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Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients., Methods: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA., Ethics and Dissemination: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025., Trial Registration: Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Spaceflights influence intracranial compliance (ICC). P2/P1 ratio, from the intracranial pressure (ICP) waveform, provides information about ICC. Additionally, non-invasive methods for ICC monitoring are needed for spaceflights. Furthermore, astronauts try to maintain good levels of cardiorespiratory fitness before and during spaceflights, not only to sustain exploratory missions, but also to prevent diseases in extreme environments., Objective: to correlate cardiorespiratory fitness levels with the P2/P1 ratio during a microgravity analog [-6° head-down tilt (HDT)]., Method: 34 individuals (11 women), mean age of 31.7 (±6.3) years and BMI 24.2 (±3.2) performed a cardiopulmonary exercise testing (CPET) with an incremental protocol on a cycle ergometer to determine the cardiopulmonary fitness through peak relative oxygen uptake (VO 2 peak) of each individual. On the second test, which was conducted in an interval of 15 days of the CPET, participants remained for 30 min at HDT with P2/P1 ratio acquired using a non-invasive strain gauge sensor. The average of the last 5 min was used for analysis. The mean P2/P1 ratio and relative VO 2 peak were correlated using the Spearman test., Results: Volunteers presented 1.05 ± 0.2 of P2/P1 ratio and VO 2 peak of 47.5 ± 7.6 mL/kg/min. The Spearman test indicated a negative and low correlation between the P2/P1 ratio and VO 2 peak (ρ = -0.388; p = 0.023)., Conclusion: The study suggests that the better the cardiorespiratory fitness, the better ICC in a weightlessness simulation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gabriela Nagai Ocamoto reports a relationship with Braincare Desenvolvimento e Inovação Tecnológica S.A. that includes: employment. Gustavo Frigieri reports a relationship with Braincare Desenvolvimento e Inovação Tecnológica S.A. that includes: employment., (© 2024 The Authors.)

Background: Blood pressure management is extremely important to prevent cerebral hypoxia and influence the outcome of critically ill patients. In medicine, precise instruments are essential to increase patient safety in the intensive care unit (ICU), including intracranial compliance (ICC) monitoring. A new technology developed by Brain4care, makes it possible to analyze the waveform of intracranial pressure (ICP) non-invasively associated with ICC, and this instrument was used in the patient for monitoring., Case Description: A 40-year-old male underwent aortic endocarditis surgery involving 182-min extracorporeal circulation and 9-min aortic clamping. Post-surgery, he exhibited a seizure bilateral mydriasis, followed by isochoric pupils and rapid foot movements. Neuroprotection measures were applied in the ICU, with noninvasive ICC monitoring initiated to assess intervention effectiveness., Conclusion: The non-invasive measurement of ICP can help clinical decision-making regarding the optimization of adapted protocols for neuroprotection in the ICU., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Intracranial hypertension (IH) is a life-threating condition especially for the brain injured patient. In such cases, an external ventricular drain (EVD) or an intraparenchymal bolt are the conventional gold standard for intracranial pressure (ICPi) monitoring. However, these techniques have several limitations. Therefore, identifying an ideal screening method for IH is important to avoid the unnecessary placement of ICPi and expedite its introduction in patients who require it. A potential screening tool is the ICP wave morphology (ICPW) which changes according to the intracranial volume-pressure curve. Specifically, the P2/P1 ratio of the ICPW has shown promise as a triage test to indicate normal ICP. In this study, we propose evaluating the noninvasive ICPW (nICPW-B4C sensor) as a screening method for ICPi monitoring in patients with moderate to high probability of IH. This is a retrospective analysis of a prospective, multicenter study that recruited adult patients requiring ICPi monitoring from both Federal University of São Paulo and University of São Paulo Medical School Hospitals. ICPi values and the nICPW parameters were obtained from both the invasive and the noninvasive methods simultaneously 5 min after the closure of the EVD drainage. ICP assessment was performed using a catheter inserted into the ventricle and connected to a pressure transducer and a drainage system. The B4C sensor was positioned on the patient's scalp without the need for trichotomy, surgical incision or trepanation, and the morphology of the ICP waves acquired through a strain sensor that can detect and monitor skull bone deformations caused by changes in ICP. All patients were monitored using this noninvasive system for at least 10 min per session. The area under the curve (AUC) was used to describe discriminatory power of the P2/P1 ratio for IH, with emphasis in the Negative Predictive value (NPV), based on the Youden index, and the negative likelihood ratio [LR-]. Recruitment occurred from August 2017 to March 2020. A total of 69 patients fulfilled inclusion and exclusion criteria in the two centers and a total of 111 monitorizations were performed. The mean P2/P1 ratio value in the sample was 1.12. The mean P2/P1 value in the no IH population was 1.01 meanwhile in the IH population was 1.32 (p < 0.01). The best Youden index for the mean P2/P1 ratio was with a cut-off value of 1.13 showing a sensitivity of 93%, specificity of 60%, and a NPV of 97%, as well as an AUC of 0.83 to predict IH. With the 1.13 cut-off value for P2/P1 ratio, the LR- for IH was 0.11, corresponding to a strong performance in ruling out the condition (IH), with an approximate 45% reduction in condition probability after a negative test (ICPW). To conclude, the P2/P1 ratio of the noninvasive ICP waveform showed in this study a high Negative Predictive Value and Likelihood Ratio in different acute neurological conditions to rule out IH. As a result, this parameter may be beneficial in situations where invasive methods are not feasible or unavailable and to screen high-risk patients for potential invasive ICP monitoring.Trial registration: At clinicaltrials.gov under numbers NCT05121155 (Registered 16 November 2021-retrospectively registered) and NCT03144219 (Registered 30 September 2022-retrospectively registered)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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., (© 2024. The Author(s).)

Background:  Increased intracranial pressure (ICP) consists of a set of signs and symptoms related to changes in intracranial compliance (ICC) and ICP., Objective:  This study presents a retrospective analysis of patients who underwent non-invasive monitoring of ICC based on complaints of headache, correlating decreased brain compliance and increased intracranial pressure., Methods:  Noninvasive ICC monitoring was performed using a Brain4care device, which contains a strain gauge and a recorder connected to a mechanical device that touches the scalp surface in the frontoparietal area lateral to the sagittal suture. This tool monitors the ICP by identifying small changes in skull measurements that are caused by pressure variations, i.e., skull deformation is associated with the detection of changes in mean ICP. A clinical evaluation of 32 patients with complaints of headache occurred from the analysis of their medical records., Results:  Of the 32 patients initially chosen, it was possible to complete the analysis of 18 due to the availability of data in the medical records. From the non-invasive monitoring of the ICC, the following data were collected: time-to-peak, P2/P1 ratio, age, and gender. From the statistical analysis of age and P2/P1 ratio, it was noted that as age increases, ICC tends to decrease regardless of sex (p < 0.05)., Conclusion:  This study concluded that there is a correlation between changes in intracranial compliance and headache complaints in outpatients. There was also a relationship between age and decreased intracranial compliance but without a specific pain pattern., Competing Interests: Dr. Nícollas Nunes Rabelo is scientific consultant of Brain4Care. Gustavo Frigieri is scientific director of Brain4Care., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: There is a strong association between hypertension and cerebrovascular diseases, but most of the mechanistic bases to justify this correlation remains misunderstood., Objective: To evaluate intracranial pressure waveform in long-term essential hypertensive patients with a non-invasive device, brain4care (b4c)., Methods: Cross-sectional study in patients with hypertension. Office blood pressure was measured with an automatic oscillometric device. Intracranial pressure evaluation was acquired through a strain sensor that could detect and monitor nanometric skull bone displacements for each cardiac cycle. Under normal physiological conditions, P1 is greater than P2, and the normal P2/P1 ratio is <1. Time to peak (TTP) is the measurement in seconds of the beginning of waveform inscription until P1 and normal values are <0.20 s. The cut-off points ≥1.2 and ≥0.25 s were used to define intracranial hypertension (ICHT)., Results: 391 consecutive patients were evaluated (75% female, mean age 64.3 ± 12.0 years). Mean value of P2/P1 ratio was 1.18 ± 0.25 and TTP 0.18 ± 0.63 s The obtained P2/P1 ratios were divided in three categories according to results of previous studies of normalcy (<1.0), intracranial compliance disturbance (1.0-1.19) and ICHT (≥1.2). Normal intracranial pressure was observed in 21.7% of patients, intracranial compliance disturbance in 32.7% and intracranial hypertension in 45.6%. Females showed a higher prevalence of ICHT (50.3%)., Conclusion: The prevalence of 45.6% intra-cranial hypertension in patients with long-term hypertension, particularly in women, and in those over 65 years old, emphasizes the importance of evaluate intracranial pressure behaviour in these patients and raise a question concerning the real ability of cerebral autoregulation and vascular barriers to protect the brain., Competing Interests: GF declares that he is cofounder and scientific director of brain4care. WB declares that he is Brazilian National Council for Scientific and Technological Development Researcher, Grant/Award Numbers: 313481/2020-2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 da Costa, Sousa, Correia, Inuzuka, Costa, Vitorino, de Toledo Piza, Frigieri, Coca and Barroso.)

Introduction: Ventriculoperitoneal (VP) shunt is the primary therapy for hydrocephalus in children; however, this technique is amenable to malfunctions, which could be detected through an assessment of clinical signs and imaging results. Furthermore, early detection can prevent patient deterioration and guide clinical and surgical treatment., Case Presentation: A 5-year-old female with a premedical history of neonatal IVH, secondary hydrocephalus, multiple VP shunts revisions, and slit ventricle syndrome was evaluated using a noninvasive intracranial pressure monitor device at the early stages of the clinical symptoms, evidencing increased intracranial pressure and poor brain compliance. Serial MRI images demonstrated a slight ventricular enlargement, leading to the use of a gravitational VP shunt, promoting progressive improvement. On the follow-up visits, we used the noninvasive ICP monitoring device to guide the shunt adjustments until symptom resolution. Furthermore, the patient has been asymptomatic for the past 3 years without requiring new shunt revisions., Discussion: Slit ventricle syndrome and VP shunt dysfunctions are challenging diagnoses for the neurosurgeon. The noninvasive intracranial monitoring has allowed a closer follow-up assisting early assessment of brain compliance changes related to a patient's symptomatology. Furthermore, this technique has high sensitivity and specificity in detecting alterations in the intracranial pressure, serving as a guide for the adjustments of programmable VP shunts, which may improve the patient's quality of life., Conclusion: Noninvasive ICP monitoring may lead to a less invasive assessment of patients with slit ventricle syndrome and could be used as a guide for adjustments of programmable shunts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cerebral edema (CE) and intracranial hypertension (IHT) are complications of numerous neurological pathologies. However, the study of CE and noninvasive methods to predict IHT remains rudimentary. This study aims to identify in traumatic brain injury (TBI) patients the relationship between the volume of the lateral ventricles and the parameters of the noninvasive intracranial pressure waveform (nICPW)., Methods: This is an analytical, descriptive, and cross-sectional study with nonsurgical TBI patients. The monitoring of nICPW was performed with a mechanical strain gauge, and the volumetry of the lateral ventricles was calculated using the free 3D Slicer software, both during the acute phase of the injury. The linear model of fixed and random mixed effects with Gamma was used to calculate the influence of nICPW parameters (P2/P1 and time-to-peak [TTP]) values on volumetry., Results: Considering only the fixed effects of the sample, there was P = 0.727 (95% CI [-0.653; 0.364]) for the relationship between P2/P1 and volumetry and 0.727 (95% CI [-1.657; 1.305]) for TTP and volumetry. Considering the fixed and random effects, there was P = 8.5e-10 (95% CI [-0.759; 0.355]) for the relationship between P2/P1 and volumetry and 8.5e-10 (95% CI [-2.001; 0.274]) for TTP and volumetry., Conclusion: The present study with TBI patients found association between nICPW parameters and the volume of the lateral ventricles in the 1 st days after injury., Competing Interests: Gustavo Frigieri declares that he has a conflict of interest with Braincare Desenvolvimento e Inovação Tecnológica SA - Brain4care, as he is a founder and Scientific Director. Sérgio Brasil declares that he has a conflict of interest with Braincare Desenvolvimento e Inovação Tecnológica SABrain4care, as he is a scientific consultant., (Copyright: © 2023 Surgical Neurology International.)

Analysis of intracranial pressure waveforms (ICPW) provides information on intracranial compliance. We aimed to assess the correlation between noninvasive ICPW (NICPW) and invasively measured intracranial pressure (ICP) and to assess the NICPW prognostic value in this population. In this cohort, acute brain-injured (ABI) patients were included within 5 days from admission in six Intensive Care Units. Mean ICP (mICP) values and the P2/P1 ratio derived from NICPW were analyzed and correlated with outcome, which was defined as: (a) early death (ED); survivors on spontaneous breathing (SB) or survivors on mechanical ventilation (MV) at 7 days from inclusion. Intracranial hypertension (IHT) was defined by ICP > 20 mmHg. A total of 72 patients were included (mean age 39, 68% TBI). mICP and P2/P1 values were significantly correlated (r = 0.49, p < 0.001). P2/P1 ratio was significantly higher in patients with IHT and had an area under the receiving operator curve (AUROC) to predict IHT of 0.88 (95% CI 0.78-0.98). mICP and P2/P1 ratio was also significantly higher for ED group (n = 10) than the other groups. The AUROC of P2/P1 to predict ED was 0.71 [95% CI 0.53-0.87], and the threshold P2/P1 > 1.2 showed a sensitivity of 60% [95% CI 31-83%] and a specificity of 69% [95% CI 57-79%]. Similar results were observed when decompressive craniectomy patients were excluded. In this study, P2/P1 derived from noninvasive ICPW assessment was well correlated with IHT. This information seems to be as associated with ABI patients outcomes as ICP.Trial registration: NCT03144219, Registered 01 May 2017 Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03144219 ., (© 2022. The Author(s).)

Professor Sérgio Mascarenhas was a Brazilian researcher with a vast legacy. His work paved the way for new research possibilities by consolidating the use of innovation and transdisciplinary science. In Medicine, he proposed changes to what had previously been well-accepted concepts, and his contributions have influenced medical practices. Although many authors consider intracranial pressure (ICP) as an unrivaled variable for monitoring and diagnosis of many diseases, its clinical applicability is still the subject of debate in the literature because of the difficulty in standardizing protocols. Mascarenhas's research and the creation of a device for noninvasive monitoring of intracranial compliance are discussed and are shown to have led to the creation of Brain4care, a start-up, and a new perspective on the debate on ICP monitoring.

Background: Intracranial compliance (ICC) has been studied to complement the interpretation of intracranial pressure (ICP) in neurocritical care and help predict brain function deterioration. It has been reported that ICC is related to maintaining ICP stability despite changes in intracranial volume. However, this has not been properly translated to clinical practice. Therefore, the main objective of this scoping review was to map the key concepts of ICC in the literature. This review also aimed to characterize the relationship between ICC and ICP and systematically describe the outcomes used to assess ICC using both invasive and non-invasive measurement methods. Methods: This review included the following: (1) population: animal and humans, (2) concept of compliance or its inverse "elastance," and (3) context: neurocritical care. Therefore, literature searches without a time frame were conducted on several databases using a combination of keywords and descriptors. Results and Discussion: 43,339 articles were identified, and 297 studies fulfilled the inclusion criteria after the selection process. One hundred and five studies defined ICC. The concept was organized into three main components: physiological definition, clinical interpretation, and localization of the phenomena. Most of the studies reported the concept of compliance related to variations in volume and pressure or its inverse (elastance), primarily in the intracranial compartment. In addition, terms like "accommodation," "compensation," "reserve capacity," and "buffering ability" were used to describe the clinical interpretation. The second part of this review describes the techniques (invasive and non-invasive) and outcomes used to measure ICC. A total of 297 studies were included. The most common method used was invasive, representing 57-88% of the studies. The most commonly assessed variables were related to ICP, especially the absolute values or pulse amplitude. ICP waveforms should be better explored, along with the potential of non-invasive methods once the different aspects of ICC can be measured. Conclusion: ICC monitoring could be considered a complementary resource for ICP monitoring and clinical examination. The combination and validation of invasive/non-invasive or non-invasive measurement methods are required., Competing Interests: GF, CYH, and DLSJ were employed by the company Braincare Desenvolvimento e Inovação Tecnológica S.A. TLR, SB, and NNR were health consultants for the company Braincare Desenvolvimento e Inovação Tecnológica S.A. GNO and RMZ received financial support in the form of research grant from the company Braincare Desenvolvimento e Inovação Tecnológica S.A. The funder Braincare Desenvolvimento e Inovação Tecnológica S.A. had the following involvement: study design., (Copyright © 2021 Ocamoto, Russo, Mendes Zambetta, Frigieri, Hayashi, Brasil, Rabelo and Spavieri Júnior.)

Background: There is a consensus on the importance of monitoring intracranial pressure (ICP) during neurosurgery, and this monitoring reduces mortality during procedures. Current knowledge of ICP and cerebrospinal fluid pulse pressure has been built thanks to more than two centuries of research on brain dynamics., Methods: Articles and books were selected using the descriptors "ICP," "cerebrospinal fluid pulse," "monitoring," "Monro-Kellie doctrine," and "ICP waveform" in electronic databases PubMed, Lilacs, Science Direct, and EMBASE., Results: Several anatomists and physiologists have helped clarify the patterns of intracranial volumes under normal and pathological conditions. Monro-Kellie doctrine was an important step in a story that is reconstructed in this article. Through documentary research, we report the contribution of important medical figures, such as Monro, Kellie, Abercrombie, Burrows, Cushing, Langfitt, Marmarou, and other physiologists and anatomists who left their marks on the history of Medicine., Conclusion: Understanding intracranial dynamics is an unfinished historical construction. Current knowledge is the result of two centuries of research that began with the investigations of Alexander Monro secundus ., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

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