Mechanistic-mathematical modeling of intracranial pressure (ICP) profiles over a single heart cycle. The fundament of the ICP curve form.

The intracranial pressure (ICP) curve with its different peaks has been comprehensively studied, but the exact physiological mechanisms behind its morphology has not been revealed. If the pathophysiology behind deviations from the normal ICP curve form could be identified, it could be vital information to diagnose and treat each single patient. A mathematical model of the hydrodynamics in the intracranial cavity over single heart cycles was developed. A Windkessel model approach was generalized but the unsteady Bernoulli equation was utilized for blood flow and CSF flow. This is a modification of earlier models using the extended and simplified classical Windkessel analogies to a model that is based on mechanisms rooted in the laws of physics. The improved model was calibrated with patient data for cerebral arterial inflow, venous outflow, cerebrospinal fluid (CSF), and ICP over one heart cycle from 10 neuro-intensive care unit patients. A priori model parameter values were obtained by considering patient data and values taken from earlier studies. These values were used as an initial guess for an iterated constrained-ODE (ordinary differential equation) optimization problem with cerebral arterial inflow data as input into the system of ODEs. The optimization routine found patient-specific model parameter values that produced model ICP curves that showed excellent agreement with clinical measurements while model venous and CSF flow were within a physiologically acceptable range. The improved model and the automated optimization routine gave better model calibration results compared to previous studies. Moreover, patient-specific values of physiologically important parameters like intracranial compliance, arterial and venous elastance, and venous outflow resistance were determined. The model was used to simulate intracranial hydrodynamics and to explain the underlying mechanisms of the ICP curve morphology. Sensitivity analysis showed that the order of the three main peaks of the ICP curve was affected by a decrease in arterial elastance, a large increase in resistance to arteriovenous flow, an increase in venous elastance, or a decrease in resistance to CSF flow in the foramen magnum; and the frequency of oscillations were notably affected by intracranial elastance. In particular, certain pathological peak patterns were caused by these changes in physiological parameters. To the best of our knowledge, there are no other mechanism-based models associating the pathological peak patterns to variation of the physiological parameters.

Validation of a mathematical model for understanding intracranial pressure curve morphology.

The physiology underlying the intracranial pressure (ICP) curve morphology is not fully understood. Recent research has suggested that the morphology could be dependent on arterial cerebral inflow and the physiological and pathophysiological properties of the intracranial cavity. If understood, the ICP curve could provide information about the patient's cerebrovascular state important in individualizing treatment in neuro intensive care patients. A mathematical model based on known physiological properties of the intracranial compartment was created. Clinical measurements from ten neuro intensive care patients in whom intracranial arterial blood inflow, venous blood outflow and cerebrospinal fluid flow over the foramen magnum had been measured with phase contrast MRI, concomitant with ICP measurements were used to validate the model. In nine patients the mathematical model was able to create an ICP curve mimicking the measured by using arterial intracranial inflow and adjusting physiological parameters of the model. The venous outflow and cerebrospinal fluid (CSF) flow over the foramen magnum predicted by the model were within physiologically reasonable limits and in most cases followed the MRI measured values in close adjunct. The presented model could produce an ICP curve in close resemblance of the in vivo measured curves. This strengthens the hypothesis that the ICP curve is shaped by the arterial intracranial inflow and the physiological properties of the intracranial cavity.

Best zero level for external ICP transducer.

BACKGROUND: Continuous monitoring of intracranial pressure (ICP) was introduced in the 1950s. For correct ICP recordings, the zero-reference point for the external pressure gauge must be placed next to a head anatomical structure. We evaluated different anatomical points as zero reference for the ICP device at different head positions and their relation to brain centre (BC), foramen of Monro (Monro), and brain surface. METHODS: Patients referred for neuroimaging due to e.g. headache all having normal 3D MRI scans were selected. Monro, BC, Orbit(O), external auditory meatus (EAM), and orbito-meatal (OM) line were identified and projected to mid-sagittal, or axial images. Each scan was evaluated like lying supine, 45° head elevations, upright, and 45° lateral position. Distances from skin to brain surface, BC, and Monro were measured. All values are presented as mean ± SD and/or range in millimetre. For conversion to mmHg, millimetre was multiplied by 0.074. RESULTS: Twenty MRI scans were examined. A zero reference at EAM or glabella was ideal at BC when head was strict supine or in the lateral position. At 45° head elevation, an overestimation of the BC-ICP by 4.8 ± 0.8 and in upright 5.6 ± 0.5 mmHg was found, and 45° lateral underestimated ICP-BC by 6.3 ± 1.0 mmHg. Monro was situated 45 ± 5 mm rostral to the mid-OM line and 24 (18-31) mm inferior and 13 (8-17) mm in front of BC. A zero-reference point aligned with the highest point of the head underestimated BC-ICP and Monro-ICP. If the ICP reading was added 5.9 or 6.3 mmHg, respectively, a deviation from BC-ICP was ≤ 1.8 mmHg and Monro-ICP was ≤ 0.9 mmHg in all head positions. CONCLUSIONS: EAM and glabella are defined anatomical structures representing BC when strict supine or lateral but with 12 mmHg variation with different head positions used in clinical practice. The OM line follows Monro at head elevation, but not when the head is turned. When the highest external point on the head is used, ICP values at brain surface as well as Monro and BC are underestimated. This underestimation is fairly constant and, when corrected for, provides the most exact ICP reading.

Increased Intracranial Pressure Attenuates the Pulsating Component of Cerebral Venous Outflow.

BACKGROUND: The underlying physiology of the intracranial pressure (ICP) curve morphology is still poorly understood. If this physiology is explained it could be possible to extract clinically relevant information from the ICP curve. The venous outflow from the cranial cavity is pulsatile, and in theory the pulsatile component of venous outflow from the cranial cavity should be attenuated with increasing ICP. In this study, we explored the relationship between ICP and the pulsatility of the venous outflow from the intracranial cavity. METHODS: Thirty-seven neuro-intensive care patients that had been examined with phase-contrast magnetic resonance imaging regarding cerebral blood flow (CBF) through the internal carotid and vertebral arteries and venous flow in the internal jugular veins were retrospectively included. The pulsatility of the jugular flow was determined by calculating the venous pulsatile index. The results were correlated to clinical data registered in the patient data monitoring system, including ICP and cerebral perfusion pressure (CPP). RESULTS: CBF was 996 ± 298 ml/min, and the flow in the internal jugular veins equaled 67 ± 17% of the CBF, with a range of 22-97%. The venous pulsatile index correlated negatively to ICP (R = - 0.47 p = 0.003). The lowest flow in the internal jugular veins over the cardiac cycle (Fmin) was not correlated to ICP. Temperature, end-tidal CO2, MAP, and CPP were not correlated to venous pulsatility. CONCLUSION: An increase in ICP correlates to a lower pulsatility of the venous outflow from the cranial cavity. A lower pulsatility could be due to increased pressure requirements to compress intracranial veins with increasing ICP.

The intracranial pressure curve correlates to the pulsatile component of cerebral blood flow.

Current methods to measure cerebral blood flow (CBF) in the neuro critical care setting cannot monitor the CBF continuously. In contrast, continuous measurement of intracranial pressure (ICP) is readily accomplished, and there is a component of ICP that correlates with arterial inflow of blood into the cranial cavity. This property may have utility in using continuous ICP curve analysis to continuously estimate CBF. We examined the data from 13 patients, monitored with an intraventricular ICP device determining the pulsatile amplitude ICPamp as well as the area under the ICP curve (AUCICP). Using an elastance measurement, the ICP curve was converted to craniospinal volume (AUCΔV). The patients were examined with Phase Contrast Magnetic Resonance Imaging (MRI), measuring flow in the carotid and vertebral arteries. This made it possible to calculate CBF for one cardiac cycle (ccCBFMRtot) and divide it into the pulsatile (ccCBFMRpuls) and non-pulsatile (ccCBFMRconst) flow. ICP derived data and MRI measurements were compared. Linear regression was used to establish wellness of fit and ANOVA was used to calculate the P value. No correlation was found between ICPamp and the ccICPMRpuls (P = 0.067). In contrast there was a correlation between the AUCICP and ccCBFMRpuls (R2 = 0.440 P = 0.013). The AUCΔV correlated more appropriately with the ccCBFMRpuls. (R2 = 0.688 P < 0.001). Our findings suggests that the pulsatile part of the intracranial pressure curve, especially when transformed into a volume curve, correlates to the pulsatile part of the CBF.

Warfarin monitoring with viscoelastic haemostatic assays, thrombin generation, coagulation factors and correlations to Owren and Quick prothrombin time.

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66-0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.

ICP curve morphology and intracranial flow-volume changes: a simultaneous ICP and cine phase contrast MRI study in humans.

BACKGROUND: The intracranial pressure (ICP) curve with its different peaks has been extensively studied, but the exact physiological mechanisms behind its morphology are still not fully understood. Both intracranial volume change (ΔICV) and transmission of the arterial blood pressure have been proposed to shape the ICP curve. This study tested the hypothesis that the ICP curve correlates to intracranial volume changes. METHODS: Cine phase contrast magnetic resonance imaging (MRI) examinations were performed in neuro-intensive care patients with simultaneous ICP monitoring. The MRI was set to examine cerebral arterial inflow and venous cerebral outflow as well as flow of cerebrospinal fluid over the foramen magnum. The difference in total flow into and out from the cranial cavity (Flowtot) over time provides the ΔICV. The ICP curve was compared to the Flowtot and the ΔICV. Correlations were calculated through linear and logarithmic regression. Student's t test was used to test the null hypothesis between paired samples. RESULTS: Excluding the initial ICP wave, P1, the mean R 2 for the correlation between the ΔICV and the ICP was 0.75 for the exponential expression, which had a higher correlation than the linear (p = 0.005). The first ICP peaks correlated to the initial peaks of Flowtot with a mean R 2 = 0.88. CONCLUSION: The first part, or the P1, of the ICP curve seems to be created by the first rapid net inflow seen in Flowtot while the rest of the ICP curve seem to correlate to the ΔICV.

Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion.

BACKGROUND: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? METHOD: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. RESULTS: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. CONCLUSIONS: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.

Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults.

BACKGROUND: Acute management of traumatic brain injury (TBI), in particular mild TBI, focuses on the detection of the 5-7 % who may be harboring potentially life-threatening intracranial hemorrhage (IH) using CT scanning. Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results. Recently, the Scandinavian Neurotrauma Committee (SNC) derived a new set of high-IH risk variables for adults with TBI using an evidence-based literature review. Unlike previous guidelines, the SNC guideline incorporates serum values of the brain protein S100B with clinical variables. METHODS: We performed a nested cohort study of adults with mild TBI presenting to six emergency departments in New York and Pennsylvania within 6 h of injury. Patients were managed according to existing guidelines for CT selection. All patients underwent head CT scanning and serum S100B measurement, as well as prospective collection of clinical variables, as a requirement of the parent study. Using the SNC guidelines, S100B values and clinical variables were applied to these subjects, classifying each into one of five pre-defined severity categories, as well as predicting the need for head CT scanning to identify IH. This classification was then compared to actual head CT results to determine guideline sensitivity and specificity. RESULTS: In total, 662 adults (mean age 42 years, range 18-96; 258 females, 549 Caucasians) were available for analysis; 36 (5%) had IH on head CT scan. The SNC guidelines had a sensitivity of 97% (95% CI, 84-100%) and a specificity of 34% (95% CI, 30-37%) for the detection of IH on head CT. Application of the SNC guidelines would have resulted in a CT reduction of 32% (211/662 patients). One patient with low-risk mild TBI and a S100B level under 0.10 µg/L had a traumatic CT abnormality and would have been discharged with strict adherence to the guidelines. However, this patient did not need any intervention for the injury and had a good outcome. CONCLUSION: Using the SNC guideline could save approximately one third of CT scans in a pre-selected cohort of mild TBI patients with little or no impact on patient outcome.

Comparing charcoal and zeolite reflection filters for volatile anaesthetics: A laboratory evaluation.

BACKGROUND: A modified heat-moisture exchanger that incorporates a reflecting filter for use with partial rebreathing of exhaled volatile anaesthetics has been commercially available since the 1990 s. The main advantages of the device are efficient delivery of inhaled sedation to intensive care patients and reduced anaesthetic consumption during anaesthesia. However, elevated arterial CO2 values have been observed with an anaesthetic conserving device compared with a conventional heat and moisture exchanger, despite compensation for larger apparatus dead space. OBJECTIVE: The objective of this study is to thoroughly explore the properties of two reflecting materials (charcoal and zeolites). DESIGN: A controlled, prospective, observational laboratory study. SETTING: Lund University Hospital, Sweden, from December 2011 to December 2012. PARTICIPANTS: None. INTERVENTIONS: Three filters, with identical volumes, were compared using different volatile anaesthetics at different conditions of temperature and moisture. The filtering materials were charcoal or zeolite. Glass spheres were used as an inert control. MAIN OUTCOME MEASURES: Consumption of volatile anaesthetics using different reflecting materials in filters at different conditions regarding temperature and moisture. CO2 reflection by the filtering materials: glass spheres, charcoal or zeolite. RESULTS: Isoflurane consumption in an open system was 60.8 g h(-1). The isoflurane consumption in dry, warm air was 39.8 g h(-1) with glass spheres. Changing to charcoal and zeolite had a profound effect on isoflurane consumption, 11.8 and 10.7 g h(-1), respectively. Heating and humidifying the air as well as the addition of N2O created only minor changes in consumption. The percentage of isoflurane conserved by the charcoal filter was independent of the isoflurane concentration (0.5 to 4.5%). Reflection of sevoflurane, desflurane and halothane by the charcoal filter was similar to reflection of isoflurane. Both charcoal and zeolite filters had CO2 reflecting properties and end-tidal CO2 increased by 3 to 3.7% compared with glass spheres. This increase was attenuated to 1 to 1.4% when the air was heated and humidified, and isoflurane was added. CONCLUSION: Charcoal and zeolite possess gas-reflecting properties, which can be used to conserve volatile anaesthetics. They also reflect CO2. The degree of CO2 reflection was reduced by heating and humidifying the air.

Cerebral blood flow and transcranial doppler sonography measurements of CO2-reactivity in acute traumatic brain injured patients.

BACKGROUND: Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI. METHOD: CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia. MAIN FINDING AND CONCLUSION: Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

Monitoring fibrinolysis in whole blood by viscoelastic instruments: a comparison of ROTEM and ReoRox.

OBJECTIVE: Increased fibrinolysis with the risk of bleeding is a consequence of thrombolytic therapy and can also be seen in clinical situations such as acute trauma. Thrombelastography and thrombelastometry are viscoelastic coagulation instruments that can detect higher degrees of fibrinolysis; hyperfibrinolysis. A newer viscoelastic instrument is the ReoRox, which uses free oscillation rheometry to detect clot formation, strength and fibrinolysis. The ReoRox has a new test for detection of fibrinolysis, called ReoLyse. The aim of this study was to compare ReoRox with its new ReoLyse test with rotational thrombelastometry (ROTEM) in the monitoring of in vitro-induced fibrinolysis. METHODS: Whole blood from 10 healthy volunteers was mixed with tissue plasminogen activator (t-PA) to obtain seven different plasma concentrations (0, 0.25, 0.5, 0.75, 1, 3 and 5 µg/mL). Whole blood samples with the different t-PA plasma concentrations were analyzed with ROTEM EXTEM and FIBTEM tests, ReoRox standard test Fib1 (clot formation/strength) and ReoLyse (fibrinolysis) tests. RESULTS: The fibrinolysis variables with the best dose-response effect were the ReoRox ReoLyse lysis variables and ROTEM EXTEM Time to complete lysis. However, these variables only detected high t-PA levels (> 1 µg/mL). CONCLUSIONS: The new ReoRox ReoLyse test provides more information on fibrinolysis compared to the ReoRox Fib1 program. Neither ReoRox nor ROTEM could detect lower degrees of fibrinolysis. ReoRox is a valuable alternative to ROTEM to study high degrees of fibrinolysis and should be evaluated in clinical situations with increased fibrinolysis and during therapeutic thrombolysis.

Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology.

BACKGROUND: Protein S100B is soon in clinical use as a sensitive marker after mild traumatic head injury in adults. Initial studies of S100B in pediatric head injury have shown promising results. Venous sampling can be challenging in children and capillary samples are often a preferred option. The aim of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples in severely brain-injured patients. METHODS: Venous, arterial and capillary blood samples for S100B were collected simultaneously once a day for a maximum of 6 days. Patients were ≥18 years old and admitted to neurointensive care due to severe brain pathology. RESULTS: Capillary S100B samples were on average 0.08 µg/L higher than venous S100B samples. Prediction of venous concentration from capillary samples yielded a prediction error of 0.07 µg/L. The mean difference between venous and arterial samples was 0.01 µg/L. The mean prediction error was 0.03 µg/L. CONCLUSIONS: Capillary and venous serum S100B are not interchangeable, and should be considered as two separate, although related, variables. Arterial measurements of S100B can successfully predict the corresponding venous concentration.

Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue.

BACKGROUND: Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here. When biochemical signs of cerebral ischemia progressed, i.v. infusion of prostacyclin was started. METHODS: Two microdialysis catheters were placed in the penumbra zones surrounding evacuated focal brain contusions. The samples were analyzed for glucose, pyruvate, lactate, glutamate, and glycerol. RESULTS: When biochemical deterioration indicated progressive secondary ischemia (increase in lactate/pyruvate ratio, decrease in glucose, and increase in glutamate levels), continuous infusion of prostacyclin (0.5-1.0 ng kg(-1) min(-1) i.v.) was started. The treatment resulted in an improvement of the lactate/pyruvate ratios and a normalization of the interstitial levels of glucose and glutamate. The glycerol levels remained within normal limits indicating that degradation of cellular membranes had not occurred. CONCLUSION: The above case supports the view that new therapies directed toward protection of the sensitive biochemical penumbra zones surrounding focal brain lesions may be evaluated by intracerebral microdialysis.

Clinical factors associated with intracranial complications after pediatric traumatic head injury: an observational study of children submitted to a neurosurgical referral unit.

BACKGROUND: Clinically validated guidelines for the management of head injury in children do not exist, and the treatment is often based upon adult management routines. In order to examine the safety of this procedure, an analysis of clinical factors associated with complications after pediatric head injury was attempted. METHOD: We performed a descriptive retrospective study, including patients who received any S06 diagnosis during treatment in the Neurointensive Care Unit at Lund University Hospital between 2002 and 2007. One hundred children were included during the 6 years. RESULTS: During 6 years, 100 children with head injury needed neurointensive care or neurosurgery for their injury in southern Sweden. Traffic accidents (50%) were the main cause of head trauma, followed by falls (36%). Thirty-two percent of all children were injured in bicycle and motorcycle accidents. Both loss of consciousness and amnesia were absent in 23% of the children with intracranial injury. Seven children with intracranial injury, 6 of them requiring neurosurgery, were classed as having minimal head injury according to the Head Injury Severity Scale (HISS). Interesting differences in intracranial injuries between helmet users and nonusers were observed. CONCLUSION: Children with minimal head injuries (according to HISS) may develop intracranial complications and may even require neurosurgical intervention. Hence, the HISS classification, as well as other risk classifications based upon unconsciousness and amnesia, are unreliable in children.

Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis.

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.

Human cerebral blood volume (CBV) measured by dynamic susceptibility contrast MRI and 99mTc-RBC SPECT.

BACKGROUND: Patients with elevated intracranial pressure risk compromising their cerebral blood flow, resulting in ischemia. Lowering of the raised intracranial pressure, is therefore, mandatory. Reduction of the cerebral blood volume (CBV) might be target. In finding ways to do so, one has to be able to measure CBV. Measurement of CBV is, however, difficult. Radio(99mTc-)labeled erythrocytes (99mTcRBC) single photon emission computer-aided tomography (SPECT) is one established method used for CBV measurement. Recently, dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), has also been successfully used for this purpose. The aim of this study was to validate the use of DSC-MRI for the measurement of CBV by the investigation of the correlation between the regional distributions of 99mTc-RBC SPECT and DSC-MRI measurement of CBV in humans. If possible, the aim was also to find a conversion constant that will enable the DCS-MRI to be interpreted as CBV (percent of brain volume). METHODS: CBV of 8 volunteers were studied under normocapnic and hypocapnic conditions. CBV was measured with both 99mTc-RBC SPECT and DSC-MRI. RESULTS: There were significant correlations between the regional distributions of CBV measured by 99mTc-RBC SPECT and DSC-MRI (rest: F=4.53, P<0.05; hypocapnia: F=9.61, P<0.005). The derived conversion factor between DSC-MRI voxel values and 99mTc-RBC SPECT CBV (percent of brain volume) at rest was 0.0059+/-0.0013. Global CBV during normocapnia was 4.3%+/-0.6% of brain volume as measured by SPECT of brain volume and 4.5%+/-0.9% as measured by MRI. Decreasing the end-tidal pCO2 by 1.8 kPa by spontaneous hyperventilation reduced the global CBV significantly to 3.9%+/-0.5% in the SPECT group and to 3.5%+/-0.6% in the MRI group. CONCLUSIONS: The comparison of 99mTc-RBC SPECT and DSC-MRI measurements in our study indicates that DSC-MRI can be a useful method to measure CBV as a percent of brain volume.

Improved lumbar infusion test analysis for normal pressure hydrocephalus diagnosis.

OBJECTIVES: Constant infusion lumbar infusion test (LIT) is an important way to find which patients, of those with signs and symptoms corresponding to normal pressure hydrocephalus (NPH) who will improve from shunt operation. LIT is a stress test on the ability for cerebrospinal fluid re-absorbtion. The aim of this study is to show how the information from LIT can be improved by quantitative analysis and avoidance of methodological pitfalls. MATERIAL AND METHODS: The potential pitfalls, and the analysis method, are described in detail. The analysis was applied on pre-operative constant infusion LIT from 31 patients operated for NPH, with known outcome. The pre- and post-operative walking speed was used to grade pathology progression or improvement. RESULTS: The maximal, plateau, intra-spinal pressure at constant infusion LIT is an ambivalent indicator for NPH: while low maximal pressure indicates no cerebrospinal fluid (CSF) absorbtion pathology, too high pressure (≥47 mmHg) may mean no diagnosis, because of stenosis of the Sylvian aqueduct. When subjects with too high intra-spinal pressure were excluded, the new analysis gave a couple of diagnostic volume parameters, of which one appears to be an optimal LIT parameter for identifying NPH patients with 14% better accuracy than plateau pressure. CONCLUSION: By avoiding methodological pitfalls, and optimal analysis of the results from lumbar infusion test, the number of NPH patients who do not have a successful outcome after shunt operation may be further decreased.

Impact of donor chest radiography on clinical outcome after lung transplantation.

BACKGROUND: Organ donation guidelines recommend a "clear" conventional bedside chest radiograph before lung transplantation despite only moderate accuracy for cardiopulmonary abnormalities. PURPOSE: To evaluate the influence of donor image interpretation on lung transplantation outcome in recipients by following early and late complications, one-year survival, and to correlate imaging findings and blood gas analysis with lung transplantation outcome in recipients. MATERIAL AND METHODS: In 35 lung donors from a single institution clinical reports and study reviews of imaging findings of the mandatory bedside chest radiographs and blood gas analyses were compared with clinical outcome in 38 recipients. Hospitalization time, peri- and postoperative complications, early complications (primary graft dysfunction, infection), 30-day and one-year survival, and forced expiratory volume in 1 s percentage of predicted normal value (FEV1%) at one-year follow-up were analyzed. RESULTS: Findings in clinical reports and study reviews differed substantially, e.g. regarding reported decompensation, edema, infection, and atelectasis. No correlation was shown between imaging findings in clinical report or study review and blood gas analyses in the lung donors compared to postoperative outcome in recipients. CONCLUSION: The interpretation of the mandatory chest radiograph in its present form does not influence one-year outcome in lung transplantation. Larger imaging studies or a change in clinical routine including computed tomography may provide evidence for future guidelines.