Characterization of intracranial compliance in healthy subjects using a noninvasive method - results from a multicenter prospective observational study.

PURPOSE: An FDA-approved non-invasive intracranial pressure (ICP) monitoring system enables the assessment of ICP waveforms by revealing and analyzing their morphological variations and parameters associated with intracranial compliance, such as the P2/P1 ratio and time-to-peak (TTP). The aim of this study is to characterize intracranial compliance in healthy volunteers across different age groups. METHODS: Healthy participants, both sexes, aged from 9 to 74 years old were monitored for 5 min in the supine position at 0º. Age was stratified into 4 groups: children (≤ 7 years); young adults (18 ≤ age ≤ 44 years); middle-aged adults (45 ≤ age ≤ 64 years); older adults (≥ 65 years). The data obtained was the non-invasive ICP waveform, P2/P1 ratio and TTP. RESULTS: From December 2020 to February 2023, 188 volunteers were assessed, of whom 104 were male, with a median (interquartile range) age of 41 (29-51), and a median (interquartile range) body mass index of 25.09 (22.57-28.04). Men exhibited lower values compared to women for both the P2/P1 ratio and TTP (p < 0.001). There was a relative rise in both P2/P1 and TTP as age increased (p < 0.001). CONCLUSIONS: The study revealed that the P2/P1 ratio and TTP are influenced by age and sex in healthy individuals, with men displaying lower values than women, and both ratios increasing with age. These findings suggest potential avenues for further research with larger and more diverse samples to establish reference values for comparison in various health conditions. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (RBR-9nv2h42), retrospectively registered 05/24/2022. UTN: U1111-1266-8006.

High Blood Pressure Is Associated With Lower Brain Volume and Cortical Thickness in Healthy Young Adults.

BACKGROUND: High blood pressure (BP) in middle-aged and older adults is associated with lower brain volume and cortical thickness assessed with structural magnetic resonance imaging (MRI). However, little evidence is available on young adults. We investigated the associations of high BP with brain volumes and cortical thickness in healthy young adults. METHODS: This cross-sectional study included 1,095 young adults (54% women, 22-37 years) from the Human Connectome Project (HCP) who self-reported not having a history of hypertension or taking antihypertensive medications. Brachial systolic (SBP) and diastolic BP (DBP) were measured with a semi-automatic or manual sphygmomanometer during study visits. Structural MRI was used to measure gray matter (GM) and white matter (WM) volume and mean cortical thickness. Associations of BP and hypertension stage with total and regional brain volumes and cortical thickness were analyzed using linear regression and analysis of covariance (ANCOVA) after adjusting for age, sex, education years, body mass index (BMI), smoking, alcohol consumption history, zygosity, and total intracranial volume. RESULTS: SBP and DBP were (mean ±â€…SD) 123.6 ±â€…14.2 and 76.5 ±â€…10.6 mm Hg, respectively, (n = 1,095). High DBP was associated with lower total GM (P = 0.012), cortical GM (P = 0.004), subcortical GM (P = 0.012), and total WM volumes (P = 0.031). High SBP and DBP were associated with lower regional cortical volume and cortical thickness. CONCLUSIONS: These findings suggest that high BP may have deleterious effects on brain health at the early stage of adulthood.

Predicting short-term outcomes in brain-injured patients: a comprehensive approach with transcranial Doppler and intracranial compliance assessment.

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.

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.

Association of Blood Pressure With Brain White Matter Microstructural Integrity Assessed With MRI Diffusion Tensor Imaging in Healthy Young Adults.

BACKGROUND: High blood pressure (BP) in middle-aged and older adults is associated with a brain white matter (WM) microstructural abnormality. However, little evidence is available in healthy young adults. We investigated the associations between high BP and WM microstructural integrity in young adults. METHODS: This study included 1015 healthy young adults (542 women, 22-37 years) from the Human Connectome Project. Brachial systolic and diastolic BP were measured using a semiautomatic or manual sphygmomanometer. Diffusion-weighted magnetic resonance imaging was acquired to obtain diffusion tensor imaging metrics of free water (FW) content, FW-corrected WM fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Using whole-brain voxel-wise linear regression models and ANCOVA, we examined associations of BP and hypertension stage with diffusion tensor imaging metrics after adjusting for age, sex, education, body mass index, smoking status, alcohol consumption history, and differences in the b value used for diffusion magnetic resonance imaging. RESULTS: Systolic and diastolic BP of the sample (mean±SD) were 122.8±13.0 and 76.0±9.9 mm Hg, respectively. Associations of BP with diffusion tensor imaging metrics revealed regional heterogeneity for FW-corrected fractional anisotropy. High BP and high hypertension stage were associated with higher FW and lower FW-corrected axial diffusivity, FW-corrected radial diffusivity, and FW-corrected mean diffusivity. Moreover, associations of high diastolic BP and hypertension stage with high FW were found only in men not in women. CONCLUSIONS: High BP in young adults is associated with altered brain WM microstructural integrity, suggesting that high BP may have damaging effects on brain WM microstructural integrity in early adulthood, particularly in men.

Short-term mild hyperventilation on intracranial pressure, cerebral autoregulation, and oxygenation in acute brain injury patients: a prospective observational study.

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO2) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO2) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO2 (ΔO2Hbi, changes in concentration of oxygenated hemoglobin of the total rSO2) decreased from 3.83 (3-6.2) µM.cm to 1.6 (0.5-3.1) µM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO2 values for ICP management.

Effects of positive end-expiratory pressure on cerebral hemodynamics in acute brain injury patients.

Background: Cerebral autoregulation is the mechanism that allows to maintain the stability of cerebral blood flow despite changes in cerebral perfusion pressure. Maneuvers which increase intrathoracic pressure, such as the application of positive end-expiratory pressure (PEEP), have been always challenged in brain injured patients for the risk of increasing intracranial pressure (ICP) and altering autoregulation. The primary aim of this study is to assess the effect of PEEP increase (from 5 to 15 cmH2O) on cerebral autoregulation. Secondary aims include the effect of PEEP increase on ICP and cerebral oxygenation. Material and Methods: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP monitoring and undergoing multimodal neuromonitoring including ICP, cerebral perfusion pressure (CPP) and cerebral oxygenation parameters obtained with near-infrared spectroscopy (NIRS), and an index which expresses cerebral autoregulation (PRx). Additionally, values of arterial blood gases were analyzed at PEEP of 5 and 15 cmH2O. Results are expressed as median (interquartile range). Results: Twenty-five patients were included in this study. The median age was 65 years (46-73). PEEP increase from 5 to 15 cmH2O did not lead to worsened autoregulation (PRx, from 0.17 (-0.003-0.28) to 0.18 (0.01-0.24), p = 0.83). Although ICP and CPP changed significantly (ICP: 11.11 (6.73-15.63) to 13.43 (6.8-16.87) mm Hg, p = 0.003, and CPP: 72.94 (59.19-84) to 66.22 (58.91-78.41) mm Hg, p = 0.004), these parameters did not reach clinically relevant levels. No significant changes in relevant cerebral oxygenation parameters were observed. Conclusion: Slow and gradual increases of PEEP did not alter cerebral autoregulation, ICP, CPP and cerebral oxygenation to levels triggering clinical interventions in acute brain injury patients.

Effects of short-term hyperoxemia on cerebral autoregulation and tissue oxygenation in acute brain injured patients.

Introduction: Potential detrimental effects of hyperoxemia on outcomes have been reported in critically ill patients. Little evidence exists on the effects of hyperoxygenation and hyperoxemia on cerebral physiology. The primary aim of this study is to assess the effect of hyperoxygenation and hyperoxemia on cerebral autoregulation in acute brain injured patients. We further evaluated potential links between hyperoxemia, cerebral oxygenation and intracranial pressure (ICP). Methods: This is a single center, observational, prospective study. Acute brain injured patients [traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH)] undergoing multimodal brain monitoring through a software platform (ICM+) were included. Multimodal monitoring consisted of invasive ICP, arterial blood pressure (ABP) and near infrared spectrometry (NIRS). Derived parameters of ICP and ABP monitoring included the pressure reactivity index (PRx) to assess cerebral autoregulation. ICP, PRx, and NIRS-derived parameters (cerebral regional saturation of oxygen, changes in concentration of regional oxy- and deoxy-hemoglobin), were evaluated at baseline and after 10 min of hyperoxygenation with a fraction of inspired oxygen (FiO2) of 100% using repeated measures t-test or paired Wilcoxon signed-rank test. Continuous variables are reported as median (interquartile range). Results: Twenty-five patients were included. The median age was 64.7 years (45.9-73.2), and 60% were male. Thirteen patients (52%) were admitted for TBI, 7 (28%) for SAH, and 5 (20%) patients for ICH. The median value of systemic oxygenation (partial pressure of oxygen-PaO2) significantly increased after FiO2 test, from 97 (90-101) mm Hg to 197 (189-202) mm Hg, p < 0.0001. After FiO2 test, no changes were observed in PRx values (from 0.21 (0.10-0.43) to 0.22 (0.15-0.36), p = 0.68), nor in ICP values (from 13.42 (9.12-17.34) mm Hg to 13.34 (8.85-17.56) mm Hg, p = 0.90). All NIRS-derived parameters reacted positively to hyperoxygenation as expected. Changes in systemic oxygenation and the arterial component of cerebral oxygenation were significantly correlated (respectively ΔPaO2 and ΔO2Hbi; r = 0.49 (95% CI = 0.17-0.80). Conclusion: Short-term hyperoxygenation does not seem to critically affect cerebral autoregulation.

Is Lumbar Puncture Needed? - Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH. MATERIALS AND METHODS: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ±â€Š11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmH2O, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed. RESULTS: In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ±â€Š4.93 cmH2O. The capability of nICP to diagnose increased LPP (LPP > 20 cmH2O) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmH2O with both a sensitivity and specificity of 0.92. Presuming 20 cmH2O as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases. CONCLUSION: The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.

Assessment of Cerebral Autoregulation Using Invasive and Noninvasive Methods of Intracranial Pressure Monitoring.

BACKGROUND: Pulse amplitude index (PAx), a descriptor of cerebrovascular reactivity, correlates the changes of the pulse amplitude of the intracranial pressure (ICP) waveform (AMP) with changes in mean arterial pressure (MAP). AMP relies on cerebrovascular compliance, which is modulated by the state of the cerebrovascular reactivity. PAx can aid in prognostication after acute brain injuries as a tool for the assessment of cerebral autoregulation and could potentially tailor individual management; however, invasive measurements are required for its calculation. Our aim was to evaluate the relationship between noninvasive PAx (nPAx) derived from a novel noninvasive device for ICP monitoring and PAx derived from gold standard invasive methods. METHODS: We retrospectively analyzed invasive ICP (external ventricular drain) and non-invasive ICP (nICP), via mechanical extensometer (Brain4Care Corp.). Invasive and non-invasive ICP waveform morphology data was collected in adult patients with brain injury with arterial blood pressure monitoring. The time series from all signals were first treated to remove movement artifacts. PAx and nPAx were calculated as the moving correlation coefficients of 10-s averages of AMP or non-invasive AMP (nAMP) and MAP. AMP/nAMP was determined by calculating the fundamental frequency amplitude of the ICP/nICP signal over a 10-s window, updated every 10-s. We then evaluated the relationship between invasive PAx and noninvasive nPAx using the methods of repeated-measures analysis to generate an estimate of the correlation coefficient and its 95% confidence interval (CI). The agreement between the two methods was assessed using the Bland-Altman test. RESULTS: Twenty-four patients were identified. The median age was 53.5 years (interquartile range 40-70), and intracranial hemorrhage (84%) was the most common etiology. Twenty-one (87.5%) patients underwent mechanical ventilation, and 60% were sedated with a median Glasgow Coma Scale score of 8 (7-15). Mean PAx was 0.0296 ± 0.331, and nPAx was 0.0171 ± 0.332. The correlation between PAx and nPAx was strong (R = 0.70, p < 0.0005, 95% CI 0.687-0.717). Bland-Altman analysis showed excellent agreement, with a bias of - 0.018 (95% CI - 0.026 to - 0.01) and a localized regression trend line that did not deviate from 0. CONCLUSIONS: PAx can be calculated by conventional and noninvasive ICP monitoring in a statistically significant evaluation with strong agreement. Further study of the applications of this clinical tool is warranted, with the goal of early therapeutic intervention to improve neurologic outcomes following acute brain injuries.