Intracranial Elastance Research Articles

DDEL-01. UTILIZING SENSOR ARRAYS FOR INTRACRANIAL PRESSURE (ICP) RESPONSE TO CEREBROSPINAL FLUID (CSF) DRUG ADMINISTRATION, AND POTENTIAL IMPLICATIONS FOR PERSONALIZED CARE IN CNS METASTASES PATIENTS

Abstract BACKGROUND Patients with leptomeningeal carcinomatosis (LC) may have elevated intracranial pressure (ICP) due to LC cancer cells having the potential to obstruct the arachnoid granulations.,Given that LC treatment may involve intrathecal (IT) drug delivery, monitoring ICP may be important for safe IT drug delivery. The EnClear device is a novel CNS drug delivery device with both intracranial and intralumbar CSF access and single-use sensing arrays that measure ICP in these dual locations. METHODS This is a non-human primate (NHP) study on three healthy NHP subjects undergoing IT gene therapy via intracerebroventricular (ICV). The sensor arrays measured ICP before, during, and after ICV infusion in both intracranial and lumbar locations. Our goal was to compare individual subject pressure response to drug administration as well as to compare lumbar and cranial pressure waveforms for concordance. Pressure response was quantified as change in pressure (ΔP) following volume (ΔV) administration, known as intracranial elastance (ΔP/ΔV). RESULTS Significant correlations were observed between ventricular and lumbar ICP waveforms with an average of 0.88 correlation coefficient. Pressure measurements between subjects demonstrated variable response to identical infusion volumes, with maximum pressures ranging from 20 mmHg to 40 mmHg. Intracranial elastance was calculated for each subject during infusions and resulted in a range of 12 to 36 mmHg/mL, a 3-fold difference in elastance between subjects. CONCLUSION In healthy NHPs, changes to cranial volume and pressure response can be measured in the lumbar space with good correlation between the two measurement locations. Despite this consistency between these two locations on the same subject, intersubject variability was seen despite identical drug administration. Pressure waveform sensing systems can be incorporated in the future to enable clinicians to understand individual patient brain compliance and leverage this knowledge for personalized drug delivery, particularly in patients with LC.

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.

Comparison Between Ventricular and Spinal Infusion Tests in Suspected Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12mmHg and 23 a Rout <12mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12mmHg and 12 a Rout <12mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.

Intraventricular infusion test accuracy in predicting short- and long-term outcome of iNPH patients: a 10-year update of a three-decade experience at a single institution.

In a previous work, we found that an Intracranial Elastance Index (IEI) ≥0.3 at ventricular infusion test had a high accuracy in predicting shunt response at 6 and 12 months in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to verify the accuracy of IEI to predict response to shunt at both short- and long-term follow-up. Retrospective evaluation of 64 patients undergoing ventriculo-peritoneal shunting for iNPH between 2006 and 2015 based on a positive ventricular infusion test (IEI≥0.3). Patients were classified according to Krauss scale and mRS preoperatively, at 1-year and at last follow-up. An improvement of at least one point at Krauss score or at mRS was considered as a good outcome; unchanged or worsened patients were grouped as poor outcome. Mean follow-up was 6.6 years. Improvement at Krauss scale was seen in 62.5% and 64.3% of patients at 1-year and last follow-up, respectively. Patients in good functional status (mRS≤2) increased from 25 in the preoperative period to 57% at both 1-year and last follow-up. IEI was significantly associated with Krauss (p=0.041) and mRS (p=0.036) outcome at last follow-up. Patients with worse preoperative Krauss and mRS had higher chance to improve but higher overall scores after treatment. At ROC curves, IEI showed a good long-term prediction of change in mRS from first year to last follow-up. IEI≥0.3 predicts outcomes at both short- and long-term, with more than 50% of patients being able to look after themselves after 6 years from treatment.

Distortion of the Intracranial Pressure Waveform by Extraventricular Drainage System.

To investigate whether intracranial pressure (ICP) waveform measurements obtained from extraventricular drainage (EVD) systems are suitable for the calculation of intracranial elastance (ICE) or cerebrovascular pressure autoregulation (PAR) indices. The transfer characteristic of an EVD system is investigated by its step and frequency responses with focus on the low frequency (LF) range from 0.02 to 0.065Hz (important in PAR) and the location of the system's first resonance frequency (important for ICE). The effects of opening the distal end of the EVD for drainage of cerebrospinal fluid and the presence of trapped air bubbles are also investigated. The EVD system exhibits a first resonant frequency below 4Hz, resulting in significant distortion of the measured ICP waveform. The frequency response in the LF range only remains flat when the EVD is closed. Opening the drain results in drops in magnitude and phase along the entire frequency range above DC. Air bubbles close to the EVD catheter tip affect the LF range while an air bubble close to the pressure transducer further decreases the first resonant frequency. Tests with actual ICP waveforms confirmed EVD-induced waveform distortions that can lead to erroneous ICE estimation. EVD-based ICP measurements distort the waveform morphology. PAR indices based on LF information are only valid if the EVD is closed. EVD-based ICE estimation is to be avoided. ICP waveform analyses to derive information about ICE and PAR should be critically questioned if only EVD derived ICP signals are at hand.

Cardiac-gated intracranial elastance in a swine model of raised intracranial pressure: a novel method to assess intracranial pressure-volume dynamics.

Previous studies have demonstrated the importance of intracranial elastance; however, methodological difficulties have limited widespread clinical use. Measuring elastance may offer potential benefit in helping to identify patients at risk for untoward intracranial pressure (ICP) elevation from small rises in intracranial volume. The authors sought to develop an easily used method that accounts for the changing ICP that occurs over a cardiac cycle and to assess this method in a large-animal model over a broad range of ICPs. The authors used their previously described cardiac-gated intracranial balloon pump and swine model of cerebral edema. In the present experiment they measured elastance at 4 points along the cardiac cycle-early systole, peak systole, mid-diastole, and end diastole-by using rapid balloon inflation to 1 ml over an ICP range of 10-30 mm Hg. The authors studied 7 swine with increasing cerebral edema. Intracranial elastance rose progressively with increasing ICP. Peak-systolic and end-diastolic elastance demonstrated the most consistent rise in elastance as ICP increased. Cardiac-gated elastance measurements had markedly lower variance within swine compared with non-cardiac-gated measures. The slope of the ICP-elastance curve differed between swine. At ICP between 20 and 25 mm Hg, elastance varied between 8.7 and 15.8 mm Hg/ml, indicating that ICP alone cannot accurately predict intracranial elastance. Measuring intracranial elastance in a cardiac-gated manner is feasible and may offer an improved precision of measure. The authors' preliminary data suggest that because elastance values may vary at similar ICP levels, ICP alone may not necessarily best reflect the state of intracranial volume reserve capacity. Paired ICP-elastance measurements may offer benefit as an adjunct "early warning monitor" alerting to the risk of untoward ICP elevation in brain-injured patients that is induced by small increases in intracranial volume.

Intracranial Pressure and Intracranial Elastance Monitoring in Neurocritical Care.

Patients with acute brain injuries tend to be physiologically unstable and at risk of rapid and potentially life-threatening decompensation due to shifts in intracranial compartment volumes and consequent intracranial hypertension. Invasive intracranial pressure (ICP) monitoring therefore remains a cornerstone of modern neurocritical care, despite the attendant risks of infection and damage to brain tissue arising from the surgical placement of a catheter or pressure transducer into the cerebrospinal fluid or brain tissue compartments. In addition to ICP monitoring, tracking of the intracranial capacity to buffer shifts in compartment volumes would help in the assessment of patient state, inform clinical decision making, and guide therapeutic interventions. We review the anatomy, physiology, and current technology relevant to clinical management of patients with acute brain injury and outline unmet clinical needs to advance patient monitoring in neurocritical care.

Noninvasive assessment of intracranial elastance and pressure in spontaneous intracranial hypotension by MRI.

Spontaneous intracranial hypotension (SIH) is often misdiagnosed, and can lead to severe complications. Conventional MR sequences show a limited ability to aid in this diagnosis. MR-based intracranial pressure (MR-ICP) may be able to detect changes of intracranial elastance and pressure. To determine whether MR-ICP is able to differentiate SIH patients from normal subjects, improve diagnostic sensitivity, and provide an insight into the pathophysiology. Prospective. Twenty-eight SIH cases with orthostatic headache and 20 healthy volunteers. Cine phase-contrast MRI on a 1.5T scanner. Intracranial elastance (IE) was derived from the ratio of the peak-to-peak cerebrospinal fluid (CSF) pressure gradient (PGcsf-pp ) and intracranial volume change, obtained by summing all flows before each sequential cardiac frame. Student's t-test was used to compare the MR-ICP indexes and flow parameters between SIH patients and healthy volunteers (P < 0.01). The SIH patients with cervical epidural venous dilatation (EVD) had an IE of 0.121 ± 0.027 mmHg/cm/ml, significantly higher than that of the normal volunteers (0.085 ± 0.027 mmHg/cm/ml; P = 0.002). In contradistinction, the EVD-negative SIH patients, including four with no sign of CSF leaks, had significantly lower IE (0.055 ± 0.012 mmHg/cm/ml) compared with the normal volunteers and the EVD-positive group (P = 0.001, P < 0.001). The EVD-negative patients had significantly lower PGcsf-pp (0.024 ± 0.007 mmHg/cm) compared with the normal volunteers and the EVD-positive group (0.035 ± 0.011 mmHg/cm, 0.040 ± 0.010 mmHg/cm; P = 0.003, P < 0.001). Additionally, the MRI flow study showed a significant decrease in transcranial inflow and outflow of SIH patients (P < 0.01). We found that the MR-ICP method is potentially more sensitive than morphological MRI in the early diagnosis of SIH. Also, contrary to common belief, our results suggest that an abnormal craniospinal elastance might be the cause of SIH, instead of CSF leak. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1255-1263.

Intracranial elastance is increased in idiopathic intracranial hypertension.

To date, no pathophysiological model has sufficiently accounted for all the findings encountered in patients with idiopathic intracranial hypertension (IIH). Intracranial elastance is an index of volume-buffering capacity known to play a role in certain disorders of cerebrospinal fluid (CSF) dynamics, which has not been previously investigated in relation to IIH patients. This was a single-center retrospective cohort study from 1 July 2011 to 1 July 2016. Values for opening pressure (PO ), closing pressure (PC ) and volume (V) of CSF removed were collected, as well as demographic and clinical covariates. Intracranial elastance (E) and pressure-volume index (PVI) were calculated according to established equations: E = (PO -PC )/V and PVI = V/log10 (PO /PC ), respectively. Those with an alternative central nervous system pathology, including meningitis, encephalitis and normal pressure hydrocephalus were excluded. Eligible patients were subdivided into two groups based on final diagnosis: a control group and an IIH group. In our cohort (n = 49), a significant association of both E (P < 0.0001) and PVI (P = 0.005) with a diagnosis of IIH was observed. Median E was 0.45 [interquartile range (IQR) 0.29-0.63] in the control group and 1 (IQR 0.59-1.29) in the IIH group, and median PVI was 98.07 (IQR 59.92-135.86) in the control group and 64.1 (IQR 42.4-91.7) in the IIH group. Neither E nor PVI were significantly associated with age, gender or body mass index. PVI was independent of opening pressure. As calculated by clinically accessible indices, our study provides evidence that intracranial elastance is increased in IIH, reflecting a novel insight into disease pathogenesis.

The correlation between pulsatile intracranial pressure and indices of intracranial pressure-volume reserve capacity: results from ventricular infusion testing.

OBJECTIVE The objective of this study was to examine how pulsatile and static intracranial pressure (ICP) scores correlate with indices of intracranial pressure-volume reserve capacity, i.e., intracranial elastance (ICE) and intracranial compliance (ICC), as determined during ventricular infusion testing. METHODS All patients undergoing ventricular infusion testing and overnight ICP monitoring during the 6-year period from 2007 to 2012 were included in the study. Clinical data were retrieved from a quality registry, and the ventricular infusion pressure data and ICP scores were retrieved from a pressure database. The ICE and ICC (= 1/ICE) were computed during the infusion phase of the infusion test. RESULTS During the period from 2007 to 2012, 82 patients with possible treatment-dependent hydrocephalus underwent ventricular infusion testing within the department of neurosurgery. The infusion tests revealed a highly significant positive correlation between ICE and the pulsatile ICP scores mean wave amplitude (MWA) and rise-time coefficient (RTC), and the static ICP score mean ICP. The ICE was negatively associated with linear measures of ventricular size. The overnight ICP recordings revealed significantly increased MWA (> 4 mm Hg) and RTC (> 20 mm Hg/sec) values in patients with impaired ICC (< 0.5 ml/mm Hg). CONCLUSIONS In this study cohort, there was a significant positive correlation between pulsatile ICP and ICE measured during ventricular infusion testing. In patients with impaired ICC during infusion testing (ICC < 0.5 ml/mm Hg), overnight ICP recordings showed increased pulsatile ICP (MWA > 4 mm Hg, RTC > 20 mm Hg/sec), but not increased mean ICP (< 10-15 mm Hg). The present data support the assumption that pulsatile ICP (MWA and RTC) may serve as substitute markers of pressure-volume reserve capacity, i.e., ICE and ICC.

A New Method of Estimating Intracranial Elastance

Current methods of calculating Intracranial Elastance Index (IEI) depend from CSF pulse-wave, whose shape may deeply change during ICP rising. The main aim of this study was to evaluate the reliability and specificity of a novel method to calculate IEI (method C), based on the integral of the CSF pulse-wave area. Twenty ventricular infusion-tests of patients with idiopathic NPH were re-evaluated. We have compared method C with the most widely used methods to calculate IEI: a modified Szewczykowski method (diastolic ICP against CSF pulse-wave amplitude-method A) and a modified Czosnyka method (diastolic ICP against the fundamental harmonic-method B). R-squared (R 2 ) was calculated for each test. Means were compared through ANOVA and t-test. Mean R 2 values for methods A, B and C were 0.91 ± 0.06, 0.9 ± 0.06 and 0.96 ± 0.03, respectively. Mean R 2 values obtained through method A vs C and through method B vs C were significantly different (p = .006 and p = .001, respectively), while values obtained through method A vs B were not (p = 1). Analysis of ICP tracks demonstrated that 9 patients showed no different shape of the ICP wave during the infusion test, while the remaining 11 did. The mean R2 values obtained through method A vs C and through method B vs C were significantly different (p < .001 for both) for patients showing a different shape of the ICP wave during the infusion test. Method C seems to be the most reliable method to calculate IEI, as it is independent from CSF pulse wave modifications. • Current methods of calculating Intracranial Elastance Index (IEI) depend from CSF pulse-wave, whose shape may deeply change during ICP rising. • We evaluated the reliability and specificity of a novel method to calculate IEI, based on the integral of the CSF pulse-wave area. • This method seems to be independent from CSF pulse wave modifications.

Use of the intrathoracic pressure regulator to lower intracranial pressure in patients with altered intracranial elastance: a pilot study

The intrathoracic pressure regulator (ITPR) is a novel noninvasive device designed to increase circulation and blood pressure. By applying negative pressure during the expiratory phase of ventilation it decreases intrathoracic pressure and enhances venous return, which increases cardiac output. It is possible that the ITPR may both decrease intracranial pressure (ICP) and increase cerebral perfusion pressure (CPP) in brain-injured patients by decreasing cerebral venous blood volume and increasing cardiac output. The authors conducted an open-label, "first-in-humans" study of the ITPR in patients with an ICP monitor or external ventricular drain and altered intracranial elastance. This prospective randomized trial commenced July 2009. Baseline hemodynamic variables and ICP were recorded prior to inserting one of the two ITPRs into the ventilator circuit based on a randomization scheme. Depending on the device selected, activation provided either -5 or -9 mm Hg endotracheal tube pressure. Hemodynamic and ICP data were recorded sequentially every 2 minutes for 10 minutes. The first device was turned off for 10 minutes, then it was removed and the second device was applied, and then the procedure was repeated for the second device. Ten patients with elevated ICP secondary to intracranial hemorrhage (n = 4), trauma (n = 2), obstructive hydrocephalus (n = 2), or diffuse cerebral processes (n = 2) were enrolled. Baseline ICP ranged from 12 to 38 mm Hg. With device application, a decrease in ICP was observed in 16 of 20 applications. During treatment with the -5 mm Hg device, there was a mean maximal decrease of 3.3 mm Hg in ICP (21.7 vs 18.4 mm Hg, p = 0.003), which was associated with an increase in CPP of 6.5 mm Hg (58.2 vs 64.7 mm Hg, p = 0.019). During treatment with the -9 mm Hg device, there was a mean maximal decrease of 2.4 mm Hg in ICP (21.1 vs 18.7 mm Hg, p = 0.044), which was associated with an increase in CPP of 6.5 mm Hg (59.2 vs 65.7 mm Hg, p = 0.001). This pilot study demonstrates that use of the ITPR in patients with altered intracranial elastance is feasible. Although this study was not powered to demonstrate efficacy, these data strongly suggest that the ITPR may be used to rapidly lower ICP and increase CPP without apparent adverse effects. Additional studies will be needed to assess longitudinal changes in ICP when the device is in use and to delineate treatment parameters.

CSF dynamics analysis in patients with post-traumatic ventriculomegaly

ObjectiveThe management of post-traumatic ventriculomegaly (PTV) is controversial. This is due to the difficulty to determine whether PTV is related to an atrophic process or to a true “active” hydrocephalus. The purpose of this study is to analyze the CSF-dynamics in patients with PTV and, possibly, to identify parameters that correlate with prognosis. Methods15 patients with PTV were treated following this protocol: 1-frontal ventriculostomy (with Rickham reservoir); 2-CSF-dynamics evaluation; 3-ventriculo-peritoneal shunt. CSF dynamics evaluation was based on an intraventricular infusion test (performed three to five days after ventriculostomy). Outflow Resistance (R-out) and Intracranial Elastance Index (EI, i.e. the reciprocal of intracranial compliance) were calculated. Patients were classified according to response to shunt into: 1-fast responders: rapid clinical improvement, i.e. within days/one month from surgery; 2-slow responders: patients presenting little clinical improvement occurring after months (despite neurorehabilitation); 3-non responders: no clinical improvement. ResultsSeven patients (46.7%) were classified as fast-responders, three patients were classified as slow-responders (20%) and five patients were classified as non-responders (33.3%). Opening CSF pressure was less than 15mmHg for all patients. R-out (cut-off >10mmHg/ml/min) had 100% sensitivity, 50% specificity, 100% negative predictive value and 63.6% positive predictive value. EI (cut-off value >0.3) had 100% specificity, 42.4% sensitivity, 100% positive predictive value and 66.7% negative predictive value. ConclusionsBased on these considerations, we can suggest that, for patients with normal pressure PTV, analysis of CSF dynamics could be of help in selecting patients for CSF-shunt. A combination of Intracranial Elastance and of R-out could help predicting shunt responsiveness.

Selection of patients with idiopathic normal-pressure hydrocephalus for shunt placement: a single-institution experience

The ability to predict outcome after shunt placement in patients with idiopathic normal-pressure hydrocephalus (NPH) represents a challenge. To date, no single diagnostic tool or combination of tools has proved capable of reliably predicting whether the condition of a patient with suspected NPH will improve after a shunting procedure. In this paper, the authors report their experience with 120 patients with the goal of identifying CSF hydrodynamics criteria capable of selecting patients with idiopathic NPH. Specifically, they focused on the comparison between CSF-outflow resistance (R-out) and intracranial elastance (IE). Between January 1977 and December 2005, 120 patients in whom idiopathic NPH had been diagnosed (on the basis of clinical findings and imaging) underwent CSF hydrodynamics evaluation based on an intraventricular infusion test. Ninety-six patients underwent CSF shunt placement: 32 between 1977 and 1989 (Group I) on the basis of purely clinical and radiological criteria; 44 between 1990 and 2002 (Group II) on the basis of the same criteria as Group I and because they had an IE slope > 0.25; and 20 between 2003 and 2005 (Group III) on the basis of the same criteria as Group II but with an IE slope > or = 0.30. Outcomes were evaluated by means of both Stein-Langfitt and Larsson scores. Patients' conditions were considered improved when there was a stable decrease (at 6- and 12-month follow-up) of at least 1 point in the Stein-Langfitt score and 2 points in the Larsson score. Group I: while no statistically significant difference in mean R-out value between improved and unimproved cases was observed, a clear-cut IE slope value of 0.25 differentiated very sharply between unimproved and improved cases. Group II: R-out values in the 2 unimproved cases were 20 and 47 mm Hg/ml/min, respectively. The mean IE slope in the improved cases was 0.56 (range 0.30-1.4), while the IE slopes in the 2 unimproved cases were 0.26 and 0.27. Group III: the mean IE slope was 0.51 (range 0.31-0.7). The conditions of all patients improved after shunting. A significant reduction of the Evans ratio was observed in 34 (40.5%) of the 84 improved cases and in none of the unimproved cases. Our strategy based on the analysis of CSF pulse pressure parameters seems to have a great accuracy in predicting surgical outcome in clinical practice.

The relationship between the intracranial pressure–volume index and cerebral autoregulation

The pressure-volume index (PVI) can be used to assess the cerebrospinal fluid dynamics and intracranial elastance in critically ill brain injured patients. The dependency of PVI on the state of cerebral autoregulation within the physiologic range of cerebral perfusion pressure (CPP) can be described by mathematical models that account for changes in cerebral blood volume during PVI testing. This relationship has never been verified clinically using direct PVI measurement and independent cerebral autoregulation assessment. PVI and cerebral autoregulation were prospectively assessed in a cohort of 19 comatose patients admitted to an academic intensive care unit in Brescia, Italy. None. PVI was measured injecting a fixed volume of 2 ml of 0.9% sodium chloride solution into the cerebral ventricles through an intraventricular catheter. Cerebral autoregulation was assessed using transcranial Doppler transient hyperaemic response (THR) test. Fifty-nine PVI assessments and 59 THR tests were performed. Mean PVI was 20.0 (SD 10.2) millilitres in sessions when autoregulation was intact (THR test >or=1.1) and 31.6 (8.8) millilitres in sessions with defective autoregulation (THR test <1.1) (DeltaPVI = 11.7 ml, 95% CI = 4.7-19.3 ml; P = 0.002). Intracranial pressure, CPP and brain CT findings were not significantly different between the measurements with intact and disturbed autoregulation. Cerebral autoregulation status can affect PVI estimation despite a normal CPP. PVI measurement may overestimate the tolerance of the intracranial system to volume loads in patients with disturbed cerebral autoregulation.

Assessment of factors affecting MRI measurement of intracranial volume changes and elastance index

Non-invasive measurement of cerebral hydrodynamic parameters may be of great use in the study and treatment of conditions involving abnormal intracranial pressure (ICP). ICP can be assessed indirectly in humans by calculation of intracranial volume changes and elastance using MRI. These two hydrodynamic parameters are derived from mathematical analysis of the relationships between blood flow to and from the brain, CSF flow and heart rate. This paper examines the variability in these three critical subject specific parameters. Three healthy adult males had measurements of blood and CSF flow to and from the brain made on three occasions. Inter-individual variation in vasculature and intra-individual variation in heart rates led to modest repeatability (defined as standard deviation divided by the mean) of intracranial volume change and elastance index in two subjects and poor repeatability in the third. Particular care is required in the selection of image planes and the blood vessels to include, and the analysis is very sensitive to differences in heart-rate. Because of these difficulties, caution is required in the interpretation of results obtained from a single examination. Techniques and methods that may reduce the variability in the derived hydrodynamic parameters are discussed.

Inhalational or intravenous anesthetics for craniotomies? Pro inhalational

In neurosurgery, anesthesiologists and surgeons focus on the same target - the brain. The nature of anesthetics is to interact with brain physiology, leading to favorable and adverse effects. Research in neuroanesthesia over the last three decades has been dedicated to identifying the optimal anesthetic agent to maintain coupling between cerebral blood flow and metabolism, keep cerebrovascular autoregulation intact, and not increase cerebral blood volume and intracranial pressure. Sevoflurane is less vasoactive than halothane, enflurane, isoflurane, or desflurane. The context sensitive half-life is short and similar to that of desflurane, which translates into fast on and offset. Compared with propofol, sevoflurane decreases cerebral blood flow to a lesser extent, while cerebral metabolism is suppressed to the same degree. Sevoflurane does not increase intracranial pressure, while propofol decreases intracranial pressure. In neurosurgical patients with normal intracranial pressure, sevoflurane might be a good alternative to propofol. In patients with reduced intracranial elastance, caused by space occupying lesions, with elevated intracranial pressure or complex surgical approaches, propofol should remain first choice.

Noninvasive intracranial compliance and pressure based on dynamic magnetic resonance imaging of blood flow and cerebrospinal fluid flow: review of principles, implementation, and other noninvasive approaches

Current techniques for intracranial pressure (ICP) measurement are invasive. All require a surgical procedure for placement of a pressure probe in the central nervous system and, as such, are associated with risk and morbidity. These considerations have driven investigators to develop noninvasive techniques for pressure estimation. A recently developed magnetic resonance (MR) imaging-based method to measure intracranial compliance and pressure is described. In this method the small changes in intracranial volume and ICP that occur naturally with each cardiac cycle are considered. The pressure change during the cardiac cycle is derived from the cerebrospinal fluid (CSF) pressure gradient waveform calculated from the CSF velocities. The intracranial volume change is determined by the instantaneous differences between arterial blood inflow, venous blood outflow, and CSF volumetric flow rates into and out of the cranial vault. Elastance (the inverse of compliance) is derived from the ratio of the measured pressure and volume changes. A mean ICP value is then derived based on a linear relationship that exists between intracranial elastance and ICP. The method has been validated in baboons, flow phantoms, and computer simulations. To date studies in humans demonstrate good measurement reproducibility and reliability. Several other noninvasive approaches for ICP measurement, mostly nonimaging based, are also reviewed. Magnetic resonance imaging-based ICP measurement may prove valuable in the diagnosis and serial evaluation of patients with a variety of disorders associated with alterations in ICP.

Quantitative assessment of cerebral autoregulation from transcranial Doppler pulsatility: a computer simulation study

Transcranial Doppler (TCD) ultrasonography is largely used today to achieve non-invasive assessment of cerebral autoregulation and cerebrovascular reactivity in neurosurgical patients. Recent experimental and clinical studies suggest that not only the pattern of mean velocity, but also velocity pulse amplitude alterations during changes in cerebral perfusion pressure (CPP) contain information on autoregulation status. The aim of this work is to investigate the relationship between cerebral autoregulation and TCD pulsatility by means of a comprehensive mathematical model of intracranial dynamics and cerebrovascular regulation. Simulation results, performed using different values of the most important clinical parameters of the model (autoregulation strength, cerebrospinal fluid (CSF) outflow resistance and intracranial elastance coefficient) show that velocity pulse amplitude increases with a reduction in CPP in patients with intact autoregulation, whereas changes in velocity pulsatility are modest in patients with weak autoregulation. Finally, velocity pulse amplitude decreases during a CPP reduction in patients with impaired autoregulation. Moreover, the relationship between the velocity pulse amplitude changes and autoregulation strength is almost linear in a wide range of CPP values, and is scarcely affected by changes in CSF circulation and intracranial elasticity. Starting from these results, we suggest a new quantitative index to assess autoregulation strength, i.e. G aut%=( s− b)/ a, where G aut % is autoregulation strength (100% means intact autoregulation, 0% means impaired autoregulation), a≃−0.03; b≃1.5 and s is the slope of the relationship ‘ percentage changes of velocity pulse amplitude to arterial pressure pulse amplitude vs. CPP changes’.

MR-Intracranial pressure (ICP): a method to measure intracranial elastance and pressure noninvasively by means of MR imaging: baboon and human study.

To develop a noninvasive method for intracranial elastance and intracranial pressure (ICP) measurement. Intracranial volume and pressure changes were calculated from magnetic resonance (MR) imaging measurements of cerebrospinal fluid (CSF) and blood flow. The volume change was calculated from the net transcranial CSF and blood volumetric flow rates. The change in pressure was derived from the change in the CSF pressure gradient calculated from CSF velocity. An elastance index was derived from the ratio of pressure to volume change. The reproducibility of the elastance index measurement was established from four to five measurements in five healthy volunteers. The elastance index was measured and compared with invasive ICP measurements in five patients with an intraventricular catheter at MR imaging. False-positive and false-negative rates were established by using 25 measurements in eight healthy volunteers and six in four patients with chronically elevated ICP. The mean of the fractional SD of the elastance index in humans was 19.6%. The elastance index in the five patients with intraventricular catheters correlated well with the invasively measured ICP (R:(2) = 0.965; P: <.005). MR imaging-derived ICPs in the eight healthy volunteers were 4.2-12.4 mm Hg, all within normal range. Measurements in three of the four patients with chronically elevated ICP were 20.5-34.0 mm Hg, substantially higher than the normal limit. MR imaging-derived elastance index correlates with ICP over a wide range of ICP values. The sensitivity of the technique allows differentiation between normal and elevated ICP.