Impaired Cerebrovascular Reserve Research Articles

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

Abstract WMP53: Revascularization Improves Cerebrovascular Reserve In Moyamoya Patients

Introduction: Cerebrovascular reserve (CVR) reflects the change in cerebral blood flow (CBF) in response to a vasoactive stimulus and can be measured using a brain stress test whereby CBF is augmented using vasodilators. Studies have demonstrated that impaired CVR was associated with a higher risk of acute stroke and that bypass can reduce the risk of strokes. Arterial spin labeling is a quantitative MRI technique that enables non-invasive CBF and CVR measurement. Studies have shown the effectiveness of ASL in identifying CVR impairment in Moyamoya patients. Here, we compare the CBF and CVR of Moyamoya patients before and after bypass using single and multiple delay ASL techniques. Methods: MRI data were acquired from 24 Moyamoya patients (16-54 years, 3 males) using a 3T MRI system. All patients had unilateral or bilateral vessel occlusion at ACA, MCA and/or PCA. The scanning parameters of the single post-labeling delay pseudo-continuous ASL (single-PLD PCASL), delay pseudo-continuous ASL (multi-PLD PCASL, 5 PLDs) 2. ASL data were acquired simultaneously at baseline and 15 minutes after the injection of the vasodilator acetazolamide (15 mg/kg with a maximum 1 g). CBF was computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Flow territories (right and left ACA, MCA, and PCA) were defined based on the Harvard-Oxford cortical and subcortical structural atlases. Mean CVR within the territories affected by occlusion and normal territories was computed for each subject. T-tests were performed to compare the mean CVR between the affected and unaffected territories. Results: For this cohort, our quantitative analysis revealed that CVR of the affected regions increased significantly by 12% and 21% measured by single and multiple delay PCASL respectively, implying improved CBF and lower risk for strokes. Discussion: ASL was effective to detect improved CBF and CVR in Moyamoya patients after bypass surgeries.

Capillary transit time heterogeneity inhibits cerebral oxygen metabolism in patients with reduced cerebrovascular reserve capacity from steno-occlusive disease

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.

Cerebrovascular Reserve Impairment in the Anterior Cerebral Artery Territory Predicts Deep Temporal Artery Enlargement After Combined Revascularization Surgery in Moyamoya Disease.

A combined surgery of direct and indirect revascularization has been frequently performed in patients with moyamoya disease, though the efficacy of indirect revascularization surgery in adult patients with moyamoya disease has not been established. This study aimed to evaluate superficial temporal artery (STA) and deep temporal artery (DTA) diameters 1day and 3months after combined revascularization surgery in patients with moyamoya disease. We also investigated clinical factors related to DTA enlargement after surgery. We examined 78 cerebral hemispheres in 57 adult and pediatric patients with moyamoya disease who underwent combined revascularization surgery [STA-MCA bypass and encephalo-duro-myo-synangiosis] in our institution. STA and DTA diameters were measured on axial magnetic resonance angiography images at 1day and 3months after surgery. DTA diameter increased in 64 hemispheres (82.1%). DTA diameter increase in association with STA diameter decrease was found in 39 hemispheres (50%). The proportion of hemispheres with a reduction in STA diameter was significantly higher in hemispheres with DTA enlargement than in hemispheres with DTA reduction (P=0.0088). Among the 64 hemispheres with DTA enlargement, 51 (79.7%) showed cerebrovascular reserve (CVR) impairment in the anterior cerebral artery (ACA) territory before surgery. CVR impairment in the ACA territory was the only clinical factor related to DTA enlargement (P<0.001). The DTA frequently enlarges after combined revascularization surgery, even in adult patients with moyamoya disease. In patients with impaired CVR in the ACA territory, blood supply from the DTA to the ACA territory can be expected after combined revascularization surgery.

Lag-Optimized Blood Oxygenation Level Dependent Cerebrovascular Reactivity Estimates Derived From Breathing Task Data Have a Stronger Relationship With Baseline Cerebral Blood Flow.

Cerebrovascular reactivity (CVR), an important indicator of cerebrovascular health, is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. Theoretical and empirical evidence suggests that baseline cerebral blood flow (CBF) modulates BOLD signal amplitude and may influence BOLD-CVR estimates. We address how acquisition and modeling choices affect the relationship between baseline cerebral blood flow (bCBF) and BOLD-CVR: whether BOLD-CVR is modeled with the inclusion of a breathing task, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. We assessed between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a breathing task addition to a resting-state acquisition, alongside lag-optimization within BOLD-CVR modeling, can improve BOLD-CVR correlations with bCBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive correlations between bCBF and BOLD-CVR, both between- and within-subjects. The physiological explanation of this positive correlation is unclear; research with larger samples and tightly controlled vasoactive stimuli is needed. Insights into what drives variability in BOLD-CVR measurements and related measurements of cerebrovascular function are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve.

Feasibility of Cerebrovascular Reserve Assessment Using Stretched Exponential Model in Major Cerebral Artery Steno-occlusive Disease: Comparison with SPECT

To clarify whether diffusion-weighted imaging using stretched exponential model can assess cerebrovascular reserve (CVR) in patients with major cerebral artery steno-occlusive disease, we compared stretched exponential parameters and single-photon emission computed tomography (SPECT). Twenty-nine patients with unilateral major cerebral artery steno-occlusive disease (25 men and 4 women; age, 69±11 years) were analyzed in this study. The patients were divided into three groups: normal CVR (CVR≥30%), moderate CVR (10%≤CVR<30%), and severe CVR (CVR<10%). The distributed diffusion coefficient (DDC) and heterogeneity index (α) from the stretched exponential model, apparent diffusion coefficient (ADC) from the monoexponential model, and CVR and resting cerebral blood flow (CBF) from SPECT were measured in the bilateral middle cerebral artery territories, and ipsilateral-to-contralateral ratios (rDDC, rα, rADC, and rCBF) were obtained. The rDDC values in severe CVR were significantly higher than those in normal CVR (P=0.003). The rDDC values were significantly negatively correlated with ipsilateral CVR (rho=-0.31, P=0.009). The rDDC values were not significantly correlated with rCBF (P=0.34). We have shown that elevated rDDC values are associated with impaired CVR. Our results suggest that diffusion-weighted imaging using stretched exponential model has a potential to evaluate hemodynamic impairment.

Cerebrovascular Reserve Capacity as a Predictor of Postoperative Delirium: A Pilot Study.

Introduction: Postoperative delirium is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Compromised regulation of the cerebral circulation may be a predisposing factor for delirium. However, the potential relationship between cerebrovascular reserve capacity and delirium is unknown. The aim of this study was to investigate if impaired cerebrovascular reserve capacity was associated with postoperative delirium.Methods: Forty-two patients scheduled for cardiac surgery with CPB were recruited consecutively. All patients underwent preoperative transcranial Doppler (TCD) ultrasound with calculation of breath-hold index (BHI). BHI < 0.69 indicated impaired cerebrovascular reserve capacity. In addition, patients were examined with preoperative neuropsychological tests such as MMSE (Mini Mental State Examination) and AQT (A Quick Test of cognitive speed). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) in which a score of ≥2 was considered as delirium.Results: Six patients (14%) scored high for postoperative delirium and all demonstrated impaired preoperative cerebrovascular reserve capacity. Median (25th−75th percentile) BHI in patients with postoperative delirium was significantly lower compared to the non-delirium group [0.26 (−0.08–0.44) vs. 0.83 (0.57–1.08), p = 0.002]. Preoperative MMSE score was lower in patients who developed postoperative delirium (median, 25th−75th percentile; 26.5, 24–28 vs. 28.5, 27–29, p = 0.024). Similarly, patients with postoperative delirium also displayed a slower performance during the preoperative cognitive speed test AQT color and form (mean ± SD; 85.8 s ± 19.3 vs. 69.6 s ± 15.8, p = 0.043).Conclusion: The present findings suggest that an extended preoperative ultrasound protocol with TCD evaluation of cerebrovascular reserve capacity and neuropsychological tests may be valuable in identifying patients with increased risk of developing delirium after cardiac surgery.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion.

Usefulness of 2D-Perfusion Analysis for the Assessment of Unilateral Cervical Internal Carotid Artery Stenosis.

We investigated the usefulness of 2D-perfusion analysis for the evaluation of cerebral blood flow in unilateral cervical internal carotid artery stenosis. We conducted a 2D-perfusion analysis during cerebral angiography and 123I-iodoamphetamine (IMP) single photon emission computed tomography (SPECT) for unilateral cervical internal carotid artery stenosis without contralateral stenosis. The relationship between the ratio of the lesion side to the normal side in the parameters obtained by 2D-perfusion and the value calculated by stereotactic extraction estimation (SEE) analysis of SPECT was statistically examined. The ratios of the lesion side to the normal side regarding the peak arrival time (AT; time to peak [TTP]) of the contrast agent and the mean filling time (mean transit time [MTT]) of the contrast agent in 2D-perfusion significantly correlated with the area of Stage II and increase ratio (I.R) ≤30% in the SEE analysis (p = 0.002, 0.003). 2D-perfusion analysis can be used to estimate the extent of impaired cerebrovascular reserve (CVR) area in unilateral internal carotid artery stenosis.

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

Letter: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

To the Editor: Recently, we read with great interest the article by Quon et al1 regarding the early diffusion magnetic resonance imaging (MRI) changes in normal-appearing brain in pediatric moyamoya disease (MMD). The authors found the significantly elevated apparent diffusion coefficient (ADC) values for MMD children in the representative brain regions could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve (CVR). We really appreciate the interesting observation for their conclusion. Meanwhile, we would like to highlight 3 important questions that it raises. First, in recent years, the researchers of MMD have gradually formed a consensus: prior to the obvious ischemic changes on MRI, the microstructural impairments caused by reduced blood supply had appeared in the brain of MMD patients.2,3 Hypoperfusion and cytotoxic edema have been considered as the major cause of microstructural impairments.4,5 There are 2 different types of cerebral ischemic edema: the early cytotoxic type and the later vasogenic type. When the stimulation of anaerobic metabolism leads to the increase of osmotic pressure of brain tissue, which leads to the swelling of permeable cells, cytotoxic edema occurrs.6 With the development of tissue necrosis and the degradation of basement membrane, the blood-brain barrier is destroyed, and serum protein begins to leak into the brain from the blood, thus further improving the water content of the tissue and a later vasogenic type occurrs.7 However, due to the insensitivity of conventional MRI to the cytotoxic edema, most MMD patients had already suffered serious brain parenchymal damage by the time they receive treatment. In the present study,1 via the high sensitivity of diffusion-weighted imaging in distinguishing cytotoxic and vasogenic edema,8 the authors found the ADC value could precisely differentiate pediatric MMD patients from normal controls in the absence of imaging evidence of ischemic stroke. This observation indicated that it is possible to detect the serious imbalance of energy supplies and demands via the ADC value before the occurrence of irreversible lesions in brain parenchyma in MMD patients, so as to timely implement the intervention measures to obtain the maximum clinical effect. Second, revascularization surgery is considered to be the most effective way to treat MMD. Previous studies have confirmed that the preoperative clinical and hemodynamic changes could indicate the outcomes and complications from revascularization surgery for MMD patients.9,10 However, which severity of the preoperative changes in MMD patients can maximize the benefits from bypass surgery has always puzzled neurosurgeons. Recently, many non-invasive examination methods and indicators, such as CVR,11 ivy sign,12 and cortical hyperintensity belt sign,13 were proposed to reflect the clinical severity of MMD before obvious (usually means serious) changes appear on conventional MRI. The same is true for the ADC value in present study. Third, the authors in present study1 tried to explain a possible relation between the elevated ADC value and the impaired CVR. Although previous studies have observed simultaneous appearance of reduced CVR and elevated ADC in MMD patients, the mechanism remains to be clarified.14 In our opinion, CVR reflects the compensatory ability of cerebral arteries to compensate for the hypoperfusion, and its mechanism may partially due to the vasodilatory stimulation of metabolites like lactate to arteries. Meanwhile, the early cytotoxic edema in MMD patients may also due to the change of metabolism in brain cells during hypoperfusion.6 Therefore, there may not be a direct causal relationship between impaired CVR and elevated ADC, they may be 2 simultaneous results of the same change (hypoperfusion). Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

Abstract WMP46: Frequency of High-Risk Features and Stroke Risk in Asymptomatic Carotid Atherosclerosis: Systematic Review and Meta-Analysis

Background: The recommended treatment of asymptomatic carotid atherosclerosis is best medical therapy since the 1% annual risk of stroke is lower than the risk of stroke from revascularization. Specific imaging features may identify patients at increased risk of stroke and optimize the risk-benefit ratio of carotid surgery. To assess the relevance and feasibility of such approach, we aimed to summarize available data on the frequency of high-risk features and the related risk of stroke in patients with asymptomatic carotid atherosclerosis. Methods: A search of Pubmed and Ovid-Embase identified prospective studies reporting findings of carotid plaque imaging and incidence of stroke in patients with asymptomatic carotid atherosclerosis. Prevalence of high-risk features and incidence of ipsilateral ischemic events were pooled using random-effect meta-analysis. Results: Thirty-five studies enrolling 5808 participants with asymptomatic carotid atherosclerosis of various grades were included. The pooled prevalence (95% CI) of high-risk features on plaque imaging was 28.8 (18.8 - 38.7). The prevalence of neovascularization was 53.5% (45.2 - 61.8), echolucency 40.0% (30.8 - 49.6), lipid-rich necrotic core 35.7% (24.1 - 48.1), thin or ruptured fibrous cap 27.5% (14.2 - 43.3), silent brain infarcts 27.0% (15.3 - 40.5), impaired cerebrovascular reserve 25.9% (10.3 - 45.5), intraplaque hemorrhage 19.2% (13.9 - 25.1), microembolic signals 14.4% (8.9 - 20.8), and ulceration 13.5% (1.3 - 34.0). In 15 cohort studies enrolling 4215 participants, the mean duration of follow-up was 3.5 years (2.0 - 4.6). The pooled incidence of ipsilateral ischemic events was 2.7 per 100 person-years (1.6 - 4.0). This incidence was higher in patients with a high-risk feature (4.9%, 2.3 - 8.2) than in those without (0.9%, 0.2 - 1.8) with an odds ratio of 4.6 (2.3 - 9.3). Conclusion: High-risk features on imaging are frequent in asymptomatic carotid atherosclerosis and associated with a fourfold increase in the annual risk of ipsilateral ischemic events. A risk-oriented selection of patients with asymptomatic carotid atherosclerosis prior to randomization in revascularization trials appears relevant and may be a strategy to prevent stroke in asymptomatic carotid atherosclerosis.

Assessment of cerebrovascular reserve impairment using the breath-holding index in patients with leukoaraiosis.

Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth People's Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).

Trials and Frontiers in Carotid Endarterectomy and Stenting.

Based on the strength of randomized trials from the 1990s, major societal guidelines recommend carotid endarterectomy (CEA) for severe (≥70%), symptomatic carotid stenosis if an operative stroke/death rate of <6% can be maintained (history and major trials in carotid revascularization are summarized in the online-only Data Supplement).1–4 Though the benefit is less evident, most guidelines also recommend consideration of CEA for 50% to 69% symptomatic stenosis.2–4 There are subtle differences in recommendations regarding carotid artery stenting (CAS) in symptomatic patients. Some guidelines stipulate that CEA should be preferred over CAS in patients with severe (≥70%) symptomatic carotid stenosis,2,5 especially if >70 years old,4 whereas others position CAS as an alternative.1,3 Though the risk of operative stroke/death is higher with CAS, major randomized clinical trials (RCTs) report event rates under the recommended 6% cutoff for both treatment modalities. Regarding asymptomatic disease, CEA is recommended for patients with stenosis ≥60% to 70% in highly selected patients as long as operative stroke/death rates <3% can be maintained.1 A predicted life expectancy of at least 3 to 5 years has also been suggested.2 The 3% threshold has been easily met by CEA cohorts in the CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial; 1.4%)6 and the ACT1 (Asymptomatic Carotid Trial; 1.7%),7 suggesting that an even lower threshold may be appropriate. Controversially, some guidelines have recommended that CAS can be considered in highly selected patients with asymptomatic carotid stenosis ≥60% to 70%,1,4,8 whereas others argue that the evidence remains insufficient.2 The lack of consensus in the management of asymptomatic carotid stenosis is reflective of an ongoing need for high-quality RCT data to guide practice. ### CEA Operative Stroke Risk and High Risk Designation Most clinical trials in carotid revascularization have focused …

Reduced Cerebrovascular Reserve Capacity in Adults with Sickle Cell Disease

Introduction: Sickle Cell Disease (SCD) is frequently complicated by stroke. Although transcranial Doppler effectively identifies children at risk for stroke, adult patients do not benefit from this test. In SCD, chronic hemolytic anemia leads to cerebral vasodilation, elevated cerebral blood flow (CBF) and subsequently, impaired cerebrovascular reserve (CVR) capacity. CVR represents the maximum increase in CBF in response to metabolic stressors. CVR mapping is a promising imaging biomarker for stroke risk assessment, potentially identifying patients with preclinical hemodynamic impairment. Our laboratory performs CVR mapping by measuring CBF prior to and following maximum cerebral vasodilation with acetazolamide (ACZ). The primary aim of this study was to quantitatively assess CVR in adult patients with SCD compared to healthy controls.Methods: Adult SCD patients (HbSS/HbSβ0) were recruited for this IRB-approved study with ACZ-induced vasodilation and venous blood sampling. Patients with a history of clinically overt stroke were excluded. Controls were selected from patients' friends and family members without SCD and matched on age, sex, and race. The following MRI images were acquired at 3T (Philips Healthcare, Best, NL): time of flight MRA for visualization of major cerebral vessels, T2 FLAIR for manual segmentation of white matter hyperintensities (WMHs), and pseudo-continuous arterial spin labeling (ASL) for CBF assessment. CBF was measured at baseline and 10min post ACZ (16mg/kg intravenous infusion over 3min). MRI images were processed with the ExploreASL toolbox, to obtain registered maps of quantified CBF and CVR (% change in CBF). We measured T1blood in each subject to improve quantification accuracy as these values can differ in SCD. Group comparisons were performed using non-parametric two-sample tests. Correlations were characterized by Spearman's rho (ρ). P<0.05 was considered significant. Median values with interquartile range (IQR) are reported for non-normally distributed variables, otherwise mean and standard deviation are reported.Results: 30 patients with SCD (mean age 33±12y,19M) and 11 controls (mean age 37±15y, 6M) were included in this cross-sectional controlled cohort study. Mean hemoglobin levels in patients with SCD were 8.8±1.4 g/dL and in healthy controls were 13.7±1.3 g/dL. Patients with SCD had higher baseline CBF compared to healthy controls (median 73(IQR:25) vs 42(IQR:6) mL/100g/min, p<0.001, F1a). CBF was inversely related to hemoglobin (ρ=-0.84, p<0.001, F1b). ACZ elicited an increase in CBF(p<0.001) which was similar in magnitude in both groups (patients 29±16, controls 35±11, mL/100g/min, F1c), resulting in a lower mean CVR in patients compared to controls (41±24% vs 81±27%, p<0.001, F1d). Baseline CBF predicted CVR (ρ=-0.68, p<0.001, F1e). WMHs were present in both groups, and WMH volume correlated with age (ρ = 0.54, p<0.001). There were no statistical associations between WMH volume and CVR (ρ = -0.15, p=0.4) or CBF(ρ = 0.02, p=0.9), however, two patients with the largest WMH volume (>6 mL) had the lowest CVR (<20%).Discussion: This study shows that regional CVR can be measured using ASL-MRI with ACZ challenge. ACZ was well-tolerated and elicited a robust cerebrovasodilatory response in both groups. However, the relative increase in oxygen delivery (CVR) was much lower in SCD patients, which suggests that patients with SCD have nearly maximal cerebrovascular dilation at baseline. Our data suggest that chronic vasodilation due to anaemia has let to outward remodelling of vessels in adult patients, permitting a larger vascular bed to compensate their anemia. Our premise is that resting O2 delivery is normal in SCD patients; we showed that increasing CBF overcomes severe anemia. However, high resting CBF limits the brain's ability to recruit additional O2 under times of stress. SCD patients have many transient interruptions in O2 delivery including aplastic crisis, splenic sequestration and sleep apnea, as well as metabolic stressors such as fever, sickle cell crisis, infection, and seizure. While baseline CBF predicted global CVR, ASL provides information regarding regional O2 delivery that may offer insight into distribution of ischemic white matter damage. Further study is needed to determine the impact of blood transfusions and hydroxyurea on CVR and whether there is a critical CVR threshold that predicts stroke risk. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of sevoflurane versus propofol on cerebrovascular reactivity to carbon dioxide during laparoscopic surgery.

PurposeCerebrovascular reactivity to carbon dioxide (CVR-CO2) reflects cerebrovascular reserve capacity, which is important in many brain disorders, including cerebrovascular and Alzheimer’s diseases. Meanwhile, there is a relationship between CVR-CO2 and cognitive function. Therefore, the study is aimed at investigating the effects of sevoflurane versus propofol on CVR-CO2 during laparoscopic surgery, as well as the role of CVR-CO2 on cognitive function during perioperative period.Patients and methodsEighty-eight patients, aged 18–65 years undergoing elective laparoscopic cholecystectomy, were randomly assigned to group S and group P. The patients in group S were induced with propofol and maintained with sevoflurane. The patients in group P were induced and maintained with propofol (target-controlled infusion). Remifentanil was given to both groups. CVR-CO2 at baseline (before induction), before pneumoperitoneum and during pneumoperitoneum, as well as Mini-Mental State Examination scores at baseline and 24 hours after surgery were recorded.ResultsIn group S, CVR-CO2 before and during pneumoperitoneum increased significantly compared with baseline (P<0.05). In group P, CVR-CO2 before pneumoperitoneum increased significantly (P<0.05), but CVR-CO2 during pneumoperitoneum was not different compared with baseline. In either group, there was no significant correlation between mean blood pressure and CVR-CO2 during surgery, and there was no significant difference between Mini-Mental State Examination scores at baseline and 24 hours after surgery.ConclusionSevoflurane could maintain CVR-CO2 at a higher level during pneumoperitoneum in surgery. Therefore, in patients with impaired cerebrovascular reserve capacity, inhaled anesthetic could be a priority strategy for anesthesia maintenance to improve the compensatory vasodilation ability of cerebral small vessels.

Brain Perfusion Imaging Under Acetazolamide Challenge for Detection of Impaired Cerebrovascular Reserve Capacity: Positive Findings with 15O-Water PET in Patients with Negative 99mTc-HMPAO SPECT Findings.

Cerebrovascular reserve capacity (CVRC) is an important parameter for treatment decisions in chronic cerebrovascular diseases. It can be assessed by measuring the acetazolamide-induced change in regional cerebral blood flow using SPECT with 99mTc-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) or PET with 15O-water. Methods: Our database was searched for patients with moyamoya vasculopathy or atherosclerotic cerebrovascular disease who had undergone 15O-water PET after normal 99mTc-HMPAO SPECT results with respect to CVRC. 15O-water PET was analyzed visually and quantitatively. Quantitative analysis was based on parametric CVRC maps generated by voxelwise image subtraction. Results: The search identified 18 patients (43 ± 15 y, 12 moyamoya vasculopathy). PET revealed impaired CVRC in 8 patients (44%). Quantitative analysis confirmed the positive visual findings in 15O-water PET and the negative findings in 99mTc-HMPAO SPECT. Conclusion:15O-water PET enables detection of impaired CVRC in a considerable fraction of symptomatic patients with stenoocclusion and negative 99mTc-HMPAO SPECT.

Motor plasticity after extra-intracranial bypass surgery in occlusive cerebrovascular disease.

To explore plasticity in patients scheduled for extra-intracranial bypass surgery due to unilateral symptomatic occlusive cerebrovascular disease via navigated transcranial magnetic stimulation. In this observational study, patients were allocated to different substudies and examined before and 3 months after operation. (1) Corticospinal excitability was determined via identification of the resting motor threshold. (2) Intracortical inhibition and facilitation were tested by paired pulse transcranial magnetic stimulation. (3) Area of cortical representation of the first dorsal interosseous muscle was identified. (1) Resting motor thresholds were higher in the affected hemispheres with impaired cerebrovascular reserve capacity compared to the unaffected hemispheres (45.7% ± 2.2% compared to 39.2% ± 1.4%, n = 39, p < 0.05). Reduced excitability normalized 3 months after revascularization (51% ± 2.6% → 45% ± 1.9%, n = 21, p < 0.05). (2) In paired pulse paradigms, there was a motor disinhibition in the operated hemispheres. (3) There was a reduction of the cortical representation areas of the first dorsal interosseous muscle (2.3 ± 0.5 cm(2) → 0.9 ± 0.6 cm(2), n = 9, p < 0.05) after operation. Our data demonstrate a reversibly impaired motor cortical function in the chronically ischemic brain. In carefully selected patients, cerebral revascularization leads to improved motor output indicated by a lower resting motor threshold, intracortical disinhibition, and more focused motor cortical representation.

Angiographic Correlates of Cerebral Hemodynamic Changes With Diamox Challenge Assessed by Quantitative Magnetic Resonance Angiography.

Impaired cerebrovascular reserve in chronic steno-occlusive disease has been shown to be associated with poor leptomeningeal collaterals (LMCs) on digital subtraction angiography and increased stroke risk. We examined the relationship between the degree of LMCs and the flow change with Diamox challenge measured using quantitative magnetic resonance angiography (QMRA). Patients with steno-occlusion in the internal carotid artery or middle cerebral artery (MCA) at our institution between 2007 and 2013 were retrospectively studied. Intracranial flows were obtained using QMRA, and flow change with Diamox (QMRAΔd) was calculated as follows: ([flow after Diamox-flow before Diamox]/[flow before Diamox])×100%. Poor LMC was defined as grade 1 or 2, and robust LMC was defined as grade 3 or 4 based on the ASITN/SIR (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) grading system on digital subtraction angiography. Thirty-eight patients had angiographic and flow data. Ipsilateral MCA QMRAΔd was significantly lower versus the contralateral side (flow, 85.5 versus 135.9 mL/min; P<0.001 and QMRAΔd, 24.0% versus 45.6%; P=0.01). If LMCs were robust (n=12), MCA QMRAΔd was significantly higher (21.4% versus -26.8%; P=0.04) compared with patients with poor LMC (n=4). We show that patients with more robust LMC have better MCA QMRAΔd. Therefore, QMRAΔd may be used for the functional assessment of LMC as a surrogate for cerebrovascular reserve in chronic internal carotid artery or MCA steno-occlusive disease.