Analysis of phase shift between pulse oscillations of macro- and microvascular cerebral blood flow in patients with traumatic brain injury.

PURPOSE: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time. METHODS: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms. RESULTS: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03). CONCLUSIONS: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

International e-Delphi survey to define best practice in the reporting of intracranial pressure monitoring recording data.

Introduction: Intracranial pressure (ICP) monitoring is a very commonly performed neurosurgical procedure but there is a wide variation in how it is reported, hindering analysis of it. The current study sought to generate consensus on the reporting of ICP monitoring recording data. Research question: "What should be included in an ICP monitoring report?" Material and methods: The exercise was completed via a modified eDelphi survey. An expert panel discussion was held from which themes were identified and used to produce a code to annotate the transcript of the discussion. Statements were generated for a further two rounds of electronic questionnaires distributed via the REDcap platform. A Likert scale was used to grade agreement with each statement in the survey. A statement was accepted if more than 70% agreement was achieved between respondents. Data was collated using Microsoft Excel and analysed using R. Results: 149 relevant statements were identified from the transcript and categorised into recording parameters, waveform characteristics or reporting. A total of 22 statements were generated for the first round of the survey which was answered by 39 respondents. Following the electronic round of surveys consensus was achieved for all but one statement regarding the acceptability of automating ICP reporting. This was put forward to a second round after which 79% agreement was reached. Discussion and conclusion: The themes and statements from this eDelphi can be used as a framework to allow the standardisation of the reporting of intracranial pressure monitoring data.

Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Reliability and variability of pressure reactivity index (prx) during oscillatory pattern in arterial blood pressure and intracranial pressure in traumatic brain injured patients.

Introduction: Pressure reactivity index (PRx) is used for continuous monitoring of cerebrovascular reactivity in traumatic brain injury (TBI). However, PRx has a noisy character. Oscillations in arterial blood pressure (ABP) introduced by cyclic positive end-expiratory pressure adjustment, can make PRx more reliable. However, if oscillations are introduced by the cycling process of an anti-decubitus-mattress the effect on PRx is confounding, as they affect directly also intracranial pressure (ICP). In our routine monitoring in TBI patients we noticed periods of highly regular, slow, spontaneous oscillations in ABP and ICP signals. Research question: We set out to explore the nature of these oscillations and establish if PRx remains reliable during the oscillations. Materials and methods: 10 TBI patients' recordings with oscillations in ICP and ABP were analysed. We computed PRx, PRx variability (hourly-average of standard-deviation, SD), phase-shift and coherence between ABP and ICP in the slow frequency range. Metrics were compared between oscillation and peri-oscillation periods. Results: During oscillations (frequency 0.006 ± 0.002Hz), a significantly lower variability of PRx (SD 0.185vs0.242) and higher coherence ABP-ICP (0.618 ± 0.09 vs 0.534 ± 0.09) were observed. No external oscillations sources could be identified. 34 out of 48 events showed signs of 'active' transmission associated with negative PRx, indicating a potential positive impact on PRx reliability. Discussion and conclusions: Spontaneous oscillations observed in ABP and ICP signals were found to enhance rather than confound PRx reliability. Further research is warranted to elucidate the nature of these oscillations and develop strategies to leverage them for enhancing PRx reliability in TBI monitoring.

Cerebral autoregulation in paediatric and neonatal intensive care: A scoping review.

Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care.

Embracing uncertainty in cerebrospinal fluid dynamics: A Bayesian approach to analysing infusion studies.

Introduction: Cerebrospinal fluid (CSF) infusion test analysis allows recognizing and appropriately evaluating CSF dynamics in the context of normal pressure hydrocephalus (NPH), which is crucial for effective diagnosis and treatment. However, existing methodology possesses drawbacks that may compromise the precision and interpretation of CSF dynamics parameters. Research question: This study aims to circumvent these constraints by introducing an innovative analysis method grounded in Bayesian inference. Material and methods: A single-centre retrospective cohort study was conducted on 858 patients who underwent a computerized CSF infusion test between 2004 and 2020. We developed a Bayesian framework-based method for parameter estimation and compared the results to the current, gradient descent-based approach. We evaluated the accuracy and reliability of both methods by analysing erroneous prediction rates and curve fitting errors. Results: The Bayesian method surpasses the gradient descent approach, reflected in reduced inaccurate prediction rates and an improved goodness of model fit. On whole cohort level both techniques produced comparable results. However, the Bayesian method holds an added advantage by providing uncertainty intervals for each parameter. Sensitivity analysis revealed significance of the CSF production rate parameter and its interplay with other variables. The resistance to CSF outflow demonstrated excellent robustness. Discussion and conclusion: The proposed Bayesian approach offers a promising solution for improving robustness of CSF dynamics assessment in NPH, based on CSF infusion tests. Additional provision of the uncertainty measure for each diagnostic metric may perhaps help to explain occasional poor diagnostic performance of the test, offering a robust framework for improved understanding and management of NPH.

Assessment of CSF Dynamics Using Infusion Study: Tips and Tricks.

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders.

Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood-brain barrier and to cerebral oedema after reperfusion therapy. The resulting fluid accumulation in the brain may contribute to a significant rise in intracranial pressure (ICP) and tissue deformation. Changes in the level of ICP are essential for clinical decision-making and therapeutic strategies. However, the measurement of ICP is constrained by clinical techniques and obtaining the exact values of the ICP has proven challenging. In this study, we propose the first computational model for the simulation of cerebral oedema following acute ischaemic stroke for the investigation of ICP and midline shift (MLS) relationship. The model consists of three components for the simulation of healthy blood flow, occluded blood flow and oedema, respectively. The healthy and occluded blood flow components are utilized to obtain oedema core geometry and then imported into the oedema model for the simulation of oedema growth. The simulation results of the model are compared with clinical data from 97 traumatic brain injury patients for the validation of major model parameters. Midline shift has been widely used for the diagnosis, clinical decision-making, and prognosis of oedema patients. Therefore, we focus on quantifying the relationship between ICP and midline shift (MLS) and identify the factors that can affect the ICP-MLS relationship. Three major factors are investigated, including the brain geometry, blood-brain barrier damage severity and the types of oedema (including rare types of oedema). Meanwhile, the two major types (stress and tension/compression) of mechanical brain damage are also presented and the differences in the stress, tension, and compression between the intraparenchymal and periventricular regions are discussed. This work helps to predict ICP precisely and therefore provides improved clinical guidance for the treatment of brain oedema.

Transmission of slow waves in Masimo O3 near infrared spectroscopy measures.

Introduction: Cerebral autoregulation (CA) dysfunction is a key complication following brain injury. CA assessment using near-infrared spectroscopy (NIRS) offers a promising alternative to the current non-invasive standard, cerebral blood flow velocity (CBFV) measured with transcranial Doppler. Research question: Can autoregulatory slow waves (frequency range 0.005-0.05 Hz) associated with spontaneous and induced changes in ABP in healthy volunteers be detected by parameters measured with the Masimo O3 NIRS device? Methods: ABP, CBFV and Masimo O3 parameters were measured in 10 healthy volunteers at baseline and during ABP oscillations induced by squat/stand manoeuvres. Transmission of slow waves was assessed with power spectral density and coherence analysis in NIRS signals and compared to that of CBFV. Results: At baseline, slow waves were detected with sufficient power that substantially exceeded the signals' measurement resolution in all parameters except cerebral oxygen saturation. During ABP oscillations in the 0.033 Hz range (induced by squat/stand), the power of slow waves increased in all parameters in a similar pattern, with total (cHb) and oxygenated (O2Hb) haemoglobin concentrations most closely mirroring CBFV (median standardised power [first-third quartile], baseline vs squat/stand: CBFV 0.35 [0.28-0.42] vs 0.50 [0.45-0.62], O2Hb 0.47 [0.33-0.68] vs 0.61 [0.59-0.69]). Coherence with ABP increased for both CBFV and NIRS measures from low at baseline (<0.4) to high during induced changes (>0.8). Conclusion: Spontaneous fluctuations in ABP can be observed in analysed Masimo O3 metrics to a varying degree. The clinical utility of Masimo O3 signals in CA assessment requires further investigation in brain injury patients.

Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

BACKGROUND AND AIM: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. METHODS: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. RESULTS: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. CONCLUSIONS: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. IMPACT: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves.

Introduction: Both intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research question: Does ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methods: A total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. Results: ICP increased (19.4 mm Hg [Q1-Q3: 18.2-23.4 mm Hg] vs. 42.7 mm Hg [Q1-Q3: 36.5-45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1-Q3: 34.8-69.5 cm/s] vs. 32.9 cm/s [Q1-Q3: 24.7-68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1-Q3: 15.74-23.0]) compared to the baselines (26.3 [Q1-Q3: 24.2-34.7], p < 0.001). Discussion and conclusion: The area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet).

Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA.

The time constant of the cerebral arterial bed: exploring age-related implications.

The time constant of the cerebral arterial bed (τ) represents an estimation of the  transit time of flow from the point of insonation at the level of the middle cerebral artery to the arteriolar-capillary boundary, during a cardiac cycle. This study assessed differences in τ among healthy volunteers across different age groups. Simultaneous recordings of transcranial Doppler cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) were performed on two groups: young volunteers (below 30 years of age), and older volunteers (above 40 years of age). τ was estimated using mathematical transformation of ABP and CBFV pulse waveforms. 77 healthy volunteers [52 in the young group, and 25 in the old group] were included. Pulse amplitude of ABP was higher [16.7 (14.6-19.4) mmHg] in older volunteers as compared to younger ones [12.5 (10.9-14.4) mm Hg; p < 0.001]. CBFV was lower in older volunteers [59 (50-66) cm/s] as compared to younger ones [72 (63-78) cm/s p < 0.001]. τ was longer in the younger volunteers [217 (168-237) ms] as compared to the older volunteers [183 (149-211) ms; p = 0.004]. τ significantly decreased with age (rS = - 0.27; p = 0.018). τ is potentially an integrative marker of the changes occurring in cerebral vasculature, as it encompasses the interplay between changes in compliance and resistance that occur with age.

Exploration of uncertainty of PRx time trends.

Introduction: PRx can be used as surrogate measure of Cerebral Autoregulation (CA) in traumatic brain injury (TBI) patients. PRx can provide means for individualising cerebral perfusion pressure (CPP) targets, such as CPPopt. However, a recent Delphi consensus of clinicians concluded that consensus could not be reached on the accuracy, reliability, and validation of any current CA assessment method. Research question: We aimed to quantify the short-term uncertainty of PRx time-trends and to relate this to other physiological measurements. Material and methods: Intracranial pressure (ICP), arterial blood pressure (ABP), end-tidal CO2 (EtCO2) high-resolution recordings of 911 TBI patients were processed with ICM + software. Hourly values of metrics that describe the variability within modalities derived from ABP, ICP and EtCO2, were calculated for the first 24h of neuromonitoring. Generalized additive models were used to describe the time trend of the variability in PRx. Linear correlations were studied for describing the relationship between PRx variability and the other physiological modalities. Results: The time profile of variability of PRx decreases over the first 12h and was higher for average PRx ∼0. Increased variability of PRx was not linearly linked with average ABP, ICP, or CPP. For coherence between slow waves of ABP and ICP >0.7, the variability in PRx decreased (R = -0.47, p < 0.001). Discussion and conclusion: PRx is a highly variable parameter. PRx short-term dispersion was not related to average ICP, ABP or CPP. The determinants of uncertainty of PRx should be investigated to improve reliability of individualised CA assessment in TBI patients.

Red solid line: Patterns of terminal loss of cerebrovascular reactivity at the bedside.

Introduction: Continuous monitoring of the pressure reactivity index (PRx) provides an estimation of dynamic cerebral autoregulation (CA) at the bedside in traumatic brain injury (TBI) patients. Visualising the time-trend of PRx with a risk bar chart in ICM + software at the bedside allows for better real-time interpretability of the autoregulation status. When PRx>0.3 is sustained for long periods, typically of at least half an hour, the bar shows a pattern called "red solid line" (RSL). RSL was previously described to precede refractory intracranial hypertension and brain death. Research question: We aimed to describe pathophysiological changes in measured signals/parameters during RSL. Material and methods: Observation of time-trends of PRx, intracranial pressure, cerebral perfusion pressure, brain oxygenation and compensatory reserve of TBI patients with RSL. Results: Three pathophysiological patterns were identified: RSL precedes intracranial hypertension, RSL is preceded by intracranial hypertension, or RSL is preceded by brain hypoperfusion. In all cases, RSL was followed by death and the RSL onset was between 1 h and 1 day before the terminal event. Discussion and conclusion: RSL precedes death in intensive care and could represent a marker for terminal clinical deterioration in TBI patients. These findings warrant further investigations in larger cohorts to characterise pathophysiological mechanisms underlying the RSL pattern and whether RSL has a significant relationship with outcome after TBI.

Mathematical modelling of cerebral haemodynamics and their effects on ICP.

Introduction: Electrical-equivalence mathematical models that integrate vascular and cerebrospinal fluid (CSF) compartments perform well in simulations of dynamic cerebrovascular variations and their transient effects on intracranial pressure (ICP). However, ICP changes due to sustained vascular diameter changes have not been comprehensively examined. We hypothesise that changes in cerebrovascular resistance (CVR) alter the resistance of the bulk flow of interstitial fluid (ISF). Research question: We hypothesise that changes in CVR alter the resistance of the bulk flow of ISF, thus allowing simulations of ICP in response to sustained vascular diameter changes. Material and methods: A lumped parameter model with vascular and CSF compartments was constructed and converted into an electrical analogue. The flow and pressure responses to transient hyperaemic response test (THRT) and CSF infusion test (IT) were observed. Arterial blood pressure (ABP) was manipulated to simulate ICP plateau waves. The experiments were repeated with a modified model that included the ISF compartment. Results: Simulations of the THRT produced identical cerebral blood flow (CBF) responses. ICP generated by the new model reacted in a similar manner as the original model during ITs. Plateau pressure reached during ITs was however higher in the ISF model. Only the latter was successful in simulating the onset of ICP plateau waves in response to selective blood pressure manipulations. Discussion and conclusion: Our simulations highlighted the importance of including the ISF compartment, which provides mechanism explaining sustained haemodynamic influences on ICP. Consideration of such interactions enables accurate simulations of the cerebrovascular effects on ICP.

Observational study of intracranial pressure instability in patients with pseudotumour cerebri syndrome.

Introduction: A fixed CSF pressure (CSFp) of 25 cmH2O (18 mmHg) has been utilised to date to define and classify pseudotumour cerebri syndrome (PTCS). Furthermore, ICP monitoring, and CSF infusion tests have not been frequently performed in this group of patients. Research question: We aimed to report typical, unusual and unstable patterns of ICP in patients with PTCS. Material and methods: We reviewed the recordings of CSF infusion tests and overnight ICP monitoring of patients with suspected or confirmed IIH between January 2003-December 2020.We excluded all patients with a shunt in situ and selected recordings that represented unstable patterns of ICP changes in PTCS. Results: 463 CSF infusion tests and 26 ICP monitorings of PTCS patients had been performed in this timeframe. We divided results of observed pattern into two group: those with known venous sinus measurements (Group A) and those without (Group B). Observed recordings formed a total of 5 and 4 different patterns respectively, based on the behaviour of ICP and slow waves at rest, overnight, and during infusion as well as in relationship to the clinical presentation of each patient. Discussion and conclusion: Accurate monitoring of ICP in PTCS is quintessential. Full understanding of each element of its pathophysiology and their interaction would be essential and include quantification of the CSF pressure not only as a number, but also with consideration of its dynamic contents. Cerebral venous pressure measurements and/or monitoring may be useful. Consideration of the presence or absence of papilloedema in the context of disturbed CSF dynamics could reveal further diagnostic and therapeutic insights.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

BACKGROUND: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. METHODS: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. RESULTS: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. CONCLUSIONS: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.