Cerebrovascular Reserve Capacity Research Articles

Amelioration of gait and balance disorders by rosuvastatin is associated with changes in cerebrovascular reactivity in older patients with hypertensive treatment.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration.

Non-Invasive Tools in Perioperative Stroke Risk Assessment for Asymptomatic Carotid Artery Stenosis with a Focus on the Circle of Willis.

This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.

Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Abstract 115: Presenting Symptoms and Neuroimaging Correlates in North American Moyamoya Vasculopathy

Introduction: Moyamoya disease (MMD) is a steno-occlusion of the supraclinoid internal carotid arteries and proximal branches with the development of collateral vessels 1 . Once thought to affect primarily females of East Asian descent, more than 11,000 hospitalizations in patients with MMD of non-Asian ancestry are reported annually in the USA, with the majority presenting with ischemic stroke. Here, we present frequent non-stroke symptomatology in North American MMD along with hemodynamic imaging profiles at presentation. Methods: Participants provided informed consent and underwent anatomical MRI with hypercapnic blood oxygenation level-dependent 2 ; time regression was applied to quantify cerebrovascular reactivity (CVR) and reactivity delay time (CVR DELAY ) 3 in right and left MCA territories. A logistic regression analysis based on the Huber-White sandwich estimator compared the CVR metrics between cohorts. Significance criterion: Bonferroni corrected two-sided p<0.05. Results: 74 patients (age=11-77 years; Asian=6%, White=65%, Black=29%) diagnosed with MMD with symptom durations spanning hours to years prior to presentation were enrolled. Non-stroke symptoms and frequency prior to stroke are listed in Table 1. In more than 1/3 rd of patients, unprovoked headaches preceded stroke-like symptoms. In patients exhibiting ischemic symptoms within six months of neuroimaging, cerebrovascular reserve capacity was reduced (p=0.007), and cerebrovascular reactivity delay time increased (p<0.001), in the flow territory from which symptoms were derived compared to the contralateral flow territory. Discussion: North American MMD is being observed with increasing frequency and increasing the awareness of non-stroke MMD presentations may lead to early diagnosis that can lead to proactive revascularization to minimize the risk of first stroke in these patients.

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.

Imaging methods in assessing the surveillance of type 2 diabetes mellitus for cerebrovascular reserve and brain disease in patients with hemodynamically significant carotid stenosis

Introduction. Type 2 diabetes is the most common form of endocrine disease. Diabetes is a well-established risk factor for stroke. Carotid endarterectomy (CEE) is the main method of preventing a serious complication of stroke in patients with carotid stenosis. Consequently, the assess of type 2 diabetes on the results of CEE is an urgent problem of angiosurgery.Aim: To assess effect of type 2 diabetes on cerebrovascular reserve capacity and brain structure in patients with carotid atherosclerosis by ultrasound and magnetic resonance diagnostic.Material and Methods. 44 patients with hemodynamically significant stenosis of the internal carotid arteries (ICA), who underwent ultrasound and magnetic resonance examinations of the carotid arteries at the pre- and postoperative stages were included in this study. Two groups were formed: group I (n =15) – with a verified diagnosis of type 2 diabetes, group II (n = 29) – without diabetes. To assess the cerebrovascular reserve, functional hypercapnic and hyperoxic tests were performed.Results. The analysis of the results showed statistically significant differences in the ICA blood flow in both groups. Intergroup comparison before surgery in the middle cerebral artery on the side of hemodynamically significant stenosis revealed a statistically significant difference in pulsation and peripheral resistance index. In the common carotid arteries on both sides, significant intergroup differences were found in the velocity parameters of blood flow after the CEE operation. The reactivity index in patients with surgical stenosis with type 2 diabetes in the hyperoxic test was statistically significantly different on the side of the stenosis compared to the same indicator in the group without diabetes. There were no statistically significant differences in the hypercapnic test. The value of reactivity index indicates a negative or paradoxical reaction.Conclusion. The use of simple and accessible functional tests to assess cerebrovascular reserve, plaque structure and changes in the brain in patients with type 2 diabetes at the stage of preoperative preparation according to ultrasound and MRI studies allows us to correct the treatment and subsequent protection of the brain at the stage of surgery to prevent possible complications.

Heterogeneous motor BOLD-fMRI responses in brain areas exhibiting negative BOLD cerebrovascular reactivity indicate that steal phenomenon does not always result from exhausted cerebrovascular reserve capacity

IntroductionBrain areas exhibiting negative blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) responses to carbon dioxide (CO2) are thought to suffer from a completely exhausted autoregulatory cerebrovascular reserve capacity and exhibit vascular steal phenomenon. If this assumption is correct, the presence of vascular steal phenomenon should subsequently result in an equal negative fMRI signal response during a motor-task based BOLD-fMRI study (increase in metabolism without an increase in cerebral blood flow due to exhausted reserve capacity) in otherwise functional brain tissue. To investigate this premise, the aim of this study was to further investigate motor-task based BOLD-fMRI signal responses in brain areas exhibiting negative BOLD-CVR. Material and methodsSeventy-one datasets of patients with cerebrovascular steno-occlusive disease without motor defects, who underwent a CO2-calibrated motor task-based BOLD-fMRI study with a fingertapping paradigm and a subsequent BOLD-CVR study with a precisely controlled CO2-challenge during the same MRI examination, were included. We compared BOLD-fMRI signal responses in the bilateral pre- and postcentral gyri – i.e. Region of Interest (ROI) with the corresponding BOLD-CVR in this ROI. The ROI was determined using a second level group analysis of the BOLD-fMRI task study of 42 healthy individuals undergoing the same study protocol. ResultsAn overall decrease in BOLD-CVR was associated with a decrease in BOLD-fMRI signal response within the ROI. For patients exhibiting negative BOLD-CVR, we found both positive and negative motor-task based BOLD-fMRI signal responses. ConclusionWe show that the presence of negative BOLD-CVR responses to CO2 is associated with heterogeneous motor task-based BOLD-fMRI signal responses, where some patients show -more presumed- negative BOLD-fMRI signal responses, while other patient showed positive BOLD-fMRI signal responses. This finding may indicate that the autoregulatory vasodilatory reserve capacity does not always need to be completely exhausted for vascular steal phenomenon to occur.

Outcome prediction of pediatric moyamoya disease using midterm cerebral blood flow measured between staged anastomoses.

Cognitive outcomes of pediatric moyamoya disease are variable and difficult to predict on the basis of initial neurological signs and examinations. To determine the best early time point for outcome prediction, we retrospectively analyzed the correlation between cognitive outcomes and the cerebrovascular reserve capacity (CRC) measured before, between, and after staged bilateral anastomoses. Twenty-two patients aged 4-15years were included in this study. CRC was measured before the first hemispheric surgery (preoperative CRC), 1year after the first surgery (midterm CRC), and 1year after the surgery on the other side (final CRC). The cognitive outcome was the Pediatric Cerebral Performance Category Scale (PCPCS) grade more than 2years after the final surgery. The 17 patients with favorable outcomes (PCPCS grades 1 or 2) showed a preoperative CRC of 4.9% ± 11.2%, which was not better than that of the five patients with unfavorable outcomes (grade 3; 0.3% ± 8.5%, p = 0.5). The 17 patients with favorable outcomes showed a midterm CRC of 23.8% ± 15.3%, which was significantly better than that of the five patients with unfavorable outcomes (-2.5% ± 12.1%, p = 0.004). The difference was much more significant for the final CRC, which was 24.8% ± 13.1% in the patients with favorable outcomes and -11.3% ± 6.7% in those with unfavorable outcomes (p = 0.00004). Cognitive outcomes were first clearly discriminated by the CRC after the first-side unilateral anastomosis, which is the optimal early timing for the prediction of individual prognosis.

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

ObjectivesCell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. MethodsDSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. ResultsDSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). ConclusionIt is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.

Validation of the Berlin Grading System for moyamoya angiopathy with the use of [15O]H2O PET

The Berlin Grading System assesses clinical severity of moyamoya angiopathy (MMA) by combining MRI, DSA, and cerebrovascular reserve capacity (CVRC). Our aim was to validate this grading system using [15O]H2O PET for CVRC. We retrospectively identified bilateral MMA patients who underwent [15O]H2O PET examination and were treated surgically at our department. Each hemisphere was classified using the Suzuki and Berlin Grading System. Preoperative symptoms and perioperative ischemias were collected, and a logistic regression analysis was performed. A total of 100 hemispheres in 50 MMA patients (36 women, 14 men) were included. Using the Berlin Grading System, 2 (2.8%) of 71 symptomatic hemispheres were categorized as grade I, 14 (19.7%) as grade II, and 55 (77.5%) as grade III. The 29 asymptomatic hemispheres were characterized as grade I in 7 (24.1%) hemispheres, grade II in 12 (41.4%), and grade III in 10 (34.5%) hemispheres. Berlin grades were independent factors for identifying hemispheres as symptomatic and higher grades correlated with increasing proportion of symptomatic hemispheres (p < 0.01). The Suzuki grading did not correlate with preoperative symptoms (p = 0.26). Perioperative ischemic complications occurred in 8 of 88 operated hemispheres. Overall, complications did not occur in any of the grade I hemispheres, but in 9.1% (n = 2 of 22) and 9.8% (n = 6 of 61) of grade II and III hemispheres, respectively. In this study, we validated the Berlin Grading System with the use of [15O]H2O PET for CVRC as it could stratify preoperative symptomatology. Furthermore, we highlighted its relevance for predicting perioperative ischemic complications.

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.

Affected Microcirculation and Vascular Hemodynamics in Takayasu Arteritis.

Introduction: Takayasu arteritis (TAK) is a rare inflammatory disease affecting aorta and its major branches. Ultrasound (US) can detect inflammatory features in the arterial wall, but less is known regarding skin microcirculation and vascular hemodynamics. The aim was to study if assessment of these variables could add valuable information regarding vascular affection in TAK. Methods: 17 patients diagnosed with TAK and 17 age- and sex-matched healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) in the skin after induced ischemia was evaluated with laser Doppler flowmetry/diffuse reflectance spectroscopy. Cerebrovascular reserve capacity (CVR) in the brain was assessed with transcranial Doppler (TCD). Pulse waves were recorded in the radial artery by the aid of applanation tonometry, for calculation of central augmentation index (AIx75). Intima-media thickness (IMT) and stenosis/occlusions were evaluated using US in carotid and central arteries. Results: Reduced OxyP (79 ± 8% vs. 87 ± 4%, p < 0.001) was seen in patients with TAK regardless of significant arterial stenosis/occlusion or not. Increased AIx75 (22.3 ± 13.6 vs. 9.2 ± 16.3, p = 0.01) was seen in TAK patients without significant stenosis/occlusions. No differences were found in CVR, regardless of proximal stenosis. However, signs of a more high-resistance flow profile were seen in arteria cerebri media. Conclusion: Regardless of arterial stenosis or not, impaired microcirculation of the skin and preserved CVR in the brain were found in subjects with TAK. Signs of increased arterial stiffness in the brain and central arteries were observed. The value of these findings for prediction of future cardiovascular events needs to be clarified in further studies.

Surgical revascularization for moyamoya angiopathy: Clinical and radiological outcomes of direct and indirect bypasses in 86 affected hemispheres

Moyamoya is a progressive cerebral angiopathy that entails a formidable natural history of repeated ischemic or haemorrhagic insults if not intervened. The potential advantages of direct/combined bypass can be harvested only if they are not outweighed by perioperative morbidity. Direct bypasses for the paediatric group have been less utilized because of small vessel calibres and an inherently more robust angioplasticity. This study was undertaken to examine the clinical and perfusion imaging outcomes of operated moyamoya disease or syndrome patients in Hong Kong’s Southeast Asian population. Comparison was made between direct/combined and indirect bypass cohorts. Subgroup analysis of the paediatric cohort was conducted to determine outcomes of a direct-bypass-first strategy. From November 2000 to September 2020, 86 hemispheres underwent revascularization at a tertiary neurosurgical unit with a mean clinical follow-up time of 70.0 months. 70.9% of the procedures involved direct bypasses. Direct/combined revascularization demonstrated superiority in restoring adequate cerebrovascular reserve capacity (CVRC) (63.2% vs 27.3%, p = 0.015), and freedom from transient ischemic attacks in the first 5 years post-operation by Kaplan-Meier plot with log-rank test (p = 0.038). Follow-up imaging revealed 96.5% of the bypass grafts remained patent. Direct/combined procedures significantly predicted restoration of adequate CVRC on follow-up perfusions scans by binary logistic regression (OR 4.57, p = 0.009). Compared to the adult cohort, direct bypasses in children carried no excessive perioperative morbidity. These results support a liberal bypass-first paradigm in both adult and paediatric cohorts.

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.

Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis.

Arteriogenesis constitutes the most efficient endogenous rescue mechanism in cases of cerebral ischaemia. The aim of this work was to investigate whether angiotensin-converting enzyme inhibitors (ACEi) stimulates, and angiotensin II receptor type 1 blockers (ARB) inhibits cerebral collateral growth by applying a three-vessel occlusion (3-VO) model in rat. Cerebral collateral growth was measured post 3-VO (1) by assessing blood flow using the cerebrovascular reserve capacity (CVRC) technique, and (2) by assessing vessel diameters in the posterior cerebral artery (PCA) via the evaluation of latex angiographies. A stimulatory effect on arteriogenesis was investigated for ACEi administration±bradykinin receptor 1 (B1R) and 2 (B2R) blockers, and an inhibitory effect was analysed for ARB administration. Results were validated by immunohistochemical analysis and mechanistic data were collected by human umbilical vein endothelial cell (HUVEC) viability or scratch assay and monocyte (THP-1) migration assay. An inhibitory effect of ARB on arteriogenesis could not be demonstrated. However, collateral growth measurements demonstrated a significantly increased CVRC and PCA diameters in the ACEi group. ACEi stimulates cell viability and migration, which could be partially reduced by additional administration of bradykinin receptor 1 inhibitor (B1Ri). ACEi inhibits the degradation of pro-arteriogenic bradykinin derivatives, but combined ACEi+B1Ri+B1Ri (BRB) treatment did not reverse the stimulatory effect. Yet, co-administration of ACEi+BRB enhances arteriogenesis and cell migration. We demonstrate a potent stimulatory effect of ACEi on cerebral arteriogenesis in rats, presumable via B1R. However, results imply a pleiotropic and compensatory effect of ACEi on bradykinin receptor-stimulated arteriogenesis.

Surgical Management of Failed Revascularization in Moyamoya Vasculopathy.

Objectives: Moyamoya vasculopathy (MMV) is a rare stenoocclusive cerebrovascular disease associated with increased risk of ischemic and hemorrhagic stroke, which can be treated using surgical revascularization techniques. Despite well-established neurosurgical procedures performed in experienced centers, bypass failure associated with neurological symptoms can occur. The current study therefore aims at characterizing the cases of bypass failure and repeat revascularization at a single center.Methods: A single-center retrospective analysis of all patients treated with revascularization surgery for MMV between January 2007 and December 2019 was performed. Angiographic data, cerebral blood flow analysis [H2O PET or single-photon emission CT (SPECT)], MRI, and clinical/operative data including follow-up assessments were reviewed.Results: We identified 308 MMV patients with 405 surgically treated hemispheres. Of the 405 hemispheres treated, 15 patients (3.7%) underwent repeat revascularization (median age 38, time to repeat revascularization in 60% of patients was within 1 year of first surgery). The most common cause of repeat revascularization was a symptomatic bypass occlusion (80%). New ischemic lesions were found in 13% of patients prior to repeat revascularization. Persistence of reduced or progressive worsening of cerebrovascular reserve capacity (CVRC) compared with preoperative status was observed in 85% of repeat revascularization cases. Intermediate-flow bypass using a radial artery graft was most commonly used for repeat revascularization (60%) followed by re-superficial temporal artery to middle cerebral artery (re-STA-MCA) bypass (26%). High-flow bypass using a saphenous vein graft and using an occipital artery to MCA bypass was each used once. Following repeat revascularization, no new ischemic events were recorded.Conclusion: Overall, repeat revascularization is needed only in a small percentage of the cases in MMV. A rescue surgery should be considered in those with neurological symptoms and decreased CVRC. Intermediate-flow bypass using a radial artery graft is a reliable technique for patients requiring repeat revascularization. Based on our institutional experience, we propose an algorithm for guiding the decision process in cases of bypass failure.

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.

Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling.

Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.

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

Evaluation of cerebrovascular reactivity by ultrasonography in type 2 diabetic patients with hypertension*

BACKGROUNDCerebrovascular reactivity (CVR) reflects cerebrovascular reserve capacity, and cerebrovascular reactivity damage prognosticates a very high risk of stroke. OBJECTIVETo evaluate CVR by detecting the increase rate of blood flow volume of middle cerebral artery (MCA) before and after breathholding in diabetic patients with hypertension, and observe the effects of hypertension on cerebrovascular reserve capacity of diabetic patients. DESIGNControlled observation. SETTINGSDepartment of Function, Affiliated Hospital of Hebei University; Department of Special Diagnosis, the 202 Hospital of Chinese PLA. PARTICIPANTSInpatients or outpatients with type 2 diabetes mellitus (DM) or primary hypertension admitted to Departments of Gastroenterology and Cardiology, Affiliated Hospital of Hebei University and the 202 Hospital of Chinese PLA from April to December 2004 were involved in this experiment. Inclusive criteria: type 2 DM met the criteria of the report on diabetes diagnosis announced in 1999 by WHO expert committee, totally 88 patients were involved. Primary hypertension met the diagnosis criteria announced in 1999 by WHO/ISH, totally 42 patients were involved. Another group of 43 concurrent subjects who received physical examination served as controls. According to the disease condition, the involved patients were assigned into 3 groups: DM group (only diabetic patients), hypertension group (only hypertension patients) and DM complicated with hypertension group (diabetic patients with hypertension). Informed consent for the examination was obtained from all the involved subjects. METHODSBefore MCA of subjects was detected, bilateral carotid artery was routinely detected by high-frequency ultrasonography. Subjects were rejected when stenosis rate of unilateral internal carotid artery or common carotid artery ≥ 70%. Vessels were expanded with transcranial color Duplex Doppler by breath holding test for detecting vascular reactivity. Hypercapnia was created by BHT. The mean velocity and diameter of blood flow were detected under the quiescent condition and 25 s after breath holding with transcranial color-coded duplex sonography. The volume of blood flow of MCA was calculated according to the following formula: Volume of blood flow of MCA (mL/ min) = (the diameter of blood flow /2)2 × π × mean blood flow velocity × 60. The increase rates of mean blood flow velocity and blood flow volume of patients with hypercapnia were calculated as compared with under the quiescent condition to evaluate cerebrovascular reactivity. MAIN OUTCOME MEASURESMean blood flow velocity, blood flow diameter and MCA blood flow volume as well as the increase rates of them. RESULTSAmong the 173 participates, 103 patients and 39 healthy controls were involved in the final analysis, and the other 31 dropped out due to not accomplishing the examination, (1)Comparison of blood flow parameter of MCA under the quiescent condition: The mean blood flow velocity of DM complicated by hypertension group was significantly higher than that of DM group (P < 0.05) and control group (P < 0.05); The blood flow diameter of DM complicated by hypertension group was significantly smaller than that of control group (P < 0.01). Under the quiescent condition, significant difference was not found in the intergroup comparison of blood flow volume of MCA. (2) Comparison of increase rate of blood flow parameter: In the DM group, hypertension group. DM complicated by hypertension group and control group, the increase rate of mean blood flow velocity of was (29.34±4.50) %, (29.35±4.35) %, (26.68±4.99) % and (30.99±3.54) %, respectively, the increase rate of blood flow volume of MCA was (35.32±5.08) %, (35.36±6.16) %, (31.78±7.11) % and (37.26±4.17) %, respectively, and the increase rate of blood flow diameter was (2.29±1.09) %, (2.27±0.95) %, (1.97±1.05) % and (2.36±0.46) %, respectively. The increase rate of mean blood flow velocity and that of blood flow volume of MCA in the DM complicated by hypertension group were significantly lower than those in the other 3 groups (P < 0.05). CONCLUSIONCVR is markedly lowered and cerebrovascular reserve capacity is damaged in diabetic patients with hypertension.