Angiotensin-converting enzyme inhibitors: a therapeutic option for controlling blood pressure associated with delayed cognitive processing speed.

Antihypertensive treatment (AT) is essential for preventing hypertension-related cognitive decline. The goals of this observational study were to compare cognitive performance (CP) between non-hypertensive (NH) volunteers and hypertensive patients and to evaluate the correlation between CP and antihypertensive drugs (AHD). Three groups were constituted: NH (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. To analyze the cognitive domains, a neuropsychological battery was applied and the raw performance values in these tests were transformed into z-scores. The domain was considered impaired if it presented a z-score below -1.5 SD. Compared to group 1, both groups of hypertensive were older (51 [ ± 12] years) and showed a worse CP in episodic memory (p = 0.014), language (p = 0.003) and processing speed (PS) [p = 0.05]. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were the most used AHD (46.3%, p = 0.01 [group 2] and 64.5%, p = 0.005 [group 3]) and showed correlations with PS. Linear regression models revealed a negative association of PS with the use of ACEi (ß = -0.230, p = 0.004), but not with the use of ARB (ß = 0.208, p = 0.008). The effect of AT on cognition appears to go beyond the search for lower blood pressure targets and also includes the mechanism of action of AHD on the brain, so that additional benefits may possibly be achieved with simple adaptations in the treatment regimen, particularly in patients without clinically manifest cognitive impairment.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation.

INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

Measurement of resistance-area product by transcranial Doppler: An alternative tool for cognitive screening in hypertensive on drug treatment?

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

Intracranial hemorrhages in patients with COVID-19: a systematic review of the literature, regarding six cases in an Amazonian population.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a public health emergency worldwide, predominantly affecting the respiratory tract. However, evidence supports the involvement of extrapulmonary sites, including reports of intracranial hemorrhages. OBJECTIVE: To describe six original cases and review the literature on intracranial hemorrhages in patients diagnosed with COVID-19 by molecular methods. METHODS: A systematic literature review was performed on MEDLINE, PubMed, and NCBI electronic databases to identify eligible studies. Of the total 1,624 articles retrieved, only 53 articles met the inclusion criteria. RESULTS: The overall incidence of intracranial hemorrhage in patients hospitalized for COVID-19 was 0.26%. In this patient group, the mean age was 60 years, and the majority were male (68%) with initial respiratory symptoms (73%) and some comorbidity. Before the diagnosis of hemorrhage, 43% of patients were using anticoagulants, 47.3% at therapeutic doses. The intraparenchymal (50%) was the most affected compartment, followed by the subarachnoid (34%), intraventricular (11%), and subdural (7%). There was a predominance of lobar over non-lobar topographies. Multifocal or multicompartmental hemorrhages were described in 25% of cases. Overall mortality in the cohort studies was 44%, while around 55% of patients were discharged from hospital. CONCLUSION: Despite the unusual association, the combination of these two diseases is associated with high rates of mortality and morbidity, as well as more severe clinicoradiological presentations. Further studies are needed to provide robust evidence on the exact pathophysiology behind the occurrence of intracranial hemorrhages after COVID-19 infection.

ANTECEDENTES: A COVID-19 emergiu como uma emergência de saúde pública em todo o mundo, proporcionando lesão principalmente do trato respiratório. No entanto, várias evidências apontam para acometimento de sítios extrapulmonares, incluindo relatos de hemorragias intracranianas. OBJETIVO: Descrever seis casos originais e revisar a literatura sobre hemorragias intracranianas em pacientes com diagnostico de COVID-19 por métodos moleculares. MéTODOS: A revisão sistemática da literatura foi feita nas bases de dados eletrônicas da MEDLINE, PubMed e NCBI para identificar os estudos elegíveis. Do total de 1.624 artigos recuperados, apenas 53 artigos preencheram os critérios de inclusão. RESULTADOS: A incidência geral de hemorragia intracraniana nos pacientes internados por COVID-19 foi de 0,26%. A média de idade foi de 60 anos, e a maioria dos pacientes era do sexo masculino (68%) com sintomas respiratórios iniciais (73%) e alguma comorbidade. Antes do diagnóstico de hemorragia, 43% estavam em uso de anticoagulantes, 47,3% destes em doses terapêuticas. O compartimento mais acometido foi o intraparenquimatoso (50%), seguido do subaracnoideo (34%), intraventricular (11%) e subdural (7%). Houve predomínio de topografias lobares sobre as não-lobares. Hemorragias multifocais ou multicompartimentais foram descritas em 25% dos casos. A mortalidade geral nos estudos de coorte foi de 44%, enquanto houve alta hospitalar em cerca de 55% dos pacientes. CONCLUSãO: Apesar da associação incomum, a combinação dessas doenças está relacionada com altas taxas de mortalidade e morbidade, bem como apresentações clínico-radiológicas mais graves. Mais estudos são necessários para oferecer evidências robustas sobre a fisiopatologia exata por trás da ocorrência de hemorragias intracranianas após infecção por COVID-19.

Intracranial hemorrhages in patients with COVID-19: a systematic review of the literature, regarding six cases in an Amazonian population / Hemorragias intracranianas em pacientes com COVID-19: uma revisão sistemática da literatura, a propósito de seis casos na população amazônica

Abstract Background Coronavirus disease 2019 (COVID-19) has emerged as a public health emergency worldwide, predominantly affecting the respiratory tract. However, evidence supports the involvement of extrapulmonary sites, including reports of intracranial hemorrhages. Objective To describe six original cases and review the literature on intracranial hemorrhages in patients diagnosed with COVID-19 by molecular methods. Methods A systematic literature review was performed on MEDLINE, PubMed, and NCBI electronic databases to identify eligible studies. Of the total 1,624 articles retrieved, only 53 articles met the inclusion criteria. Results The overall incidence of intracranial hemorrhage in patients hospitalized for COVID-19 was 0.26%. In this patient group, the mean age was 60 years, and the majority were male (68%) with initial respiratory symptoms (73%) and some comorbidity. Before the diagnosis of hemorrhage, 43% of patients were using anticoagulants, 47.3% at therapeutic doses. The intraparenchymal (50%) was the most affected compartment, followed by the subarachnoid (34%), intraventricular (11%), and subdural (7%). There was a predominance of lobar over non-lobar topographies. Multifocal or multicompartmental hemorrhages were described in 25% of cases. Overall mortality in the cohort studies was 44%, while around 55% of patients were discharged from hospital. Conclusion Despite the unusual association, the combination of these two diseases is associated with high rates of mortality and morbidity, as well as more severe clinicoradiological presentations. Further studies are needed to provide robust evidence on the exact pathophysiology behind the occurrence of intracranial hemorrhages after COVID-19 infection.

Resumo Antecedentes A COVID-19 emergiu como uma emergência de saúde pública em todo o mundo, proporcionando lesão principalmente do trato respiratório. No entanto, várias evidências apontam para acometimento de sítios extrapulmonares, incluindo relatos de hemorragias intracranianas. Objetivo Descrever seis casos originais e revisar a literatura sobre hemorragias intracranianas em pacientes com diagnostico de COVID-19 por métodos moleculares. Métodos A revisão sistemática da literatura foi feita nas bases de dados eletrônicas da MEDLINE, PubMed e NCBI para identificar os estudos elegíveis. Do total de 1.624 artigos recuperados, apenas 53 artigos preencheram os critérios de inclusão. Resultados A incidência geral de hemorragia intracraniana nos pacientes internados por COVID-19 foi de 0,26%. A média de idade foi de 60 anos, e a maioria dos pacientes era do sexo masculino (68%) com sintomas respiratórios iniciais (73%) e alguma comorbidade. Antes do diagnóstico de hemorragia, 43% estavam em uso de anticoagulantes, 47,3% destes em doses terapêuticas. O compartimento mais acometido foi o intraparenquimatoso (50%), seguido do subaracnoideo (34%), intraventricular (11%) e subdural (7%). Houve predomínio de topografias lobares sobre as não-lobares. Hemorragias multifocais ou multicompartimentais foram descritas em 25% dos casos. A mortalidade geral nos estudos de coorte foi de 44%, enquanto houve alta hospitalar em cerca de 55% dos pacientes. Conclusão Apesar da associação incomum, a combinação dessas doenças está relacionada com altas taxas de mortalidade e morbidade, bem como apresentações clínico-radiológicas mais graves. Mais estudos são necessários para oferecer evidências robustas sobre a fisiopatologia exata por trás da ocorrência de hemorragias intracranianas após infecção por COVID-19.

Point-Counterpoint: Cerebral perfusion pressure is a high-risk concept.

Cerebral perfusion pressure (CPP) is calculated as the difference between mean arterial blood pressure and mean intracranial pressure, being commonly applied in neurocritical care. This commentary discusses recent physiological advances in knowledge as well as bedside practice issues that in combination indicate considering CPP under this perspective may lead to inaccurate assumptions and potentially misleading decision making.

Ischemic stroke caused by large-artery atherosclerosis: a red flag for subclinical coronary artery disease.

Background: The coronary calcium score (CAC) measured on chest computerized tomography is a risk marker of cardiac events and mortality. We compared CAC scores in two multiethnic groups without symptomatic coronary artery disease: subjects in the chronic phase after stroke or transient ischemic attack and at least one symptomatic stenosis ≥50% in the carotid or vertebrobasilar territories (Groupathero) and a control group (Groupcontrol). Methods: In this cross-sectional study, Groupathero included two subgroups: GroupExtraorIntra, with stenoses in either cervical or intracranial arteries, and GroupExtra&Intra, with stenoses in at least one cervical and one intracranial artery. Groupcontrol had no history of prior stroke/transient ischemic attacks and no stenoses ≥50% in cervical or intracranial arteries. Age and sex were comparable in all groups. Frequencies of CAC ≥100 and CAC > 0 were compared between Groupathero and Groupcontrol, as well as between GroupExtraorIntr, GroupExtra&Intra, and Groupcontrol, with bivariate logistic regressions. Multivariate analyses were also performed. Results: A total of 120 patients were included: 80 in Groupathero and 40 in Groupcontrol. CAC >0 was significantly more frequent in Groupathero (85%) than Groupcontrol (OR, 4.19; 1.74-10.07; p = 0.001). Rates of CAC ≥100 were not significantly different between Groupathero and Groupcontrol but were significantly greater in GroupExtra&Intra (n = 13) when compared to Groupcontrol (OR 4.67; 1.21-18.04; p = 0.025). In multivariate-adjusted analyses, "Groupathero" and "GroupExtra&Intra" were significantly associated with CAC. Conclusion: The frequency of coronary calcification was higher in subjects with stroke caused by large-artery atherosclerosis than in controls.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Combined assessment by transcranial sonography and Sniffin' Sticks test has a similar diagnostic accuracy compared to brain SPECT for Parkinson's disease diagnosis.

OBJECTIVES: This study aimed to investigate the accuracy of TCS combined with the Sniffin' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99 mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex- matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the diagnostic accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p = 0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS diagnostic accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% diagnostic accuracy for the diagnosis of PD. SST-16 values equal or less than 9 points showed an 85.8% diagnostic accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the diagnostic accuracy to 95% for PD diagnosis. CONCLUSION: Combined SST-16 and TCS assessment was indicated as accurate for distinguishing PD patients from healthy controls. The diagnostic accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT.

Assessing ultrasonographic optic nerve sheath diameter in animal model with anesthesia regimens.

PURPOSE: To determine the normal optical nerve sheath (ONS) diameter ultrasonography (ONSUS) and evaluate the possible effects of drugs on ONS diameter during anesthetic induction in healthy pigs. METHODS: Healthy piglets were divided into three groups: a control group, that received xylazine and ketamine (X/K); other that received xylazine, ketamine and propofol (X/K/P); and a third group that received xylazine, ketamine, and thiopental (X/K/T). The sheath diameter was assessed by ultrasonography calculating the average of three measurements of each eye from the left and right sides. RESULTS: 118 animals were anesthetized (49 X/K 33 X/K/P and 39 X/K/T). Mean ONS sizes on both sides in each group were 0.394 ± 0.048 (X/K), 0.407 ± 0.029 (X/K/P) and 0.378 ± 0.042 cm (X/K/T) (medians of 0.400, 0.405 and 0.389, respectively). The ONS diameter varied from 0.287-0.512 cm (mean of 0.302 ± 0.039 cm). For group X/K, the mean diameter was 0.394 ± 0.048 cm. Significant differences in ONS sizes between the groups P and T (X/K/P > X/K/T, p = 0.003) were found. No statistically significant differences were detected when other groups were compared (X/K = X/K/P, p = 0.302; X/K = X/K/T, p = 0.294). CONCLUSIONS: Sedation with thiopental lead to significative ONS diameter reduction in comparison with propofol. ONSUS may be useful to evaluate responses to thiopental administration.

Cerebral Vasculopathy in Children With Sickle Cell Disease in an Amazonian Population.

Introduction: Sickle cell disease is the most prevalent hereditary disease in the country. The aim of this study was to use transcranial Doppler as a screening method for identifying cerebral vasculopathy in children with sickle cell disease. Methods: An epidemiologic, descriptive, and cross-sectional study was conducted. Patients aged 2-16 years with sickle cell disease and followed at a neurology referral service between January 2014 and March 2020 underwent transcranial Doppler and complementary examinations to screen for cerebral vasculopathy. Results: Screening and confirmatory examinations diagnosed 14 of 164 patients (8.5%) with cerebral vasculopathy. Regarding stroke risk, as measured by cerebral blood flow velocity, 2 of 14 patients (14.2%) were classified as conditional risk (170-199 cm/s) and 12 of 14 (85.7%) as high risk of stroke. Conclusion: Complementary examinations should be performed in all patients with changes on transcranial Doppler to confirm cerebral vasculopathy. Further studies, particularly genetic, are needed to better understand the relationship between sickle cell disease and cerebral vasculopathy.

Evaluation of cerebral hemodynamics by transcranial Doppler ultrasonography and its correlation with intracranial pressure in an animal model of intracranial hypertension / Avaliação da hemodinâmica encefálica utilizando Doppler transcraniano e sua correlação com a pressão intracraniana em um modelo animal de hipertensão intracraniana

ABSTRACT Background: Transcranial Doppler has been tested in the evaluation of cerebral hemodynamics as a non-invasive assessment of intracranial pressure (ICP), but there is controversy in the literature about its actual benefit and usefulness in this situation. Objective: To investigate cerebral blood flow assessed by Doppler technique and correlate with the variations of the ICP in the acute phase of intracranial hypertension in an animal model. Methods: An experimental animal model of intracranial hypertension was used. The experiment consisted of two groups of animals in which intracranial balloons were implanted and inflated with 4 mL (A) and 7 mL (B) for controlled simulation of different volumes of hematoma. The values of ICP and Doppler parameters (systolic [FVs], diastolic [FVd], and mean [FVm] cerebral blood flow velocities and pulsatility index [PI]) were collected during the entire procedure (before and during hematoma simulations and venous hypertonic saline infusion intervention). Comparisons between Doppler parameters and ICP monitoring were performed. Results: Twenty pigs were studied, 10 in group A and 10 in group B. A significant correlation between PI and ICP was obtained, especially shortly after abrupt elevation of ICP. There was no correlation between ICP and FVs, FVd or FVm separately. There was also no significant change in ICP after intravenous infusion of hypertonic saline solution. Conclusions: These results demonstrate the potential of PI as a parameter for the evaluation of patients with suspected ICP elevation.

RESUMO Antecedentes: O Doppler transcraniano (DTC) é uma técnica não invasiva para a avaliação da hemodinâmica cerebral, porém existem controvérsias na literatura sobre sua aplicabilidade preditiva em situações de elevada pressão intracraniana (PIC). Objetivo: Investigar o fluxo sanguíneo cerebral pelo DTC e correlacioná-lo com as variações da PIC na fase aguda da hipertensão intracraniana em modelo animal. Métodos: Dois grupos de animais (suínos) foram submetidos a hipertensão intracraniana secundária à indução de diferentes volumes de hematoma, por meio da insuflação de balão intracraniano controlado com 4 e 7 mL de solução salina fisiológica (grupos A e B, respectivamente). Em seguida, administrou-se infusão venosa de solução salina hipertônica (SSH 3%). Foram coletados os valores dos parâmetros de PIC e DTC (velocidade sistólica [FVs], diastólica [FVd] e média [FVm] do fluxo sanguíneo cerebral), bem como o índice de pulsatilidade (IP). Comparações entre os parâmetros do DTC e o monitoramento da PIC foram realizadas. Resultados: Vinte porcos foram estudados, dez no grupo A e dez no grupo B. Correlação significativa entre IP e PIC foi obtida, principalmente logo após a elevação abrupta da PIC. Não houve correlação entre PIC e FVs, FVd ou FVm separadamente. Também não houve alteração significativa na PIC após a infusão de SSH. Conclusões: Esses resultados demonstram o potencial do IP como um bom parâmetro para a avaliação de pacientes com suspeita de elevação da PIC.

Evaluation of cerebral hemodynamics by transcranial Doppler ultrasonography and its correlation with intracranial pressure in an animal model of intracranial hypertension.

BACKGROUND: Transcranial Doppler has been tested in the evaluation of cerebral hemodynamics as a non-invasive assessment of intracranial pressure (ICP), but there is controversy in the literature about its actual benefit and usefulness in this situation. OBJECTIVE: To investigate cerebral blood flow assessed by Doppler technique and correlate with the variations of the ICP in the acute phase of intracranial hypertension in an animal model. METHODS: An experimental animal model of intracranial hypertension was used. The experiment consisted of two groups of animals in which intracranial balloons were implanted and inflated with 4 mL (A) and 7 mL (B) for controlled simulation of different volumes of hematoma. The values of ICP and Doppler parameters (systolic [FVs], diastolic [FVd], and mean [FVm] cerebral blood flow velocities and pulsatility index [PI]) were collected during the entire procedure (before and during hematoma simulations and venous hypertonic saline infusion intervention). Comparisons between Doppler parameters and ICP monitoring were performed. RESULTS: Twenty pigs were studied, 10 in group A and 10 in group B. A significant correlation between PI and ICP was obtained, especially shortly after abrupt elevation of ICP. There was no correlation between ICP and FVs, FVd or FVm separately. There was also no significant change in ICP after intravenous infusion of hypertonic saline solution. CONCLUSIONS: These results demonstrate the potential of PI as a parameter for the evaluation of patients with suspected ICP elevation.

Improvement in neurological outcome and brain hemodynamics after late cranioplasty.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001), and Barthel Index (p = 0.002). Outpatient waiting time for cranioplasty was 15.23 (SD 17.66) months. PCT showed a significant decrease in the mean transit time (MTT) and cerebral blood volume (CBV) only on the operated side. Although most previous studies have shown an increase in cerebral blood flow (CBF), we noticed a slight and nonsignificant decrease, despite a significant increase in the middle cerebral artery flow velocity in both hemispheres on TCD. There was a moderate correlation between the MTT and contralateral muscle strength (r = - 0.4; p = 0.034), as well as between TCD and neurological outcomes ipsilateral (MMSE; r = 0.54, p = 0.03) and contralateral (MRS; p = 0.031, r = - 0.48) to the operated side. CONCLUSION: Even 1 year after DC, cranioplasty may improve cerebral perfusion and neurological outcomes and should be encouraged.

Cerebral Hemodynamics and Intracranial Compliance Impairment in Critically Ill COVID-19 Patients: A Pilot Study.

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 < 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 > 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.

CAAos platform: an integrated platform for analysis of cerebral hemodynamics data.

Objective.The purpose of this article is to introduce readers to the concept and structure of the CAAos (CerebralAutoregulationAssessmentOpenSource) platform, and provide evidence of its functionality.Approach.The CAAos platform is a new open-source software research tool, developed in Python 3 language, that combines existing and novel methods for interactive visual inspection, batch processing and analysis of multichannel records. The platform is scalable, allowing for the customization and inclusion of new tools.Main results.Currently, the CAAos platform is composed of two main modules, preprocessing (containing artefact removal, filtering and signal beat to beat extraction tools) and cerebral autoregulation (CA) analysis modules. Two methods for assessing CA have been implemented into the CAAos platform: transfer function analysis (TFA) and the autoregulation index (ARI). In order to provide validation of the TFA and ARI estimates derived from the CAAos platform, the results were compared with those derived from two other algorithms. Validation was performed using data from 28 participants, corresponding to 13 acute ischemic stroke patients and 13 age- and sex-matched control subjects. Agreement between estimates was assessed by intraclass correlation coefficient and Bland-Altman analysis. No significant statistical difference between the algorithms was found. Moreover, there was an excellent correspondence between the curves of all parameters analysed, with the intraclass correlation coefficient ranging from 0.98 (95%CI 0.976-0.999) to 1.00 (95%CI 1 -1). The mean differences revealed a very small magnitude bias indicating an excellent agreement between the estimates.Significance.As open-source software, the source code for the software is freely available for noncommercial use, reducing barriers to performing CA analysis, allowing inspection of the inner-workings of the algorithms, and facilitating networked activities with common standards. The CAAos platform is a tailored software solution for the scientific community in the cerebral hemodynamic field and contributes to the increasing use and reproducibility of CA assessment.

Transcranial Doppler: A Useful Tool to Predict Brain Death Still Not Confirmed by Clinical Assessment.

BACKGROUND: Diagnosing brain death (BD) with accuracy and urgency is of great importance because an early diagnosis may guide the clinical management, optimize hospital beds, and facilitate organ transplantation. The clinical diagnosis of nonreactive and irreversible coma can be confirmed with additional tests. Among the complimentary exams that may testify brain circulatory arrest, transcranial Doppler (TCD) can be an option. It is a real-time, bedside, inexpensive, noninvasive method that assesses cerebral blood flow. In patients with suspected BD, especially those who are under sedative drugs, early diagnosis is imperative. The aim of the present study was to evaluate the role of TCD in predicting BD. METHODS: One hundred consecutive comatose patients with a Glasgow Coma Scale score of less than 5, owing to different etiologies, were included. TCD was performed in all patients. The TCD operator was blinded for clinical and neurologic data. This study is in compliance with the Declaration of Helsinki. RESULTS: Sixty-nine patients with TCD-brain circulatory collapse were diagnosed later with BD. Of the 31 patients with brain circulatory activity, 8 (25.8%) were clinically brain dead and 23 (74.2%) were alive. TCD showing brain circulatory collapse had a sensitivity of 89.6%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 74.2%. CONCLUSION: TCD is highly specific (100%) and sensitive (89.6%) as a method to confirm the clinical diagnosis of BD, even in patients under sedation. The possibility of patients presenting with cerebral circulatory activity and clinical diagnosis of BD was demonstrated to occur.

Cerebral Autoregulation in Ischemic Stroke: From Pathophysiology to Clinical Concepts.

Ischemic stroke (IS) is one of the most impacting diseases in the world. In the last decades, new therapies have been introduced to improve outcomes after IS, most of them aiming for recanalization of the occluded vessel. However, despite this advance, there are still a large number of patients that remain disabled. One interesting possible therapeutic approach would be interventions guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). Supportive hemodynamic therapies aiming to optimize perfusion in the ischemic area could protect the brain and may even extend the therapeutic window for reperfusion therapies. However, the knowledge of how to implement these therapies in the complex pathophysiology of brain ischemia is challenging and still not fully understood. This comprehensive review will focus on the state of the art in this promising area with emphasis on the following aspects: (1) pathophysiology of CA in the ischemic process; (2) methodology used to evaluate CA in IS; (3) CA studies in IS patients; (4) potential non-reperfusion therapies for IS patients based on the CA concept; and (5) the impact of common IS-associated comorbidities and phenotype on CA status. The review also points to the gaps existing in the current research to be further explored in future trials.