Changes In Cerebral Autoregulation Research Articles

Abstract 55: Cerebral Autoregulatory Curves in Postpartum Individuals With and Without Preeclampsia

Introduction: Risk of maternal stroke is higher in patients with preeclampsia (PEC), with the highest risk seen in those with chronic hypertension with superimposed preeclampsia (siPEC). Most strokes occur postpartum. Changes in cerebral autoregulation (CA) could contribute to elevated postpartum stroke risk. We describe CA curves in postpartum patients with no hypertension, PEC and siPEC. Methods: We prospectively recruited postpartum patients with and without PEC and measured 10-minute continuous mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) with finger plethysmography and transcranial Doppler within 1 week of delivery. We generated polynomial S-curves to derive limits of CA, CA plateaus (defined as slope < 0.15), and mean and minimum slopes between CA limits. We calculated Pearson correlation coefficients (Mx) between normalized MAP and CBVF; Mx > 0.3 indicates high MAP-CBFV correlation, suggesting impaired CA. Results: CA curves were produced from 71 patients (28% normotensive, 42% PEC, 30% siPEC). Group means for MAP were higher in those with PEC and siPEC (normotensive 72 mmHg, PEC 88, siPEC 87 [p=0.001]). CA was preserved in all groups, with Mx nadirs below 0.3 (Figure). The normotensive group demonstrated a wide, flat plateau in the S-curve (minimum slope 0.02). In the PEC group, we observed a narrower and slightly steeper autoregulatory plateau (minimum slope 0.05). The siPEC group displayed the narrowest and steepest plateau (minimum slope 0.15). Conclusion: In conclusion, in our sample of postpartum patients with normotension, PEC and siPEC, we observed a gradient in CA plateau range and slope. Compared with the normotensive group, the PEC and siPEC groups had progressively narrower and steeper CA plateaus, suggesting a more limited CA range and diminished CA efficacy. Future studies should investigate whether sustained MAP outside CA limits contributes to adverse maternal outcomes, particularly in those with siPEC.

Changes in cerebral autoregulation, stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale closure in severe migraine patients.

This study aimed to investigate changes in dynamic cerebral autoregulation (dCA), 20 stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale (PFO) closure in severe migraine patients. Patent foramen ovale severe migraine patients, matched non-PFO severe migraine patients, and healthy controls were included. dCA and autonomic regulation were evaluated in each participant at baseline, and within 48-h and 30 days after closure in PFO migraineurs. A panel of stroke-related blood biomarkers was detected pre-surgically in arterial-and venous blood, and post-surgically in the arterial blood in PFO migraineurs. Forty-five PFO severe migraine patients, 50 non-PFO severe migraine patients, and 50 controls were enrolled. The baseline dCA function of PFO migraineurs was significantly lower than that of non-PFO migraineurs and controls but was rapidly improved with PFO closure, remaining stable at 1-month follow-up. Arterial blood platelet-derived growth factor-BB (PDGF-BB) levels were higher in PFO migraineurs than in controls, which was immediately and significantly reduced after closure. No differences in autonomic regulation were observed among the three groups. Patent foramen ovale closure can improve dCA and alter elevated arterial PDGF-BB levels in migraine patients with PFO, both of which may be related to the preventive effect of PFO closure on stroke occurrence/recurrence.

Multimodal Neuromonitoring in Pediatric Neurocritical Care: Current Perspectives.

Children with neurological illness in the critical care unit are always at higher risk of developing secondary brain injury (SBI). Brain insult can lead to changes in cerebral autoregulation, intracranial pressure (ICP), cerebral oxygenation, and metabolism. This can cause a raised ICP, cerebral ischemia, hypoxia, excitotoxicity, cellular energy failure, and nonconvulsive status epilepticus. Simultaneous and continuous assessment of these parameters will help to improve patient care and neurological outcomes. Even thoughclinical examination and neuroimaging can help in the initial diagnosis of the neurological illness, they may not be helpful in continuous monitoring of cerebralpathophysiological changes. The ideal single neuromonitoring device to detect these real-time changes is currently unavailable. However, a range of invasive and noninvasive monitors are available to monitor these cerebral functional parameters. Invasive monitoring techniques include invasive ICP monitoring, cerebral autoregulation monitoring, brain tissue partial oxygen pressure, and cerebral microdialysis. Noninvasive-monitoring techniques include pupillometry, brain and ocular ultrasonography, near-infraredspectroscopy, and electrophysiological monitoring. Multimodal (MM) neuromonitoring involves incorporating these techniques and tools for the early identification and treatment of primary and secondary brain insults. The utility and feasibility of most of these techniques are well described in adult neurocritical care. Even though the evidence on their usage in children is primarily available in pediatric traumatic brain injury, the emerging data help to further expand their utility in pediatric nontraumatic coma. MM neuromonitoring aims to provide clinical and pathophysiological information to the intensivists to improve their understanding of the child's neurological status and to formulate patient-specific treatment approaches.

Investigation of Cerebral Autoregulation Using Time-Frequency Transformations.

The authors carried out the study of the state of systemic and cerebral hemodynamics in normal conditions and in various neurosurgical pathologies using modern signal processing methods. The results characterize the condition for the mechanisms of cerebral circulation Institute of Computer Science and Control, Higher School of Cyber-Physical Systems and Control regulation, which allows for finding a solution to fundamental and specific clinical problems for the effective treatment of patients with various pathologies. The proposed method is based on the continuous wavelet transform of systemic arterial pressure and blood flow velocity signals in the middle cerebral artery recorded by non-invasive methods of photoplethysmography and transcranial doppler ultrasonography. The study of these signals in real-time in the frequency range of Mayer waves makes it possible to determine the cerebral autoregulation state in certain diseases before and after surgical interventions. The proposed method uses a cross-wavelet spectrum, which helps obtain wavelet coherence and a phase shift between the wavelet coefficients of systemic arterial pressure signals and blood flow velocity in the Mayer wave range. The obtained results enable comparing the proposed method with that based on the short-time Fourier transform. The comparison showed that the proposed method has higher sensitivity to changes in cerebral autoregulation and better localization of changes in time and frequency.

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P=0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P=0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

ED BP Management for Subarachnoid Hemorrhage

To review most recent literature on management of blood pressure in acute aneurysmal subarachnoid hemorrhage (SAH) and provide practice recommendations for the emergency clinician. There is increased risk of aneurysmal rebleeding with systolic blood pressure (SBP) greater than 160mmHg in the acute setting. Avoiding large degrees of blood pressure variability improves clinical outcomes in aneurysmal SAH. Acute lowering of SBP to a range of 140-160mmHg decreases risk of rebleeding while also maintaining cerebral perfusion pressure (CPP) after aneurysmal rupture. Treatment with a short acting antihypertensive agent allows for rapid titration of blood pressure (BP) and reduces BP variability. Elevations in intracranial pressure occur commonly after SAH due to increased intracranial blood volume, cerebral edema, or development of hydrocephalus. Clinicians should be familiar with changes in cerebral autoregulation and effects on CPP when treating elevated BP, in order to mitigate the risk of secondary neurological injury.

Impaired Cerebral Autoregulation in Parkinson's Disease: An Orthostatic Hypotension Analysis.

Orthostatic hypotension (OH) is an early non-motor manifestation of Parkinson's disease (PD). However, the underlying mechanism of hemodynamic changes in patients with PD and OH remains unclear. This study aimed to investigate the dynamic cerebral autoregulation changes in patients with PD with OH. Ninety patients with PD and 20 age- and sex-matched healthy controls (HCs) were recruited. The patients' non-invasive blood pressure (BP) and cerebral blood flow velocity were simultaneously recorded at supine and orthostatic positions during the active standing test (AST). Transfer function analysis was used to determine autoregulatory parameters including gain [i.e., damping effect of dynamic cerebral autoregulation (dCA) on the magnitude of BP oscillation] and phase difference (i.e., the time delay of the cerebral blood flow response to BP). Sixteen patients (17.8%) in the PD population were diagnosed with OH (PD-OH). The AST results were normal for 74 patients (82.2%) (PD-NOR). In the supine position, the PD-OH group had a lower phase degree than the PD-NOR group (50.3 ± 23.4 vs. 72.6 ± 32.2 vs. 68.9 ± 12.1, p = 0.020); however, no significant difference was found upon comparing with the HC group. In the orthostatic position, the normalized gain was significantly higher for the symptomatic OH group than for the asymptomatic OH group and HC group (1.50 ± 0.58 vs. 0.97 ± 0.29 vs. 1.10 ± 0.31, p = 0.019). A symptomatic OH in the PD population indicates an impaired cerebral autoregulation ability in the orthostatic position. Cerebral autoregulation tends to be impaired in the supine position in the OH population.

Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke.

Stroke is currently the second leading cause of death worldwide, and results in significant morbidity, and poorer quality of life for those affected (1). Stroke can be classified under two major sub-types: ischaemic and haemorrhagic. Ischaemic stroke accounts for ~70% of all stroke, and results from arterial occlusion, usually through embolism or small vessel thrombosis (2). Haemorrhagic stroke is a result of arterial rupture in the brain (2). However, the two sub-types frequently co-exist, with similar risk factors (e.g., hypertension), and overlap in pathological mechanisms (3). Although stroke incidence has declined in high-income countries, it remains a prevalent issue amongst low and middle-income countries, disproportionately affecting a younger, working age population in these areas (1). The treatment of acute ischaemic stroke (AIS) has advanced over recent decades. Notably, the advent of both thrombolysis and mechanical thrombectomy has revolutionised the management of AIS, associated with reduced mortality, and improved functional outcome (2, 4, 5). Despite these advances, the management of haemorrhagic stroke has lagged behind, and treatment options are largely confined to reversal of anticoagulants and intensive blood pressure (BP) lowering (2). Conversely, in AIS, the target for BP management remains uncertain, and trials have largely shown equivalence (6, 7), or harm (8), associated with aggressive BP management strategies. To understand the mechanistic implications of BP lowering in AIS, studies have investigated the temporal changes in cerebral autoregulation (CA) following stroke (9). In healthy states, CA maintains a constant cerebral perfusion, despite fluctuations in systemic BP (10). However, the ability of the brain maintain CA may be compromised in the acute phase of stroke, increasing the vulnerability of the brain to hypoperfusion with intensive BP management strategies (11, 12). Conversely, surges in BP during this vulnerable phase may risk haemorrhagic transformation of the infarct, resulting in poorer outcomes (11, 12). Thus, understanding the temporal nature of CA in the acute phase of stroke could provide important mechanistic insights to guide BP management strategies in the clinical setting. A related concept to CA is the physiological mechanism of neurovascular coupling (NVC). Under healthy conditions, neuronal activity is tightly coupled to cerebral blood flow (CBF), such that increases in neuronal activity will result in increases in CBF to ensure the metabolic demands of the brain are met. Intact NVC is integral to maintain optimal cognitive function, and thus may be an important physiological mechanism in the chronic or rehabilitation phase of stroke. The following sections consider the evidence to support a role for CA and NVC as important mechanistic factors in the acute and chronic phases of stroke, and the key clinical and research implications going forward.

Cerebrovascular tone and resistance measures differ between healthy control and patients with acute intracerebral haemorrhage: exploratory analyses from the BREATHE-ICH study

Objective. Cerebral autoregulation impairment in acute neurovascular disease is well described. The recent BREATHE-ICH study demonstrated improvements in dynamic cerebral autoregulation, by hypocapnia generated by hyperventilation, in the acute period following intracranial haemorrhage (ICH). This exploratory analysis of the BREATHE-ICH dataset aims to examine the differences in hypocapnic responses between healthy controls and patients with ICH, and determine whether haemodynamic indices differ between baseline and hypocapnic states. Approach. Acute ICH patients were recruited within 48 h of onset and healthy volunteers were recruited from a university setting. Transcranial Doppler measurements of the middle cerebral artery were obtained at baseline and then a hyperventilation intervention was used to induce hypocapnia. Patients with ICH were then followed up at 10–14 D post-event for repeated measurements. Main results. Data from 43 healthy controls and 12 patients with acute ICH met the criteria for statistical analysis. In both normocapnic and hypocapnic conditions, significantly higher critical closing pressure and resistance area product were observed in patients with ICH. Furthermore, critical closing pressure changes were observed to be sustained at 10–14 D follow up. During both the normocapnic and hypocapnic states, reduced autoregulation index was observed bilaterally in patients with ICH, compared to healthy controls. Significance. Whilst this exploratory analysis was limited by a small, non-age matched sample, significant differences between ICH patients and healthy controls were observed in factors associated with cerebrovascular tone and resistance. These differences suggest underlying cerebral autoregulation changes in ICH, which may play a pivotal role in the morbidity and mortality associated with ICH.

The Effects of Hypocapnia on Brain Tissue Pulsations.

Hypocapnia is known to affect patients with acute stroke and plays a key role in governing cerebral autoregulation. However, the impact of hypocapnia on brain tissue pulsations (BTPs) is relatively unexplored. As BTPs are hypothesised to result from cerebrovascular resistance to the inflow of pulsatile arterial blood, it has also been hypothesised that cerebral autoregulation changes mediated by hypocapnia will alter BTP amplitude. This healthy volunteer study reports measurements of BTPs obtained using transcranial tissue Doppler (TCTD). Thirty participants underwent hyperventilation to induce mild hypocapnia. BTP amplitude, EtCO2, blood pressure, and heart rate were then analysed to explore the impact of hypocapnia on BTP amplitude. Significant changes in BTP amplitude were noted during recovery from hypocapnia, but not during the hyperventilation manoeuvre itself. However, a significant increase in heart rate and pulse pressure and decrease in mean arterial pressure were also observed to accompany hypocapnia, which may have confounded our findings. Whilst further investigation is required, the results of this study provide a starting point for better understanding of the effects of carbon dioxide levels on BTPs. Further research in this area is needed to identify the major physiological drivers of BTPs and quantify their interactions with other aspects of cerebral haemodynamics.

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation. A retrospective cohort study. Tertiary PICU. Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018. Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group. This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.

INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke.

RationaleDisturbances in dynamic cerebral autoregulation after ischemic stroke may have important implications for prognosis. Recent meta-analyses have been hampered by heterogeneity and small samples.Aim and/or hypothesisThe aim of study is to undertake an individual patient data meta-analysis (IPD-MA) of dynamic cerebral autoregulation changes post-ischemic stroke and to determine a predictive model for outcome in ischemic stroke using information combined from dynamic cerebral autoregulation, clinical history, and neuroimaging.Sample size estimatesTo detect a change of 2% between categories in modified Rankin scale requires a sample size of ∼1500 patients with moderate to severe stroke, and a change of 1 in autoregulation index requires a sample size of 45 healthy individuals (powered at 80%, α = 0.05). Pooled estimates of mean and standard deviation derived from this study will be used to inform sample size calculations for adequately powered future dynamic cerebral autoregulation studies in ischemic stroke.Methods and designThis is an IPD-MA as part of an international, multi-center collaboration (INFOMATAS) with three phases. Firstly, univariate analyses will be constructed for primary (modified Rankin scale) and secondary outcomes, with key co-variates and dynamic cerebral autoregulation parameters. Participants clustering from within studies will be accounted for with random effects. Secondly, dynamic cerebral autoregulation variables will be validated for diagnostic and prognostic accuracy in ischemic stroke using summary receiver operating characteristic curve analysis. Finally, the prognostic accuracy will be determined for four different models combining clinical history, neuroimaging, and dynamic cerebral autoregulation parameters.Study outcome(s)The outcomes for this study are to determine the relationship between clinical outcome, dynamic cerebral autoregulation changes, and baseline patient demographics, to determine the diagnostic and prognostic accuracy of dynamic cerebral autoregulation parameters, and to develop a prognostic model using dynamic cerebral autoregulation in ischemic stroke.DiscussionThis is the first international collaboration to use IPD-MA to determine prognostic models of dynamic cerebral autoregulation for patients with ischemic stroke.

Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning.

Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning.

The effect of caffeine loading on cerebral autoregulation in preterm infants.

To evaluate cerebral autoregulation changes in preterm infants receiving a loading dose of caffeine base. In a cohort of 30 preterm infants, we extracted measures of cerebral autoregulation using time and frequency domain techniques to determine the correlation between mean arterial pressure (MAP) and tissue oxygenation index (TOI) signals. These measures included the cerebral oximetry index (COx), cross-correlation and coherence measures, and were extracted prior to caffeine loading and in the 2hours following administration of 10mg/kg caffeine base. We observed acute reductions in time domain correlation measures, including the cerebral oximetry index (linear mixed model coefficient -0.093, standard error 0.04; p=0.028) and the detrended cross-correlation coefficient (ρ5 coefficient -0.13, standard error 0.055; p=0.025). These reductions suggested an acute improvement in cerebral autoregulation. Features from detrended cross-correlation analysis also showed greater discriminative value than other methods in identifying changes prior to and following caffeine administration. We observed a reduced correlation between MAP and TOI from near-infrared spectroscopy following caffeine administration. These findings suggest an acute enhanced capacity for cerebral autoregulation following a loading dose of caffeine in preterm infants, contributing to our understanding of the physiological impact of caffeine therapy.

Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson Correlation–Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility in a Mechanistic Model

Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PRx) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PRx is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (ΔCPP) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PRx; and 3) the determinants of greater ΔCPP. Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, PaCO2, and cerebral blood flow. University critical care integrative modeling and precision physiology research group. None, in silico studies. Simulations in blood pressure, intracranial pressure, PaCO2, and impairment of cerebral autoregulation, with examination of "output" cerebral perfusion pressure versus PRx-plots, optimal cerebral perfusion pressure, and ΔCPP. In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PRx occurs even with intact cerebral autoregulation. In relation to ΔCPP, for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of PaCO2 maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows ΔCPP greater than 10 mm Hg and less than -10 mm Hg, respectively. These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PRx and ΔCPP. PRx and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure.

Cerebral Perfusion and Cerebral Autoregulation after Cardiac Arrest.

Out of hospital cardiac arrest is the leading cause of death in industrialized countries. Recovery of hemodynamics does not necessarily lead to recovery of cerebral perfusion. The neurological injury induced by a circulatory arrest mainly determines the prognosis of patients after cardiac arrest and rates of survival with a favourable neurological outcome are low. This review focuses on the temporal course of cerebral perfusion and changes in cerebral autoregulation after out of hospital cardiac arrest. In the early phase after cardiac arrest, patients have a low cerebral blood flow that gradually restores towards normal values during the first 72 hours after cardiac arrest. Whether modification of the cerebral blood flow after return of spontaneous circulation impacts patient outcome remains to be determined.

Exposure to rotational acceleration over the course of one athletic season is related to impairments in an index of dynamic cerebral autoregulation

ObjectiveTo examine the relationship between cerebral autoregulation changes and impact exposuresthroughout a season of contact sports (hockey or football).DesignProspective Cohort.SettingLaboratory.Participants40 male contact sport athletes (19.4±1.2 years); to date, 3 cross-country athletes (20.0±1.0 years) have completed testing (non-contact controls).InterventionParticipants completed testing prior to the start of their athletic seasons (T1), and again after the conclusion of each season (T2). Blood pressure (BP) oscillations were driven by stand-squat manoeuvres at 0.05 and 0.10 Hz. BP and cerebral blood velocity (CBV) in the middle cerebral artery were indexed non-invasively using finger photoplethysmography and transcranial Doppler ultrasound, respectively. RM-ANOVA independent variables included time (2) and frequency (2).Outcome measuresPoint-estimates ofcoherence(correlation),phase(synchronisation), andgain(amplitude buffer) transfer function analysis metrics were calculated. Biomechanical data on head-impact exposure was estimated in a subset of contact-sport athletes (n=29) using the xPatch (X2 Biosystems), affixed to the right mastoid.ResultsSignificant frequency-time interaction forgainin contact-sport athletes (p=0.048) but not controls (p=0.213). Simple effects analysis revealed a time effect at 0.10 Hz (p<0.001), wherebygainincreased at T2 (95% CI: 0.070–0.229%/%). The ΔgainT2-T1at 0.10 Hz was correlated withestimated cumulativerotational acceleration exposure (r=0.462, p=0.015).ConclusionsThese findings suggest cumulative exposure to the rotational component of sustained head-impactsduring participation in a season of contact-sport (hockey or football) impairs the ability of the cerebrovasculature to buffer BP challenges experienced during everyday activities.Competing interestsNone.

Phase shift between respiratory oscillations in cerebral blood flow velocity and arterial blood pressure

We aim to investigate whether phase shift between respiratory oscillations in cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) is associated with changes in cerebral autoregulation (CA) or reflects the mechano-elastic properties of the cerebrovascular bed. The relationships between respiratory phase shift and slow wave phase shift versus cerebrovascular time constant (the product of cerebrovascular resistance and compliance) and the index of CA (Mx) were analyzed during breathing at 6, 10, and 15 breaths min−1 in 39 volunteers. With increasing respiratory rate the time constant, Mx, and respiratory phase shift decreased, whereas slow wave phase shift increased. The time constant correlated moderately strongly with the respiratory phase shift (R = 0.49, p 0.001) and did not correlate with the slow wave phase shift. The slow wave phase shift was significantly associated with Mx (R = −0.46, p 0.001). The respiratory phase shift more accurately reflects the mechano-elastic properties of the cerebrovascular bed, whereas CA is better described by the slow wave phase shift.

Continuous positive airway pressure might not solve your cerebral autoregulation problem if you have obstructive sleep apnoea.

In an intriguing paper in this issue of The Journal of Physiology, Waltz et al. (2016) tackle a very important question: can we reduce the impairment in cerebral autoregulation that is found in subjects with obstructive sleep apnoea (OSA) through the use of continuous positive airway pressure (CPAP)? It has previously been shown by Nasr et al. (2009) that, under normocapnic conditions, there is a correlation between the severity of OSA and impairment in cerebral autoregulation. OSA is also a risk factor for stroke: the recent review by Torabi-Nami et al. (2015) considers the impact of OSA on both cerebral autoregulation and neurocognition. However, we have only a poor understanding of this area and so this study's attempt to improve cerebral autoregulation is both novel and very welcome. The first interesting finding by Waltz et al. is that during normoxia there is impaired cerebral autoregulation in subjects with severe OSA compared to normal subjects, but that this difference is not found during (isocapnic) hypoxia. Waltz et al. make an interesting suggestion about the relationship between isocapnic hypoxia and sympathetic activity, although this may be very difficult to demonstrate. The importance of hypoxia provides an immediate link to studies performed at altitude where it has been shown that changes in cerebral autoregulation are directly linked to hypoxia (Subudhi et al. 2014). Focusing on hypoxia might well be a promising avenue for future work in this and other contexts. This does of course raise the question of cause and effect. Do alterations in oxygenation level directly cause impaired cerebral autoregulation, at either normocapnia or hypercapnia, and over what time period does this occur? Is OSA the risk factor for both cerebral autoregulation impairment and stroke or is it a risk factor for cerebral autoregulation impairment, which is then a risk factor for stroke? The interactions between these three conditions are of great physiological interest; however, to untangle the different causes and effects is challenging. What treatment would be best is clearly a difficult question to answer. The second result of Waltz et al. does, though, come as a surprise. Treatment of OSA might be thought to be critical to reducing cerebral autoregulation impairment with a possible further effect on stroke risk. However, Waltz et al. show that the treatment of OSA with CPAP does not alter cerebral autoregulation, even after 1 month of therapy. It is not yet clear whether or not this will affect the risk of stroke. After all, although impaired cerebral autoregulation is implicated in a number of pathological conditions, we do not yet know whether it is a cause or a symptom (Payne, 2016). We do need to understand how longer-term CPAP or other treatments might affect this impairment in cerebral autoregulation. Indeed, we should note that there is surprisingly little evidence that cerebral autoregulation can be ‘improved’; this study shows that it is unlikely to be straightforward or quick in the context of OSA. What is needed are longer term studies that look at patients over a prolonged period to see if therapies can improve cerebral autoregulation and/or reduce the risk of stroke. The question is also raised of whether it is possible to identify OSA patients early enough to keep the risks of impaired cerebral autoregulation and/or stroke low. Answers to these questions would help to disentangle the relationship between OSA, cerebral autoregulation and stroke in terms of cause and effect. This is very important in the context of a widespread chronic problem that affects a significant proportion of the population and with the continuing increase in obesity levels is likely to rise further. The risks associated with OSA do need to be more widely known to aid in prevention, even if we are not yet able to provide a cure for the impaired autoregulation. Finally, it is worth noting that the studies by Waltz et al. and Subudhi et al. both used transfer function analysis (with different parameter values), whilst the study by Nasr et al. used the Mx correlation metric. Future studies in this area should build upon recent recommendations on the implementation of transfer function analysis for cerebral autoregulation (Claassen et al. 2016), so that direct comparisons can be made. Modelling will also help to interpret these metrics, so that we can understand what an altered transfer function means and how it relates to the underlying physiology: without this, it is difficult to relate the analysis to the physiology. This combination of techniques should aid in trying to identify alternative suitable future therapies. None declared.

Changes in cerebral autoregulation in the second half of pregnancy and compared to non-pregnant controls.

The mechanism by which pregnancy affects the cerebral circulation is unknown, but it has a central role in the development of neurological complications in preeclampsia, which is believed to be related to impaired autoregulation. We evaluated the cerebral autoregulation in the second half of pregnancy, and compared this with a control group of healthy, fertile non-pregnant women. In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously collected for 7min. The autoregulation index (ARI) was calculated. ARI values of 0 and 9 indicated absent and perfect autoregulation, respectively. ANOVA and Pearson's correlation coefficient were used, with p<0.05 considered significant. A total of 76 pregnant and 18 non-pregnant women were included. The ARI did not change during pregnancy, but pregnant women had a significantly higher ARI than non-pregnant controls (ARI 6.7±0.9 vs. 5.3±1.4, p<0.001). This remained significant after adjusting for EtCO2 (p<0.001). Cerebral autoregulation functionality is enhanced in the second half of pregnancy, when compared to non-pregnant fertile women, even after controlling for EtCO2. The autoregulation does not change with advancing gestational age.