Cerebral Flow Velocity Research Articles

A New Monitor of Pressure Autoregulation: What Does It Add?

Cerebrovascular pressure autoregulation is a vital, protective mechanism that constrains cerebral blood flow during changes in arterial blood pressure. Pressure autoregulation is known to fail during profound hypotension, and the so-called lower limit of autoregulation (LLA) is diverse for different subjects. 1 The measurement and monitoring of pressure autoregulation is specifically useful to discriminate safe from harmful blood pressure: when arterial blood pressure is within range to render normal pressure autoregulation measurements, the brain is protected; when arterial blood pressure is too low and pressure autoregulation measurements show impairment, the brain is vulnerable. 2,3 In the present study, Hori et al. 4 present a novel method to measure pressure autoregulation using the Ornim UT-light technology (Ornim, Inc., Kfar Saba, Israel), rendered as a cerebral flow velocity index (CFVx). The UT-light method is proprietary and quantifies relative tissue blood movement from the Doppler shift of near-infrared light caused by red cells in motion. It is an uncalibrated, surrogate measure of cerebral blood flow. How does this measure autoregulation? How is this to be evaluated and validated? Not fewer than 15 metrics purported to measure autoregulation have infused the medical literature within hundreds of manuscripts in the past 2 decades. 5 It would be instructive to know how these metrics are related and to consider the evidentiary burden required to deploy them clinically. Pressure autoregulation is distinct from, but often confused with, other servomechanisms that contribute to the homeostasis of cerebral blood flow. Examples include neurovascular coupling (or metabolic autoregulation), which rapidly matches cerebral blood flow to local metabolic demands 6 ; the systemic vasoconstrictive response to shock, which diverts cardiac output from sympathetic, angiotensin, and vasopressin-reactive vascular beds to the brain and heart, which respond differently to these neurohormonal cues 7–9 ; and cerebral vasodilatory and constrictive responses caused by changes in arterial carbon dioxide. 10 Each of these operates at the same point of action, that is to affect a change or to prevent a change in cerebral blood flow. The pressure autoregulation mechanism can be measured even when cerebral blood flow is influenced by the other mechanisms listed if the metric used is attuned to the proper frequency. Three components are needed to construct a metric of autoregulation:

Reference values for cerebral blood flow velocities in critically ill, sedated children.

Transcranial Doppler ultrasound (TCD) is increasingly being used in the pediatric intensive care unit to assess cerebral hemodynamics during critical illness. However, no normative data in this patient population have been published to date. Therefore, we aimed to describe the anterior and posterior cerebral blood flow velocities in critically ill children undergoing mechanical ventilation and sedation. A prospective, observational cohort study was performed. Children with known or suspected acute or chronic neurologic conditions were excluded. Participants underwent TCD measurement of middle cerebral and basilar artery flow velocities. One hundred and forty children newborn to 17years of age were enrolled. Measured values were lower in this cohort of children than the previously published cerebral flow velocities of normal, healthy children. Cerebral blood flow velocities of the basal cerebral arteries in critically ill, mechanically ventilated, sedated children are lower than in healthy children of the same age and gender published in previous studies. As such, the cerebral blood flow velocity (CBFV) values reported here may serve as a more accurate reference point when using TCD as a clinical tool to diagnose CBFV abnormalities and guide therapy in this patient population.

Neuroimaging and the preterm infant brain

In this issue of Journal of Pediatric Neuroradiology, Leijser et al. [1] explore the correlation between morphology of the intracranial vasculature and cerebral blood flow velocity, non-invasively respectively assessed using magnetic resonance angiography (MRA) and Doppler ultrasound in term-born infants and preterm infants at term equivalent age. Preterm birth is increasing and the rate of neurodevelopmental impairment, including motor and neurocognitive impairment, remains high in survivors [2]. Clinicians routinely need to provide parents and caregivers with prognostic information for these vulnerable newborns. Prediction of cognitive outcome early in life is of paramount importance to plan targeted cognitive intervention and neurorehabilitation. Non-invasive imaging techniques, in particular ultrasound, have been widely used in clinical practice to provide prognostic information. Magnetic resonance imaging (MRI) is less widely available and more expensive; however, the use of 3 Tesla field strength scanners and parallel imaging technique has significantly decreased exam duration and the need for sedation in the newborn population. Knowledge of the prognostic value of cranial ultrasound and MRI relies on a relatively small number of studies [3]. While normal ultrasound or MRI studies predict a low risk of future motor impairment in preterm infants, the prognostic implications of many abnormal findings, as well as of morphological and functional differences between term and preterm infants detected by ultrasound and MRI are not well understood. Therefore, there is a strong need to better comprehend the prognostic correlates of neuroimaging findings in preterm newborns. Previous neuroimaging studies have identified differences in cortical folding, gray matter volume, and white matter abnormalities between preterm and term born infants [4–7]. Dr. Leijser and her group focus their attention on the functional and morphological differences of the intracranial vasculature in these two groups of infants in the absence of overt brain pathology. After investigating the effects of preterm delivery on neonatal cerebral vasculature using MRA [8], the authors examine the correlation between vascular morphology assessed using MRA and functional metrics obtained using Doppler ultrasound [1]. This work is important for several reasons. First, a functional and morphological evaluation of the developing intracranial vasculature is only feasible using non-invasive imaging techniques, because post-mortem assessment of the brain cannot assess vascular geometry and functionality. Alterations in cerebral blood flow play a crucial role in the development of hypoxic-ischemic injury in preterm and term newborns and the cerebral flood flow velocity data provided in this paper may serve as a reference for many potential applications in research and clinical practice. Understanding patterns of cerebrovascular morphology and cerebral blood flow velocity in preterm neonates and their correlation with neurological outcome could be proven useful in the future to identify infants at risk of developmental and cognitive deficit. *Address for correspondence: Maria Vittoria Spampinato, Department of Radiology and Radiological Sciences, Medical University of South Carolina, 96 Jonathan Lucas Street, MSC 323, Charleston, SC, USA. Tel.: +1 843 792 0209; Fax: +1 843 792 1705; E-mail: spampin@ musc.edu. Journal of Pediatric Neuroradiology 2 (2012) 69–70 DOI 10.3233/PNR-2012-012 IOS Press 69

Cerebral Blood Flow Regulation is Affected Throughout the Menstrual Cycle

The aim of our study was to determine if cerebral blood flow regulation in women is affected by the menstrual cycle, which could lend insight into whether hormone levels in women may affect their susceptibility to cerebrovascular injury. Four young (mean age 22 ±1.4 years) healthy women were tested at three time points; during menstruation (M), late follicular (F), and the luteal phase (L) of the menstrual cycle. Each visit consisted of a cerebrovascular reactivity test and a sit-to-stand test. Beat-by-beat blood pressure, ECG, PETCO2, and transcranial doppler sonography of the middle and anterior cerebral artery were taken for each subject. During the F phase compared to the other phases, average heart rate was significantly lower (M: 76±1; F: 69±1; L: 73±2 bpm, P=0.026), mean cerebral flow velocity while standing was significantly lower (M: 100±2; F: 94±1; L: 99±1 %, P=0.003), and cerebrovascular resistance increased while standing (M: 0.03±0.01; F: 0.06±0.02; L: 0.01±0.06 mmHg/%, P=0.049). In contrast, blood pressure changes during standing were unaffected by cycle phase. Examining cerebral autoregulation, autoregulatory index values were higher during the menstrual phase with a tendency for decreasing scores during F and L in the MCA (M: 4.4±0.6; F: 3.4±0.4; L: 2.0±0.6, P=0.032) but not the ACA (M: 4.2±0.6; F: 3.4±0.4; L: 2.0±0.5, P=NS). PETCO2 values might account for some of these changes but this needs more exploration. While more data is necessary to fully interpret the findings, our results indicate that phase of the cycle may affect cerebrovascular tone and ability to maintain cerebral blood flow when upright. In addition, the impairment in autoregulatory response during the luteal phase may be related to increasing progesterone levels.

Middle cerebral arterial flow changes on transcranial color and spectral Doppler sonography in patients with increased intracranial pressure.

Intracranial pressure usually increases after severe brain injury. However, a method for noninvasive evaluation of intracranial pressure is still lacking. The purpose of this study was to explore the potential role of transcranial color Doppler sonography in assessing intracranial pressure by observing the middle cerebral artery blood flow parameters in patients with increased intracranial pressure of varying etiology. The hemodynamic changes in the middle cerebral artery in patients with varying degrees of increased intracranial pressure were investigated by transcranial color Doppler sonography in 93 patients who had emergency surgery for brain injury. Middle cerebral artery Doppler flow spectra changed regularly as intracranial pressure increased. The pulsatility index (PI) and resistive index (RI) had a significantly positive correlation with intracranial pressure (r = 0.90 and 0.89, respectively; P< .001), whereas the middle cerebral artery diastolic velocity showed a significant negative correlation with intracranial pressure (r = -0.52; P< .01). A receiver operating characteristic curve showed that the RI and PI cutoff values were 0.705 and 1.335, respectively, for predicting increased intracranial pressure, with sensitivity of 0.885 and specificity of 0.970. In addition to the PI and RI, middle cerebral artery diastolic flow velocity measurement by transcranial color Doppler sonography may also be a useful variable for evaluating intracranial pressure in patients with acute brain injury.

Increases in sympathetic activity during cold pressor test does not cause cerebral vasoconstriction (1183.8)

The objective of this work was to determine whether increased sympathetic activity results in cerebral vasoconstriction. To assess the role of sympathetic activity, 10 healthy individuals participated in a cold pressor test in which they immersed their hand in ice cold water for 57.5±16.6 seconds. We continuously monitored beat‐by‐beat blood pressure, cerebral flow velocity in the middle (MCA) and anterior cerebral artery (ACA), common carotid artery (CCA) flow and end tidal CO2. As expected the cold pressor test produced a significant increase in sympathetic outflow causing mean arterial pressure to increase from 104±7 to 117±10 mmHg, P=0.005. In contrast CCA diameter did not change (6.7±0.2 to 6.7±0.2 mm), and flow increased slightly but non‐significantly (+6.0±6.2%). Similarly, we saw slight increases in flow velocity in the MCA (+3.0±6.7 %) and ACA (+7.5±4.9 %) but non‐significant. End tidal CO2 values did not change from baseline to end of cold pressor (40.3±1.1 vs 40.0±1.2 mmHg). In contrast, cerebrovascular resistance increased in the MCA (+9.7±5.7 %) and ACA (+11.5±5.0 %), likely due to the cerebral autoregulatory response to the increase mean arterial pressure. These data demonstrate that increased sympathetic activity was associated with a slight increase in common carotid, middle and anterior cerebral flow, all ~5%, indicating there was no cerebral vasoconstriction to reduce flow. The increase in cerebral flow was likely in response to increased neural activation due to pain and sensory inputs. Our finding that CCA flow increased the same amount as MCA and ACA supports the concept that sympathetic activity does not cause vasoconstriction at either the arteriolar or MCA level.Grant Funding Source: Supported by Dept of Veteran Affairs and NIH R21 DC009900

Post‐traumatic stress disorder does not affect cerebrovascular reactivity (1068.18)

Post‐traumatic stress disorder (PTSD) is a chronic psychiatric disorder, with symptoms of hyperarousal, which can alter the biological stress response. Our objective was to determine whether possible increased sympathetic tone in veterans with PTSD affected cerebrovascular function due to altered autonomic control. To assess this we measured sympathetic activity from low frequency blood pressure (BP) and heart rate (HR) variability and cerebrovascular function during hyper/hypocapnia using transcranial Doppler in 29 Veterans (10 with PTSD). There was no difference in BP or cerebral flow velocity in the middle (MCA: 51±5 vs 53±3 cm/s) or anterior cerebral artery (ACA: 48±7 vs 49±3 cm/s). Examination of autonomic indicators found no difference in low frequency power in HR or BP variance. Similarly PTSD status did not affect cerebrovascular reactivity for either the MCA (2.2±0.1 vs 2.2±0.1 %/mmHg) or ACA (2.0±0.2 vs 2.3±0.2 %/mmHg). Surprisingly, regardless of PTSD status, all veterans had a blunted response to hypercapnia (MCA: 1.3±0.2; ACA: 1.3±0.2 %/mmHg) compared to hypocapnia (MCA: 2.8±0.2; ACA: 2.7±0.2 %/mmHg). In contrast to our hypothesis, we did not find increased sympathetic activity in PTSD or impaired cerebral blood flow regulation. One explanation for this finding is that our PTSD sample was not of the hyperarousal type. Since we anticipate that hyperarousal is associated with increased sympathetic outflow, if our subjects mainly had dissociative type PTSD, there could be no difference in autonomic function. The finding of impaired vasodilation to CO2 but not vasoconstriction in all Veterans may indicate impaired cerebral vascular function.Grant Funding Source: Supported by NIH R21DC009900 (Serrador) as well as the WRIISC and the Office of VA Public Health

Therapeutic plasma exchange and intravenous immunoglobulin as primary therapy for D alloimmunization in pregnancy precludes the need for intrauterine transfusion

Maternal D alloimmunization detected in early gestation requires aggressive intervention to prevent severe fetal anemia. An intrauterine transfusion (IUT) is indicated to prevent fetal death once severe fetal anemia has been detected, but is not without risk. Protocols combining therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG) have been described, but they usually bridge to IUT. We describe a 27-year-old G4, P0-1-2-0 Caucasian female with a history of ruptured ectopic pregnancy presented at 12 weeks' gestation with a very high anti-D titer (2048). TPE was performed on that week and twice more in the following week, with a fourth final exchange during Week 14. A loading dose of IVIG (2 g/kg) was administered over 2 days after the third TPE and then 1 g/kg per week until Week 28 (total, 14 doses). The antibody titer decreased to 256 by the beginning of 15 weeks' gestation and remained stable at that level for the remainder of the pregnancy. Doppler ultrasonographic measurements of the fetal middle cerebral artery peak flow velocity performed throughout gestation showed no evidence of fetal anemia. A healthy male infant was delivered at 37 weeks' gestation with mild immune-mediated hemolysis. The infant underwent successful treatment with an IVIG dose of 750 mg/kg and a red blood cell exchange. Our unique TPE-IVIG protocol was successful at preventing the onset of severe fetal anemia in a patient with high titer anti-D. Since IUT may be fatal, our approach offers a safer and less-invasive treatment regime that can adequately sustain a fetus until term.

Impaired Cerebral Perfusion After Bilateral Pulmonary Arterial Banding in Patients With Hypoplastic Left Heart Syndrome

Recent studies have shown that bilateral pulmonary artery banding (bil-PAB) for hypoplastic left heart syndrome (HLHS) is not superior to the neonatal Norwood procedure in terms of overall mortality and neurodevelopmental outcome. We tested our hypothesis that bil-PAB is associated with negative hemodynamic effects on cerebral circulation. The acute effects of bil-PAB on cerebral circulation were assessed by serial measurements of cerebral Doppler flow velocities in 9 patients immediately after bil-PAB. To evaluate the chronic effects of bil-PAB on cerebral perfusion, the oxygen demand-supply balance between the lower and upper body, designated as oxygenation balance index (OBI), was calculated in another set of 13 patients using oxymetric data before stage II palliation. Data were compared with those of 13 patients who underwent the Norwood operation. The preoperative cerebral blood flow velocities of the patients were at the lowest levels reported in healthy neonates. Bil-PAB did not increase cerebral blood flow in the first week after the procedure. OBI was significantly lower in patients treated with bil-PAB (p < 0.005) than in those treated with the Norwood procedure, indicating impaired cerebral perfusion after bil-PAB. Importantly, the OBI in the bil-PAB group, but not in the Norwood group, significantly decreased with time after the procedure. In addition, cerebral perfusion was more vulnerable to the changes in pulmonary and systemic blood flow in the bil-PAB group than in the Norwood group. A hybrid approach followed by comprehensive stage II palliation may not be an optimal strategy for HLHS and should be evaluated further.

Effects of Race on Dynamic Cerebral Autoregulation in Elderly People

Race is known to affect cardiovascular dynamics, but no research has examined cerebrovascular dynamics. Therefore, we retrospectively examined measures of cerebral autoregulation in a group of elderly individuals recruited into the population‐based MOBILIZE Boston Study.Of 765 community‐dwelling volunteers that were recruited for the MOBILIZE Boston study, cerebral flow velocity measures were obtained on 451 individuals (78±5 yrs) of which self reported race was African American ‐ AA (43), White (385) and Other (23). Cerebral flow velocity (TCD), beat‐by‐beat blood pressure (Finapres) and end‐tidal CO2 (capnography) were measured during a sit to stand maneuver and while seated.Race was associated with significant differences in Phase in both the 0.04–0.07 Hz range (AA: 28±41°, White: 46±34°, Other: 55±28°, p&lt;0.05) and 0.07–0.15 Hz range (AA: 7±57°, White: 39±42°, Other: 33±33°, p&lt;0.01). In contrast there was no difference in Gain or Coherence values. Autoregulatory Index was similar across groups (AA: 5.3±2.8, White: 4.8±2.5, Other: 5.0±2.2) as was CO2 Vasoreactivity (AA: 3.0±0.8, White: 3.0±0.7, Other: 3.0±0.7 %/mmHg). We controlled for age, diabetes, hypertension and prescription drugs.Our preliminary data suggest that race may be an important factor to consider in understanding cerebral autoregulation. The finding that AA had reduced phase suggests impaired autoregulation and may partially explain the increased risk of cerebrovascular events in AA. However, future work is necessary using larger numbers to validate our findings.

Acute Hypovolemia Does Not Affect Dynamic Cerebral Autoregulation in Humans

While it is well known that cerebral perfusion pressure is the primary determinant of cerebral blood flow, it has been suggested that cardiac output and stroke volume may also play an important role. To test the role of stroke volume and cardiac output on dynamic cerebral autoregulation we performed sit to stand tests on a group of volunteers prior to and following administration of furosemide to reduce blood volume. These subjects were participating in a larger artificial gravity study. As expected furosemide resulted in a significant reduction in stroke volume while seated (63±5 vs. 51±4 mL, P=0.000). In contrast cardiac output was unchanged due to increases in heart rate (72±3 vs 94±3 bpm, P=0.000). Upon standing subjects demonstrated similar drops in SV, cardiac output and increases in HR from pre to post infusion. Blood pressure was unchanged by infusion while sitting and had similar drops upon standing (−20±4 vs −21±12 mmHg). Similarly cerebral flow velocity decreases were unchanged (−15±7 vs −17±8 mmHg). Examination of the Autoregulatory Index found no change from pre to post infusion (4.7±0.6 vs 4.8±0). These data demonstrate that hypovolemia and reduced stroke volume do not affect dynamic cerebral autoregulation or the cerebrovascular response to standing. Further work is needed to determine the role of cardiac output. Supported by NASA and VA.

Doppler Flow Velocity Indices (RI, PI, S/D &amp; PSV) of Fetal Middle Cerebral Artery in Normal Pregnancies: Correlation with Gestational Age of 20 to 40 Weeks

This observational type of descriptive study was carried out in the Department of Radiology and Imaging, BIRDEM selecting 70 Bangladeshi pregnant babies with the aim to find out the normogram of foetal middle cerebral artery Doppler flow velocity indices and correlation between Doppler flow velocity indices [Resistance Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D) &amp; Peak Systolic Velocity (PSV)] of foetal middle cerebral artery and gestational age in normal pregnancies of 20 to 40 weeks. It was observed that RI, PI and S/D were decreased with the advance of gestational age but PSV was increases with the advance of gestational age. Statistical analyses showed there were significant difference between mean PSV, RI and PI before and after 25 weeks of gestation. No significant difference was found between mean S/D before and after 25 weeks of gestation. It was observed from Correlation analysis between Doppler indices with independent gestational age that all the Doppler indices of foetal middle cerebra artery was positively correlated with the whole gestation period. The statistical analysis showed only PSV and RI were significantly correlated with the gestational age. Simple regression analysis between dependent Doppler index with independent gestational age before and after 25 weeks revealed that all the Doppler indices had positive relationship with the corresponding gestational age but relationship between PSV and PI (before 25 weeks) with their corresponding gestational ages were only statistically significant.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12306 Birdem Med J 2012; 2(2) 77-80

Transcranial Doppler monitoring of middle cerebral flow velocity in a patient with a ventriculoperitoneal shunt undergoing laparoscopy

Laparoscopic surgery is possibly associated with a risk of intracranial pressure (ICP) increase due to pneumoperitoneum in patients with ventriculoperitoneal shunts (VPS). Invasive techniques for shunt pressure monitoring are not routinely used because of the possible complications. Transcranial Doppler (TCD) is a non-invasive, safe method which gives accurate information about blood-flow velocities in basal cerebral arteries and indirectly about the ICP. Moreover it is inexpensive and simple in use. We report the use of TCD for middle cerebral flow velocity monitoring in a patient with a VPS who underwent laparoscopic surgery. In the case we present, during 60 min of pneumoperitoneum, TCD showed a sustained, but not clinically significant increase of the Pulsatility Index, with a recorded maximum change of 31 %. We consider that the use of TCD may increase the safety of laparoscopic procedures in patients with preexisting VPS.

Uterine artery, umbilical, and fetal cerebral Doppler velocities after epidural analgesia during labor

ObjectiveTo evaluate the effects of epidural analgesia on uterine artery, umbilical, and fetal cerebral Doppler velocities during labor. MethodsIn a prospective study at Beaujon Hospital, Paris, France, between September and December 2010, uterine artery, umbilical, and fetal cerebral Doppler flow velocities were measured in 12 pregnant women during spontaneous labor with epidural analgesia. The data were registered in a period of uterine relaxation before, and 20 and 60minutes after the first administration of epidural analgesic drugs. The changes in Doppler velocimetry values and fetal heart rate after epidural analgesia were analyzed. ResultsUterine artery velocities, but neither umbilical nor fetal cerebral Doppler velocities, were decreased significantly at 20minutes and 1hour after epidural analgesia (P<0.005). Women with the greatest decrease in uterine artery Doppler flow velocities delivered neonates with the lowest values of umbilical artery blood pH. ConclusionThe data suggest that the Doppler flow velocity of uterine arteries is affected by epidural analgesia during labor. Numerous Doppler flow studies of the effect of neuraxial blockade during labor on umbilical and uterine arteries have been published with incredibly variable and inconsistent results.

Cerebral Compliance Changes With Sympathetic Activation During Cold Pressor Test

The role of sympathetic activation on arterial compliance has yet to be examined. This study examined cerebral flow velocity and cerebral compliance in response to sympathetic activation.Healthy subjects (n=13) performed a cold pressor test in which their forearms were immersed in a bucket of ice water for up to 3 minutes. Cerebral flow velocity (CFV) (middle (MCA), anterior cerebral (ACA), vertebral arteries (VA), external carotid), blood pressure, and end‐tidal CO2 were measured. Data was collected at baseline, first and final 15 sec of immersion.Compared to initial immersion, CFV increased the most in the last 15 sec of the protocol: ACA (+9.5±3.2%, P&lt;0.02), MCA (+10.0±2.8%, P&lt;0.02), VA (+15.4±4.6%, P&lt;0.02). At the end of the protocol, significant increases in blood pressure were seen (+15.5±2.5 mmHg, P&lt;0.001). Pulse wave velocity (PWV) increased in the periphery from baseline and through each time point: ACA (7.2±0.4 to 8.5±0.8 to 8.5±0.7 m/s); MCA (7.2±0.4 to 9.9±1.6 to 9.2±0.6 m/s); VA (6.7±0.5 to 7.0±0.4 to 8.5±1.4 m/s).Findings suggest that increasing sympathetic activity does not cause cerebral vasoconstriction, but increases CFV while reducing arterial compliance. Sympathetically mediated reductions in compliance may be an adaptive mechanism to enhance pressure transmission to the brain when humans are upright and pressure at the brain is lower due to the hydrostatic gradient. Supported by NASA/NIH.

Cerebral Vascular Blood Flow Changes During ‘Brain Freeze’

‘Brain freeze’ commonly occurs when ice cold food or liquid is rapidly consumed. It's mechanism remains unclear, however rapid cooling of the brain through the upper palate may cause local cerebral blood flow changes. The purpose of this study was to examine whether ‘brain freeze’ induces the hypothesized cerebrovascular changes.Using transcranial Doppler, we evaluated cerebral blood flow velocity (CBFV) in the middle (MCA) and anterior (ACA) cerebral arteries in 13 healthy adults while consuming ice and ambient water. Subjects drank ice water through a straw against the palate until pain developed. CBFV, heart rate, and blood pressure were analyzed, before pain, during pain and after pain.Consumption of ice water produced a tendency towards increased cerebral flow velocity in the ACA (P=0.078) but not the MCA (P=0.24). Ice water also resulted in greater cerebrovascular resistance during the experimentally induced “brain freeze” when compared to following ambient water consumption.Our results support a vascular mechanism for brain freeze. Ice water consumption resulted in a significantly greater cerebrovascular resistance as compared to that during ambient water consumption. However, the fact that cerebral flow increased during pain along with increases in blood pressure may suggest autoregulation was not as effective. Supported by NASA and NIH.

Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease

Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke,making primary stroke prevention a reality. A cross-sectional study of145 Nigerian children aged ≥3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 ±27.0 cm/sec and122 ±22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C cases. Cerebral flow velocities showed a negative correlation with age and hematocrit. Compared with African-American children, Nigerian children with Hb SS disease have a considerably higher prevalence of CR velocities.

Elderly Women Regulate Brain Blood Flow Better Than Men Do

Orthostatic intolerance and falls differ between sexes and change with age. However, it remains unclear what role cerebral autoregulation may play in this response. This study was designed to determine whether cerebral autoregulation, assessed using transcranial Doppler ultrasound, is more effective in elderly females than in males. We used transcranial Doppler ultrasound to evaluate cerebral autoregulation in 544 (236 male) subjects older than age 70 years recruited as part of the MOBILIZE Boston study. The MOBILIZE Boston study is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. We assessed CO2 reactivity and transfer function gain, phase, and coherence during 5 minutes of quiet sitting and autoregulatory index during sit-to-stand tests. Male subjects had significantly lower CO2 reactivity (males, 1.10 ± 0.03; females, 1.32 ± 0.43 (cm/s)/%CO2; P<0.001) and autoregulatory indices (males, 4.41 ± 2.44; female, 5.32 ± 2.47; P<0.001), higher transfer function gain (males, 1.34 ± 0.49; females, 1.19 ± 0.43; P=0.002), and lower phase (males, 42.7 ± 23.6; females, 49.4 ± 24.9; P=0.002) in the autoregulatory band, implying less effective cerebral autoregulation. However, reduced autoregulation in males was not below the normal range, indicating autoregulation was intact but less effective. Female subjects were better able to maintain cerebral flow velocities during postural changes and demonstrated better cerebral autoregulation. The mechanisms of sex-based differences in autoregulation remain unclear but may partially explain the higher rates of orthostatic hypotension-related hospitalizations in elderly men.

Gender-related asymmetric brain vasomotor response to color stimulation: a functional transcranial Doppler spectroscopy study

Background and PurposeThe present study was designed to examine the effects of color stimulation on cerebral blood mean flow velocity (MFV) in men and women.MethodsThe study included 16 (8 men and 8 women) right-handed healthy subjects. The MFV was recorded simultaneously in both right and left middle cerebral arteries in Dark and white Light conditions, and during color (Blue, Yellow and Red) stimulations, and was analyzed using functional transcranial Doppler spectroscopy (fTCDS) technique.ResultsColor processing occurred within cortico-subcortical circuits. In men, wavelength-differencing of Yellow/Blue pairs occurred within the right hemisphere by processes of cortical long-term depression (CLTD) and subcortical long-term potentiation (SLTP). Conversely, in women, frequency-differencing of Blue/Yellow pairs occurred within the left hemisphere by processes of cortical long-term potentiation (CLTP) and subcortical long-term depression (SLTD). In both genders, there was luminance effect in the left hemisphere, while in men it was along an axis opposite (orthogonal) to that of chromatic effect, in women, it was parallel.ConclusionGender-related differences in color processing demonstrated a right hemisphere cognitive style for wavelength-differencing in men, and a left hemisphere cognitive style for frequency-differencing in women. There are potential applications of fTCDS technique, for stroke rehabilitation and monitoring of drug effects.

Addition of Hydroxyurea to Transfusion Programme to Treat Progressive Cerebral Vasculopathy

AbstractAbstract 4813Cerebro-vascular accidents (CVA) amongst paediatric patients with sickle cell disease (SCD) cause significant morbidity and mortality. Regular blood transfusions are used to prevent progressive cerebral vasculopathy. In primary stroke prevention, transcranial Doppler (TCD) studies are used to identify children at high risk of developing CVA and maintaining regular transfusion to keep HaemoglobinS (HbS) below 30% has shown to reduce this risk by 90%. However, about 10% children maintained on regular blood transfusions continue to have progressive vasculopathy despite maintaining HbS% below 30. There are few established options to try and prevent progressive vasculopathy despite adequate transfusion; possible approaches include intensifying the transfusion regime to maintain an even lower HbS%, revascularization surgery and correction of other thrombogenic risk factors. Hydroxyurea (HU) has been used in SCD to reduce the frequency of painful crises and acute chest syndrome. Its primary mode of action is thought to be to increase HbF levels but other mechanisms of action which may be beneficial include the reduction in white cell count, endothelium stabilization, improved expression profile of adhesion molecules, and nitric oxide donation. Herein we present our experience of combining treatment with HU to a transfusion programme in paediatric sickle cell patients with evidence of progressive cerebral vasculopathy whilst optimally transfused.4 paediatric patients with SCD were transfused as secondary stroke prevention, but had progressive cerebrovascular disease on magnetic resonance imaging (MRI/MRA). Following detailed discussions with the parents, HU was started in addition to the transfusion to try and arrest the progression. The dose of HU was gradually increased whilst monitoring counts, assessing tolerability with a view to achieving doses of at least 25mg/kg. All patients had regular clinical review, full blood counts, HbF and HbS percentages monitored baseline pre and post transfusion. All patients had annual TCD to assess cerebral circulation flow velocities and MRI/MRA. Iron chelation was commenced or continued as appropriate to their clinical circumstances for secondary iron overload.In this cohort, there were 2 females and 2 males, all of African descent. The mean age at diagnosis of first CVA was 5years (Range3-5yrs) with a mean steady state Hb of 7g/dl, mean HbF of 2.8% and mean HbS of 82.1%. MRI/MRA showed middle cerebral artery (MCA) cortical infarction in all patients at diagnosis but in addition showed varying degrees of areas of watershed infarction, small vessel disease with deep white matter ischemic change and moya-moya formation with small haemorrhages. The cohort remained on transfusions for a mean period of 55 months (Range 25–108) and received transfusions at a mean of 4 weekly intervals (Range 2–6 weeks). Mean Hb values post transfusion were 10.8g/dl with a mean HbF of 2% and HbS of 24.2%. TCD velocities in non-stenosed vessels showed a mean decrease in MCA by 26cm/sec (-11.8%), and in Internal carotid artery (ICA) by 14cm/sec (-8%). All 4 patients had evidence of clinical symptoms with new neurological deficits, and MRI/MRA scans showed a worsening picture of cerebral vasculopathy with increasing stenosis and new vessel formation. The mean duration of treatment with HU and transfusion was 18 months (Range 12–32months) with a mean Hb value of 11.4g/dl with a mean HbF of 5.8% and HbS of 14.6%. TCD on treatment with HU and transfusion showed a further mean reduction in flow velocity in MCA by 8cm/sec (-4.1%) in the non-stenosed vessels, and in ICA by 4cm/sec (-2.5%). MRI/MRA showed no evidence of progression. One patient had clinical symptoms of TIAs without further infarction and underwent neuro-revascularization.Our study shows that a carefully selected cohort of paediatric patients with advancing cerebral vasculopathy, may benefit from HU in addition to transfusion with modest but clinically significant improvement in HbF% and TCD profile over and above the substantial improvement seen after transfusions. It is possible that this added benefit is by way of HU reducing vascular endothelial damage, mild increases in HbF% and as yet, undefined mechanism. Further, larger studies are needed to assess the value of combining HU and transfusion, although our experience suggests that it is safe, well tolerated and potentially beneficial. Disclosures:No relevant conflicts of interest to declare.