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Objective Multiple factors have been identified as causes of intracranial compliance impairment (ICCI) among patients with obesity. On the other hand, obesity has been linked with worst outcomes in COVID‐19. Thus, the hypothesis of severe acute respiratory syndrome (SARS) conducing to cerebral hemodynamic disorders (CHD) able to worsen ICCI and play an additional role on prognosis determination for COVID‐19 among obese patients becomes suitable. Methods 50 cases of SARS by COVID‐19 were evaluated, for the presence of ICCI and cerebrovascular circulatory disturbances in correspondence with whether unfavorable outcomes (death or impossibility for mechanical ventilation weaning [MVW]) within 7 days after evaluation. The objective was to observe whether obese patients (BMI ≥ 30) disclosed worse outcomes and tests results compared with lean subjects with same clinical background. Results 23 (46%) patients among 50 had obesity. ICCI was verified in 18 (78%) obese, whereas in 13 (48%) of 27 non‐obese (p = 0,029). CHD were not significantly different between groups, despite being high prevalent in both. 69% unfavorable outcomes were observed among obese and 44% for lean subjects (p = 0,075). Conclusion In the present study, intracranial compliance impairment was significantly more observed among obese subjects and may have contributed for SARS COVID‐19 worsen prognosis.

Brown adipose tissue (BAT) is an endocrine adipose tissue with attributes to dissipate energy as heat in response to changes in temperature and diet. Infrared thermography (IRT) has been studied in recent years in the assessment of BAT thermogenesis, as an option to positron emission tomography - computed tomography (PET-CT), because of several advantages. We performed a systematic review on the use of IRT in BAT assessment. Comprehensive online search was performed in different databases. The QUADAS 2 tool was used to evaluate studies' quality. 12 studies fit the inclusion criteria, whereas only one of these was considered of low risk of bias. 10 studies were favorable to IRT appliance in BAT evaluation, observing elevation of supraclavicular skin temperature correlated with BAT activity. Studies were heterogeneous in design, and a meta-analysis was precluded. Further studies with similar methodologies are needed. Conclusion: Despite the large number of published methodologies, IRT is a promising method for detecting BAT activation. Current knowledge already allows a better understanding of thermography to improve and standardize the technique.

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.

Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.

Background: Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP &gt, 20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of acute brain injury were included. A continuous record of 10 min-length for the beat-by-beat analysis of ICPW was performed, with ICP elevation produced by means of ultrasound-guided manual internal jugular vein compression at the end of the record. ICPW features (peak amplitude ratio (P2/P1), time interval to pulse peak (TTP) and pulse amplitude) were counterweighed between baseline and compression periods. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. A total of 21 (36%) presented no skull defects, 21 (36%) belonged to group 2, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±15.11 for intact, 15.33 for group 2 and ±20.81 mmHg for group 3, with ICP-induced elevation also similar between groups (p = 0.56). Significant elevation was observed for the P2/P1 ratio for groups 1 and 2, whereas a reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, but a reduction of 0.03 for group 3, p = 0.01), and no significant results were obtained for TTP and pulse amplitudes. Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPW indicated DC to be protective for further influences of ICP elevations over the brain. The analysis of ICPW seems to be an alternative to real-time ICC assessment.

Early cranioplasty has been encouraged after decompressive craniectomy (DC), aiming to reduce consequences of atmospheric pressure over the opened skull. However, this practice may not be often available in low-middle-income countries (LMICs). We evaluated clinical improvement, hemodynamic changes in each hemisphere, and the hemodynamic balance between hemispheres after late cranioplasty in a LMIC, as the institution’s routine resources allowed. Prospective cohort study included patients with bone defects after DC evaluated with perfusion tomography (PCT) and transcranial Doppler (TCD) and performed neurological examinations with prognostic scales (mRS, MMSE, and Barthel Index) before and 6 months after surgery. A final sample of 26 patients was analyzed. Satisfactory improvement of neurological outcome was observed, as well as significant improvement in the mRS (p = 0.005), MMSE (p

Background: Invasive monitoring of intracranial pressure (ICP) is currently the gold standard method for the safe diagnosis and treatment of intracranial hypertension (ICHy), but it is subject to hemorrhage, infection and malfunction. Ultrasound of the optic nerve sheath diameter (ONSD) has been applied as a non-invasive alternative that is cost effective and available at the bedside. However, ONSD time-lapse behavior in a set of ICHy and its relief by means of whether saline infusion or surgery is still unknown. The objective of this study was to correlate intracranial pressure and ultrasonography of the optic nerve sheath in an experimental animal model of ICHy, and the interval needed to ONSD to return to its baseline levels.Methods: An experimental study was conducted on 30 male and female pigs weighing about 20 kg. The diameter of the optic nerve sheath was evaluated by ultrasound at different measures of ICP given by intraventricular catheter and intracranial balloon inflation, saline infusion and balloon deflation. Laboratory and hemodynamic data were collected from the animals. ICP and ONSD values were correlated at each time point of the study.Results: All the variables obtained by ONSD ultrasonography as left optic nerve, right optic nerve and average of optic nerve sheath (AON) diameter were statistically significant to estimate ICP value. ONSD values changed immediately at balloon inflation, with a delay of 30 minutes average to return to baseline levels after balloon deflation (p = 0.016). No statistical significance was observed in ICP and ONSD values with hypertonic saline infusion. Correlation between ICP and ONSD was linear and can be estimated using the formula: -80.5 + 238.2 x AON, in this swine model. Conclusion: In the present study, ultrasound of optic nerve sheath diameter disclosed linear correlation with ICP, although a short delay in returning to its baseline levels may be observed in the case of sudden intracranial hypertension relief.

In the last decades, the development of new noninvasive technologies in critical care allowed physicians to continuously monitor clinical parameters, aggregating important information that has been previously inaccessible or restricted due to the invasiveness of the existing techniques. The aim of this chapter is to present noninvasive methods in use on intensive care units (ICU) for brain injured patients monitoring, collaborating to the diagnosis and follow-up, aiding medical teams to achieve better outcomes.

Intracranial pressure (ICP) can be analyzed for its absolute value, usually in mmHg or cmH2O, its tendency over time and the waveform of its pulse. This chapter will focus on the waveform of the ICP pulse (ICPwf), already observed since 1881, and for a long time not understood. Studies conducted in recent decades show the correlation between the ICPwf and intracranial compliance (ICC), another important clinical parameter added to the practice in the second half of the last century. ICC allows physicians early analyzing patients’ neurological conditions related to disorders resulting from variations in cerebrospinal fluid (CSF), blood and intracranial tissue volumes. This chapter is an invitation to dive into the history and development of ICPwf analysis, clinical uses already adopted and others still under study.

Background: Monitoring patients with acute brain injury is crucial in neurocritical care. Intracranial compliance (ICC) has been studied to complement the interpretation of intracranial pressure (ICP) and help the neurocritical care team to anticipate brain function deterioration. ICC has been found to be related to compensatory mechanisms that maintain the stability of ICP (e.g., the higher the compensation, the higher the compliance of intracranial content to adapt to changes in volume and pressure). However, ICC has not been properly translated to clinical practice and has remained a critical technology gap in clinical neuroscience. The objective of this study is to establish a protocol for a scoping review to map the key concepts of ICC in the literature. In addition, this study is designed to characterize the relationship between ICC and ICP, as well as systematically describe the outcomes that are used to assess ICC, considering both the invasive and noninvasive methods.Methods: The scoping review protocol will be conducted according to the Joanna Briggs Institute’s recommendation. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews will be followed. Animals and humans are considered as the population to be investigated. No age criteria or health condition will be considered. ICC, as well as the relationship between ICC and ICP, will be considered as a core concept in this review. Information will be screened based on the context of neurocritical care. Several databases (PubMed, CINAHL, Web of Science, EMBASE, Epistemonikos, Grey Literature Report, clinical trial registries, and Cochrane Clinical Trials) will be searched to identify literature using a combination of keywords and descriptors, and there will be no restriction on the time frame. Data will be extracted systematically by the research team and the results will be summarized.Discussion: No systematic review has mapped the concepts of ICC and its relationship with ICP. Providing the key concepts of ICC and the methods of assessment might show its possible applications in clinical practice and the gaps in research.Systematic review registration: Currently, scoping review protocols are not eligible for registration in the International Prospective Register of Systematic Review database.

We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.

Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC) due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcomes. Methods: Fifty consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and non-invasive monitoring of ICC. Subjects were included upon ICU admission, CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI), and estimated cerebral perfusion pressure (eCPP), while ICC was assessed by using the P2/P1 ratio of the non-invasive ICP curve. A CVH/ICC score was computed using all these variables. The primary composite outcome was unsuccessful in weaning from respiratory support or death on day 7 (defined as UO). Results: At the first assessment (n = 50), only the P2/P1 ratio (median 1.20 [IQRs 1.00–1.28] vs. 1.00 [0.88–1.16], p = 0.03) and eICP (14 [11–25] vs. 11 [7–15] mmHg, p = 0.01) were significantly higher among patients with an unfavorable outcome (UO) than others. Patients with UO had a significantly higher CVH/ICC score (9 [8–12] vs. 6 [5–7], p &lt, 0.001) than those with a favorable outcome, the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75–0.97), a score &gt, 8.5 had 63 (46–77)% sensitivity and 87 (62–97)% specificity to predict UO. For those patients undergoing a second assessment (n = 29), after a median of 11 (5–31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n = 30) and survivors were observed. Conclusions: ICC impairment and CVH disturbances are often present in COVID-19 severe illness and could accurately predict an early poor outcome.

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.

OBJECTIVEThe present study was designed to answer several concerns disclosed by systematic reviews indicating no evidence to support the use of computed tomography angiography (CTA) in the diagnosis of brain death (BD). Therefore, the aim of this study was to assess the effectiveness of CTA for the diagnosis of BD and to define the optimal tomographic criteria of intracranial circulatory arrest.METHODSA unicenter, prospective, observational case-control study was undertaken. Comatose patients (Glasgow Coma Scale score ≤ 5), even those presenting with the first signs of BD, were included. CTA scanning of arterial and venous vasculature and transcranial Doppler (TCD) were performed. A neurological determination of BD and consequently determination of case (BD group) or control (no-BD group) was conducted. All personnel involved with assessing patients were blinded to further tests results. Accuracy of BD diagnosis determined by using CTA was calculated based on the criteria of bilateral absence of visualization of the internal cerebral veins and the distal middle cerebral arteries, the 4-point score (4PS), and an exclusive criterion of absence of deep brain venous drainage as indicated by the absence of deep venous opacification on CTA, the venous score (VS), which considers only the internal cerebral veins bilaterally.RESULTSA total of 106 patients were enrolled in this study; 52 patients did not have BD, and none of these patients had circulatory arrest observed by CTA or TCD (100% specificity). Of the 54 patients with a clinical diagnosis of BD, 33 met the 4PS (61.1% sensitivity), whereas 47 met the VS (87% sensitivity). The accuracy of CTA was time related, with greater accuracy when scanning was performed less than 12 hours prior to the neurological assessment, reaching 95.5% sensitivity with the VS.CONCLUSIONSCTA can reliably support a diagnosis of BD. The criterion of the absence of deep venous opacification, which can be assessed by use of the VS criteria investigated in this study, can confirm the occurrence of cerebral circulatory arrest.Clinical trial registration no.: 12500913400000068 (clinicaltrials.gov)

Summary Background Several complications make the diagnosis of brain death (BD) medically challenging and a complimentary method is needed for confirmation. In this context, computed tomography angiography (CTA) and computed tomography perfusion (CTP) could represent valuable alternatives; however, the reliability of CTA and CTP for confirming brain circulatory arrest remains unclear. Methods A systematic review was performed to identify relevant studies regarding the use of CTA and CTP as ancillary tests for BD confirmation. Results Three hundred twenty-two patients were eligible for the meta-analysis, which exhibited 87.5% sensitivity. CTA image evaluation protocol exhibited variations between medical institutions regarding which intracranial vessels should be considered to determine positive or negative test results. Conclusions For patients who were previously diagnosed with BD according to clinical criteria, CTA demonstrated high sensitivity to provide radiologic confirmation. The current evidence that supports the use of CTA in BD diagnosis is comparable to other methods applied worldwide.

Indivíduos acometidos de doença de Chagas em fase crônica foram tratados com corticóide, em virtude de afecções concomitantes. A fim de avaliar repercussões sobre a infecção devida ao Trypanosoma cruzi, houve adoção de procedimentos de várias ordens, representados por métodos referentes à parasitose, exames inespecíficos e subsídios clínico, eletrocardiográfico e radiológico, tendo também sido mantido, para comparação, grupo controle. Através do xenodiagnóstico ficou constatada acentuação da parasitemia, diretamente relacionada com a dose de corticóide, sem influência na evolução da enfermidade parasitária, pelo menos durante o período no qual ocorreu a investigação. Patients with chronic Chagas'disease and simultaneous medical problems treated with corticosteroid were studied in order to evaluate steroid influence on chronic Trypanosoma cruzi infection. Parasitological assessment, radiological and electrocardiographic studies as well as non specific tests were performed in patients and in a control group that included chronic infected patients not treated with steroid. Xenodiagnosis showed a clear increase in T. cruzi parasitemia, related to the corticosteroid dosage, without clinical manifestations during the study follow-up period.

ResumoObjetivoDescrever apresentação clínica incomum de sequestro pulmonar extralobar intra‐abdominal em um paciente de dois anos e nove meses e avaliar aspectos diagnósticos e de tratamento dessa patologia.Descrição do casoUma massa intra‐abdominal indefinida em topografia suprarrenal direita de feto masculino. A avaliação pós‐natal com imagens de ultrassom, tomografia computadorizada, ressonância magnética e testes laboratoriais não foi suficiente para determinar a natureza da lesão. Após dois anos, a ressecção laparoscópica da massa e o exame histopatológico do espécime cirúrgico permitiram estabelecer o diagnóstico de sequestro pulmonar extralobar intra‐abdominal.ComentáriosEssa malformação pode ser monitorada clinicamente; entretanto, a excisão cirúrgica frequentemente é feita, provavelmente devido à impossibilidade de diagnóstico com métodos não invasivos, como ocorreu no presente caso, na qual a lesão apresentou‐se em posição não habitual para sequestro pulmonar extralobar intra‐abdominal. Desse modo, a abordagem cirúrgica parece ser a chave para o diagnóstico e a condução desde tipo de malformação congênita.AbstractObjectiveTo describe an unusual clinical presentation of intra‐abdominal extralobar pulmonary sequestration in a 2‐year, 9 month‐old patient and assess diagnostic and treatment aspects of this pathology.Case descriptionAn undefined intra‐abdominal mass was identified in the right adrenal region in a male fetus. Postnatal evaluation with ultrasound images, computed tomography, magnetic resonance imaging and laboratory testing was insufficient to determine the nature of the lesion. After two years, laparoscopic resection of the mass and histopathological examination of the surgical specimen allowed to establish the diagnosis of intra‐abdominal extralobar pulmonary sequestration.CommentsThis malformation can be monitored clinically; however, surgical excision is often performed, probably due to the impossibility of attaining diagnosis with non‐invasive methods, such as in the present case, in which the lesion appeared in an unusual position for intra‐abdominal extralobar pulmonary sequestration. Therefore, the surgical approach seems to be the key to attain the diagnosis and establish the conduct for this type of congenital malformation.

Objective: To describe an unusual clinical presentation of intra-abdominal extralobar pulmonary sequestration in a 2-year, 9 month-old patient and assess diagnostic and treatment aspects of this pathology. Case description: An undefined intra-abdominal mass was identified in the right adrenal region in a male fetus. Postnatal evaluation with ultrasound images, computed tomography, magnetic resonance imaging and laboratory testing was insufficient to determine the nature of the lesion. After two years, laparoscopic resection of the mass and histopathological examination of the surgical specimen allowed to establish the diagnosis of intra-abdominal extralobar pulmonary sequestration. Comments: This malformation can be monitored clinically; however, surgical excision is often performed, probably due to the impossibility of attaining diagnosis with non-invasive methods, such as in the present case, in which the lesion appeared in an unusual position for intra-abdominal extralobar pulmonary sequestration. Therefore, the surgical approach seems to be the key to attain the diagnosis and establish the conduct for this type of congenital malformation.