Cerebral Autoregulatory Mechanisms Research Articles

P43 Unmasking posterior reversible encephalopathy syndrome: a hidden threat in juvenile lupus

Abstract Introduction Posterior reversible encephalopathy syndrome (PRES) is a neurological condition identifiable through clinical presentation and magnetic resonance imaging (MRI). While PRES has been rarely documented in children as a complication of juvenile lupus, it remains a potentially reversible condition. However, it can be complicated by vasculopathy, infarction, or haemorrhage. The pathogenesis of PRES is still unclear. In juvenile lupus, the risk factors for PRES are multifaceted and interact with each other, including vasculitis, lupus nephritis, chronic kidney disease (CKD) leading to renal-origin hypertension, and iatrogenic hypertension caused by several hypertension-inducing drugs commonly used as first-line treatments for lupus. Case description A 14-year-old girl diagnosed with lupus presented with persistent fatigue, lower limb oedema, and abdominal symptoms (vomiting and diarrhoea). She experienced two episodes of PRES, three months apart. Active SLE was confirmed through clinical and laboratory findings, including positive autoimmune and serologic results for ENA antibody screen, high levels of anti-double-stranded DNA (>400), and low complements C3 (0.15 g/L) and C4 (<0.03 g/L). Urine analysis revealed 2+ RBCs, 3+ proteins, and an estimated glomerular filtration rate (eGFR) of ∼21 ml/min/1.73 m² with a plasma creatinine of 226 micromol/L. Renal biopsy identified lupus nephritis class IV and chronic kidney disease (CKD) changes, leading to a diagnosis of CKD stage 4. Initial treatment included a course of pulse methylprednisolone (1 g daily for 3 days) alongside rituximab and MMF for remission induction followed by high-dose oral prednisone (2 mg/kg/d). Her blood pressure started to increase following the first methylprednisolone pulse. In addition, two weeks later, severe fluid overload necessitated dialysis. Despite dialysis and the use of four antihypertensive agents (lisinopril, amlodipine, atenolol, doxazosin), her blood pressure fluctuated and remained uncontrolled. A week later, she experienced focal seizures. While a CT brain scan showed no abnormalities, an MRI revealed multifocal areas of bilateral cerebral hemispheric cortico-subcortical signal and diffusion alteration, indicating evolving PRES. A steroid weaning plan was implemented, and IV cyclophosphamide was initiated according to the National Institutes of Health protocol. Eight weeks later, she had another PRES episode, presenting with seizures confirmed by MRI findings. On both occasions, hypertensive encephalopathy was promptly recognized, and she was transferred to the PICU. Fortunately, her symptoms completely resolved within 12 hours of anticonvulsant and antihypertensive therapies. Discussion Common triggers of PRES include autoimmune conditions such as systemic lupus erythematosus (SLE), hypertensive encephalopathy, and drug toxicities (mainly cytotoxic and immunosuppressive drugs), all of which interact in lupus patients. However, it remains unclear how each factor contributes to the development of PRES. Additionally, the exact pathophysiological mechanism behind PRES is still debated. The two most widely accepted hypotheses involve: firstly, increased arterial blood pressure overwhelming cerebral autoregulatory mechanisms, leading to vascular leakage and vasogenic oedema. Secondly, endothelial dysfunction, where endothelial damage caused by circulating toxins enhances the release of vasoactive and immunogenic agents, altering vascular permeability. Our patient’s development of PRES is multifactorial, with lupus nephritis being a primary cause, aggravated by chronic kidney disease, leading to salt and water retention, which was further exacerbated by prednisolone. Other drugs, such as rituximab and cyclophosphamide, might have also been implicated in causing hypertension. PRES following rituximab infusion has been documented, with onset ranging from immediately after infusion to up to four weeks later. Proposed mechanisms include compromised blood-brain barrier integrity and immune dysregulation. Intravenous cyclophosphamide has also been identified as a potential trigger for PRES in patients with and without SLE, though the exact reason for this remains unclear. The dual role of these drugs in potentially precipitating life-threatening risks like PRES while being therapeutic agents presents a confusing dilemma. Much remains to be learned to enable the prevention and prompt response to PRES. Key learning points • Juvenile lupus with PRES is an uncommon neurological manifestation influenced by multiple factors. • Risk factors for PRES in juvenile lupus include lupus nephritis, CKD secondary to lupus, and iatrogenic hypertension including steroids, rituximab, and cyclophosphamide. These factors commonly exist and interplay together. • The pathogenesis of PRES in lupus, including the role of drugs, remains unclear. • Patients with lupus should be closely monitored, particularly their blood pressure. • Early diagnosis and prompt treatment of PRES can reverse radiologic and neurologic findings, leading to a favourable prognosis.

Modeling the mechanisms of non-neurogenic dynamic cerebral autoregulation.

Dynamic cerebral autoregulation (dCA) refers to a collection of mechanisms that act to maintain steady state cerebral blood flow (CBF) near constant despite changes in arterial blood pressure (ABP), but which is known to become impaired in various cerebrovascular diseases. Currently, the mechanisms of dCA and how they are affected in different physiological conditions are poorly understood. The objective of this study was to disentangle the magnitudes and time scales of the myogenic and metabolic responses of dCA, in order to investigate how each mechanism is affected in impaired dCA. A physiological model of dCA was developed, where both the myogenic and metabolic responses were represented by a gain and time constant. Model parameters were optimized with pressure-flow impulse responses under normocapnia, thigh cuff, and hypercapnia conditions. The impulse responses were derived by applying transfer function analysis (TFA) to experimental recordings of ABP (Finapres), end-tidal CO2 (capnograph), and CBF velocity (transcranial doppler ultrasound in bilateral middle cerebral arteries). The myogenic gain to time constant ratio was significantly smaller (p-values < 0.001 using both univariate and multivariate TFA), and the metabolic time constant was significantly larger (p-values < 0.001 using both univariate and multivariate TFA) in hypercapnia compared to normocapnia. Both the myogenic and metabolic responses were shown to be affected in impaired dCA, and the metabolic response was shown to be slowed down. This study contributes to the understanding of the complexities of dCA and how it is affected in different physiological conditions.

Cerebral multi-autoregulation model based enhanced external counterpulsation treatment planning for cerebral ischemic stroke.

Enhanced external counterpulsation (EECP) treatment for cerebral ischemic stroke patients with differing severity of stenosis, is subject to uncertainties due to the varying effects of the cerebral autoregulation mechanism on haemodynamics. The current study reports the development of a cerebral multi-autoregulation (MR) mathematical model, based on cerebral arteriole regulation of neurogenic, vascular smooth muscle reflex and shear stress mechanisms which takes into account the severity of stenosis. The model was evaluated by comparison to authentic clinical measurements of cerebral autoregulatory efficiency. Then it was applied to a 0D/3D geometric multi-scale haemodynamic model of a cerebral artery. Haemodynamic indicators were calculated under different pressurization durations of EECP to evaluate the efficacy for different stenosis lesions. Moderate stenosis of 50% to 60% produced excessive time-averaged wall shear stress in the distal area of the stenosis (>7 Pa) during prolonged pressurization and may result in damage to vascular endothelial cells. However, prolonged pressurization did not result in haemodynamic risk for severe stenosis of 70% to 80%, indicating that the duration of pressurization may be extended with increasing severity of stenosis. The current MR model accurately simulated cerebral blood flow and has relevance to the simulation of cerebral haemodynamics in a clinical setting.

Impact of early percutaneous dilatative tracheostomy in patients with subarachnoid hemorrhage on main cerebral, hemodynamic, and respiratory variables: A prospective observational study.

Patients with poor-grade subarachnoid hemorrhage (SAH) admitted to the intensive care unit (ICU) often require prolonged invasive mechanical ventilation due to prolonged time to obtain neurological recovery. Impairment of consciousness and airway protective mechanisms usually require tracheostomy during the ICU stay to facilitate weaning from sedation, promote neurological assessment, and reduce mechanical ventilation (MV) duration and associated complications. Percutaneous dilatational tracheostomy (PDT) is the technique of choice for performing a tracheostomy. However, it could be associated with particular risks in neurocritical care patients, potentially increasing the risk of secondary brain damage. We conducted a single-center, prospective, observational study aimed to assess PDT-associated variations in main cerebral, hemodynamic, and respiratory variables, the occurrence of tracheostomy-related complications, and their relationship with outcomes in adult patients with SAH admitted to the ICU of a neurosurgery/neurocritical care hub center after aneurysm control through clipping or coiling and undergoing early PDT. We observed a temporary increase in ICP during early PDT; this increase was statistically significant in patients presenting with higher therapy intensity level (TIL) at the time of the procedural. The episodes of intracranial hypertension were brief, and appeared mainly due to the activation of cerebral autoregulatory mechanisms in patients with impaired compensatory mechanisms and compliance. The low number of observed complications might be related to our organizational strategy, all based on a dedicated "tracheo-team" implementing both PDT following a strictly defined protocol and accurate follow-up.

COMPUTATIONAL SIMULATION OF THE INTERACTION AMONG AUTOREGULATION MECHANISMS REGULATING CEREBRAL BLOOD FLOW RATE IN SYSTOLIC HEART FAILURE

In this study, a lumped parameter model which includes systemic circulation, cerebral blood vessels, systemic arteriolar resistance control, heart rate control, cerebral autoregulation mechanisms and cerebral CO2 reactivity was developed to simulate healthy and heart failure conditions. In the healthy cardiovascular system model, the results were obtained with all control mechanisms connected to the model. Whilst heart failure cases were simulated, all control mechanisms were removed from the model. Then, cerebral autoregulation and cerebral CO2 reactivity mechanisms were connected to the model. Lastly, systemic arteriolar resistance and heart rate control mechanisms were connected to the model. Also, Monte Carlo Analysis was performed to determine the range of parameters controlled for simulations of healthy and heart failure conditions. The results showed that blood flow rate in cerebral circulation can be simulated more accurately by modeling interaction among autoregulatory mechanisms rather than studying separately.

HYPERTENSIVE ENCEPHALOPATHY: TO BE DIAGNOSED AND TREATED IMMEDIATELY

It is important to have a good understanding of the pat­hogenetic diagnosis and treatment features of the severe complication with high mortality – hypertensive encepha­lopathy (HE) because of the amount of people suffering from chronic arterial hypertension is constantly increa­sing. Thus, this article briefly reviews the mechanism of cerebral blood flow autoregulation, HE pathophysiology, and the main aspects of diagnosis and treatment. An HE episode is caused by a sudden and significant increase in arterial blood pressure, when the autoregulatory mecha­nism of cerebral blood flow becomes ineffective. Along with increased blood pressure, the patient gradually deve­lops neurological symptoms ranging from intense heada­che to vision loss, loss of consciousness, and convulsions. The diagnosis of HE is based on the clinical signs – acute arterial hypertension and the subsequent neurological symptoms. Also, the diagnosis of HE can be determined retrospectively when the neurological symptoms rapi­dly disappear with effective antihypertensive treatment. Computed tomography is important in differentiating HE from intracerebral hemorrhage and ischemic stroke. In management of HE it is recommended to return to the limits of cerebral blood flow autoregulation by immedi­ately reducing mean arterial blood pressure by 20-25%. In order to achieve the maximum rapid antihyperten­sive effect, it is suggested to administer the medication only intravenously. Labetalol and sodium nitroprusside are currently recommended first-line drugs for the treat­ment of HE. Patients with HE should be hospitalized in the intensive care unit for continuous control of decre­asement of arterial blood pressure while observing the cautious dynamics of the neurological condition. The outcome of patients depends on the urgency and effici­ency of treatment in returning arterial blood pressure to the limits of cerebral blood flow autoregulation, as well as on comorbidities, the severity of the condition and possible complications.

Ln silico simulation of the interaction among autoregulatory mechanisms regulating cerebral blood flow rate in the healthy and systolic heart failure conditions during exercise

In this study, a computational model was proposed to assess the interaction among systemic arteriolarresistance control, heart rate control, ventricular elastance control, venous compliance control, respiratory control, cerebral autoregulation mechanisms, and cerebral CO2 reactivity for both healthy and heart failure conditions. The aim of the study is to develop a computational model to evaluate cerebral blood flow rate during exercise for both healthy and systolic heart failure conditions. The simulations were performed at rest and during exercise. Furthermore, Monte Carlo analysis was used to estimate the range of the controlled parameters for each condition. The mean arterial pressure increased progressively with respect to workload during exercise in both healthy and heart failure conditions. Total cerebral blood flow rate was found 730mL/min at rest in the healthy cardiovascular system model. As for the simulation during exercise, the increments in cerebral blood flow rate were 11% at 25W workload, 20% at 50W workload, and 24% at 75W workload. The left ventricular ejection fraction decreased from 54 to 26% in the cardiovascular model simulating heart failure. Also, total cerebral blood flow rate decreased to 604mL/min at rest in the cardiovascular system model simulating heart failure. The increments in cerebral blood flow rate in the simulation during exercise were 14% at 25W workload, 24% at 50W workload, and 30% at 75W workload in the case of heart failure. The proposed numerical model simulates cerebral blood flow rate within physiological range during exercise and heart failure.

The haemodynamic effects of umbilical cord milking in term infants: a randomised controlled trial.

Umbilical cord milking (UCM) is a method that allows for postnatal placental transfusion. The benefits of UCM have been demonstrated in some studies, but knowledge about its haemodynamic effects in term infants is limited. The aim of this study was to evaluate the haemodynamic effects of UCM in term infants. In this prospective, randomised controlled study, 149 healthy term infants with a birth week of ≥37 weeks were randomly assigned to either the UCM or immediate cord clamping (ICC) group. Blinded echocardiographic evaluations were performed in all the neonates in the first 2-6 h. Superior vena cava (SVC) flow measurements were higher in the UCM group compared to the ICC group (132.47 ± 37.0 vs. 126.62 ± 34.3 mL/kg/min), but this difference was not statistically significant. Left atrial diameter (12.23 ± 1.99 vs. 11.43 ± 1.78 mm) and left atrium-to-aorta diastolic diameter ratio (1.62 ± 0.24 vs. 1.51 ± 0.22) were significantly higher in the UCM group. There were no significant differences in other echocardiographic parameters between the two groups. We found no significant difference in the SVC flow measurements in term infants who underwent UCM versus those who underwent ICC. This lack of significant difference in SVC flow may be explained by the mature cerebral autoregulation mechanism in term neonates.

Evaluation of cerebral hemodynamic status in patients with unilateral symptomatic carotid artery stenosis during motor tasks, through use of transcranial Doppler sonography.

Carotid artery stenosis increases cerebral ischemic event risk through changing different cerebral hemodynamic parameters. To investigate how cerebral hemodynamics in the M1 segment of middle cerebral artery change in patients with carotid artery stenosis, after motor tasks using transcranial Doppler sonography (TCD). Thirty-two healthy subjects and 30 patients with unilateral symptomatic carotid artery stenosis were recruited. The patient population was divided into three groups according to the degree of stenosis (group 1: ≥50 to 69%, group 2: 70 to 89% and group 3: ≥90 to 99%). TCD was used to measure the pulsatility index (PI) and cerebral vasomotor reactivity (CVR). In the patient group, significant differences for symptomatic side PI values (p=0.01) and mean CVR increases (p=0.05) were observed, compared with the healthy controls. However, the difference was not statistically significant for asymptomatic side PI values and mean CVR increases. The results from the intergroup comparison showed significantly higher percentages of symptomatic and asymptomatic side CVR increases in group 1, compared with groups 2 and 3 (p=0.001 and p=0.002, respectively). Our study showed that cerebral autoregulation and hemodynamic mechanisms are impaired in patients with carotid artery stenosis. Furthermore, the impairment of PI and CVR tends to get worse with increasing degrees of stenosis. In addition, this study demonstrated that assessment of these two hemodynamic parameters in clinical practice might be helpful for monitoring the progress of carotid artery stenosis.

Machine Learning Models and Statistical Complexity to Analyze the Effects of Posture on Cerebral Hemodynamics.

The mechanism of cerebral blood flow autoregulation can be of great importance in diagnosing and controlling a diversity of cerebrovascular pathologies such as vascular dementia, brain injury, and neurodegenerative diseases. To assess it, there are several methods that use changing postures, such as sit-stand or squat-stand maneuvers. However, the evaluation of the dynamic cerebral blood flow autoregulation (dCA) in these postures has not been adequately studied using more complex models, such as non-linear ones. Moreover, dCA can be considered part of a more complex mechanism called cerebral hemodynamics, where others (CO2 reactivity and neurovascular-coupling) that affect cerebral blood flow (BF) are included. In this work, we analyzed postural influences using non-linear machine learning models of dCA and studied characteristics of cerebral hemodynamics under statistical complexity using eighteen young adult subjects, aged 27 ± 6.29 years, who took the systemic or arterial blood pressure (BP) and cerebral blood flow velocity (BFV) for five minutes in three different postures: stand, sit, and lay. With models of a Support Vector Machine (SVM) through time, we used an AutoRegulatory Index (ARI) to compare the dCA in different postures. Using wavelet entropy, we estimated the statistical complexity of BFV for three postures. Repeated measures ANOVA showed that only the complexity of lay-sit had significant differences.

Research progress on the mechanism of cerebral blood flow regulation in hypoxia environment at plateau

ABSTRACT The plateau is a special environment with low air pressure and low oxygen content. The average altitude of Qinghai-Tibet is 3,500 m, and the atmospheric oxygen partial pressure in most areas is lower than 60% of that at sea level. In order to adapt to the plateau low-oxygen environment, the human body has developed corresponding physiological structure and functions adjust. In the present review, the regulation mechanism of cerebral blood flow (CBF) under high-altitude environments was elaborated in eight aspects: the arterial blood gas, endogenous substances in the nerve and blood, the cerebral neovascularization, the hematocrit, cerebral auto-regulation mechanism, cerebrovascular reactivity, pulmonary vasoconstriction, and sympathetic automatic regulation, aiming to further explore the characteristics of changes in brain tissue and cerebral blood flow in a hypoxic environment.

Cerebral Autoregulation during Orthostatic Challenge in Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P < 0.01) and a 29% increase in minutes of impaired autoregulation (P < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.

Respiration is a Confounder of the Closed Loop Relationship Between Mean Arterial Pressure and Mean Cerebral Blood Flow.

This study tested the hypothesis that respiration (RESP) is a confounder or suppressor of the closed loop relationship responsible for the cerebrovascular dynamical interactions as assessed from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). The evaluation was carried out in the information domain via transfer entropy (TE) estimated through a linear model-based approach comparing TE markers computed solely over MAP and MCBF series with TE indexes accounting for the eventual action of RESP over MAP and MCBF. We considered 11 patients (age: 76±5 yrs, 7 males) undergoing surgical aortic valve replacement (SAVR) at supine resting (REST) and during active standing (STAND) before and after SAVR surgery. The decrease of the predictive ability of MCBF to MAP when accounting for RESP compared to the one assessed when disregarding RESP suggested that RESP is a confounder of the link from MCBF to MAP along the Cushing reflex instead of being a suppressor. This result was more evident in POST when autonomic control was dramatically depressed and in an unchallenged condition such as REST. RESP did not affect significantly the link from MAP to MCBF along the pressure-to-flow relationship. Clarification of the type of RESP influence on the MAP-MCBF closed loop relationship could favor a deeper characterization of cerebrovascular interactions and the comprehension of cerebral autoregulation mechanisms.Clinical Relevance- This study suggests that respiration is a confounder of the closed loop relationship between MAP and MCBF, especially of the flow-to-pressure causal link. This result might open new possibilities in elucidating the mechanisms of cerebral autoregulation in healthy and pathological populations.

Церебральна ауторегуляція та цереброваскулярні ураження у передчасно народжених дітей: сучасні погляди на патогенез, діагностику і превентивні стратегії

Представлений огляд наукових джерел спрямований на висвітлення досягнень у розумінні особливостей ауторегуляції церебральної перфузії у передчасно народжених дітей, встановлення значення сучасних методів її моніторингу та визначення загальних підходів до профілактики цереброваскулярних порушень. У статті розглянуто історію дослідження реактивності церебральних судин, висвітлено функцію внутрішнього нейропротективного фізіологічного феномену — церебральної ауторегуляції відповідно до новітніх міжнародних досліджень. Проведений огляд комплексу інтегрованих механізмів церебральної ауторегуляції. Наведені результати досліджень ролі міогенних, нейрогенних і метаболічних механізмів у здійсненні церебральної ауторегуляції, а також можливий генез їх розладів у передчасно народжених дітей. Відповідно до наведених у дослідженнях даних незрілість ауторегуляційних механізмів, анатомічні особливості мозкової тканини, численні внутрішні та зовнішні фактори, що впливають на цереброваскулярні структури, обумовлюють високий ризик уражень центральної нервової системи у передчасно народжених дітей. Зусилля дослідників спрямовані на розвиток неінвазивних діагностичних технологій, які можуть допомогти тривалий час проводити моніторинг церебральної оксигенації, сприяти своєчасній корекції терапевтичних підходів. Параінфрачервона спектроскопія є відносно новим у інтенсивній неонатології методом, який вже довів свою безпечність та ефективність при прийнятті тактичних рішень під час виходжування передчасно народжених дітей. У огляді наведено отримані дослідниками референтні значення для передчасно народжених дітей різного гестаційного віку, які можна використовувати у практиці інтенсивної неонатології для оптимізації інфузійної терапії та респіраторної підтримки немовлят на доклінічному етапі розвитку цереброваскулярних уражень. У статті розглянуто питання щодо діагностики гіпотензії у недоношених новонароджених, окремі фармакологічні підходи до профілактики та лікування порушень церебрального кровообігу.

A multiscale model of cerebral autoregulation

The mechanism of cerebral autoregulation ensures a continuous and sufficient blood supply to the brain to maintain normal function in the presence of changes in blood pressure. Impaired cerebral autoregulation is implicated in a range of brain diseases. We thus present here a multiscale model of cerebral autoregulation to provide a more detailed basis for a better understanding of the mechanisms behind impaired autoregulation. This model is built around a model of single arteriole, which includes a model of Nitric Oxide (NO) transport, the myogenic response, and a 4-state kinetic model coupled to a mechanical model of the vessel wall. In particular, the NO component of the model is added here to better understand the interaction mode between NO and the myogenic response, since the role of NO, the recognized effective vasodilator, is poorly understood in this context. This vessel model is then integrated within a model of the full-brain vasculature. The model is validated using a range of experimental data from the literature, both steady-state and dynamic. The model is able to predict the response of the arteriole to changes in both driving pressure and baseline pressure, indicating that the model captures well the balance between the myogenic and metabolic mechanisms. We next plan to examine the ways in which impaired autoregulation is manifested in different patient groups, potentially leading to improved therapy.

Cerebral perfusion responses to active standing are attenuated in patients with vasovagal syncope

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Irish Research Council (IRC): Government of Ireland Postgraduate Scholarship Programme 2018, Dublin, Ireland Fundació Universitària Agustí Pedro i Pons, Universitat de Barcelona, Barcelona, Spain Background Syncope is a transient loss of consciousness due to cerebral hypoperfusion. While traditionally peripheral haemodynamics are monitored during clinical assessment of syncope, relatively little is known about cerebrovascular haemodynamics during orthostasis in patients with syncope. Purpose Here we investigated whether young patients with syncope present an altered cerebral perfusion when compared to healthy controls. Given potential hyper-reactivity of the autonomic nervous system previously reported in these patients, we hypothesise that an overly active cerebral autoregulation will be present in patients with syncope. Methods Consecutive patients were prospectively recruited from a National Falls and Syncope Unit, and a convenience sample of young healthy community dwelling adults was recruited from a local university (16-30 years). Participants performed a 3 minute active stand test with continuous measurement of beat-to-beat peripheral haemodynamics (blood pressure (BP), heart rate (HR)) and changes in concentration of oxygenated Δ[O2Hb] and deoxygenated Δ[HHb] haemoglobin were derived from a near-infrared spectroscopy (NIRS) monitor. Baseline, steady state and other time domain features were derived for Δ[O2Hb] (nadir, overshoot, overshoot-to-nadir, overshoot-to-nadir recovery rate) and Δ[HHb] (peak, trough, peak-to-trough, peak-to-trough recovery rate) and multiple linear regression was used to compare differences between the two groups correcting for covariates (p &amp;lt; 0.05 significant). Results Patients (n = 40) were younger (20(5.5) vs 23(1) years, p = 0.003) than controls (n = 17) and were well matched in gender, weight, height, BMI and resting haemodynamics. Patients had a smaller Δ[O2Hb] overshoot-to-nadir difference (β: -0.749, CI:(-1.593 0.094), p = 0.08), a slower Δ[O2Hb] recovery rate (β: -0.186, CI:(-0.388 0.016), p = 0.071), and smaller Δ[HHb] peak-to-trough difference (β: -0.530, CI:( -0.921 0.138), p = 0.018) and slower Δ[HHb] recovery rate (β: -0.151, CI: (0.244 0.057), p = 0.008). Conclusion Patients with syncope had signs of an attenuated cerebral oxygenation response to an AS when compared to controls. We hypothesise that this is due to hyper-reactive cerebral autoregulation mechanism, which might be related to a hyper-sensitive autonomic system. Furthering our understanding of vasovagal syncope physiology can help inform future interventions and treatments. This study shows the clinical value of measuring cerebral perfusion using NIRS, an easy to use and readily applicable tool, in the assessment of syncope. Abstract Figure. Cerebral oxygenation upon standing

Multiparameter Biosignal Analysis in Elderly Ischemic Stroke Patients

Biosignal can provide information about body conditions, including physiological conditions of ischemic stroke. The regulation of blood in the brain is regulated through the mechanism of Cerebral Autoregulation (CA). Some parameters that can be used to determine this mechanism are Blood Flow Velocity (BFV) and Blood Pressure (BP). Stroke is also related to nervous system activity, which is represented through the Heart Rate Variability (HRV). This study aims to determine the relationship between those biosignals and their effects on the physiology of ischemic stroke sufferers. The subjects were divided into two groups (20 strokes and 20 controls). BFV data is obtained in the Middle Cerebral Artery (MCA), BP is obtained through the arteries of the upper arms, and 3 leads electrocardiogram is placed in the chest. The results showed that there was a relationship between BP and BFV in the control group (p-value &lt; 0.05; r = -0.574). This correlation was not found in the stroke group. The relationship between BP and HRV was only found in the stroke group, which was associated with high sympathetic activity and lower parasympathetic activity (p-values &lt; 0.05 and r &gt; 0.4). It was based on SDRR, RMSSD, CVRR, LF, and SD1 parameters. In the control group, there was no relationship between HRV and BP. The relationship between BFV and HRV in the control group was not found statistically. Still, in the stroke group, this relationship was found in the LF and LF/HF Ratio parameters (p-value &lt; 0.05; r &gt; 0.4). Based on this research, parameters on HRV that can be used to determine the characteristics of stroke patients in all positions are MeanRR, VLF, and LF

Plateau Waves of Intracranial Pressure: Methods for Automatic Detection and Prediction.

Plateau waves are recurrent phenomena observed in traumatic brain injury (TBI) patients, characterised by an increase in intracranial pressure (ICP) above 40mmHg combined with an almost zero arterial blood pressure (ABP) variation and, hence, a decrease in cerebral perfusion pressure (CPP). A raised ICP for a long period of time, namely plateau waves, can lead to a secondary brain injury. Due to the impaired cerebral autoregulation mechanism these TBI patients present, they are admitted to neurocritical care units (NCCUs) to be under continuous multimodal monitoring, which allows a correct diagnosis for each patient. Plateau waves can end naturally by activating a vasoconstriction mechanism which decreases the amount of blood available in the brain. Alternatively, the phenomenon can end with therapeutic treatment.In this sense, the present study consists in the development of an algorithm capable of automatically detecting plateau waves using offline data, i.e. data already collected from patients. This creates an extra tool which allows for faster detection of events to assist their identification and final diagnosis. Despite the additional steps that can be included to improve the algorithm, the results show good performance, and thus it may be applied in NCCUs.

Features of cerebral autoregulation and reactivity in patients with arterial hypertension in older age groups with orthostatic hypotensive reactions

Aim. To study the condition of cerebrovascular autoregulation and reactivity in different variants of orthostatic hypotensive reactions (OНR) in elderly patients with hypertension (АН).&#x0D; Materials and methods. 50 patients with AH were examined (80% of women) aged 60 to 82 years (68.55.3). The duration of hypertension is from 2 to 43 years (16.811.6 years).The daily blood pressure profile was evaluated by the method of daily monitoring of blood pressure (BPLab, Russia). A study of OНR was carried out using an active orthostatic test (AOP) with continuous monitoring of cerebral blood flow (CBF) and with a minute measurement of blood pressure by the oscillometric method and continuous non-invasive measurement of SBP (systolic blood pressure) and DBP (diastolic blood pressure) in the finger artery (Task Force Monitor CNSystems Austria). The CBF velocity in the middle cerebral artery (SMA) was estimated using a transcranial sensor with a frequency of 2 MHz on an Angiodin-2K ultrasound machine (BIOSS company, Russia). In SMA, systolic (Vs), diastolic (Vd), average cerebral blood flow velocity ACBF (Vm), pulsation index (Pi), and vascular resistance index (Ri) were recorded. The difference between the indicators was calculated initially and during AOP (in the first 30 seconds and for 3 minutes): Vm30s, %, Vm3m, %. Reactivity was assessed using a hypercapnic test (HCP) with breath holding. The relative change in the CBF indicators in the MCA was calculated by the formula: Kr = (Vm1Vm2)100%/Vm1, where Kr is the reactivity coefficient, Vm1 ACBF at rest; Vm2 ACBF during the test. Statistical analysis was performed using the non-parametric MannWhitney method using Statistica 6.0.&#x0D; Results. In 17 (34%) patients with AH, OGR was detected. In 6 (12%) examined patients, initial OHR (IOH) was detected, in 6 (12%) classic OHR (COH), in 5 (10%) there was a combination of COH+IOH. According to the ABPM data, in patients with OHR compared with patients without OHR, there were no significant differences in the daily level of blood pressure (mmHg), SBP: 131.712.2 vs 131.313.8, p0.05; DBP 74.311.8 vs 75.38.9, p0.05). In AOP, patients with OHR significantly decreased Vm in orthostasis compared with patients without OHR, both in the first30 seconds and at 3 minutes (Vm30s: 25.05.5 vs 30.44.7, p0.05; Vm3m: 27.05.2 vs 31.24.7, p0.05; Vm30s,%: 17.06.5 vs 8.34, 1, p0.05; Vm3m,%: 11.76.3 vs 5.82.4, p0.05). When performing HCТ between patients with OHR and without OHR, statistically significant differences in the indices Pi (0.790.08 vs 0.780.16, p0.05) and Ri (0.510.09 vs 0.530.07, p0.05) was not detected, however, in patients with OHR there is a tendency to a less pronounced increase in АCBF at the peak of HCT compared with patients without OHR (36.86.4 vs 40, 06.6, p=0.13). In patients with OHR, the cerebral reactivity coefficient was lower than in patients without OHR (13.43.9 vs 20.76.6, p0.05).&#x0D; Conclusions. In patients with AH of older age groups with OHR, a statistically significant decrease in ACBF in orthostasis was revealed. Patients with IOH showed a decrease in ACBF in the first seconds of orthostasis with its subsequent stabilization. Persons with COH have preserved the mechanisms of cerebral autoregulation in the first seconds of orthostasis, but with prolonged orthostatic load (3 minutes), the effectiveness of autoregulatory mechanisms decreases. OHR in patients with hypertension of older age groups is associated with a decrease in cerebral reactivity.

Hemodynamics of Prefrontal Cortex in Ornithine Transcarbamylase Deficiency: A Twin Case Study.

Ornithine transcarbamylase deficiency (OTCD) is the most common form of urea cycle disorder characterized by the presence of hyperammonemia (HA). In patients with OTCD, HA is known to cause impairments in domains of executive function and working memory. Monitoring OTCD progression and investigating neurocognitive biomarkers can, therefore, become critical in understanding the underlying brain function in a population with OTCD. We used functional near infrared spectroscopy (fNIRS) to examine the hemodynamics of prefrontal cortex (PFC) in a fraternal twin with and without OTCD. fNIRS is a non-invasive and wearable optical technology that can be used to assess cortical hemodynamics in a realistic clinical setting. We quantified the hemodynamic variations in total-hemoglobin as assessed by fNIRS while subjects performed the N-back working memory (WM) task. Our preliminary results showed that the sibling with OTCD had higher variation in a very low frequency band (<0.03 Hz, related to mechanism of cerebral autoregulation) compared to the control sibling. The difference between these variations was not as prominent in the higher frequency band, indicating the possible role of impaired autoregulation and cognitive function due to presence of HA. We further examined the functional connectivity in PFC, where the OTCD sibling showed lower interhemispheric functional connectivity as the task load increased. Our pilot results are the first to show the utility of fNIRS in monitoring OTCD cortical hemodynamics, indicating the possibility of inefficient neurocognitive function. This study provides a novel insight into the monitoring of OTCD focusing on the contribution of physiological process and neurocognitive function in this population.