Intracranial Pressure Monitoring: Invasive versus Non-Invasive Methods—A Review

Monitoring of intracranial pressure (ICP) has been used for decades in the fields of neurosurgery and neurology. There are multiple techniques: invasive as well as noninvasive. This paper aims to provide an overview of the advantages and disadvantages of the most common and well-known methods as well as assess whether noninvasive techniques (transcranial Doppler, tympanic membrane displacement, optic nerve sheath diameter, CT scan/MRI and fundoscopy) can be used as reliable alternatives to the invasive techniques (ventriculostomy and microtransducers). Ventriculostomy is considered the gold standard in terms of accurate measurement of pressure, although microtransducers generally are just as accurate. Both invasive techniques are associated with a minor risk of complications such as hemorrhage and infection. Furthermore, zero drift is a problem with selected microtransducers. The non-invasive techniques are without the invasive methods' risk of complication, but fail to measure ICP accurately enough to be used as routine alternatives to invasive measurement. We conclude that invasive measurement is currently the only option for accurate measurement of ICP

Post-traumatic hypoxia exacerbates neurological deficit, neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles.</p> <p>Methods</p> <p>Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O₂/88% N₂) or normoxic (22% O₂/78% N₂) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique.</p> <p>Results</p> <p>TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1β and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels.</p> <p>Conclusion</p> <p>Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction.</p

Evaluation of novel computerized tomography scoring systems in human traumatic brain injury : An observational, multicenter study

Background Traumatic brain injury (TBI) is a major contributor to morbidity and mortality. Computerized tomography (CT) scanning of the brain is essential for diagnostic screening of intracranial injuries in need of neurosurgical intervention, but may also provide information concerning patient prognosis and enable baseline risk stratification in clinical trials. Novel CT scoring systems have been developed to improve current prognostic models, including the Stockholm and Helsinki CT scores, but so far have not been extensively validated. The primary aim of this study was to evaluate the Stockholm and Helsinki CT scores for predicting functional outcome, in comparison with the Rotterdam CT score and Marshall CT classification. The secondary aims were to assess which individual components of the CT scores best predict outcome and what additional prognostic value the CT scoring systems contribute to a clinical prognostic model. Methods and findings TBI patients requiring neuro-intensive care and not included in the initial creation of the Stockholm and Helsinki CT scoring systems were retrospectively included from prospectively collected data at the Karolinska University Hospital (n = 720 from 1 January 2005 to 31 December 2014) and Helsinki University Hospital (n = 395 from 1 January 2013 to 31 December 2014), totaling 1,115 patients. The Marshall CT classification and the Rotterdam, Stockholm, and Helsinki CT scores were assessed using the admission CT scans. Known outcome predictors at admission were acquired (age, pupil responsiveness, admission Glasgow Coma Scale, glucose level, and hemoglobin level) and used in univariate, and multivariable, regression models to predict long-term functional outcome (dichotomizations of the Glasgow Outcome Scale [GOS]). In total, 478 patients (43%) had an unfavorable outcome (GOS 1-3). In the combined cohort, overall prognostic performance was more accurate for the Stockholm CT score (Nagelkerke's pseudo-R-2 range 0.24-0.28) and the Helsinki CT score (0.18-0.22) than for the Rotterdam CT score (0.13-0.15) and Marshall CT classification (0.03-0.05). Moreover, the Stockholm and Helsinki CT scores added the most independent prognostic value in the presence of other known clinical outcome predictors in TBI (6% and 4%, respectively). The aggregate traumatic subarachnoid hemorrhage (tSAH) component of the Stockholm CT score was the strongest predictor of unfavorable outcome. The main limitations were the retrospective nature of the study, missing patient information, and the varying follow-up time between the centers. Conclusions The Stockholm and Helsinki CT scores provide more information on the damage sustained, and give a more accurate outcome prediction, than earlier classification systems. The strong independent predictive value of tSAH may reflect an underrated component of TBI pathophysiology. A change to these newer CT scoring systems may be warranted.Peer reviewe

Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review

Background: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term “effective half-life” (t₁⁄₂) in order to describe the “fall” rate in serum. Materials and methods: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. Results: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t₁⁄₂ of about 24 h, even if very early sampling in these patients reveals rapid decreases (1–2 h) though possibly of non-cerebral origin. In contrast, the t₁⁄₂ for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t₁⁄₂ of about 24–48 h in severe TBI. The protein UCH-L1 (n = 9) presents a ₁⁄₂ around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. Conclusion: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.ET: Swedish Society of Medicine (Grant no. SLS-587221). FZ: Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada—Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. AB: Hungarian Brain Research Program—Grant No. KTIA_13_NAP-A- II/8. DM: National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DM. The authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150). AH: Medical Research Council, Cambridge Biomedical Research Centre, Royal College of Surgeons of England. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people: results from seven large European cohorts within the ELAPSE project

Background Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). Methods In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000-11; follow-up until 2011-17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. Findings We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021-1·085) per 5 μg/m3 increment in PM2·5, 1·044 (1·019-1·069) per 10 μg/m3 NO2, and 1·039 (1·018-1·059) per 0·5 × 10−5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 μg/m3) and NO2 (40 μg/m3) were 1·078 (1·046-1·111) per 5 μg/m3 PM2·5 and 1·049 (1·024-1·075) per 10 μg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032-1·092) for exposure lower than 1·5× 10−5/m, and 1·081 (0·966-1·210) for exposure lower than 1·0× 10−5/m. Interpretation Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions

A serum protein biomarker panel improves outcome prediction in human traumatic brain injury

Brain-enriched protein biomarkers of tissue fate are being introduced clinically to aid in traumatic brain injury (TBI) management. The aim of this study was to determine how concentrations of six different protein biomarkers, measured in samples collected during the first weeks after TBI, relate to injury severity and outcome. We included neuro-critical care TBI patients that were prospectively enrolled from 2007 to 2013, all having 1 to 3 blood samples drawn during the first two weeks. The biomarkers analyzed were S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), tau and neurofilament-Light (NF-L). Glasgow Outcome Score (GOS) was assessed at 12 months. In total, 172 patients were included. All serum markers were associated with injury severity as classified on computed tomography scans at admission. Almost all biomarkers outperformed other known outcome predictors with higher levels the first five days, correlating with unfavorable outcomes, and UCH-L1 (0.260 pseduo-R2) displaying the best discrimination in univariate analyses. After adjusting for acknowledged TBI outcome predictors, GFAP and NF-L added most independent information to predict favorable/unfavorable GOS, improving the model from 0.38 to 0.51 pseudo-R2. A correlation matrix indicated substantial co-variance, with the strongest correlation between UCH-L1, GFAP and tau (r=0.827 to 0.880). Additionally, the principal component analysis exhibited clustering of UCH-L1 and tau, as well as GFAP, S100B and NSE, which was separate from NF-L. In summary, a panel of several different protein biomarkers, all associated with injury severity, with different cellular origin and temporal trajectories, improve outcome prediction models

Perceived annoyance and asthmatic symptoms in relation to vehicle exhaust levels outside home: a cross-sectional study

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Exhaust emissions from vehicles is a well known problem with both epidemiological and experimental studies showing increasing adverse health effects with elevating levels. Many of the studies concerning vehicle exhausts and health are focused on health outcomes where the proportion attributed to exhaust is low, while there is less information on early and more frequent subjective indicators of adverse effects. Methods: The primary aim of this study was to study perceived annoyance in relation to vehicle exhaust concentrations using modelled levels of nitrogen dioxide outside the home as an indicator with high spatial resolution. Almost 2800 persons in a random sample from three Swedish cities (Umea, Uppsala and Gothenburg) responded to our questionnaire. Questions were asked to determine the degree of annoyance related to vehicle exhausts and also the prevalence of irritating and asthmatic symptoms. Exposure was described for each participants home address by meteorological dispersion models with a 50 meter resolution. Results: We found a significant increase of peoples &apos; self-assessed annoyance with rising levels of NO2. The odds of being very annoyed by vehicle exhausts increased by 14 % per 1 µg/m3 increas

Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement

<p>Abstract</p> <p>Background</p> <p>Cerebral microdialysis (MD) is used to monitor local brain chemistry of patients with traumatic brain injury (TBI). Despite an extensive literature on cerebral MD in the clinical setting, it remains unclear how individual levels of real-time MD data are to be interpreted. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are important continuous brain monitors in neurointensive care. They are used as surrogate monitors of cerebral blood flow and have an established relation to outcome. The purpose of this study was to investigate the relations between MD parameters and ICP and/or CPP in patients with TBI.</p> <p>Methods</p> <p>Cerebral MD, ICP and CPP were monitored in 90 patients with TBI. Data were extensively analyzed, using over 7,350 samples of complete (hourly) MD data sets (glucose, lactate, pyruvate and glycerol) to seek representations of ICP, CPP and MD that were best correlated. MD catheter positions were located on computed tomography scans as pericontusional or nonpericontusional. MD markers were analyzed for correlations to ICP and CPP using time series regression analysis, mixed effects models and nonlinear (artificial neural networks) computer-based pattern recognition methods.</p> <p>Results</p> <p>Despite much data indicating highly perturbed metabolism, MD shows weak correlations to ICP and CPP. In contrast, the autocorrelation of MD is high for all markers, even at up to 30 future hours. Consequently, subject identity alone explains 52% to 75% of MD marker variance. This indicates that the dominant metabolic processes monitored with MD are long-term, spanning days or longer. In comparison, short-term (differenced or Δ) changes of MD vs. CPP are significantly correlated in pericontusional locations, but with less than 1% explained variance. Moreover, CPP and ICP were significantly related to outcome based on Glasgow Outcome Scale scores, while no significant relations were found between outcome and MD.</p> <p>Conclusions</p> <p>The multitude of highly perturbed local chemistry seen with MD in patients with TBI predominately represents long-term metabolic patterns and is weakly correlated to ICP and CPP. This suggests that disturbances other than pressure and/or flow have a dominant influence on MD levels in patients with TBI.</p

The role of the complement system in traumatic brain injury: a review

Traumatic brain injury (TBI) is an important cause of disability and mortality in the western world. While the initial injury sustained results in damage, it is the subsequent secondary cascade that is thought to be the significant determinant of subsequent outcomes. The changes associated with the secondary injury do not become irreversible until some time after the start of the cascade. This may present a window of opportunity for therapeutic interventions aiming to improve outcomes subsequent to TBI. A prominent contributor to the secondary injury is a multifaceted inflammatory reaction. The complement system plays a notable role in this inflammatory reaction; however, it has often been overlooked in the context of TBI secondary injury. The complement system has homeostatic functions in the uninjured central nervous system (CNS), playing a part in neurodevelopment as well as having protective functions in the fully developed CNS, including protection from infection and inflammation. In the context of CNS injury, it can have a number of deleterious effects, evidence for which primarily comes not only from animal models but also, to a lesser extent, from human post-mortem studies. In stark contrast to this, complement may also promote neurogenesis and plasticity subsequent to CNS injury. This review aims to explore the role of the complement system in TBI secondary injury, by examining evidence from both clinical and animal studies. We examine whether specific complement activation pathways play more prominent roles in TBI than others. We also explore the potential role of complement in post-TBI neuroprotection and CNS repair/regeneration. Finally, we highlight the therapeutic potential of targeting the complement system in the context of TBI and point out certain areas on which future research is needed