Impaired Dynamic Cerebral Autoregulation Research Articles

Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome

BackgroundHalf of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption.MethodsA cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption.ResultsForty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index.ConclusionsDysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure.Graphical

Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure.

ObjectivesTo assess whether vertebrobasilar artery ischemia (VBI) affects cortical cerebral blood flow (CBF) regulation. Material and Methods107 consecutive patients (mean age 65 ± 15 years; women 21) with VBI underwent structured stroke care with assessment of dynamic cerebral autoregulation (dCA) in both middle cerebral arteries (MCAs) by transfer function analysis using spontaneous oscillations of blood pressure (BP) and CBF velocity that yields by extraction of phase and gain information in the very low (0.02-0.07 Hz), low (0.07-0.15 Hz) and high frequency (0.15-0.5 Hz) ranges. Additionally, power spectrum analysis of BP and heart rate variability (HRV) was performed. The control group consists of 29 age- and sex-matched healthy persons. ResultsCompared to controls, phase in the VBI patients was significantly reduced and gain increased in the very low frequencies (VLF), in the low (LF), phase was significantly reduced only ipsilaterally. In the high frequencies (HF), phase reduction was only marginally significant. BP power spectral density (PSD) was much higher in the patients than in the controls across all frequencies. In the PSD of heart rate variability the controls but not the patients exhibited a strong peak around 0.11Hz, while the patients, but not the controls, exhibit a strong peak around 0.36 Hz. In regression analysis, patient's phase and gain results were not related to age, sex, arterial hypertension, diabetes mellitus, renal dysfunction, heart failure as indicated by left ventricular ejection fraction, stroke subtype, presence or absence of cerebral small vessel disease. ConclusionPatients with VBI exhibit bilateral cortical autoregulation impairment in association with an autonomic nervous system disbalance. ClinicalTrials.gov IdentifierNCT04611672

Impaired Dynamic Cerebral Autoregulation as a Predictor for Cerebral Hyperperfusion After Carotid Endarterectomy: A Prospective Observational Study

Cerebral hyperperfusion syndrome (CHS) is a severe complication of carotid endarterectomy (CEA). Because cerebral hyperperfusion (CH) reduces the benefits of CEA, it is important to identify patients at high risk of developing CH. We investigated dynamic cerebral autoregulation (dCA) as a potential predictor of CH after CEA. In a prospective observational study of 90 patients, we defined CH as a ≥100% increase in the transcranial Doppler ultrasound-derived mean flow velocity of the middle cerebral artery compared to baseline, with or without clinical manifestations. We examined dCA in the supine position and during squat-stand maneuvers using the transfer function, analyzing phase, gain, and coherence. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the relationships between variables and outcomes. Cerebral hyperperfusion (CH) occurred in 18 patients after CEA. The CH group had a lower ipsilateral phase for both body postures than the non-CH group at very low and low frequencies, respectively (both P<0.01). Postoperative CH was independently associated with the preoperative peak systolic velocity (PSV)sten/PSVdis ratio and the ipsilateral phase in both body postures at a very low frequency. Receiver operating characteristic (ROC) curve analysis showed that the ipsilateral phase had excellent CH predictive accuracy in the supine position and squat-stand maneuvers at a very low frequency (areas under the curve: 0.809 and 0.839, respectively, both P<0.001; cutoff values: 24.7 and 11.7, respectively). The lower ipsilateral phase may serve as a predictor of CH after CEA.

Reduced-order modeling and analysis of dynamic cerebral autoregulation via diffusion maps

Objective. A data-driven technique for parsimonious modeling and analysis of dynamic cerebral autoregulation (DCA) is developed based on the concept of diffusion maps. Specifically, first, a state-space description of DCA dynamics is considered based on arterial blood pressure, cerebral blood flow velocity, and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. We assessed the reliability of the technique by considering healthy individuals and patients with unilateral internal carotid artery (ICA) stenosis or occlusion. We computed the sensitivity of the technique to detect the presumed side-to-side difference in the DCA function of the second group (assuming hypoactive dynamics on the occluded or stenotic side), using McNemar’s chi square test. The results were compared with transfer function analysis (TFA). The performance of the two methods was also compared under the assumption of missing data. Main results. Both diffusion maps and TFA suggested a physiological side-to-side difference in the DCA of ICA stenosis or occlusion patients with a sensitivity of 81% and 71%, respectively. Further, both two methods suggested the difference between the occluded or stenotic side and any two sides of the healthy group. However, the diffusion maps captured additional difference between the unoccluded side and the healthy group, that TFA did not. Furthermore, compared to TFA, diffusion maps exhibited superior performance when subject to missing data. Significance. The eigenvalues ratio derived using the diffusion maps technique can be potentially used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function.

Impaired dynamic cerebral autoregulation: A potential mechanism of orthostatic hypotension and dementia in Parkinson's disease.

BackgroundOrthostatic hypotension (OH) and cognitive impairment are common non-motor symptoms of Parkinson’s disease (PD). This study aimed to investigate whether impaired dynamic cerebral autoregulation (dCA) is associated with OH and Parkinson’s disease dementia (PDD), and analyze the related risk factors in patients with PDD.Materials and methodsWe enrolled 89 patients with PD and 20 age- and sex-matched healthy controls (HCs). Cognition and different cognitive domains were assessed by the Montreal Cognitive Assessment scale. Non-invasive continuous beat-to-beat blood pressure and cerebral blood flow velocity were assessed using a servo-controlled finger plethysmograph and transcranial Doppler, respectively. dCA was examined using supine and orthostatic changes with transfer function analysis to derive the autoregulatory parameters of phase, gain, and coherence. Logistic regression analysis was performed to determine the risk factors for PDD.ResultsWe found that 21 (23.6%) patients with PD had OH. These patients showed worse cognitive performance in specific cognitive tasks, such as language and orientation. The patients with OH also had poorer dCA; the very low frequency (VLF) phase in two different postures was lower than that in patients without OH as well as HCs (both P < 0.05). And the normalized gain in the VLF and low frequency (LF) in standing position was higher in PD patients with and without OH than in HCs. PDD patients also had significantly higher LF normalized gain when standing than patients without dementia (P = 0.015), indicating impaired dCA. LF normalized gain in standing (odds ratio: 3.756, 95% confidence interval: 1.241–11.367) and education were significantly associated with PDD.ConclusionDiminished dCA may represent a potential mechanism for OH and cognitive impairment and low educational level might be a significant factor contributing to the increased risk of PDD.

Cerebral Augmentation Effect Induced by External Counterpulsation Is Not Related to Impaired Dynamic Cerebral Autoregulation in Ischemic Stroke.

Background and PurposeDynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke.MethodsForty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain.ResultsThe cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R2 = 0.108, P = 0.038).ConclusionThe degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation.

Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

Superior Fitting of Arterial Resistance and Compliance Parameters With Genetic Algorithms in Models of Dynamic Cerebral Autoregulation.

The capacity of discriminating between normal and impaired dynamic cerebral autoregulation (dCA), based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF), has considerable clinical relevance. This study aimed to quantify the separate contributions of vascular resistance and compliance as parameters that could reflect myogenic and metabolic mechanisms to dCA. Forty-five subjects were studied under normo and hypercapnic conditions induced by breathing a mixture of 5% carbon dioxide in air. Dynamic cerebrovascular resistance and compliance models with ABP as input and CBFV as output were fitted using Genetic Algorithms to identify parameter values for each subject, and respiratory condition. The efficiency of dCA was assessed from the model's generated CBFV response to an ABP step change, corresponding to an autoregulation index of 5.56 ± 1.57 in normocapnia and 2.38 ± 1.73 in hypercapnia, with an area under the ROC curve (AUC) of 0.9 between both conditions. Vascular compliance increased from 0.75 ± 0.7 ml/mmHg in normocapnia to 5.82 ± 12.0 ml/mmHg during hypercapnia, with an AUC of 0.88. Further work is needed to validate this approach in clinical applications where individualised model parameters could provide relevant diagnostic and prognostic information about dCA impairment.

Impaired dynamic cerebral autoregulation is associated with the severity of neuroimaging features of cerebral small vessel disease.

AimsCerebral small vessel disease (CSVD) is characterized by functional and structural changes in small vessels. We aimed to elucidate the relationship between dynamic cerebral autoregulation (dCA) and neuroimaging characteristics of CSVD.MethodsA case‐control study was performed. Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and spontaneous arterial blood pressure were simultaneously recorded. Transfer function analysis was used to calculate dCA parameters (phase, gain, and the rate of recovery of CBFV [RoRc]). Neuroimaging characteristics of CSVD patients were evaluated, including lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), and the total CSVD burden.ResultsOverall, 113 patients and 83 controls were enrolled. Compared with the control group, the phase at low frequency and the RoRc in CSVD patients were lower, and the gain at very low and low frequencies were higher, indicating bilaterally impaired dCA. Total CSVD burden, WMH (total, periventricular and deep), severe PVS, and lobar CMBs were independently correlated with the phase at low frequency.ConclusionsOur findings suggested that dCA was compromised in CSVD patients, and some specific neuroimaging characteristics (the total CSVD burden, WMH, severe PVS and lobar CMBs) might indicate more severe dCA impairment in CSVD patients.

Experimental high thoracic spinal cord injury impairs the cardiac and cerebrovascular response to orthostatic challenge in rats.

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats (n = 34) were subjected to a sham or T3-SCI surgery and survived into the chronic period postinjury (i.e., 8 wk). Cardiac function was tracked via ultrasound pre- to post-SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not sham animals. In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared with sham (P < 0.034), whereas heart rate was increased in sham but decreased in SCI (P < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP (P < 0.033), implying impaired dynamic cerebral autoregulation. Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation.NEW & NOTEWORTHY This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.

Impaired dynamic cerebral autoregulation in young adults with mild depression.

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18-35years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty-three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression.

Separation of normal and impaired dynamic cerebral autoregulation using deep embedded clustering: a proof-of-concept study

Objective. A previous study has shown that a data-driven approach can significantly improve the discriminative power of transfer function analysis (TFA) used to differentiate between normal and impaired cerebral autoregulation (CA) in two groups of data. The data was collected from both healthy subjects (assumed to have normal CA) and symptomatic patients with severe stenosis (assumed to have impaired CA). However, the sample size of the labeled data was relatively small, owing to the difficulty in data collection. Therefore, in this proof-of-concept study, we investigate the feasibility of using an unsupervised learning model to differentiate between normal and impaired CA on TFA variables without requiring labeled data for learning. Approach. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), which were recorded simultaneously for approximately 10 min, were included from 148 subjects (41 healthy subjects, 31 with mild stenosis, 13 with moderate stenosis, 22 asymptomatic patients with severe stenosis, and 41 symptomatic patients with severe stenosis). Tiecks’ model was used to generate surrogate data with normal and impaired CA. A recently proposed unsupervised learning model was optimized and applied to separate the normal and impaired CA for both the surrogate data and real data. Main results. It achieved 98.9% and 74.1% accuracy for the surrogate and real data, respectively. Significance. To our knowledge, this is the first attempt to employ an unsupervised data-driven approach to assess CA using TFA. This method enables the development of a classifier to determine the status of CA, which is currently lacking.

Joint time-frequency analysis of dynamic cerebral autoregulation using generalized harmonic wavelets

Objective: To develop a joint time-frequency analysis technique based on generalized harmonic wavelets (GHWs) for dynamic cerebral autoregulation (DCA) performance quantification. Approach: We considered two groups of human subjects to develop and validate the method: 55 healthy volunteers and 35 stroke-free subjects with unilateral internal carotid artery stenosis (CAS). We determined the mean and coherence-weighted average of the phase shift (PS) of appropriately defined GHW-based transfer functions, based on data points over the joint time-frequency domain. We compared agreement of standard transfer function analysis (TFA) and GHW analyses in healthy subjects using Bland-Altman plots. We assessed sensitivity of each metric to detect the presumed side-to-side difference in DCA function in CAS subjects (with decreased PS on the occluded side), using McNemar’s chi square test to compare each metric to the standard TFA approach. An alternative Morlet wavelet-based approach was also considered. Main results: The GHW and TFA methods exhibited strong agreement in healthy subjects. Among CAS subjects, GHW metrics outperformed TFA and Morlet wavelet-based approaches in identifying expected side-to-side differences: TFA sensitivity was 40.0% (95%CI 23.9–57.9), Morlet 60.0% (95%CI 42.1–76.1), and GHW >70% for both metrics (GHW mean PS sensitivity 74.3, 95%CI 56.7–87.5, p = 0.0027 versus TFA; GHW coherence-weighted PS sensitivity 71.4, 95%CI 53.7–85.4, p = 0.0009 versus TFA). Significance: In comparison to the widely used stationary Fourier transform-based TFA and to Morlet wavelet-based analysis, our data suggest that the GHW-based analysis performs better in identifying DCA asymmetry between the two cerebral hemispheres in patients with high grade unilateral carotid stenosis. Our method may provide enhanced confidence in employing DCA metrics as a sensitive diagnostic tool for detecting impaired DCA function in a variety of pathological settings.

An Investigation of Dynamic Cerebral Autoregulation in Adolescent Concussion.

Although cerebrovascular impairments are believed to contribute to concussion symptoms, little information exists regarding brain vasomotor control in adolescent concussion, particularly autoregulatory control that forms a fundamental response mechanism during changes in blood pressure. This research tested the hypothesis that adolescent concussion is marked by impaired dynamic cerebral autoregulation. Nineteen concussed adolescents (15 ± 2 yr, 13 females) and 18 healthy controls (15 ± 2 yr, 9 females) completed two sit-to-stand trials. Brachial artery blood pressure and cerebral blood flow velocity in the right middle cerebral artery were measured continuously. Dynamic rate of regulation was calculated as the rate of change in cerebrovascular resistance relative to the change in arterial blood pressure. The concussed adolescents were followed through their rehabilitation for up to 12 wk. At the first visit, the concussed adolescents demonstrated reduced rate of regulation compared with the healthy controls (0.12 ± 0.04 vs 0.19 ± 0.06 s, P ≤ 0.001). At the concussed adolescents final visit, after symptom resolution, the rate of regulation improved to levels that were not different from the healthy controls (n = 9; 0.15 ± 0.08 vs 0.19 ± 0.06 s, P= 0.06). Two distinct groups were observed at the final visit with some individuals experiencing recovery of dynamic cerebral autoregulation and others showing no marked change from the initial visit. Adolescents demonstrate an impairment in dynamic cerebral autoregulation after concussion that improves along with clinical symptoms in some individuals and remains impaired in others despite symptom resolution.

Dynamic cerebral autoregulation during cognitive task: effect of hypoxia.

Changes in cerebral blood flow (CBF) subsequent to alterations in the partial pressures of oxygen and carbon dioxide can modify dynamic cerebral autoregulation (CA). While cognitive activity increases CBF, the extent to which it impacts CA remains to be established. In the present study we determined whether dynamic CA would decrease during a cognitive task and whether hypoxia would further compound impairment. Fourteen young healthy subjects performed a simple Go/No-go task during normoxia and hypoxia (inspired O2 fraction = 12%), and the corresponding relationship between mean arterial pressure (MAP) and mean middle cerebral artery blood velocity (MCA Vmean) was examined. Dynamic CA and steady-state changes in MCA V in relation to changes in arterial pressure were evaluated with transfer function analysis. While MCA Vmean increased during the cognitive activity ( P < 0.001), hypoxia did not cause any additional changes ( P = 0.804 vs. normoxia). Cognitive performance was also unaffected by hypoxia (reaction time, P = 0.712; error, P = 0.653). A decrease in the very low- and low-frequency phase shift (VLF and LF; P = 0.021 and P = 0.01) and an increase in LF gain were observed ( P = 0.037) during cognitive activity, implying impaired dynamic CA. While hypoxia also increased VLF gain ( P < 0.001), it failed to cause any additional modifications in dynamic CA. Collectively, our findings suggest that dynamic CA is impaired during cognitive activity independent of altered systemic O2 availability, although we acknowledge the interpretive complications associated with additional competing, albeit undefined, inputs that could potentially distort the MAP-MCA Vmean relationship. NEW & NOTEWORTHY During normoxia, cognitive activity while increasing cerebral perfusion was shown to attenuate dynamic cerebral autoregulation (CA) yet failed to alter reaction time, thereby questioning its functional significance. No further changes were observed during hypoxia, suggesting that impaired dynamic CA occurs independently of altered systemic O2 availability. However, impaired dynamic CA may reflect a technical artifact, given the confounding influence of additional inputs that could potentially distort the mean arterial pressure-mean middle cerebral artery blood velocity relationship.

Non-linear models for the detection of impaired cerebral blood flow autoregulation.

The ability to discriminate between normal and impaired dynamic cerebral autoregulation (CA), based on measurements of spontaneous fluctuations in arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable clinical relevance. We studied 45 normal subjects at rest and under hypercapnia induced by breathing a mixture of carbon dioxide and air. Non-linear models with BP as input and CBF velocity (CBFV) as output, were implemented with support vector machines (SVM) using separate recordings for learning and validation. Dynamic SVM implementations used either moving average or autoregressive structures. The efficiency of dynamic CA was estimated from the model’s derived CBFV response to a step change in BP as an autoregulation index for both linear and non-linear models. Non-linear models with recurrences (autoregressive) showed the best results, with CA indexes of 5.9 ± 1.5 in normocapnia, and 2.5 ± 1.2 for hypercapnia with an area under the receiver-operator curve of 0.955. The high performance achieved by non-linear SVM models to detect deterioration of dynamic CA should encourage further assessment of its applicability to clinical conditions where CA might be impaired.

Predictive Value of Dynamic Cerebral Autoregulation Assessment in Surgical Management of Patients with High-Grade Carotid Artery Stenosis.

Dynamic cerebral autoregulation (DCA) capacity along with the degree of internal carotid artery (ICA) stenosis and characteristics of the plaque can also play an important role in selection of appropriate treatment strategy. This study aims to classify the patients with severe ICA stenosis according to preoperative state of DCA and to assess its dynamics after surgery. Thirty-five patients with severe ICA stenosis having different clinical type of disease underwent reconstructive surgery. DCA was assessed with transfer function analysis (TFA) by calculating phase shift (PS) between Mayer waves of blood flow velocity (BFV) and blood pressure (BP) before and after operation. In 18 cases, regardless of clinical type, preoperative PS on ipsilateral side was within the normal range and did not change considerably after surgery. In other 17 cases preoperative PS was reliably lower both in patients with symptomatic and asymptomatic stenosis. Surgical reconstruction led to restoration of impaired DCA evidenced by significant increase of PS in postoperative period. Our data suggest that regardless clinical type of disease various state of DCA may be present in patients with severe ICA stenosis. This finding can contribute to establishing the optimal treatment strategy, and first of all for asymptomatic patients. Patients with compromised DCA should be considered as ones with higher risk of stroke and first candidates for reconstructive surgery.

Impaired Dynamic Cerebral Autoregulation to Postural Stress Following Concussive Injuries in Adolescents

Concussions disproportionately affect adolescents and ongoing maturation places this population at increased risk for prolonged recovery and long‐term impairments in neurologic functioning. Although cerebrovascular impairments are believed to contribute to concussion symptoms and recovery, little information exists regarding brain vasomotor control in adolescent concussion, particularly during rapid changes in blood pressure that demand a dynamic cerebral autoregulatory response. The current investigation tested the hypothesis that adolescent concussion is marked by impaired dynamic cerebral autoregulation (CA). Twenty‐two adolescents diagnosed with a concussion (CONC; 13 females; 15 ± 1 years; 26 ± 20 days post‐injury, SCAT3 symptom score = 12 ± 6) and twenty‐seven healthy controls (CTRL; 15 females; 14 ± 2 years; SCAT3 symptom score = 6 ± 4) completed two repeated sit‐to‐stand trials. CONC were followed through their rehabilitation for up to 12‐weeks. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), end‐tidal carbon dioxide partial pressure (PetCO2), and heart rate (HR) were measured continuously with finger photoplethysmography (Finapres Medical Systems BV), transcranial Doppler ultrasound (Multigon Industries), a gas analyzer (AD Instruments), and a standard 3‐lead electrocardiogram (ECG), respectively. Furthermore, cardiac output (CO) was provided via the Model flow algorithm and cerebrovascular resistance (CVR) was calculated. The rate of the drop in CVR relative to the change in ABP provided the rate of regulation (RoR). The drop in ABP with standing was similar between CONC and CTRL (25 ± 8 vs. 24 ± 7 mmHg; p = 0.62) although the time to ABP nadir was longer in CONC compared with CTRL (7.2 ± 1.1 vs. 6.1 ± 1.3 sec; p = 0.002). Similarly, time to CBFV nadir was longer in CONC compared with CTRL (5.9 ± 1.4 vs. 4.4 ± 2.0 sec; p = 0.003). Compared to CTRL, RoR was reduced in CONC at study entry (0.21 ± 0.06 vs. 0.16 ± 0.04 sec−1; p = 0.005). However, at the time of CONC final visit (SCAT3 symptom score = 4 ± 5), RoR improved to levels similar to CTRL (0.20 ± 0.08 vs. 0.21 ± 0.06 sec−1; p = 0.55). During sitting and standing, CONC and CTRL had similar PetCO2. The change in heart rate with standing was similar between CONC and CTRL (30 ± 6 vs. 26 ± 9 bpm; p = 0.09) although the time to peak HR was longer in CONC compared with CTRL (10.8 ± 2.5 vs. 9.4 ± 2.0 sec; p = 0.004). Furthermore, a similar increase in CO was witnessed with standing in CONC and CTRL (1.4 ± 1.6 vs. 1.7 ± 0.7 L/min; p = 0.28). Impairments in dynamic CA are evident in adolescents following a concussive injury which recover in accordance with clinical symptoms. Therefore, RoR may aid decisions regarding diagnosis, rehabilitation, and recovery of adolescent concussion.Support or Funding InformationResearch supported by the Children's Health Research Institute (London, Canada).

Cerebral blood flow autoregulation in ischemic heart failure.

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

Effects of short-term mechanical hyperventilation on cerebral blood flow and dynamic cerebral autoregulation in critically ill patients with sepsis

In sepsis, higher PaCO2 levels are associated with impaired dynamic cerebral autoregulation (dCA), which may expose the brain to hypo- and hyperperfusion during acute fluctuations in blood pressure. We hypothesised that short-term mechanical hyperventilation would dCA in critically ill patients with sepsis. Seven mechanically ventilated septic patients were included. We assessed dCA before and after 30 min of mechanical hyperventilation. Transfer function analysis of spontaneous oscillations in transcranial Doppler-based middle cerebral artery blood flow velocity (MCAv) and invasive mean arterial blood pressure was used to assess dCA. Mechanical enhance hyperventilation reduced the median PaCO2 from 5.3 (IQR, 5.0–6.5) to 4.7 (IQR, 4.2–5.1) kPa (p < 0.05). This was associated with a reduction in the median MCAv from 57 (IQR, 33–68) to 32 (IQR, 21–40) cm sec−1 (p < 0.05). Apart from a small increase in gain in the low frequency range (2.32 [IQR 1.80–2.41] vs. 2.59 (2.40–4.64) cm mmHg−1 sec−1; p < 0.05), this was not associated with any enhancement in dCA. In conclusion, cerebral CO2 vasoreactivity was found to be preserved in septic patients; nevertheless, and in contrast to our working hypothesis, short-term mechanical hyperventilation did not enhance dCA.