Measurement Of Cerebral Blood Flow Velocity Research Articles

Cerebral blood flow dynamics during cardiac surgery in infants.

In this pilot study, we investigated continuous cerebral blood flow velocity measurements to explore cerebrovascular hemodynamics in infants with congenital heart disease undergoing cardiac surgery. A non-invasive transfontanellar cerebral Doppler monitor (NeoDoppler) was used to monitor 15 infants (aged eight days to nine months) during cardiac surgery with cardiopulmonary bypass. Numerical and visual analyses were conducted to assess trends and events in Doppler measurements together with standard monitoring equipment. The mean flow index, calculated as the moving Pearson correlation between mean arterial pressure and time averaged velocity, was utilized to evaluate dynamic autoregulation. Two levels of impaired autoregulation were defined (Mean flow index >0.3/0.45), and percentage of time above these limits were calculated. High quality recordings were achieved during 90.6% of the monitoring period. There was a significant reduction in time averaged velocity in all periods of cardiopulmonary bypass. All patients showed a high percentage of time with impaired dynamic autoregulation, with Mean flow index >0.3 and 0.45: 73.71% ± 9.06% and 65.16% ± 11.27% respectively. Additionally, the system promptly detected hemodynamic events. Continuous transfontanellar cerebral Doppler monitoring could become an additional tool in enhancing cerebral monitoring in infants during cardiac surgery. This pilot study demonstrates the feasibility of continuous transfontanellar Doppler monitoring of cerebral blood flow velocities during cardiac surgery in infants. It also demonstrates a high proportion of time with impaired cerebral autoregulation during cardiac surgery based on the Mean flow index. Continuous transfontanellar Doppler could become a useful tool to improve cerebral monitoring and provide new pathophysiological insight.

Cerebral blood flow alterations associated with high volume caudal block in infants

BackgroundHigh-volume (1.5 ml kg−1) caudal block in infants results in major reductions of cerebral blood flow velocity (CBFV) and cerebral oxygenation, caused by rostral CSF movement which increases intracranial pressure. The primary aim of this study was to determine the relationship between injected volume and CBFV changes. We hypothesised that this volume–blood flow relationship would have a similar albeit inverted shape to the well-known intracranial pressure volume–pressure curve. MethodsFifteen subjects, age 0–6 months, mean (range) weight 4.9 (2.1–6.4) kg, were studied. A 1.5 ml kg−1 caudal injection of 0.2% ropivacaine was administered in three phases separated by two pauses. Subjects were randomised into five groups, in whom the pauses were implemented at different pre-set proportions of the total injected volume. Middle cerebral artery Doppler ultrasonography was used for CBFV measurements (Vmax, peak CBF velocity; Vmin, lowest CBF velocity; velocity time index). Mean flow velocity, pulsatility index, and resistivity index were calculated, and haemodynamic parameters were recorded. ResultsCBFV parameters decreased in all patients. The most affected parameter, Vmin, was reduced by ∼50% (range 15–68%) compared with baseline. There was a nonlinear relationship between the volume of the first phase injection and the CBFV measurement during the first pause. Across all time points, there was a linear relationship between volume administered and CBFV. Systemic haemodynamic parameters remained stable throughout the study. ConclusionsInjection pauses appear to attenuate adverse CBFV increases during administration of a high-volume caudal block.

Estimation of Cerebral Vasomotor Reactivity with Near Infrared Spectroscopy in Young Adults

Cerebral vasomotor reactivity (CVMR) reflects the ability of cerebral blood vessels to regulate cerebral blood flow (CBF) in response to changes in carbon dioxide (CO2). Transcranial Doppler (TCD) measurement of CBF velocity (CBFV) in the large cerebral arteries has been widely used to evaluate CVMR. However, assessment of CVMR in the cerebral microcirculation using near infrared spectroscopy (NIRS) has not been fully explored. The aims of this study are to characterize CVMR during hypo‐ and hypercapnia using NIRS, and to investigate the relationship between CVMRs assessed by NIRS and TCD. Thirty‐six healthy adults aged 21 to 45 (women: n=23) underwent CBFV and brain tissue oxygenation measurements using both NIRS and TCD during hyperventilation (hypocapnia) and modified CO2 rebreathing (hypercapnia). NIRS was placed on the forehead to measure brain tissue oxygenation index (TOI), TCD was used to measure CBFV in the middle cerebral artery, and capnography was used to measure end‐tidal CO2 (EtCO2). The percentage changes in TOI and CBFV relative to the baseline level in response to changes in EtCO2 were calculated to assess CVMR. Both TOI (−6±2 %) and CBFV (−41±10 %) were reduced during hypocapnia, and elevated during hypercapnia (TOI: 6±2 %, CBFV: 62±20 %) (Fig. 1). CVMR assessed by NIRS was significantly lower than that measured with TCD in both hypocapnia (0.33±0.16 vs. 2.21±0.43 %/mmHg, p< 0.001) and hypercapnia (0.52±0.19 vs. 3.88±1.22 %/mmHg, p< 0.001, Fig. 2). CVMRs assessed by NIRS and TCD were correlated in hypocapnia (r=0.40, p=0.02), but not in hypercapnia (r=0.10, p=0.55). These findings suggest that NIRS measurement of TOI in responses to changes in CO2 likely reflects CVMR of the cerebral microcirculation, which is in difference from that measured in the large cerebral arteries using TCDSupport or Funding InformationThe study was supported by National Institutes of Health (R01AG033106 and R01HL102457). JingShang was supported by the China Scholarship Council.The typical recordings of hyperventilation (hypocapnia) and the modified CO2 rebreathing (hypercapnia).Figure 1Average values of the relative change in CBFV and TOI in 4‐mmHg bins of ΔEtCO2 during hypercapnia induced by CO2 rebreathing. Error bars indicate standard deviation. ΔEtCO2 refers to change in EtCO2 from baseline.Figure 2

Quantification of dynamic cerebral autoregulation and CO2 dynamic vasomotor reactivity impairment in essential hypertension

The study of dynamic cerebral autoregulation (DCA) in essential hypertension has received considerable attention because of its clinical importance. Several studies have examined the dynamic relationship between spontaneous beat-to-beat arterial blood pressure data and contemporaneous cerebral blood flow velocity measurements (obtained via transcranial Doppler at the middle cerebral arteries) in the form of a linear input-output model using transfer function analysis. This analysis is more reliable when the contemporaneous effects of changes in blood CO2 tension are also taken into account, because of the significant effects of CO2 dynamic vasomotor reactivity (DVR) upon cerebral flow. In this article, we extract such input-output predictive models from spontaneous time series hemodynamic data of 24 patients with essential hypertension and 20 normotensive control subjects under resting conditions, using the novel methodology of principal dynamic modes (PDMs) that achieves improved estimation accuracy over previous methods for relatively short and noisy data. The obtained data-based models are subsequently used to compute indexes and markers that quantify DCA and DVR in each subject or patient and therefore can be used to assess the effects of essential hypertension. These model-based DCA and DVR indexes were properly defined to capture the observed effects of DCA and VR and found to be significantly different (P < 0.05) in the hypertensive patients. We also found significant differences between patients and control subjects in the relative contribution of three PDMs to the model output prediction, a finding that offers the prospect of identifying the physiological mechanisms affected by essential hypertension when the PDMs are interpreted in terms of specific physiological mechanisms.NEW & NOTEWORTHY This article presents novel model-based methodology for obtaining diagnostic indexes of dynamic cerebral autoregulation and dynamic vasomotor reactivity in hypertension.

Estimation of cerebral blood flow velocity during breath-hold challenge using artificial neural networks

The effect of untreated Obstructive Sleep Apnoea (OSA) on cerebral haemodynamics and CA impairment is an active field of research interest. A breath-hold challenge is usually used in clinical and research settings to simulate cardiovascular and cerebrovascular changes that mimic OSA events. This work utilises temporal arterial oxygen saturation (SpO2) and photoplethysmography (PPG) signals to estimate the temporal cerebral blood flow velocity (CBFv) waveform. Measurements of CBFv, SpO2, and PPG, were acquired concurrently from volunteers performing two different protocols of breath-hold challenge in the supine position. Past values of the SpO2 and PPG signals were used to estimate the current values of CBFv using different permutations and topologies of supervised learning with shallow artificial neural networks (ANNs). The measurements from one protocol were used to train the ANNs and find the optimum topologies, which in turn were tested using the other protocol. Data collected from 10 normotensive, healthy subjects (four females, age 28.5 ± 6.1 years, Body Mass Index (BMI) 24.0 ± 4.7 kg/m2) were used in this study. The results show that different subjects have different optimum topologies for ANNs, thus indicating the effects of inter-subject variability on ANNs. Successfully reconstructed blind waveforms for the same subject group in the second protocol showed a reasonable accuracy of 60–80% estimation compared to the measured waveforms. HypothesisTemporal waveforms for SpO2 and PPG contain adequate information to estimate the temporal CBFv waveform using ANNs. MethodologyConcurrent measurements of SpO2 and PPG using pulse oximetry from the forehead and CBFv from the middle cerebral artery (MCA) using transcranial Doppler (TCD) were recorded from healthy, normotensive subjects performing a breath-hold challenge. The breath-hold challenge mimicked the cerebrovascular response to apnoea, and was recorded by measuring CBFv in MCA. Two protocols were used, each consisting of five breath-holding manoeuvres and differing in terms of the time between the five successive breath-holds. Using data from one protocol, several permutations of the temporal values of SpO2 and PPG signals were used as inputs to different ANN topologies, in order to train and find the optimum model. The optimum model was evaluated using the data from the other protocol as a blind dataset. ResultsUsing the first protocol for training, optimum ANN configurations were found to be different for each subject, and accuracy of 75–87% was achieved. When these optimum ANN models were tested using the second protocol as a blind dataset, the accuracy achieved was around 60–80%. ConclusionsA novel approach employing temporal records of SpO2 and PPG can be used to estimate the CBFv waveform using ANNs with acceptable accuracy. Increases in the size and diversity of the population dataset and the use of features extracted from SpO2 and PPG signals are needed for generalisation of the method and potential future clinical applications.

A Wearable Transcranial Doppler Ultrasound Phased Array System.

Practical deficiencies related to conventional transcranial Doppler (TCD) sonography have restricted its use and applicability. This work seeks to mitigate several such constraints through the development of a wearable, electronically steered TCD velocimetry system, which enables noninvasive measurement of cerebral blood flow velocity (CBFV) for monitoring applications with limited operator interaction. A highly-compact, discrete prototype system was designed and experimentally validated through flow phantom and preliminary human subject testing. The prototype system incorporates a custom two-dimensional transducer array and multi-channel transceiver electronics, thereby facilitating acoustic beamformation via phased array operation. Electronic steering of acoustic energy enables algorithmic system controls to map Doppler power throughout the tissue volume of interest and localize regions of maximal flow. Multi-focal reception permits dynamic vessel position tracking and simultaneous flow velocimetry over the time-course of monitoring. Experimental flow phantom testing yielded high correlation with concurrent flowmeter recordings across the expected range of physiological flow velocities. Doppler power mapping has been validated in both flow phantom and preliminary human subject testing, resulting in average vessel location mapping times <14 s. Dynamic vessel tracking has been realized in both flow phantom and preliminary human subject testing. A wearable prototype CBFV measurement system capable of autonomous vessel search and tracking has been presented. Although flow phantom and preliminary human validation show promise, further human subject testing is necessary to compare velocimetry data against existing commercial TCD systems. Additional human subject testing must also verify acceptable vessel search and tracking performance under a variety of subject populations and motion dynamics-such as head movement and ambulation.

Relationships between cerebral flow velocities and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury.

This study aimed to determine relationships between cerebral blood flow and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury (TBI). Children with TBI, a Glasgow Coma Score of 8-12, and abnormal brain imaging were enrolled prospectively. Cerebral blood flow velocity (CBFV) was assessed within 24h of trauma and daily thereafter through death, discharge, or hospital day 8, whichever came first. Twelve months from injury, participants completed neurodevelopmental testing. Sixty-nine patients were enrolled. Low flow velocities (< 2 SD below age/gender normal) were found in 6% (n = 4). No patient with a single low CBFV measurement had a good neurologic outcome (Pediatric Glasgow Outcome Scale (GOS-E Peds) ≤ 4)). Normal flow velocities (± 2 SD around age/gender normal) were seen in 43% of participants (n = 30). High flow velocities (> 2 SD above age and gender normal with a Lindegaard ratio (LR) < 3) were identified in 23% of children (n = 16), and vasospasm (> 2 SD above age/gender normal with LR ≥ 3) was identified in 28% (n = 19). Children with good outcomes based on GOS-E Peds scoring were more likely to have had normal flow velocity than other flow patterns. No other differences in neurodevelopmental outcomes were noted. Individual patient responses to TBI in terms of CBFV alterations were heterogeneous. Low flow was uniformly associated with a poor outcome. Patients with good outcomes were more likely to have normal flow. This suggests CBFV may serve as a prognostic indicator in children with TBI. Future studies are needed to determine if aberrant CBFVs are also a therapeutic target.

Extrapyramidal symptoms in schizophrenia: evidence of blunted cerebral hemodynamics during a planning task.

Acute extrapyramidal symptoms (EPS) occur frequently in schizophrenia, mostly caused by antidopaminergic substances. There have been no published reports on the impact of acute EPS on cerebral blood flow (CBF) or related measures. In the following study, we examined schizophrenic patients with and without EPS during a planning task and measurements of CBF velocity. Sixteen patients with chronic schizophrenia and 16 healthy participants performed a planning paradigm during bilateral functional transcranial Doppler sonography of the middle cerebral arteries. Patients with acute EPS showed blunted CBF velocity exclusively during difficult planning tasks, and correlation analyses confirmed that higher EPS scores were associated with reduced adaption of CBF velocity. EPS in schizophrenia are associated with a detrimental effect on CBF velocity. Hypothetically, compromised adaptation of cerebral hemodynamics during difficult, but not during easy planning tasks is one correlate of dysfunctional frontostriatal circuits in schizophrenic patients with EPS.

Reduction of Cerebral Mean Blood Flow Velocity and Oxygenation After High-Volume (1.5 mL kg−1) Caudal Block in Infants

Background We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined ‘the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. Methods Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (CRSO2) were followed during 5 min after the initial caudal injection (1.5 ml kg−1, ropivacaine 0.2%) in 12 infants Results The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation CRSO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. Conclusion High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to ‘the CSF rebound mechanism' for secondary spread of high-volume caudal block.

Reduction of cerebral mean blood flow velocity and oxygenation after high-volume (1.5 ml kg−1) caudal block in infants

We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined 'the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (C(R)SO2) were followed during 5 min after the initial caudal injection (1.5 ml kg(-1), ropivacaine 0.2%) in 12 infants <3 months of age. The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation C(R)SO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to 'the CSF rebound mechanism' for secondary spread of high-volume caudal block.

Neuromonitoring of Neonatal Extracorporeal Membrane Oxygenation Patients Using Serial Cranial Ultrasounds*

Neuromonitoring of Neonatal Extracorporeal Membrane Oxygenation Patients Using Serial Cranial Ultrasounds*

Cerebral Autoregulation of Blood Velocity and Volumetric Flow During Steady-State Changes in Arterial Pressure

The validity of using transcranial Doppler measurement of cerebral blood flow velocity (CBFV) to assess cerebral autoregulation (CA) still is a concern. This study measured CBFV in the middle cerebral artery using transcranial Doppler and volumetric cerebral blood flow (CBF) in the internal carotid artery (ICA) using color-coded duplex ultrasonography to assess CA during steady-state changes in mean arterial pressure (MAP). Twenty-one healthy adults participated. MAP was changed stepwise by intravenous infusion of sodium nitroprusside and phenylephrine. Changes in CBFV, CBF, cerebrovascular resistance (CVR=MAP/CBF), or cerebrovascular resistance index (CVRi=MAP/CBFV) were measured to assess CA by linear regression analysis. The relationship between changes in ICA diameter and MAP was assessed. All values were normalized as percentage changes from baseline. Drug-induced changes in MAP were from -26% to 31%. Changes in CBFV and CVRi in response to MAP were linear, and the regression slopes were similar between middle cerebral artery and ICA. However, CBF in ICA remained unchanged despite large changes in MAP. Consistently, a steeper slope of changes in CVR relative to CVRi was observed (0.991 versus 0.804; P<0.05). The ICA diameter changed inversely in response to MAP (r=-0.418; P<0.05). These findings indicate that CA can be assessed with transcranial Doppler measurements of CBFV and CVRi in middle cerebral artery. However, it is likely to be underestimated when compared with the measurements of CBF and CVR in ICA. The inverse relationship between changes in ICA diameter and MAP suggests that large cerebral arteries are involved in CA.

One-lung ventilation does not result in cerebral desaturation during application of lung protective strategy if normocapnia is maintained

Previously a report has suggested that administration of lung protective strategy for one-lung ventilation(OLV) results in oxygen desaturation of the brain parenchyma. The aim of our work was to confirm that the maintenance of normocapnia during protective OLV strategy results in alteration of cerebral blood fl ow and cerebral oxygen saturation as compared to double-lung ventilation. Data were obtained from 24 patients undergoing thoracic surgery. Cerebral oxygen saturation (rSO2) was continuously monitored by INVOS 5100C Cerebral Oxymeter System along with measurement of cerebral blood fl ow velocity (MCAV) by transcranial Doppler sonography. Arterial blood samples were taken for blood gas analysis in the awake state, in the supine and lateral decubitus position during double-lung ventilation (DLV), and during OLV. When ventilation was changed from DLV to OLV, no significant change was observed in rSO2. A significant decrease of rSO2 was found compared to the value observed during DLV in lateral decubitus at the time point 60 minutes after the start of OLV. No clinically significant changes in the MCAV was observed throughout the course of the thoracic surgical procedure. OLV does not result in clinically relevant decreases in cerebral blood fl ow and cerebral oxygen saturation during application of lung protective ventilation if normocapnia is maintained.

Extracorporeal Membrane Oxygenation and Cerebral Blood Flow Velocity in Children

To determine how extracorporeal membrane oxygenation affects cerebral blood flow velocity and to determine whether specific changes in cerebral blood flow velocity may be associated with neurologic injury. Prospective, observational study. PICU in a tertiary care academic center. Children (age less than or equal to 18 yr) requiring extracorporeal membrane oxygenation support. None. Eighteen patients (age 3.8 ± 7.2 years; venovenous neck, n = 5; venoarterial neck, n = 8; venoarterial chest, n = 5) requiring extracorporeal membrane oxygenation underwent daily transcranial Doppler ultrasound measurements of cerebral blood flow velocity in bilateral middle cerebral arteries. Cerebral blood flow velocity measurements were recorded as a percentage of age and gender normal value. On extracorporeal membrane oxygenation, cerebral blood flow velocities in patients not suffering clinically evident neurologic injury were decreased with systolic flow velocity (Vs) 54% ± 3% predicted and mean flow velocity (Vm) 52% ± 4% predicted. After decannulation, Vs and Vm were higher than while on extracorporeal membrane oxygenation at 73% ± 3% predicted (p = 0.0007 vs. value on extracorporeal membrane oxygenation) and 64% ± 4% predicted (p = 0.01 vs. value on extracorporeal membrane oxygenation).Patients who developed clinically evident cerebral hemorrhage had higher Vs, diastolic flow velocity (Vd), and Vm compared with those who did not: 123% ± 8% predicted, 130% ± 18% predicted, 127% ± 9% predicted (p < compared to values in children not suffering neurological injury). Supranormal flow velocities were noted 2-6 days before clinical recognition of cerebral hemorrhage in all four patients. There were no significant differences in mean arterial blood pressure, circuit flow, or hematocrit between the children who suffered cerebral hemorrhage and those who did not. Partial pressure of carbon dioxide was lower in the group of patients who experienced cerebral hemorrhage than in those who did not (38 ± 2 vs. 44 ± 1 mm Hg, p = 0.03). In children who did not suffer clinically apparent neurologic injury, cerebral blood flow velocities were lower than normal while on extracorporeal membrane oxygenation support and increased after decannulation. However, children who developed cerebral hemorrhage had higher than normal cerebral blood flow velocities noted for days prior to clinical recognition of bleeding. Cerebral blood flow velocity measurement may represent a portable, noninvasive way to predict cerebral complications of extracorporeal membrane oxygenation and deserves further study.

Are Hand-Held TCD Measurements Acceptable for Estimates of CBFv?

Cerebral blood flow velocity (CBFv) and the autoregulation index (ARI) can be reproducibly assessed by noninvasive transcranial Doppler (TCD) methodology using frame-held (FH) ultrasound probes. However, FH techniques may be impractical in severe head injury patients and neonates, where CBFv and ARI estimates are an important component of clinical assessment and management. Therefore, the aim of this study was to investigate the feasibility of an alternative hand-held (HH) approach to CBFv and ARI measurement. In a healthy volunteer population of 11 subjects, mean age 37 years, CBFv and ARI estimates were not significantly different between HH and FH acquisition techniques. In addition, in the hands of a single observer, good reproducibility over two visits, a mean of 6 days apart, was observed: intra-visit coefficient of variation (CV) 5.3% and 15.8%; and intraclass correlation coefficient (ICC) 0.8 and 0.4 for CBFv and ARI, respectively. Further work is required to assess the use of alternative sites to the middle cerebral artery (MCA) for the assessment of CBFv and ARI using HH rather than FH techniques and the applicability of this methodology in patient populations.

Effects of antenatal magnesium sulfate therapy on cerebral and systemic hemodynamics in preterm newborns

To investigate whether antenatal magnesium sulfate (MgSO(4)) exposure has an influence on cerebral blood flow and systemic hemodynamics in preterm infants during the first few days of life. Prospective case-control study. University affiliated referral hospital. A total of 48 women who delivered preterm (30-34 weeks) and their offspring. Mothers and newborns were divided into two groups based on maternal exposure to MgSO(4) (n = 28) or not (n = 20). Cerebral blood flow velocity measurements were obtained from the neonatal anterior cerebral artery and right and left middle cerebral arteries. Neonatal Doppler examinations of the brain circulation, heart rate, systemic blood pressure and echocardiographic assessment of ductus arteriosus shunting during the first week of life. Maternal MgSO(4) had a significant lowering effect on neonatal cerebral blood flow. Peak systolic velocity was significantly lower in anterior cerebral artery and right and left middle cerebral arteries (p = 0.031, 0.027 and 0.039, respectively), as was end-diastolic velocity (p = 0.035, 0.012 and 0.025, respectively) and mean velocity (p = 0.036, 0.024 and 0.003, respectively). The resistance index and relative vascular resistance in the three cerebral arteries showed no significant difference between the two studied groups. Antenatal MgSO(4) exposure before preterm birth has potent systemic vascular effects in the preterm offspring, which is reflected in decreased neonatal cerebral perfusion during the critical first few days of life. This is associated with an increased incidence of patent ductus arteriosus, which may require operative intervention.

Increased phase synchronization and decreased cerebral autoregulation during fainting in the young

Vasovagal syncope may be due to a transient cerebral hypoperfusion that accompanies frequency entrainment between arterial pressure (AP) and cerebral blood flow velocity (CBFV). We hypothesized that cerebral autoregulation fails during fainting; a phase synchronization index (PhSI) between AP and CBFV was used as a nonlinear, nonstationary, time-dependent measurement of cerebral autoregulation. Twelve healthy control subjects and twelve subjects with a history of vasovagal syncope underwent 10-min tilt table testing with the continuous measurement of AP, CBFV, heart rate (HR), end-tidal CO2 (ETCO2), and respiratory frequency. Time intervals were defined to compare physiologically equivalent periods in fainters and control subjects. A PhSI value of 0 corresponds to an absence of phase synchronization and efficient cerebral autoregulation, whereas a PhSI value of 1 corresponds to complete phase synchronization and inefficient cerebral autoregulation. During supine baseline conditions, both control and syncope groups demonstrated similar oscillatory changes in phase, with mean PhSI values of 0.58+/-0.04 and 0.54+/-0.02, respectively. Throughout tilt, control subjects demonstrated similar PhSI values compared with supine conditions. Approximately 2 min before fainting, syncopal subjects demonstrated a sharp decrease in PhSI (0.23+/-0.06), representing efficient cerebral autoregulation. Immediately after this period, PhSI increased sharply, suggesting inefficient cerebral autoregulation, and remained elevated at the time of faint (0.92+/-0.02) and during the early recovery period (0.79+/-0.04) immediately after the return to the supine position. Our data demonstrate rapid, biphasic changes in cerebral autoregulation, which are temporally related to vasovagal syncope. Thus, a sudden period of highly efficient cerebral autoregulation precedes the virtual loss of autoregulation, which continued during and after the faint.

Cerebral vasoreactivity decreases overnight in severe obstructive sleep apnea syndrome: A study of cerebral hemodynamics

Background OSAS has been associated with surrogate markers of atherosclerosis and is a known risk factor for stroke. However, there is limited data on the effects of recurring apneas in severe OSAS on cerebral circulation and their consequences on cerebrovascular reactivity and compliance. Objective To evaluate cerebral blood flow velocity (CBFV) changes and vascular compliance in patients with severe obstructive sleep apnea syndrome (OSAS) using transcranial Doppler sonography (TCD) and cerebral pulse transit time (PTT). Methods Seven patients (1 woman, 6 men, mean age 57.4 years) with severe OSAS underwent polysomnography at the sleep laboratory of the Neurology Department of Innsbruck Medical University. TCD was performed continuously during the whole night using a pulsed wave probe and was co-registered with routine polysomnography. Cerebrovascular reactivity was assessed by calculation of apnea and hypopnea-related CBFV changes. Arterial compliance was characterized by PTT derived from phase difference analysis between ECG and TCD signals. Sleep time was dichotomized into periods with high density of consecutive respiratory events (CRE) vs. periods with low density of consecutive respiratory events (non-CRE). TCD measurements of CBFV showed a regular, undulating pattern with flow minima immediately before apneas or hypopneas and maxima closely after their termination, reciprocally to peripheral O 2 saturation. CBFV reactivity was significantly diminished in CRE compared to non-CRE periods. PTT phase differences were reduced in non-CRE, and even more so in CRE periods, compared to initial wake phases. Conclusion We found severe disturbances of cerebrovascular reactivity in OSAS patients. Our data demonstrate loss of vasoreactivity and increase of arterial stiffness, indicated by CBF hyporeactivity and PTT reduction, especially during CRE periods. These changes are likely to impair cerebral circulation and may be detrimental to the endothelium.

Cerebral Blood Flow Velocity Asymmetry, Neurobehavioral Maturation, and the Cognitive Development of Premature Infants Across the First Two Years

Premature infants are at risk of adverse developmental outcomes even with no demonstrable neurological damage. Neonatal physiological measures that can serve as indicators of later development are therefore important for early evaluation and intervention. We followed the development of 51 low birth weight, premature infants across the first 2 years. Mean systolic cerebral blood flow velocity (CBFV) in the left and right middle cerebral arteries was measured at 37 weeks gestational age, neurobehavioral maturation was assessed with the Neonatal Behavior Assessment Scales (NBAS), and cognitive development was evaluated at 6, 12, and 24 months. Different patterns emerged for CBFV in the right versus left middle cerebral artery. Greater absolute values of right systolic CBFV were related to poorer performance on the habituation and orientation scales of the NBAS, whereas greater left systolic CBFV absolute values were related to better Mental Development Index (MDI) scores at 24 months. Right systolic CBFV asymmetry was related to poor neonatal orientation and low MDI score at 24 months. On the other hand, infants with left systolic CBFV asymmetry showed a more rapid increase in cognitive skills from 12 to 24 months and better cognitive performance at 2 years. Measurement of systolic CBFV in the neonatal period may assist in identifying infants at risk of poor developmental outcome.

Increased cerebral blood flow velocity in children with mild sleep-disordered breathing: a possible association with abnormal neuropsychological function.

SLEEP-DISORDERED BREATHING (SDB) encompasses a spectrum of upper airway obstruction in sleep from simple primary snoring, through the upper airways resistance syndrome, to obstructive sleep apnea (OSA). Primary snoring is estimated to affect on average 10% of preschool children1-3 at a time when adenotonsillar size is maximal relative to the airway.4 Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls.5 Furthermore, a population-based survey identified that habitual snoring was associated with hyperactive and inattentive behavior independent of measures of nocturnal hypoxia.6 Uncertainty persists regarding clinical thresholds for medical or surgical intervention in SDB,7 underlining the need to better understand the pathophysiology of this condition. The causative pathway from SDB to neurocognitive dysfunction in children is poorly understood. Beebe and Gozal8 proposed a model of prefrontal cortical dysfunction resulting from the intermittent hypoxia and sleep fragmentation characteristic of OSA and recommended study of executive function domains in future pediatric research. There is emerging evidence for an executive function deficit in children with SDB.9,10 Systematic review11 and a recent population study12 have supported the hypothesis that intermittent hypoxia may be an important mediator of neurocognitive deficits. The lack of consistent strong correlations between polysomnographic variables and measurable neurocognitive outcomes in studies of childhood SDB9,13 suggests a complex relationship between clinically measurable pathophysiological processes and behavioral abnormality. One possibility is that there are structural and functional adaptations in the brain and its vasculature that obscure any direct effect of exposure to hypoxia or arousals but eventually have deleterious effects. The association between OSA and stroke risk14 in adults has prompted researchers to look for evidence of cerebrovascular disease. Ultrasonography has revealed increased carotid intima-media thickness in adults with OSA.15 Transcranial Doppler (TCD) cerebral blood flow velocity (CBFV)16 measurement in the intracranial arteries17 has demonstrated significant sleep apnea-related fluctuations in CBFV in adult OSA,18 as well as reduced daytime cerebrovascular reactivity to hypercapnia.19 There has been little focus on cerebrovascular function in children with SDB, partly reflecting the need for sedation in neuroimaging of young children and the ethical constraints on using these techniques in research. However, this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature.20-22 Amin et al23 demonstrated that increased mean blood pressure variability in children correlated with polysomnographic indices of SDB severity. Increased systemic blood pressure variability in adult populations is associated with cerebrovascular disease and brain atrophy in adults.24 There are advantages to studying cardiovascular morbidity in children who lack the comorbid atherogenic disease that complicates adult clinical research.25 Furthermore, increased CBFV has been associated with deficits on measures of intelligence26,27 and attention28 in children with sickle cell disease, a condition associated with chronic hypoxemia in childhood, suggesting that it is a marker for vulnerable brain tissue with reduced function. We aimed to determine whether CBFV differed between children with mild SDB, below the conventional threshold for surgical intervention, and age and socioeconomically similar controls. Secondary aims were twofold: (1) to explore a possible relationship between polysomnographic indices of SDB (eg, apnea/hypopnea index and pulse oxygen saturation [Spo2]) and CBFV and (2) to explore the extent to which CBFV is associated with SDB and neuropsychological/behavioral scores.