarachnoid hemorrhage (SAH)., Methods: Prospective observational study was conducted in a neurological intensive care unit of a university hospital. Fifty-seven fluid challenges were administered to ten consecutive comatose SAH patients that underwent multimodality monitoring of CI, intracranial pressure (ICP), and PbtO(2), according to a standardized fluid management protocol., Results: The relationship between CI and PbtO(2) was analyzed with logistic regression utilizing generalized estimating equations. Of the 57 fluid boluses analyzed, 27 (47 %) resulted in a ≥ 10 % increase in CI. Median absolute (+5.8 vs. +1.3 mmHg) and percent (20.7 vs. 3.5 %) changes in PbtO(2) were greater in CI responders than in non-responders within 30 min after the end of the fluid bolus infusion. In a multivariable model, a CI response was independently associated with PbtO(2) response (adjusted odds ratio 21.5, 95 % CI 1.4-324, P = 0.03) after adjusting for mean arterial pressure change and end-tidal CO(2). Stroke volume variation showed a good ability to predict CI and PbtO(2) response with areas under the ROC curve of 0.86 and 0.81 with the best cut-off values of 9 % for both responses., Conclusion: Bolus fluid resuscitation resulting in augmentation of CI can improve cerebral oxygenation after SAH.

Background: Cerebral microbleeds (CMBs) are commonly found after stroke but have not previously been studied in patients with subarachnoid hemorrhage (SAH)., Objective: To study the prevalence, radiographic patterns, predictors, and impact on outcome of CMBs in patients with SAH., Methods: We analyzed retrospectively 39 consecutive patients who underwent T2*-weighted gradient-echo imaging within 7 days after onset of spontaneous SAH. We report the frequency and location of CMBs and show their association with demographics, vascular risk factors, the Hunt-Hess grade, the modified Fisher Scale, the Acute Physiological and Chronic Health Evaluation II, magnetic resonance imaging findings including diffusion-weighted imaging lesions, and laboratory data, as well as data on rebleeding, global cerebral edema, delayed cerebral ischemia, seizures, the Telephone Interview for Cognitive Status, and the modified Rankin Scale., Results: Eighteen patients (46%) had CMBs. Of these patients, 9 had multiple CMBs, and overall a total of 50 CMBs were identified. The most common locations of CMBs were lobar (n = 23), followed by deep (n = 15) and infratentorial (n = 12). After adjustment for age and history of hypertension, CMBs were related to the presence of diffusion-weighted imaging lesions (odds ratio, 5.24; 95% confidence interval, 1.14-24.00; P = .03). Three months after SAH, patients with CMBs had nonsignificantly higher modified Rankin Scale scores (odds ratio, 2.50; 95% confidence interval, 0.67-9.39; P = .18)., Conclusion: This study suggests that CMBs are commonly observed and associated with diffusion-weighted imaging lesions in patients with SAH. Our findings may represent a new mechanism of tissue injury in SAH. Further studies are needed to investigate the clinical implications of CMBs.

Background: The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury., Methods: We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality., Results: A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P < 0.001). Low brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P < 0.03) in addition to Glasgow Coma Scale scores (P = 0.029)., Conclusions: Reduced brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

Conserved from yeast to humans, TFIIH is essential for RNA polymerase II transcription and nucleotide excision repair (NER). TFIIH consists of a core that includes the DNA helicase Xeroderma pigmentosum B (XPB) and a kinase subcomplex. Trypanosoma brucei TFIIH harbours all core complex components and is indispensable for RNA polymerase II transcription of spliced leader RNA genes (SLRNAs). Kinetoplastid organisms, however, possess two highly divergent XPB paralogues with only the larger being identified as a TFIIH subunit in T. brucei. Here we show that a knockout of the gene for the smaller paralogue, termed XPB-R (R for repair) resulted in viable cultured trypanosomes that grew slower than normal. XPB-R depletion did not affect transcription in vivo or in vitro and XPB-R was not found to occupy the SLRNA promoter which assembles a RNA polymerase II transcription pre-initiation complex including TFIIH. However, XPB-R(-/-) cells were much less tolerant than wild-type cells to UV light- and cisplatin-induced DNA damage, which require NER. Since XPB-R(-/-) cells were not impaired in DNA base excision repair, XPB-R appears to function specifically in NER. Interestingly, several other protists possess highly divergent XPB paralogues suggesting that XPBs specialized in transcription or NER exist beyond the Kinetoplastida., (© 2013 John Wiley & Sons Ltd.)

Background: Hematoma expansion, the leading cause of neurologic deterioration after intracerebral hemorrhage (ICH), remains one of the few modifiable risk factors for poor outcome. In the present study, we explored whether common genetic variants within the hemostasis pathway were related to hematoma expansion during the acute period after ICH., Methods: Patients with spontaneous ICH who were admitted to the institutional Neuro-ICU between 2009 and 2011 were enrolled in the study, and clinical data were collected prospectively. Hematoma size was measured in patients admitted on or before postbleed day 2. Baseline models for hematoma growth were constructed using backwards stepwise logistic regression. Genotyping of single-nucleotide polymorphisms for 13 genes involved in hemostasis was performed, and the results were individually included in the above baseline models to test for independent association of hematoma expansion., Results: During the study period, 82 patients were enrolled in the study and had complete data. The mean age was 65.9 ± 14.9 years, and 38% were female. Only von Willebrand factor was associated with absolute and relative hematoma growth in univariate analysis (P < .001 and P = .007, respectively); von Willebrand factor genotype was independently predictive of relative hematoma growth but only approached significance for absolute hematoma growth (P = .002 and P = .097, respectively)., Conclusions: Our genomic analysis of various hemostatic factors identified von Willebrand factor as a potential predictor of hematoma expansion in patients with ICH. The identification of von Willebrand factor single-nucleotide polymorphisms may allow us to better identify patients who are at risk for hematoma enlargement and will benefit the most from treatment. The relationship of von Willebrand factor with regard to hematoma enlargement in a larger population warrants further study., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Hypothermia has long been recognized as an effective therapy for acute neurologic injury. Recent advances in bedside technology and greater understanding of thermoregulatory mechanisms have made this therapy readily available at the bedside. Critical care management of the hypothermic patient can be divided into 3 phases: induction, maintenance, and rewarming. Each phase has known complications that require careful monitoring. At present, hypothermia has only been shown to be an effective neuroprotective therapy in cardiac arrest survivors. The primary use of hypothermia in the neurocritical care unit is to treat increased intracranial pressure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood., Methods: We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury., Results: Intracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p = 0.001), blood pressure (p < 0.001), and respiratory rate (p < 0.001). There were trends for rising cerebral perfusion pressure (p = 0.03) and intracranial pressure (p = 0.06) seen after seizure onset. Intracortical seizure-associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p = 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively)., Interpretation: We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside., (© 2013 American Neurological Association.)

Background: Altered cerebral vasomotor reactivity leading to vasospasm can be seen both in patients with primary headache disorders (PHD) and in patients with subarachnoid hemorrhage (SAH). The pathogenesis of vasospasm in post-SAH patients and in headache disorder sufferers may be related. To address this hypothesis, we analyzed a large cohort of SAH patients to determine whether a diagnosis of PHD predisposes to vasospasm, delayed cerebral ischemia, or worsened clinical outcome., Methods: Prospectively collected data from patients enrolled in the SAH Outcomes Project between 1996 and 2006 were analyzed. Patients were segregated based on whether they had a diagnosis of PHD or not and were subsequently compared for differences in clinical and radiographic outcome., Results: A total of 921 SAH patients were analyzed, 265 of which had a diagnosis of PHD. In total, symptomatic vasospasm was seen in 17%, while angiographic vasospasm was seen in 28%. Vasospasm rates were similar among patients with a PHD and in those without a PHD (p > 0.05). However, on multivariate analysis new ischemic infarcts were more common in patients with a PHD as compared to patients without a PHD (p = 0.015). Functional outcomes at 3 months were similar among PHD and non-PHD patients (p > 0.05)., Conclusion: A history of PHD is associated with an increased rate of ischemic infarcts during admission for SAH. Increased rates of vasospasm within small cerebral blood vessels may be implicated. Further studies are warranted to more closely link the mechanisms of vasospasm in PHD and SAH patients.

Cerebral microbleeds (CMBs) are commonly found in patients with stroke and cerebral amyloid angiopathy. However, there have been no reports of CMBs or their acute appearance in patients with status epilepticus. Herein we describe two patients with refractory status epilepticus of uncertain origin. Both patients were previously healthy, and their initial imaging showed no underlying CMBs. One patient's follow-up susceptibility-weighted imaging 29 days after initial imaging showed 63 new CMBs. The other patient's follow-up susceptibility-weighted imaging 41 days after initial imaging showed 14 new CMBs. Multimodal neuromonitoring revealed increase in lactate-pyruvate ratio, decrease in partial brain tissue oxygen tension, increase in pressure reactivity index, and fluctuations of blood pressure and cerebral perfusion pressure. This report demonstrates that multiple new CMBs may develop in patients with refractory status epilepticus (SE)., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Conserved from yeast to mammals, phosphorylation of the heptad repeat sequence Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7) in the carboxy-terminal domain (CTD) of the largest RNA polymerase II (RNA Pol II) subunit, RPB1, mediates the enzyme's promoter escape and binding of RNA-processing factors, such as the m(7)G capping enzymes. The first critical step, Ser(5) phosphorylation, is carried out by cyclin-dependent kinase 7 (CDK7), a subunit of the basal transcription factor TFIIH. Many early-diverged protists, such as the lethal human parasite Trypanosoma brucei, however, lack the heptad repeats and, apparently, a CDK7 ortholog. Accordingly, characterization of trypanosome TFIIH did not identify a kinase component. The T. brucei CTD, however, is phosphorylated and essential for transcription. Here we show that silencing the expression of T. brucei cdc2-related kinase 9 (CRK9) leads to a loss of RPB1 phosphorylation. Surprisingly, this event did not impair RNA Pol II transcription or cotranscriptional m(7)G capping. Instead, we observed that CRK9 silencing led to a block of spliced leader (SL) trans splicing, an essential step in trypanosome mRNA maturation, that was caused by hypomethylation of the SL RNA's unique cap4.

Introduction: It is still unknown whether subsequent perihaematomal oedema (PHE) formation further increases the odds of an unfavourable outcome., Methods: Demographic, clinical, radiographic and outcome data were prospectively collected in a single large academic centre. A multiple logistic regression model was then developed to determine the effect of admission oedema volume on outcome., Results: 133 patients were analysed in this study. While there was no significant association between relative PHE volume and discharge outcome (p=0.713), a strong relationship was observed between absolute PHE volume and discharge outcome (p=0.009). In a multivariate model incorporating known predictors of outcome, as well as other factors found to be significant in our univariate analysis, absolute PHE volume remained a significant predictor of poor outcome only in patients with intracerebral haemorrhage (ICH) volumes ≤30 cm(3) (OR 1.123, 95% CI 1.021 to 1.273, p=0.034). An increase in absolute PHE volume of 10 cm(3) in these patients was found to increase the odds of poor outcome on discharge by a factor of 3.19., Conclusions: Our findings suggest that the effect of absolute PHE volume on functional outcome following ICH is dependent on haematoma size, with only patients with smaller haemorrhages exhibiting poorer outcome with worse PHE. Further studies are needed to define the precise role of PHE in driving outcome following ICH.

Object: The authors evaluated the rates of ventriculostomy-related infections (VRIs) after antibiotic-coated extraventricular drains (ac-EVDs) were introduced as the standard of care., Methods: A retrospective chart review was conducted of adult patients admitted to NewYork-Presbyterian Hospital neurological intensive care unit in whom an EVD was placed between February 2007 and November 2009, excluding individuals receiving EVDs due to an infection of a primary device. Three time periods were defined depending on type of EVD in use: Period 1, conventional EVDs; Period 2, either ac-EVDs or conventional EVDs; and Period 3, ac-EVDs. Definite/probable VRIs that occurred during the 3 periods were evaluated and established as determinants of VRIs by using a Cox proportional hazards model. Prolonged systemic antibiotics were given for the duration of EVD placement in each of the 3 periods per institutional policy., Results: Data from 141 individuals were evaluated; mean patient age was 53.8 ± 17.2 years and 54% were female. There were 2 definite and 19 probable VRIs. The incidence of definite/probable VRI (per 1000 person-catheter days) decreased from Period 1 to 3 (24.5, 16.2, and 4.4 in Periods 1, 2, and 3, respectively; p < 0.0001). Patients with VRIs were more likely to be female than male (23.7% vs 3.1%, p < 0.003) and have had an EVD in place for a longer duration, although there was no significant difference among the 3 periods (7.9 ± 6.7 [Period 1], 8.1 ± 7.1 [Period 2], and 8.6 ± 5.8 [Period 3] mean days; p = 0.87, ANOVA). Analysis of effect modification in a stepwise model showed that period, age, and age and female interaction were significant predictors of VRIs. The period was the strongest predictor of VRI (p = 0.0075). After adjustment for age and age and sex interaction, the survival rate was 53% at the end of Period 2 and 91% at the end of Period 3., Conclusions: Rates of VRIs have decreased with the addition of ac-EVDs to the routine use of prolonged systemic antibiotics at the authors' institution.

Background: Early neurological deterioration occurs frequently after subarachnoid haemorrhage (SAH). The impact on hospital course and outcome remains poorly defined., Methods: We identified risk factors for worsening on the Hunt-Hess grading scale within the first 24 h after admission in 609 consecutively admitted aneurysmal SAH patients. Admission risk factors and the impact of early worsening on outcome was evaluated using multivariable analysis adjusting for age, gender, admission clinical grade, admission year and procedure type. Outcome was evaluated at 12 months using the modified Rankin Scale (mRS)., Results: 211 patients worsened within the first 24 h of admission (35%). In a multivariate adjusted model, early worsening was associated with older age (OR 1.02, 95% CI 1.001 to 1.03; p=0.04), the presence of intracerebral haematoma on initial CT scan (OR 2.0, 95% CI 1.2 to 3.5; p=0.01) and higher SAH and intraventricular haemorrhage sum scores (OR 1.05, 95% CI 1.03 to 1.08 and 1.1, 95% CI 1.01 to 1.2; p<0.001 and 0.03, respectively). Early worsening was associated with more hospital complications and prolonged length of hospital stay and was an independent predictor of death (OR 12.1, 95% CI 5.7 to 26.1; p<0.001) and death or moderate to severe disability (mRS 4-6, OR 8.4, 95% CI 4.9 to 14.5; p=0.01) at 1 year., Conclusions: Early worsening after SAH occurs in 35% of patients, is predicted by clot burden and is associated with mortality and poor functional outcome at 1 year.

Background: Nicardipine and labetalol are two commonly used antihypertensives for treating elevated blood pressures in the setting of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). There are no studies comparing these two agents as continuous infusions., Methods: A retrospective chart review was conducted of patients admitted between November 2009 and January 2011 with ICH and SAH to compare effectiveness and safety between both agents. Percent time spent at goal was set as the primary outcome. The secondary outcomes included blood pressure variability, time to goal, incidence of bradycardia, tachycardia, and hypotension., Results: A total of 81 patients were available for analysis, 10 initiated on labetalol (LAB), 57 on nicardipine (NIC), and 14 required the combination of these agents (COMB) to reach goal. We found no difference between NIC, LAB, and the COMB groups in the median percent time at goal [88 % (61-98); 93 % (51-99); 66 % (25-95), (p = NS)]. Median percentage of blood pressure variability, hypotension, and bradycardia were also comparable between groups, however, more tachycardia was observed in the COMB group versus both LAB and NIC groups (45 vs. 0 vs. 3 %; p < 0.001). Mean time to goal SBP in 24 patients who had BP readings available at 1st h of initiation was 32 ± 34 min in the NIC group and 53 ± 42 min in the LAB group (p = 0.03)., Conclusions: Both agents appear equally effective and safe for blood pressure control in SAH and ICH during the initial admission hours. A prospective study is needed to validate these findings.

Introduction: Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients., Methods: This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials., Results: Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed., Conclusions: Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit.

Objective: Although brain swelling is an important cause of neurological deterioration, real time measurement of brain edema does not currently exist. Because thermal conductivity is proportional to percentage water content, we used the thermal conductivity constant to estimate brain water content (BWC)., Methods: Between June 2008 and November 2010, 36 comatose brain-injured patients underwent cerebral blood flow monitoring using a thermal diffusion probe in our neurocritical care unit. BWC was estimated hourly utilizing the measured thermal conductivity and the known temperature-adjusted thermal conductivity of water. In vitro experiments were performed to validate this formula using agar, glycerol, and water mixtures with different water content., Results: Thermal conductivity was highly correlated (R(2) = 0.99) and estimated water content was well correlated with actual water content (mean difference, 0.58%) in the in vitro preparations. The majority of the 36 patients (median age, 57 years; 44% female) had subarachnoid hemorrhage (n = 14) or cardiac arrest (n = 9). Initial BWC at the time of monitoring ranged from 67.3 to 85.5%. Brain regions appearing edematous on computed tomography showed higher estimated BWC than normal-appearing brain regions (79.1 vs 70.2%; p < 0.01). Bolus osmotherapy (20% mannitol or 23.4% hypertonic saline) decreased BWC from 77.2 ± 0.7% (mean ± standard error) at baseline to 76.1 ± 0.5% at 1 hour, 76.5 ± 0.3% at 2 hours, and 76.7 ± 0.2% at 3 hours (all p ≤ 0.03)., Interpretation: Real time monitoring of BWC is feasible using thermal conductivity. Further studies are needed to confirm the clinical utility of this technique., (Copyright © 2012 American Neurological Association.)

Background: Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH., Methods: This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined., Results: Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P < 0.001) and a 1.22 mmHg decrease in CPP (P < 0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P < 0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased., Conclusions: Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

The ICH score is a validated method of assessing the risk of mortality and morbidity after intracerebral hemorrhage (ICH). We sought to compare the ability of the ICH score to predict outcome assessed with three of the most widely used scales: the Barthel Index (BI), modified Rankin Scale (mRS), and Glasgow Outcome Score (GOS). All patients with ICH treated at our institution between February 2009 and March 2011 were followed-up at three months using the mRS, GOS, and BI. The ICH score was highly correlated with the three-month mRS (ρ=0.59, p<0.001), BI (ρ=-0.57, p<0.001) and GOS (ρ=0.61, p<0.001). The ICH score also predicted dependency for each measure well, with areas under the curve falling between 0.826 and 0.833. Our results suggest that future clinical studies that use the ICH score to stratify patients may employ any of the three outcome scales and expect good discrimination of disability., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Alteration in platelet aggregation has been shown to promote bleeding and affect outcome after intracerebral hemorrhage (ICH).We investigated the influence of genetic variants of platelet aggregation, and their effects on admission ICH volume and clinical outcome., Methods: Our prospective study analyzed selected candidate single-nucleotide polymorphisms (SNPs) previously associated with platelet aggregation phenotype in previous genome-wide association studies, with regards to outcome and ICH volume. Patients were assessed at the Columbia University Medical Center Neuro-Intensive Care Unit. Exclusion criteria included age <18 years, ICH following trauma, hemorrhagic transformation, or tumor, no consent for genetic analysis, or incomplete data. Radiological variables (location and volume of acute ICH, presence of intraventricular extension, midline shift, and hydrocephalus) and clinical variables (mortality and modified Rankin score at discharge) were prospectively recorded., Results: One hundred and twenty-two patients with spontaneous ICH between February 2009 and May 2011 diagnosed via clinical assessment and admission computed tomography scan were included. The median admission Glasgow coma scale score (GCS) was 11·5. Univariate predictors of mortality at discharge included systolic blood pressure, presence of intraventricular hemorrhage, anticoagulant use, and GCS, the only independent predictor of discharge mortality (P<0·001). Age, intraventricular hemorrhage, and GCS were associated with poor functional outcome; age (P = 0·001) and GCS (P<0·001) were significant in the multivariate model. Admission GCS (P<0·01), antiplatelet use, and rs342286 (PIK3CG; P = 0·04; R(2) = 0·247) had univariate associations with hematoma volume., Discussion: We identified SNP rs342286 as an independent predictor of admission hematoma volume. Our findings suggest that PIK3CG function, which is previously linked to this SNP and affects platelet aggregation, impacts the severity of the intraparenchymal bleed.

Object: Intracerebral hemorrhage (ICH) is frequently complicated by acute hydrocephalus, necessitating emergency CSF diversion with a subset of patients, ultimately requiring long-term treatment via placement of permanent ventricular shunts. It is unclear what factors may predict the need for ventricular shunt placement in this patient population., Methods: The authors performed a retrospective analysis of a prospective database (ICH Outcomes Project) containing patients with nontraumatic ICH admitted to the neurological ICU at Columbia University Medical Center between January 2009 and September 2011. A multiple logistic regression model was developed to identify independent predictors of shunt-dependent hydrocephalus after ICH. The following variables were included: patient age, admission Glasgow Coma Scale score, temporal horn diameter on admission CT imaging, bicaudate index, admission ICH volume and location, intraventricular hemorrhage volume, Graeb score, LeRoux score, third or fourth ventricle hemorrhage, and intracranial pressure (ICP) and ventriculitis during hospital stay., Results: Of 210 patients prospectively enrolled in the ICH Outcomes Project, 64 required emergency CSF diversion via placement of an external ventricular drain and were included in the final cohort. Thirteen of these patients underwent permanent ventricular CSF shunting prior to discharge. In univariate analysis, only thalamic hemorrhage and elevated ICP were significantly associated with the requirement for permanent CSF diversion, with p values of 0.008 and 0.033, respectively. Each remained significant in a multiple logistic regression model in which both variables were present., Conclusions: Of patients with ICH requiring emergency CSF diversion, those with persistently elevated ICP and thalamic location of their hemorrhage are at increased odds of developing persistent hydrocephalus, necessitating permanent ventricular shunt placement. These factors may assist in predicting which patients will require permanent CSF diversion and could ultimately lead to improvements in the management of this disorder and the outcome in patients with ICH.

Background and Purpose: The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage., Methods: We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI., Results: There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt-Hess score of 3. Adjusting for Hunt-Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (P=0.01), mean n-6:n-3 FFA ratio (P=0.02), and mean oxygen consumption level (P=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (P<0.001), younger age (P=0.05), and modified Fisher scale (P=0.004) were associated with time to DCI., Conclusions: Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.

Hypothermia is widely accepted as the gold-standard method by which the body can protect the brain. Therapeutic cooling--or targeted temperature management (TTM)--is increasingly being used to prevent secondary brain injury in patients admitted to the emergency department and intensive care unit. Rapid cooling to 33 °C for 24 h is considered the standard of care for minimizing neurological injury after cardiac arrest, mild-to-moderate hypothermia (33-35 °C) can be used as an effective component of multimodal therapy for patients with elevated intracranial pressure, and advanced cooling technology can control fever in patients who have experienced trauma, haemorrhagic stroke, or other forms of severe brain injury. However, the practical application of therapeutic hypothermia is not trivial, and the treatment carries risks. Development of clinical management protocols that focus on detection and control of shivering and minimize the risk of other potential complications of TTM will be essential to maximize the benefits of this emerging therapeutic modality. This Review provides an overview of the potential neuroprotective mechanisms of hypothermia, practical considerations for the application of TTM, and disease-specific evidence for the use of this therapy in patients with acute brain injuries.

Introduction: We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH)., Methods: We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR)>40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE)., Results: Daily mean caloric intake received was 13.8±6.9 cal/kg and mean serum glucose was 7.9±1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and <1% indicated a state of critical brain hypoglycemia (<0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald=6.07, P=0.048), more insulin administered (Wald=108, P<0.001), higher body mass index (Wald=213.47, P<0.001), and lower body temperature (Wald=4.1, P=0.043). Enteral feeding (Wald=1.743, P=0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald=67.41, P<0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald=8.26, P=0.017), independent of serum glucose levels., Conclusions: In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.

Background and Purpose: Limited data exist to recommend specific cerebral perfusion pressure (CPP) targets in patients with intracerebral hemorrhage. We sought to determine the feasibility of brain multimodality monitoring for optimizing CPP and potentially reducing secondary brain injury after intracerebral hemorrhage., Methods: We retrospectively analyzed brain multimodality monitoring data targeted at perihematomal brain tissue in 18 comatose intracerebral hemorrhage patients (median monitoring, 164 hours). Physiological measures were averaged over 1-hour intervals corresponding to each microdialysis sample. Metabolic crisis was defined as a lactate/pyruvate ratio >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH) was defined as P(bt)O(2) <15 mm Hg. Pressure reactivity index and oxygen reactivity index were calculated., Results: Median age was 59 years, median Glasgow Coma Scale score was 6, and median intracerebral hemorrhage volume was 37.5 mL. The risk of BTH, and to a lesser extent metabolic crisis, increased with lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated with a greater risk of BTH (odds ratio, 1.5; 95% confidence interval, 1.1-2.1; P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%). Survivors had significantly higher CPP and P(bt)O(2) and lower ICP values starting on postbleed day 4, whereas lactate/pyruvate ratio and pressure reactivity index values were persistently lower, indicating preservation of aerobic metabolism and pressure autoregulation., Conclusions: P(bt)O(2) monitoring can be used to identify CPP targets for optimal brain tissue oxygenation. In patients who do not undergo multimodality monitoring, maintaining CPP >80 mm Hg may reduce the risk of BTH.

Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and is a major cause of morbidity and mortality. Despite advances in management, numerous clinical trials have failed to demonstrate significant benefit of medical and surgical interventions, underscoring the need for the identification of novel therapeutic targets based on improved understanding of ICH pathophysiology and optimal risk stratification based on reliable and effective prognosticators. The alternative complement cascade has been implicated as an important contributor to neurological injury after ICH. Therefore, common, functionally relevant genetic variants in the key components of this pathway have been associated with greater inflammation post-ictus, further cerebral damage, and ultimately, a worse outcome. We investigated the affects of single-nucleotide polymorphisms (SNP) on mortality in complement component 3 C3 (rs2230199), complement component 5 C5 (rs17611), and Complement Factor H (CFH; rs1061170) genes, which are associated with the onset and progression of several neurological diseases, in a prospective cohort of patients with spontaneous ICH. From February 2009 through May 2010, adult patients with spontaneous ICH were admitted to the Columbia University Neurological Intensive Care Unit and enrolled in the Intracerebral Hemorrhage Outcomes Project. Demographic, clinical, radiographic, and treatment data were prospectively collected. Buccal swabs were obtained, and isolated cells were sequenced for the aforementioned SNP. A total of 103 patients were admitted with ICH, and of these, 82 consented for genetic testing and were included in the analysis. The median age was 61 years and 39% were females. The median Glasgow Coma Scale score on admission was 11.5. The CFH SNP was significantly associated with both discharge (p = 0.01) and 6-month mortality (p = 0.02), while no such association was observed for C3 (p = 0.545 and p = 0.830) or C5 (p = 0.983 and p = 0.536) SNP. Additionally, after controlling for pertinent variables identified in the univariate analysis, the CFH genotype independently predicted mortality at discharge (p = 0.019, odds ratio [OR] 7.62, 95% confidence interval [CI] 1.40-41.6) and at 6 months (p = 0.041, OR 1.822, 95% CI 1.025-3.239). The CFH genotype was also independently predictive of survival duration (p = 0.041, OR 1.822, 95% CI 1.025-3.239). We concluded that CFH Y402H polymorphism independently predicts mortality at discharge and 6-months and survival duration after spontaneous ICH., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Purpose: Unruptured intracranial aneurysms (UIAs) are being identified more frequently and endovascular coil embolization has become an increasingly popular treatment modality. Our study evaluates patient outcomes with changing patterns of treatment of UIA., Methods: We conducted a retrospective, longitudinal cohort study of 3132 hospital discharges for UIA identified from the New York Statewide Database (SPARCS) in 2005 to 2007 and 2200 discharges from 1995 to 2000. The rates of endovascular coiling and surgical clipping were examined along with hospital variables and discharge outcome. Anatomic specifics of UIA were unavailable for analysis., Results: The case rate for treatment of UIA doubled from 1.59 (1995 to 2000) to 3.45 per 100,000 (2005 to 2007, P<0.0001) and increased in the case treatment rate for coiling of UIA (0.36 versus 1.98 per 100,000, P<0.0001). Compared with the old epoch, there were more UIAs clipped at high-volume centers (55.8% versus 78.8%, P<0.0001) but fewer coiled at high-volume centers (94.8% versus 84.5%, P<0.0001) in the new epoch. Coiling and increasing hospital UIA treatment volume were associated with good discharge outcome. However, there was no significant improvement in overall good outcome when comparing 1995 to 2000 versus 2005 to 2007 (79% versus 81%, P=0.168) and a worsening of good outcomes for clipping (76.3% versus 71.7%, P=0.0132)., Conclusions: Despite coiling being associated with an increased incidence of good outcome relative to clipping of UIA, the increase in coiling has failed to improve overall patient outcome. The shift in coiling venue from high-volume centers to low-volume centers and decreasing microsurgical volume accompanied by a worsening in microsurgical results contribute to this. This argues for greater centralization of care.

Objective: To report changes of cerebral blood flow and metabolism associated with status epilepticus after cardiac arrest., Design: Case report., Setting: Neurological intensive care unit in a university hospital., Patient: An 85-year-old man resuscitated from out-of-hospital cardiac arrest underwent brain multimodality monitoring and treatment with therapeutic hypothermia., Main Outcome Measures: Changes of cerebral blood flow and metabolism., Results: Repetitive electrographic seizure activity detected at the start of monitoring was associated with dramatic reductions in brain tissue oxygen tension and striking surges in cerebral blood flow and brain temperature. Intravenous lorazepam and levetiracetam administration resulted in immediate cessation of the seizures and these associated derangements. The lactate to pyruvate ratio was initially elevated and trended down after administration of anticonvulsants., Conclusion: Brain multimodality monitoring is a feasible method for evaluating secondary brain injury associated with seizure activity after cardiac arrest.

Background and Purpose: Subarachnoid hemorrhage (SAH) is known to result in elevated systemic oxygen consumption (Vo(2)) and increases in high-sensitivity C-reactive protein (hsCRP), although the relationship among hsCRP, Vo(2), and delayed cerebral ischemia (DCI) after SAH remains unknown. We hypothesized that hsCRP is directly associated with Vo(2) and that elevated Vo(2) is a predictor of DCI after SAH., Methods: Prospective serial assessments of Vo(2) and hsCRP over 4 prespecified time periods during the first 14 days after bleed in consecutive SAH patients admitted to a single academic medical center for a 2-year period., Results: One hundred ten SAH patients met study criteria (mean age, 55±16 years; 62% women), with a median admission Hunt Hess grade of 3 (interquartile range, 2-4). In multivariate generalized estimating equation model of the first 14 days after bleed, Vo(2) was associated with younger age (P=0.01), male gender (P=0.01), and hsCRP levels (P=0.03). Twenty-four (22%) patients had DCI develop, with a median onset on day 7 after bleed (interquartile range, 5-11). The mean Vo(2) (291±65 mL/min versus 226±55 mL/min; P=0.003) was higher in DCI patients. In a multivariable Cox proportional hazards model, younger age (hazard ratio, 1.2 per 5 years; 95% CI, 1.1-1.3), a higher modified Fisher scale score (hazard ratio, 3.4 per 1-point increase; 95% CI, 1.7-6.9), and higher Vo(2) (HR, 1.2 per 50-mL/min increase; 95% CI, 1.1-1.3) were predictive of DCI., Conclusions: Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI.

Background and Methods: We report the case of a young woman with delayed cerebral infarction and intracranial hypertension following subarachnoid hemorrhage requiring hemicraniectomy, who underwent multimodality neuromonitoring of the contralateral hemisphere before and after craniectomy., Results: Intracranial hypertension was preceded by signs of ischemia and impaired brain metabolism diagnosed through cerebral microdialysis and PbtO2 monitoring, as well as a decrease in cerebral perfusion pressure (CPP) to <40 mmHg despite increasing vasopressor requirements. We describe how a comprehensive multimodality neuromonitoring approach was utilized to inform the decision to perform an early decompressive hemicraniectomy. Post-operatively, CPP and intracranial pressure (ICP) normalized, and the patient was weaned off all pressors within hours. The modified Rankin score at 3 and 12 months was 5., Conclusions: Delayed rescue hemicraniectomy can be life-saving after poor grade SAH. The role of multimodality brain monitoring for determining the optimal timing of hemicraniectomy deserves further study.

Object: Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H(2)S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H(2)S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI., Results: There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis., Conclusions: Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H(2)S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.

Background and Purpose: Global cerebral edema is common among patients with poor-grade subarachnoid hemorrhage and is associated with poor outcome. Currently no targeted therapy exists largely due to an incomplete understanding of the underlying mechanisms., Methods: This is a prospective observational study including 39 consecutive patients with poor-grade subarachnoid hemorrhage with multimodal neuromonitoring. Levels of microdialysate lactate-pyruvate ratio, episodes of cerebral metabolic crisis (lactate-pyruvate ratio >40 and brain glucose <0.7 mmol/L), brain tissue oxygen tension, cerebral perfusion pressure, and transcranial Doppler sonography flow velocities were analyzed., Results: Median age was 54 years (range, 45 to 61 years) and 62% were female. Patients with global cerebral edema on admission (n=24 [62%]) had a higher incidence of metabolic crisis in the first 12 hours of monitoring (n=15 [15% versus 2%], P<0.05) and during the total time of neuromonitoring (20% versus 3%, P<0.001) when compared to those without global cerebral edema. There was no difference in brain tissue oxygen tension or cerebral perfusion pressure between the groups; however, in patients with global cerebral edema, a higher cerebral perfusion pressure was associated with lower lactate-pyruvate ratio (P<0.05). Episodes of metabolic crisis were associated with poor outcome (modified Rankin Scale score 5 or 6, P<0.05)., Conclusions: In patients with poor-grade subarachnoid hemorrhage, global cerebral edema is associated with early brain metabolic distress.

Background: As the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control., Methods: All patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded., Results: We collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions., Conclusions: A significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Background: Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series., Methods: We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt-Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome., Results: Of the 21 patients 13 were Hunt-Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4-5), and 4 had moderate-to-no disability (mRS = 1-3)., Conclusions: Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.

Background and Purpose: To identify a minimally acceptable cerebral perfusion pressure threshold above which the risks of brain tissue hypoxia (BTH) and oxidative metabolic crisis are reduced for patients with subarachnoid hemorrhage (SAH)., Methods: We studied 30 poor-grade SAH patients who underwent brain multimodality monitoring (3042 hours). Physiological measures were averaged over 60 minutes for each collected microdialysis sample. Metabolic crisis was defined as a lactate/pyruvate ratio>40 with a brain glucose concentration≤0.7 mmol/L. BTH was defined as PbtO2<20 mm Hg. Outcome was assessed at 3 months with the Modified Rankin Scale., Results: Multivariable analyses adjusting for admission Hunt-Hess grade, intraventricular hemorrhage, systemic glucose, and end-tidal CO2 revealed that cerebral perfusion pressure≤70 mm Hg was significantly associated with an increased risk of BTH (OR, 2.0; 95% CI, 1.2-3.3; P=0.007) and metabolic crisis (OR, 2.1; 95% CI, 1.2-3.7; P=0.007). Death or severe disability at 3 months was significantly associated with metabolic crisis (OR, 5.4; 95% CI, 1.8-16; P=0.002) and BTH (OR, 5.1; 95% CI, 1.2-23; P=0.03) after adjusting for admission Hunt-Hess grade., Conclusions: Metabolic crisis and BTH are associated with mortality and poor functional recovery after SAH. Cerebral perfusion pressure levels<70 mm Hg was associated with metabolic crisis and BTH, and may increase the risk of secondary brain injury in poor-grade SAH patients.

Background: Ventriculostomy-related infection (VRI) is a severe complication of external ventricular drain use, occurring in 5% to 23% of patients. Preventive measures for VRI include prolonged prophylactic systemic antibiotics (PSAs) and an antibiotic-coated external ventricular drains (ac-EVDs)., Objective: We performed a systematic review of all studies evaluating PSAs and ac-EVD for VRI prevention through July 2010., Methods: Two reviewers independently assessed eligibility and evaluated study quality based on pre-established criteria. Observational studies and randomized clinical trials (RCTs) that fulfilled inclusion criteria were included in the meta-analysis., Results: Three RCTs and 7 observational studies met our inclusion criteria and were included in the analysis. The type of antibiotics and VRI definitions varied among these studies. Pooled analysis showed a protective effect of PSAs and ac-EVDs for VRI (risk ratio: 0.32; 95% CI: 0.18-0.56). Results showed moderate heterogeneity (I(2) = 53%) explained by the difference in quality among the studies and the inclusion of 1 large positive cohort study. The effect of PSAs and ac-EVDs was unrelated to the type of study (RCT or observational, P for interaction = .55), the route of antibiotic administration (PSAs or ac-EVDs, P = .13), or the quality of the studies (suboptimal vs good/excellent, P = .55)., Conclusion: RCTs and observational-derived evidence support the use of PSAs throughout the duration of external ventricular drainage; similarly, the use of ac-EVDs to prevent VRI seems to be beneficial. Available data are heterogeneous and of suboptimal quality. Further research is needed to confirm the findings of this meta-analysis. There are not sufficient data to compare the protective effect of ac-EVDs and PSAs.

Background: Silent infarction is common in poor-grade subarachnoid hemorrhage (SAH) patients and associated with poor outcome. Invasive neuromonitoring devices may detect changes in cerebral metabolism and oxygenation., Methods: From a consecutive series of 32 poor-grade SAH patients we identified all CT-scans obtained during multimodal neuromonitoring and analyzed microdialysis parameters and brain tissue oxygen tension (PbtO2) preceding CT-scanning., Results: Eighteen percent of the reviewed head-CTs (12/67) revealed new infarcts. Of the eight infarcts in the vascular territory of the neuromonitoring, seven were clinically silent. Neuromonitoring changes preceding radiological evidence of infarction included lactate-pyruvate-ratio elevation and brain glucose decreases when compared to those with distant or no ischemia (P ≤ 0.03, respectively). PbtO2 was lower, but this did not reach statistical significance., Conclusions: These data suggest that there may be distinct changes in brain metabolism and oxygenation associated with the development of silent infarction within the monitored vascular territory in poor-grade SAH patients. Larger prospective studies are needed to determine whether treatment triggered by neuromonitoring data has an impact on outcome.

Background: The impact of osmotic therapies on brain metabolism has not been extensively studied in humans. The authors examined if mannitol treatment of raised intracranial pressure will result in an improvement in brain metabolism together with the expected drop in intracranial pressure (ICP)., Methods: This is a retrospective review of prospectively collected data. Twenty episodes of raised ICP (>20 mm Hg) resistant to standard therapy that required infusions of mannitol were studied in 12 comatose patients with multimodality monitoring including ICP, PbtO(2) and microdialysis. The authors compared mean arterial blood pressure, ICP, cerebral perfusion pressure, PbtO(2), brain lactate, pyruvate and glucose using cerebral microdialysis, for 3 h preceding and 4 h after hyperosmolar therapy. Time-series data were analysed using a multivariable general linear model utilising generalised estimating equations for model estimation to account for within-subjects and between-subjects variations over time., Results: 20% mannitol solution (1 g/kg) was administered at the discretion of the attending neurointensivist. ICP decreased 30 min (from 27 ± 13 to 19 ± 16 mm Hg, p<0.001) and cerebral perfusion pressure increased 45 min (from 73 ± 18 to 85 ± 22 mm Hg, p=0.002) after the start of mannitol infusions, whereas mean arterial blood pressure and PbtO(2) did not change significantly. The peak lactate-pyruvate ratio was recorded at the time of initiating osmotherapy (44 ± 20) with an 18% decrease over 2 h following mannitol therapy (35 ± 16; p=0.002). Brain glucose remained unaffected., Conclusions: Mannitol effectively reduces ICP and appeared to benefit brain metabolism as measured by the lactate-pyruvate ratio.