Cerebral Artery Flow Velocity Research Articles

Correlation between Decreased Parasympathetic Activity and Reduced Cerebrovascular Reactivity in Patients with Lacunar Infarct.

Reduced cerebrovascular reactivity (CVR) was found in patients with recent lacunar infarct. However, its mechanisms were controversial. The breath holding maneuver as a vasodilatory stimulus is clinically useful for an estimation of cerebrovasomotor reactivity in well co-operative patients. Patients with lacunar infarct have no higher cortical dysfunction and remain well co-operation. The breath holding maneuver is feasible and safe to perform in patients with lacunar infarct. Autonomic nervous system regulates systemic vascular activity. Regulation of autonomic function to cerebrovascular reactivity has been reported in the literature. We examined the correlation between autonomic functions with frequency and nonlinear heart rate variability (HRV) and cerebrovascular reactivity in patients with lacunar infarct by application of breath holding maneuver. Fifteen patients with lacunar infarct (8 women, age 65.6 ± 13.61) and 16 healthy controls (11 women, age 27.33 ± 3.85) were continuously monitored at baseline before maneuver (basal phase), during CVR induction (experimental phase) with breath holding maneuver and after maneuver (recovery phase), for arterial blood pressure (ABP), electrocardiography (EKG), mean cerebral blood flow velocity (mCBFV) of middle cerebral arteries (MCA) by transcranial doppler (TCD). The short term-one minute HRV was analyzed from EKG signals for low frequency (LF)/ high frequency (HF) ratio, nonlinear of standard deviation 1 (SD1), standard deviation 2 (SD2), cardiac Sample Entropy (SampEn) and Shannon Entropy. Significant increasing in mCBFV, LF/HF ratio, SD2/SD1, Shannon Entropy and inversely decreasing SampEn during breath holding maneuver compared with baseline were found in both groups (p<0.05). The trend of cerebrovascular reactivity is similar in both groups. However, there were differences of mCBFV, systolic blood pressure (SysBP) in the whole phases (basal, experiment and recovery) between patients and controls (p<0.05). Less scattered signals of SD1 with low value in patient group were illustrated from Poincaré (p<0.05). This indicated less degree of parasympathetic drive in the patients compared to the controls. Moreover, significant positive correlation between systolic bloods pressure and mCBFV in patients suggests impact of autonomic control and cerebral blood flow on the patho-physiological mechanism of vasodilatation, triggered by hypercapnia from breath holding maneuver in patients with lacunar infarct. Reduction of cerebrovascular reactivity in patients with lacunar infarct may relate with decreased parasympathetic activity. Further study is required to demonstrate whether these findings mean mechanisms of lacunar infarct or the effect of hypertensive response.

Relationship between Changes in Cerebral Blood Flow with Symptoms of Acute Mountain Sickness in Men Repeatedly Exposed to Simulated High Altitude

Objective: To study the relationship between changes in the cerebral blood flow (CBF) velocity with symptoms of acute mountain sickness (AMS) during simulated high altitude. Research Design and Methods: Mean middle arterial cerebral flow velocity (MCAv) was assessed by transcranial Doppler sonography in 8 healthy lowland male adults aged 20 - 24 yrs before and after 6 h and 48 h at simulated altitude corresponding to 4572 m. The same study was repeated three weeks later in the same subjects. End-tidal pCO2 (ETCO2) and arterial oxygen saturation (SaO2) were measured by standardized procedures. AMS symptoms were recorded using the modified environmental symptoms questionnaire after 6 h and 48 h exposure to calculate the mean score of cerebral (AMS-C) symptoms. Results: Mean MCAv significantly increased with high altitude (HA) by 4% at 6 h HA and 24% at 48 h HA (P 2 (mean ± SD 32 ± 4 mmHg; r = 0.47, P 2 (77% ± 8%; r = - 0.43, P 2 (r = - 0.55, P

Abstract TP446: Independent Measures of Cerebral Blood Flow in Asymptomatic Carotid Artery Disease.

Background: Cerebral blood flow (CBF) regulation is a critical element in cerebrovascular pathophysiology, particularly in large vessel disease. Different methods to assess hemodynamics may represent different aspects of blood flow regulation, however, uniquely affecting outcomes and management. We examined 4 different blood-flow related measures in patients with high-grade unilateral carotid disease, assessing asymmetry between the occluded vs non-occluded side, and the correlations among the measures. Methods: Thirty-three patients (age 50-93, 19M) with unilateral 80-100% ICA occlusion but no stroke underwent: 1) quantitative resting CBF using continuous arterial spin labeling (CASL) MRI, 2) mean flow velocity (MFV) in both middle cerebral arteries (MCAs) by transcranial Doppler, 3). Vasomotor reactivity (VMR) in response to 2 minutes of 5% CO2 inhalation, and 4) Dynamic cerebral autoregulation (DCA) using continuous insonation of both MCAs for 10 minutes at depth 56mm with a standard head frame. Phase shift (PS) between spontaneous oscillations in blood pressure (measured with finger photoplethysmography) and MCA MFV at frequencies .06-.12 Hz was calculated for each hemisphere using transfer function analysis. Lower PS indicated worse autoregulation. Paired T-tests and Pearson correlations were used to look for side-to-side differences within each measure, and correlations between measures (SPSS v.22). Results: CASL CBF (p=.001), MFV (p&lt;.001), VMR (p=.008), and DCA (p=.047) all showed significantly lower values on the occluded side. The 4 measures were independent of each other on correlation analysis, even when controlling for age and anterior circle of Willis collateral (correlation coefficients all &lt;0.40, p-values &gt;0.09). Conclusions: These 4 measures showed high sensitivity to the occluded carotid artery, but appear to represent independent aspects of cerebral blood flow (CASL: resting gray matter CBF; MFV: whole-hemisphere CBF; VMR: cerebrovascular reserve, and DCA: homeostatic blood flow regulation) suggesting that any given measure only partially characterizes hemodynamic state. Further investigation will use these 4 measures to predict outcomes including vascular cognitive impairment.

Diagnostic and prognostic potential of non-invasive assessment of cerebral blood flow autoregulation

Purpose. To study the potential of non-invasive assessment of cerebral blood flow autoregulation (CA) using cross-spectral analysis of slow dopplerographic patterns. Materials and methods. The study involved 40 healthy volunteers and 228 patients with different neurosurgical pathology: cerebral aneurysm - 50 cases, arteriovenous malformation - 52, traumatic brain injury - 61, communicating hydrocephalus - 24, parasagittal meningioma - 20, stenosis and thrombosis of the carotid arteries - 21. Blood flow velocity (BFV) in middle cerebral arteries was monitored using Multi Dop X (DWL, Germany), systemic blood pressure (BP) - noninvasively with Finapres (Ohmeda 2100 USA) within 4 minutes. CA was assessed by calculating the phase shift (PSM) between spontaneous slow oscillations of BP and BFV within the range of systemic Mayer waves (80-120 mHz) and amplitude of intracranial B-waves of BFV (AB) within the range from 8 to 50 mHz). Results and discussion. CA demonstrated different patterns in neurosurgical patients and varied from normal autoregulation to its complete absence. This indicates the degree of compensation of cerebral hemodynamics in pathological conditions such as intracranial hypertension, vasospasm, traumatic edema, ischemia, abnormal arteriovenous shunting. On the basis of perioperative evaluation of PSM and AB, the predictors of efficacy and outcome have been identified in patients with cerebral aneurysms in an acute period of hemorrhage, severe brain injury, cerebral arteriovenous malformations and communicating hydrocephalus. Conclusions. Analysis of slow-wave dopplerographic patterns of BFV in intracranial cerebral arteries and BP is informative, adequate, safe non-invasive way to assess CA in normal and pathological conditions. Perioperative assessment of these patterns can be used to predict the effectiveness of treatment in patients with different neurosurgical pathology.

Abstract T MP55: Utility of 4D-MRA to Measure Blood Flow Velocity in Cerebral Major Arteries

Transcranial Doppler is widely used clinically to measure blood flow velocity (BFV) in cerebral major arteries. This method, however, has a limitation in that its successful measurement depends on the accessibility of patients’ cranial window and the technical ability of operators. We therefore developed a novel method to measure BFV in cerebral major arteries with 4D-MRA, which was less susceptible to patients and the conditions of the operators. Methods: 4D-MRA was performed with a 3T MR unit (Achieva TX; Philips Medical Systems) using arterial spin labeling methods. The blood flow through the internal carotid arteries (ICA) and the basilar artery (BA) within imaging range was visualized by using look-locker readout methods. BFV was calculated by dividing the flow distance traveled in the arteries by the time elapsed. BFV of 34 patients (non-vascular disease:11, ICA stenotic disease:6, moyamoya disease:9, and cerebral aneurysm:8) were measured using the 4D-MRA method and the 2D phase contrast method. Results: In the case of patients with non-vascular diseases, mean BFV of the right ICA, the left ICA, and the BA was 24.5±7.0, 23.3±6.9, and 17.2±5.1 cm/sec, respectively. Correlation between BFV values from the 4D-MRA method and those from the 2D phase contrast method was statistically significant (r=0.78, p&lt;0.01). In the case of patients with ICA severe stenosis (more than 90%), BFV of the stenotic ICA was decreased to 9~11cm/sec (40~50% of BFV of the contralateral ICA). In the case of patients with advanced-stage moyamoya disease, BFV of the ICA was decreased to 9~16cm/sec (30~50% of BFV of the BA). The BFV decreases were related to CBF reduction in some cases if the development of the collateral circulation was insufficient. In the patients with aneurysm, BFV of the artery proximal to aneurysm tended to be increased except for the decrease in cavernous ICA giant aneurysm. Conclusions: We could steadily obtain BFV in all patients by using the 4D-MRA method without any operational difficulties. In this preliminary study, we observed BFV decrease in ICA stenotic disease and moyamoya disease, and BFV increase in cerebral aneurysm. This novel 4D-MRA method to measure BFV may become a promising tool for pathophysiological evaluation of cerebrovascular diseases.

Abstract W P397: Severity of White Matter Hyperintensities Is Associated With Impaired Cerebral Autoregulation During Cardiac Surgery

Introduction: Impaired autoregulation during cardiac surgery with cardiopulmonary bypass (CPB) is associated with perioperative mortality and morbidity. Identifying risk factors for impaired autoregulation during CPB surgery may facilitate risk stratification, and guide intra- and postoperative monitoring of high-risk patients. Hypothesis: We hypothesized that severity of white matter hyperintensities (WMHs) detected with MRI is associated with impaired cerebral autoregulation during CPB surgery. Methods: From a prospective cohort of 280 patients whom underwent cerebral autoregulation monitoring during CPB, 97 patients had research brain MRIs within 5-7 days of surgery. Intraoperative autoregulation monitoring was performed by generating a continuous moving Pearson’s correlation coefficient between mean arterial pressure (MAP) and cerebral blood flow velocity of the middle cerebral arteries measured with transcranial Doppler to generate the mean velocity index (Mx). Impaired autoregulation was defined as an Mx ≥ 0.4 at all MAPs. WMHs were assessed by blinded review of FLAIR images of all patients. WMHs were graded on a 0 to 9 scale. Logistic regression was used to explore associations between the degree of WMHs and impaired autoregulation as the primary outcome. Results: Twenty-two (22.7%) of 97 patients had impaired autoregulation. Age, sex, race, and other medical comorbidities did not significantly differ between patients with intact and impaired autoregulation. In univariate analysis, each 1-point increase in white matter (WM) score was associated with 1.64-fold increased odds (95% confidence interval [CI] 1.18-2.27, p=0.003) of impaired autoregulation. WM score remained an independent predictor of impaired autoregulation after adjusting for age, sex, race, hypertension, and prior stroke (OR 1.79, 95% CI 1.21-2.63, p=0.003). In adjusted models, severe white matter disease (WM score ≥3) was associated with nearly 5-times higher odds of impaired autoregulation compared to a WM score &lt;3 (OR 4.75, 95% CI 1.58-14.27, p=0.005). Conclusions: WMHs are independently associated with impaired cerebral autoregulation during cardiac surgery and may increase the risk for perioperative morbidity and mortality.

Sickle cell disease in children: chronic complications and search of predictive factors for adverse outcomes.

Sickle cell disease (SCD) has extremely variable phenotypes, and several factors have been associated with the severity of the disease. To analyze the chronic complications of SCD and look for predictive risk factors for increased severity and number of complications. Retrospective study including all children followed for SCD in the Paediatric Haematology Unit of a tertiary hospital in Portugal, who completed 17yr old between the years 2004 and 2013. We identified 44 patients, 55% female and 98% black. Chronic complications occurred in 80% of cases. Slight dilatation of the left ventricle was the most frequent complication (47.7%), followed by respiratory function disturbs (43.2%), microlithiasis or cholelithiasis (40.9%), increased flow velocity of cerebral arteries (31.8%), enuresis, delayed puberty and bone abnormalities (6.8% each), sickle cell retinopathy and leg ulcer (4.6% each) and recurrent priapism (2.3%). We identified a statistically significant association between leukocytes >15000/μL and a higher number of hospitalizations (P<0.001) and chronic complications of the disease (P=0.035). The occurrence of dactylitis in first year of life was also significantly associated with a higher number of hospitalizations (P=0.004) and chronic complications (P=0.018). The presence of α-thalassemia was associated with a lower number of chronic complications (P=0.036). Leucocytosis and dactylitis in the first year of life can be predictors of SCD severity, while the presence of α-thalassemia can be protective. The determination of early predictors of chronic complications of SCD may improve the comprehensive care of these patients.

Continuous Selective Intra-Arterial Application of Nimodipine in Refractory Cerebral Vasospasm due to Aneurysmal Subarachnoid Hemorrhage

Background. Cerebral vasospasm is one of the leading courses for disability in aneurysmal subarachnoid hemorrhage. Effective treatment of vasospasm is therefore one of the main priorities for these patients. We report about a case series of continuous intra-arterial infusion of the calcium channel antagonist nimodipine for 1–5 days on the intensive care unit. Methods. In thirty patients with aneurysmal subarachnoid hemorrhage and refractory vasospasm continuous infusion of nimodipine was started on the neurosurgical intensive care unit. The effect of nimodipine on brain perfusion, cerebral blood flow, brain tissue oxygenation, and blood flow velocity in cerebral arteries was monitored. Results. Based on Hunt & Hess grades on admission, 83% survived in a good clinical condition and 23% recovered without an apparent neurological deficit. Persistent ischemic areas were seen in 100% of patients with GOS 1–3 and in 69% of GOS 4-5 patients. Regional cerebral blood flow and computed tomography perfusion scanning showed adequate correlation with nimodipine application and angiographic vasospasm. Transcranial Doppler turned out to be unreliable with interexaminer variance and failure of detecting vasospasm or missing the improvement. Conclusion. Local continuous intra-arterial nimodipine treatment for refractory cerebral vasospasm after aSAH can be recommended as a low-risk treatment in addition to established endovascular therapies.

Brain Circulation during Panic Attack: A Transcranial Doppler Study with Clomipramine Challenge.

Introduction. Cerebral blood flow has been well studied in patients with panic disorder, but only few studies analyzed the mechanisms underlying the onset of a panic attack. The aim of the present study was to monitor the cerebral hemodynamics modifications during a panic attack. Materials and Methods. 10 panic disorder patients with recent onset, fully drug naïve, were compared to 13 patients with panic disorder with a previous history of treatment and to 14 controls. A continuous bilateral monitoring of mean flow velocities in right and left middle cerebral arteries was performed by transcranial Doppler. Clomipramine was chosen as challenge. Results. Eight out of 10 patients drug naïve and 6 control subjects out of 13 had a full blown panic attack during the test, whereas none of the patients with a history of treatment panicked. The occurrence of a panic attack was accompanied by a rapid decrease of flow velocities in both right and left middle cerebral arteries. Discussion. The bilateral acute decrease of mean flow velocity during a panic attack suggests the vasoconstriction of the microcirculation of deep brain structures perfused by middle cerebral arteries and involved in the so-called “fear circuitry,” thus suggesting that cerebral homeostatic dysfunctions seem to have a key role in the onset of a panic attack.

Evaluation of transcranial Doppler flow velocity changes in intracerebral hemorrhage rats using ultrasonography

This study investigated the blood flow velocity changes in seven major arteries in rat brain before and after intracerebral hemorrhage (ICH) using high frequency transcranial Doppler (TCD) ultrasonography (13–4MHz). Eighteen adult Sprague Dawley rats received either the collagenase-injection surgery (ICH, n=12) or the saline-injection surgery (control, n=6) after baseline TCD flow velocity values were recorded. The TCD flow velocity changes were measured at 0.5h after the surgery and daily for the following 8days in seven major cerebral arteries, including bilateral internal carotid arteries, bilateral middle cerebral arteries (MCAs), bilateral posterior cerebral arteries (PCAs), and basilar artery. The results showed a significant decrease of TCD flow velocity in the right MCA at 0.5h and 24h after the collagenase-injection surgery, and in the right PCA at 0.5h in the ICH group rats. The TCD flow velocities in these two arteries gradually increased and then returned to the baseline values in the following days. The control group rats did not show significant changes in TCD flow velocity in all monitored arteries. This study demonstrates the feasibility and reliability of monitoring TCD flow velocity in cerebral arteries using ultrasonography technique in a rat ICH model. The results of this study extend our knowledge in the cerebrovascular changes during intracranial hemorrhage and suggest a possibility of clinical application of TCD ultrasonography in studying the dynamic cerebral circulation after strokes. Moreover, this method could be extensively applied in further studies using potential neuroprotective treatments that affect the cerebral dynamics in the intracerebral hemorrhage.

Delayed ischemic stroke associated with bromocriptine-induced reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndromes (RCVS) are a group of disorders characterized by prolonged but reversible vasoconstriction of the cerebral arteries, usually associated with acute-onset, severe, recurrent headaches, with or without additional neurologic signs and symptoms [1]. These syndromes are known to occur secondarily to the use of drugs such as cannabis, cocaine, ecstasy, amphetamine, selective serotonin-reuptake inhibitors (SSRIs) and nasal decongestants, or during pregnancy or the puerperal period itself [2]. RCVS which presents at puerperium is known as postpartum cerebral angiopathy (PCA) and is associated with the concomitant use of vasospastic drugs such as bromocriptine [3]. However, RCVS induced by bromocriptine beyond the puerperal period has not so far been reported. We describe here a case of bromocriptineinduced RCVS with ischemic stroke arising 1 year after the birth of second baby. A 32-year-old woman presented with an episode of transient left-sided weakness and dysarthria that lasted approximately 15 min, and a progressively worsening headache over several days. She had given birth to a second healthy baby 1 year before the present admission and it was uncomplicated as was her first pregnancy. Sixteen days before admission she had started on a course of 2.5 mg oral bromocriptine mesylate twice a day for 7 days to suppress lactation. After 7 days use of the bromocriptine, she was admitted to an outside hospital because of severe headache, transient left-sided weakness and dysarthria. At that time her vital signs were stable, including blood pressure of 130/85 mmHg and neurologic examination was unremarkable. Diffusion and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) revealed focal high-signal areas in the right frontal lobe (Fig. 1a, b) and magnetic resonance angiography (MRA) showed up severe stenosis in both middle cerebral arteries (Fig. 2a). A transcranial Doppler (TCD) disclosed abnormally high flow velocities in both middle cerebral arteries, and a CSF examination was normal. Low-dose acetylsalicylic acid (100 mg once a day) was initiated on a suspicion of transient ischemic attack with right middle cerebral artery stenosis. The patient was referred to our hospital 9 days after the onset of her symptoms due to recurrent severe headache. Upon arrival, vital signs were stable including a blood pressure of 125/80 mmHg. The patient had severe headache without any abnormalities of neurologic examination. Laboratory examinations including renal function, urinalysis, international normalized ratio, partial thromboplastin time, thrombin time, antithrombin III, protein C, protein S, D-dimer, and fibrin monomers were unremarkable. In addition, tests for antinuclear and anticardiolipin antibodies, and complement indices were normal. On the second day in our hospital, her headache worsened with newly developed left-sided weakness and dysarthria. At that time, diffusion and FLAIR images demonstrated extended highsignal areas in the bilateral fronto-parietal area (Fig. 1c, d). Y. S. Kim W. Baek J. Kim H. Y. Kim Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea

Impaired cerebral and systemic hemodynamics under cognitive load in young hypotensives: a transcranial Doppler study

Reduced sympathetic outflow and deficits in cerebral hemodynamics have been considered as possible factors mediating the impaired cognitive performance in essential hypotension. However, the relationship between systemic blood pressure (BP), cerebral blood flow and cognitive functioning is still poorly understood. The present study was aimed at clarifying the physiological processes underlying cerebral and systemic hemodynamics in young hypotensives during cognitive engagement. Doppler sonography blood flow velocities in both middle cerebral arteries were measured from 17 hypotensives and 15 normotensives during a working memory task. Impedance cardiographic and BP measures were also recorded continuously. Lower increases in systolic and diastolic BP were observed in hypotensives. However, no evidence of lower sympathetic control was found for this group, as assessed by pre-ejection period. Flow velocity in middle cerebral arteries showed a lower increase in hypotensives throughout the task. Moreover, significant positive correlations between BP changes and blood flow velocities in middle cerebral arteries during the task were obtained for this group only, suggesting a less effective cerebral autoregulation. No difference was found between groups in task performance. Results suggest that during cognitive challenge hypotensives show impaired hemodynamic adjustments, both central and peripheral. However, such alterations do not directly affect cognitive performance, at least under moderate cognitive load.

Abstract 3539: Can Stop Trial Velocity Criteria Be Applied To Iranian Children With Sickle Cell Disease?

Background&amp;Purpose: Although sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population, Iranian children with Saudi-Asian haplotype are less affected by this complication. TCD is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We therefore aimed first to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. Subjects&amp;Methods: Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) aged 3 to 16 years were prospectively recruited from pediatric outpatient clinic over a period of 9 months. All children had no previous stroke or any neurologic deficit. No transfusion was given within one month prior to TCD examination and patients were not on any medication that may affect cerebral hemodynamics. We performed TCD examinations in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). Mann-Whitney U test was used to compare TCD variables between the two groups. Results: Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (mean 8.83±1.43 g/dL vs. 10.3±1.03 g/dL, p&lt;0.001). In children with SCD, the highest MCA MFV (92 cm/s vs. 67 cm/s, p&lt;0.001) and the highest TICA MFV (62 cm/s vs. 45 cm/s, p&lt;0.001) were significantly higher than in controls. Among asymptomatic Iranian children with SCD only 1/30 (3%) had conditional &gt;170 cm/s MFV. Conclusions: Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities could be much lower than those observed in STOP studies, and some of the high risk group may be identified with velocities lower than 170 cm/s. A prospective validation of ethnicity-specific diagnostic criteria is warranted.

Abstract 4037: Dynamic Cerebral Autoregulation in Patients with Subarachnoid Hemorrhage and Delayed Cerebral Ischemia

Introduction: We have previously shown that early impairments in dynamic cerebral autoregulation are strongly associated with subsequent development of angiographic cerebral vasospasm. While angiographic cerebral vasospasm is associated with delayed cerebral ischemia (DCI), the relationship between cerebral autoregulation and DCI has not been previously investigated. Our study is designed to specifically test the relationship between early changes in dynamic cerebral autoregulation and subsequent development of DCI. Methods: Thirty-nine consecutive patients with acute non-traumatic subarachnoid hemorrhage (SAH) and adequate transcranial Doppler windows, presenting within 24 hours of symptom onset, have been prospectively studied so far. Daily 5-minute measures of continuous beat-to-beat bilateral middle cerebral artery (MCA) flow velocity and mean arterial blood pressure (MAP) recordings were obtained on days 1-10. Transfer function analysis of spontaneous MAP and MCA mean flow velocity (MFV) oscillations were performed in the very low (0.03-0.07 Hz), low (0.07-0.15 Hz), and high (0.15-0.3 Hz) frequency ranges. Non contrast head CTs were reviewed by a neurologist and neuroradiologist blinded to the autoregulatory and angiographic data. Infarctions present within 6 weeks after SAH, which could not be attributed to instrumentation or peri-op strokes, were identified as DCI. Results: Patients with DCI had significantly higher Hunt and Hess (H&amp;H) scores (median=4 vs 3, p&lt;0.0001) compared to those without DCI. There was no difference in MAP (p=0.746), right MCA (p=0.8327)) or left MCA MFV (p=0.4278) between patients with and without DCI across all time points. Patients with DCI had a lower transfer function phase in the very low frequency (autoregulatory frequency) range. Subgroup analysis of patients with H&amp;H scores ≥3 (N=14) showed that those with DCI had significantly lower phases on day 3 compared to those without DCI (-13±80 vs. 63±26, p=0.048). Conclusion: Our preliminary data show that dynamic cerebral autoregulation, as measured by transfer function phase in the autoregulatory frequency range, is significantly impaired in the early days after SAH and that this early impairment is associated with the development of DCI. We are continuing to collect data on additional patients with SAH to confirm our findings in a larger cohort. Impairments in dynamic cerebral in the early days post SAH may be reliable predictors for identifying patients at higher risk of delayed cerebral ischemia.

Integrated human physiology: breathing, blood pressure and blood flow to the brain

The cerebral vasculature rapidly adapts to changes in perfusion pressure (cerebral autoregulation), regional metabolic requirements of the brain (neurovascular coupling), autonomic neural activity, and humoral factors (cerebrovascular reactivity). Regulation of cerebral blood flow (CBF) is therefore highly controlled and involves a wide spectrum of regulatory mechanisms that together work to maintain optimum oxygen and nutrient supply. It is well-established that the cerebral vasculature is highly sensitive to changes in arterial blood gases, in particular the partial pressure of arterial carbon dioxide (). The teleological relevance of this unique feature of the brain is likely to lie in the need to tightly control brain pH and its related impact on ventilatory control at the level of the central chemoreceptors. Changes in arterial blood gases, in particular those that cause hypoxaemia and hypercapnia, also lead to widespread effects on the systemic vasculature often leading to sympathoexcitation and related blood pressure (BP) elevations via vasoconstriction (Ainslie et al. 2005). In this issue of The Journal of Physiology an elegant study by Battisti-Charbonney and co-workers provide a relevant example of integrative human physiology (Battisti-Charbonney et al. 2011). Using continuous bilateral measurements of blood flow velocity in the middle cerebral arteries (as a surrogate index of CBF) and BP, the authors gauged the CBF responses to CO2 changes under the background condition of either hyperoxia or hypoxia. The key findings indicate that the relationship between CBF velocity over a wide range of end-tidal () values during hypocapnia (: ∼25 mmHg) and hyperoxic or hypoxic rebreathing (: 55–60 mmHg and 45–50 mmHg, respectively) are optimally fitted using a sigmoid (logistic) curve rather than a linear curve. Above the upper limits of CO2 reactivity (i.e. near the threshold (∼55 to 60 mmHg) where CBF velocity has plateaued despite further elevations in ) linear elevations in BP then progressed, presumably via chemoreflex-induced elevations in sympathetic nerve activity (SNA). Notably, the authors are the first to integrate this logistic and linear fitting approach to document the influence of and related changes in mean arterial pressure (MAP) on CBF. Collectively, these experiments demonstrate that rebreathing tests – when analysed as described – may provide an estimate of the cerebrovascular response to CO2 (and O2) at a constant BP, as well as an estimate of the cerebrovascular passive response to both BP and CO2. In the broader context of integrative physiology, these findings are noteworthy on many levels. For example, impairment in cerebrovascular reactivity to CO2 and failure to effectively counter-regulate (or autoregulate) against systemic BP fluctuations could lead to a predisposition to adverse cerebrovascular events such as stroke, infarct extension and haemorrhagic transformation of existing strokes (Aries et al. 2010). However, the critical physiological and methodological consideration is that traditional tests to assess cerebrovascular reactivity to CO2 or cerebrovascular autoregulation treat these factors as separate identities. Clearly they are not: elevations in will lead to sympathoexcitation and increases in BP via vasoconstriction (Ainslie et al. 2005). The latter, as exampled by Battisti-Charbonney and co-workers, will have independent effects on CBF from those of (Lucas et al. 2010). Conversely, emerging evidence indicates that acute changes in BP may then impact on alveolar ventilation and thus , in part via the aptly named ‘ventilatory baroreflex’ (Stewart et al. 2011). Moreover, because the brain is relatively pressure-passive (Lucas et al. 2010) and since elevations in also ‘impair’ the brain's capability to defend against BP changes (Panerai et al. 1999), considerations of BP as a critical determinant of CBF is warranted in these conditions. An example of these integrated changes in and BP occur in a myriad everyday activities: postural change, coughing, laughing, defecation, exercise, sexual activity, to name but a few. The merit of the newly proposed method as a useful clinical tool to explore the separate and combined quantification of the cerebrovascular reactivity to CO2 and BP needs to be established. However, consideration of the combined influence of both and BP on the brain would seem meritorious from a systems physiology viewpoint. In summary, in view of the article by Battisti-Charbonney et al., we have attempted to highlight some of the common factors that independently, synergistically and often antagonistically participate in the regulation of CBF. Research exploring these complex interactions is currently lacking. Future studies with particular focus on these integrative physiological mechanisms are clearly warranted in both health and disease states.

Interactions between systemic hemodynamics and cerebral blood flow during attentional processing

The study explored interactions between systemic hemodynamics and cerebral blood flow during attentional processing. Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries (MCA) of both hemispheres were recorded while 50 subjects performed a cued reaction time task. Finger arterial pressure and heart rate were also continuously monitored. Doppler sonography revealed a right dominant blood flow response. The extent of the increase measured in second two of the interstimulus interval showed a clear positive association with reaction speed. Task-related changes in blood pressure and heart rate proved predictive of changes in MCA flow velocities in limited time windows of the response. Besides an association between cerebral blood flow and attentional performance, the results suggest a marked impact of systemic hemodynamics on the blood flow response. All observed interactions are highly dynamic in time.

Normal values of cerebral blood flow velocities in neonates

There was used color Doppler ultrasonography (cD-USI), allowing simultaneous examination of parenchymal and vascular cerebral structures. The evaluation of blood flow velocities in cerebral arteries is important in the assessment of cerebral circulation in hypoxic-ischaemic and haemorrhagic brain damage in neonates. The aim of this study was to estimate normal values of cerebral blood flow velocities (CBFV) and Doppler indices--pulsatility index (PI) and resistance index (RI)--in the anterior cerebral artery (ACA) during the first days of life in infants. CBFV, PI and RI were obtained during the first week of life with cD-US in 70 infants divided in four groups of gestational age (GA): < or =28 gestational weeks (GW); 29-32 GW; 33-36 GW; and > or =37 GW. Infants with congenital malformations, severe perinatal asphyxia, cerebral haemorrhagic lesion, DAP or severe hypotension were excluded. The mean GA of infants was 34.5 +/- 5.5 GW (range 26-40 GW) and the mean birth weight (BW) was 2540 +/- 950 g (range 750-4000 g). In the 1st group of 10 infants, < or =28 GW, the mean BW was 950 +/- 110 g and values of RI were 0.59 +/- 0.10 and PI 1.06 +/- 0.080. In the 2nd group of 20 infants, 29-32 GW, the mean BW was 1350 +/- 290 g and values of RI were 0.60 +/- 0.10 and PI 1.10 +/- 0.15. In the 3rd group of 20 infants, 33-36 GW, the mean BW was 1950 +/- 750 g and values of RI were 0.63 +/- 0.08 and PI 1.15 +/- 0.30. In the 4th group of 20 infants, > or =37 GW, the mean BW was 3540 +/- 950 g and values of RI were 0.65 +/- 0.05 and PI 1.18 +/- 0.35. Values of CBFV progressively increase with GA and BW due to progressive increase of cardiac output, blood pressure and closing of ductus arteriosus. Values of RI and PI gradually increase with GA and BW as a result of progressive maturation and opening of vascular cerebral bed with a reduction of the cerebrovascular resistance.

Effect of cilostazol on cerebral arteries in secondary prevention of ischemic stroke

To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin. Sixty-eight patients who had ischemic stroke during the recent 1-6 months were recruited and randomized into cilostazol or aspirin group. Cerebrovascular condition was assessed by magnetic resonance angiography (MRA) and transcranial doppler ultrasonography (TCD) at the beginning of the study and after 12-month medication. During the clinical follow-up, ischemic stroke recurred in 2 patients in cilostazol group, while in aspirin group, one case of ischemic stroke recurrence and one case of acute myocardial infarction were found. MRA revealed that in aspirin group, the percentages of patients experiencing aggravation and attenuation of cerebrovascular condition were 3.3% and 6.7%, respectively, while in aspirin group, they were 3.3% and 10%, respectively. Moreover, TCD revealed that 26.9% of the patients in aspirin group and 14.3% of the patients in cilostazol group experienced aggravation of cerebrovascular condition. However, the systolic peak flow velocity of the previously abnormal arteries increased by 42.9% after 12-month medication of cilostazol, which was significantly higher than that after aspirin medication (27.5%) (P = 0.04). Furthermore, as a major side effect of antiplatelet therapy, the frequency of bleeding was much less in cilostazol group (0 case in cilostazol group vs 5 in aspirin, P< 0.05). Cilostazol is as effective as aspirin in preventing the aggravation of cerebral arteries in secondary prevention of ischemic stroke. Besides, it is more safe. Cilostazol can increase the systolic peak flow velocity of cerebral arteries, which may improve the blood supply of focal ischemia.

The diagnostic iter of patent foramen ovale in migraine patients: an update

Patent foramen ovale (PFO) is a frequent finding in migraine patients. The standard technique for PFO diagnosis is actually trans-oesophageal echocardiography (TEE). It requires the injection of a contrast agent unable to pass the pulmonary filter; hence, it is possible to detect a right-to-left shunt by observing the presence of the contrast medium in the cardiac left compartment. The transcranial Doppler (TCD) device accurately measures the blood flow velocities in different cerebral arteries. It can record microembolic signals (MES) backscattered by microbubbles travelling in the cerebral circulation, and distinguish cardiac shunts from pulmonary shunts. The number of MES is correlated to the entity of the shunt. The near-infrared spectroscopy (NIRS) technique tracks the changes in the concentration of oxygenated and reduced haemoglobin in the brain tissue. PFO is revealed by an alteration of the normal vasoreactivity pattern of the subject during functional stimuli. Magnetic resonance imaging (MRI) provides, at the same time, detailed anatomical information and functional measurements. MRI dynamic perfusion sequences can be used to reliably detect PFO either by visual assessment or by signal-time curves in the pulmonary artery and in the left atrium. A good correlation between TEE and MRI grading scores has been demonstrated, even though the interindividual variability of performing the Valsalva manoeuvre could greatly reduce the sensitivity of the method. Further prospective studies are needed to confirm the PFO MRI grading and to assess the sensitivity and specificity of the method.

Relation between pulsed and continuous Doppler velocimetry of the anterior cerebral artery in newborn infants

Continuous wave (cw) and pulsed wave (pw) Doppler velocimetry are both used to measure blood flow velocity in cerebral arteries. We examined whether data obtained with the two methods are interchangeable and equally useful for clinical application. We studied 20 infants at an age between 1 day and 2 1/2 months and a body weight between 1.2 and 3.4 kg. Cw Doppler measurements were performed using an Angiomatic (Medimatic) and pw measurements using a Mark 600 Duplex Scanner (ATL). We applied both methods within an interval as short as possible. For the data analysis the pulsatility index (PI) was used, a parameter fairly independent of the emission angle. PI was 0.66 +/- 0.06 (mean +/- SD) using the cw and 0.8 +/- 0.08 using the pw method. The linear correlation between the pulsatility indices obtained with the cw and the pw method respectively was statistically significant (r = 0.53, n = 20, p less than 0.0025), the variation around the regression line rather large. The slope of the regression line differed significantly from that of the identity line (y = 0.391x + 0.54). Therefore the PI values obtained with the two methods are not interchangable and require to be judged according to normal values. Both methods, however, yield PI values which correlate and can thus be equally used. The choice of the method rather depends on the goal to be achieved. The pw method seems to be more suitable for precise momentaneous descriptions and the cw method for continuous monitoring of cerebral blood flow.