Cerebrovascular Reserve Research Articles

Impact of cortical hemodynamic failure on both subsequent hemorrhagic stroke and effect of bypass surgery in hemorrhagic moyamoya disease: a supplementary analysis of the Japan Adult Moyamoya Trial.

Here, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease. Data from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup. The hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07-27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04-0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22-11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056). Hemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp).

High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease.

Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling-derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease. Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient's 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute-based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively. A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968-0.988) and 1.8 percentage points (95% CI, 0.3-3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively. Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

Abstract WMP41: The Value of Arterial Spin-Labeling Imaging in the Cerebral Collateral Circulation Evaluation of Carotid Occlusive Disease; Correlation Study With Acetazolamide-Stress Single Photon Emission Computed Tomography

Introduction: We investigated the relationship between the level of cerebral collateral circulation on arterial spin-labeling (ASL) magnetic resonance imaging (MRI) and cerebrovascular reserve (CVR) on acetazolamide (ACZ)-stress single photon emission computed tomography (SPECT) brain scans in internal carotid artery (ICA) stenosis. Methods: This study enrolled 129 patients with severe ICA stenosis (>70%). Collateral circulation was assessed in pulsed ASL images based on the presence of arterial transit artifact (ATA) that late-arriving flow appears as serpiginous high ASL signal within cortical vessels. CVR based on rest-SPECT and ACZ-stress SPECT with Tc-99m-ECD was calculated. The ASL CBF maps were independently assessed by two neuroradiologists blinded to clinical information. The two neuroradiologists graded on two slices of ASL images corresponding to Alberta Stroke Program Early Computed Tomography Score (ASPECTS) location using a 4-point scale for ASL intensity. Results: With ACZ-stress SPECT, the 88/129 (68%) patients showed normal CVR and 41/129 (32%) patients showed decreased CVR. In 73/88 (82%) of the normal CVR group patients, ASL showed ATA in ipsilateral to the stenosis. In 19/41 (46%) of the decreased CVR group patients, ASL showed no evidence of ATA in ipsilateral to the stenosis. Significant positive relationship was observed between the normal CVR group and the ATA showing group in ICA stenosis patients (p = 0.001, chi-square test). The ASL-based ASPECTS scores of brain in the ipsilateral side was lower than the scores in the contralateral side to the ICA stenosis (p < 0.0001, Wilcoxon signed rank test). The ASL-based ASPECTS scores of brain ipsilateral side to the ICA stenosis was lower in the reduced CVR group than normal CVR group (p = 0.005). Conclusion: This study demonstrated the statistically significant positive correlation between good collaterals on ASL MRI and intact CVR in patients with ICA stenosis.

Abstract TP133: Assessment of Hemodynamic Compromise by Neuro-Parenchymal Blood-Volume System: Comparison With Acetazolamide Challenged Single Photon Emission Computed Tomography

Objective: To investigate whether Neuro-parenchymal blood-volume (PBV) measurements could be used instead of acetazolamide (ACZ)-challenged single-photon emission computed tomography (SPECT) to evaluate hemodynamic compromise in patients with cerebrovascular steno-occlusive disease. Methods: Thirteen patients with unilateral carotid artery steno-occlusive disease were enrolled from April 2018 to June 2019, and the severity of hemodynamic compromise was assessed by Neuro PBV system (syngo Neuro PBV IR, Siemens Medical Solutions, Erlangen, Germany) and acetazolamide-challenged SPECT of the brain. Cerebral blood volume (CBV) was measured using a C-arm flat detector angiographic system. The asymmetry ratio of CBV in the middle cerebral artery (MCA) territory (CBV AR ) was defined as the (CBV on the ipsilateral side / CBV on the contralateral side) х 100 (%). Cerebral blood flow (CBF) was quantified by SPECT using the quantitative SPECT/dual-table autoradiography method. Cerebrovascular reserve (CVR) in the MCA territory was defined as (CBF after ACZ challenge – CBF at rest) / CBF at rest х 100 (%) and classified as reduced (<18.4%) or non-reduced (≥18.4%). Results: Five patients showed reduced CVR. The CBV AR was significantly lower in the reduced CVR group than in the non-reduced CVR group (71.6% vs. 110.0%, P = 0.003). The cut-off value of CBV AR for predicting reduced CVR obtained from analysis of the receiver operating characteristic curve was 99.0% (sensitivity 100% and specificity 87.5%), and the area under the curve was 0.975 (95% confidence interval: 0.906-1). Conclusion: This is the first report to evaluate the correlation between CBV AR measured using the Neuro PBV system and CVR assessed by SPECT. CBV AR is useful indicator for evaluating reduced CVR in the MCA territory, as an alternative to ACZ-challenged SPECT.

Validation and Application for the Berlin Grading System of Moyamoya Disease in Adult Patients.

Traditional moyamoya disease (MMD) classification relies on morphological digital subtraction angiography (DSA) assessment, which do not reflect hemodynamic status, clinical symptoms, or surgical treatment outcome. To (1) validate the new Berlin MMD preoperative symptomatology grading system and (2) determine the clinical application of the grading system in predicting radiological and clinical outcomes after surgical revascularization. Ninety-six MMD patients (192 hemispheres) with all 3 investigations (DSA, magnetic resonance imaging [MRI], Xenon-CT) performed preoperatively at our institution (2007-2013) were included. Two clinicians independently graded the imaging findings according to the proposed criteria. Patients' modified Rankin Score (mRS) scores (preoperative, postoperative, last follow-up), postoperative infarct (radiological, clinical) were collected and statistical correlations performed. One hundred fifty-seven direct superficial temporal artery-middle cerebral artery bypasses were performed on 96 patients (66 female, mean age 41 yr, mean follow-up 4.3 yr). DSA, MRI, and cerebrovascular reserve capacity were independent factors associated hemispheric symptomatology (when analyzed individually or in the combined grading system). Mild (grade I), moderate (grade II), severe (grade III) were graded in 45, 71, and 76 hemispheres respectively; of which, clinical symptoms were found in 33% of grade I, 92% of grade II, 100% of grade III hemispheres (P<.0001). Two percent of grade I, 11% of grade II, 20% of grade III hemispheres showed postoperative radiological diffusion weighted image-positive ischemic changes or hemorrhage on MRI (P=.018). Clinical postoperative stroke was observed in 1.4% of grade II, 6.6% of grade III hemispheres (P=.077). The grading system also correlated well to dichotomized mRS postoperative outcome. The Berlin MMD grading system is able to stratify preoperative hemispheric symptomatology. Furthermore, it correlated with postoperative new ischemic changes on MRI, and showed a strong trend in predicting clinical postoperative stroke.

Abstract TP488: Postoperative Remodeling of Donor Arteries on MR Angiography Can Predict Development of Surgical Collaterals in Moyamoya Disease

Object: The calibers of donor arteries can change dynamically after bypass surgery in moyamoya disease (MMD). The present study aimed to evaluate the cut-offs of caliber changes in donor arteries associated with good surgical revascularization and to assess the impact of clinical factors potentially related to bypass development. Methods: We studied 71 hemispheres of 30 adults and 16 children with MMD, who underwent combined revascularization. We quantitatively measured the calibers of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) with magnetic resonance angiography (MRA) source images and calculated the postoperative caliber change ratios (CCRs), to assess direct and indirect bypass development. They were compared with the findings of digital subtraction angiography, in which revascularization areas were categorized into 3 groups (poor, good, and excellent). Results: In both adult and pediatric hemispheres, median STA and DTA CCRs were higher in better revascularization groups (p &lt; 0.05), while MMA CCRs were not significantly different among the groups. Receiver operation characteristic analysis revealed that the cut-off of &gt;1.1 and &gt;1.3 STA CCRs were associated with good direct revascularization in adult and pediatric hemispheres, respectively. The cut-off of &gt;1.6 and &gt;1.2 DTA CCRs were associated with good indirect revascularization in adult and pediatric hemispheres, respectively. Considering these cut-off values, STA and DTA CCRs showed high median values, irrespective of age, severity of cerebrovascular reserve, disease stage, and disease onset type. Conclusions: Caliber changes in STA and DTA can be easily measured by MRA, which could be indicators of direct and indirect bypass development. The combined bypass procedure could maximize revascularization in both adults and children with MMD.

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.

Abstract WP171: Are We Correctly Measuring Cerebrovascular Reserve Capacity: A Study on Multiple Sequential Post-Acetazolamide Injection Cerebral Blood Flow Measurements Using Arterial Spin Labeling in a Moyamoya Patient Population?

Introduction: Cerebrovascular reserve capacity (CVRC), an important predictor and prognostic factor for patients with moyamoya disease (MMD), can be derived by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Commonly, a single CBF measurement is performed after ACZ injection at a time point varying between 5 to 20 minutes, whereas the dynamic temporal response using sequential CBF measurements has not been studied extensively. Furthermore, current literature reports group averaged CVRCs with high standard deviations indicating a patient-specific CVRC is spread over a wide range of values. The aim of this study was to assess the temporal dynamic response of CBF and derived CVRC during the ACZ challenge using arterial spin labeling in patients with MMD. Methods: Ten patients with MMD were included before and/or after revascularisation surgery and examined on a 3T MR scanner. CBF maps, based on 3D-pseudocontineous arterial spin labeling, were acquired before and 5, 15 and 25 minutes after an i.v. ACZ injection and registered to each patient’s 3D-T1-weighted image. A vascular territory template was spatially normalised to patient-specific space, defined by the 3D-T1-weighted image, including bilateral ACA, MCA and PCA. A post label delay of 2500 ms and large regions-of-interests were used to account for possible arterial transit time artefacts. CVRC was calculated as CBF augmentation post-ACZ injection relative to baseline. Results: A total of sixteen examinations were analysed. Average peak CBF augmentation occurred at 5 min post-ACZ injection, successively decreasing at 15 - and 25 min post-ACZ injection . CVRC followed a similar pattern. Peak CBF augmentation mostly occurred at 5 min for all vascular regions (frequency distribution 5 min: 64 %, 15 min: 23 %, 25 min: 13 %). Average ratio between CVRC calculated using 15 min CBF augmentation and CVRC using true peak CBF augmentation (5, 15 or 25 min) was 0.80 to 0.90 for all vascular regions. Conclusion: CVRC assessed using 15 min as a single post-ACZ injections time point may underestimate CVRC in average by 10 % to 20 % because of individual temporal patient response. The use of multiple post-injection time points is warranted.

Measurement of cerebrovascular reserve by multimodal imaging for cerebral arterial occlusion or stenosis patients: protocol of a prospective, randomized, controlled clinical study

BackgroundCerebrovascular reactivity (CVR) is the change in cerebral blood flow in response to a vaso-active stimulus, and may assist the treatment strategy of ischemic stroke. However, previous studies reported that a therapeutic strategy for stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters (e.g., cerebral blood flow and CVR). Hence, measurement of CVR by multimodal imaging techniques may improve the treatment of ischemic stroke.Methods/designThis is a prospective, randomized, controlled clinical trial that aimed to examine the capability of multimodal imaging techniques for the evaluation of CVR to improve treatment of patients with ischemic stroke. A total of 66 eligible patients will be recruited from Renji Hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR > 10% group and CVR < 10% group. The patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary endpoint is all adverse events and ipsilateral stroke recurrence at 6, 12, and 24 months after management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, and 24 months.DiscussionMeasurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, parallel, randomized, controlled registry study, together with other ongoing studies, should present more evidence for optimal individualized accurate treatment of ischemic stroke.Trial registrationChinese Clinical Trial Registry, ID: ChiCTR-IOR-16009635; Registered on 16 October 2016.All items are from the World Health Organization Trial Registration Data Set and registration in the Chinese Clinical Trial Registry: ChiCTR-IOR-16009635.

Long-term results of surgical brain revascularization in patients with chronic cerebral insufficiency

The study objective is to evaluate long-term effectiveness of extracranial-intracranial (EC-IC) bypass in patients with symptomatic occlusion of the internal carotid artery (ICA).Materials and methods. From 2013 to 2015, 129 patients (aged 41 to 78, average age – 60 years) were applied EC-IC bypass on the side of ICA symptomatic occlusion at the Department of Neurosurgery of N.V. Sklifosovsky Research Institute for Emergency Medicine. We revealed right ICA occlusion in 54 patients, left ICA occlusion – in 67, bilateral occlusion – in 8. Symptomatic ICA occlusion was 5 times more often in men. We assessed neurological status in 1, 2, and 3 years using modified Rankin Scale, National Institutes of Health Stroke Scale, and Rivermead Mobility Index. Computed tomography (CT) angiography of extracranial and intracranial arteries, ultrasound of the anastomosis zone, single-photon emission computed tomography (SPECT) were performed.Results. In the early postoperative period, according to CT angiography and ultrasound, the anastomosis functioned in 125 (97 %) patients; improvement of regional cerebral perfusion according to SPECT was observed in all examined patients (n = 62). We examined 31 patients in the remote postoperative period. According to CT angiography and ultrasound, anastomosis functioned in 30 (97 %) patients, 30 (97 %) patients demonstrated positive dynamics of neurological status and brain perfusion. There were no repeated ischemic-type cerebral circulatory disorders and repeated transient ischemic attacks in the long-term postoperative period.Conclusion. Positive dynamics after EC-IC bypass was revealed both in early and in distant periods (within 1–3 years). During the surgery, it is necessary to take into account cases of ischemic strokes or transient ischemic attack, ICA occlusion according to CT angiography, a decrease in cerebrovascular reserve (&lt;10 %) according to brain SPECT when tested with acetazolamide. To prevent complications, EC-IC bypass should not be used in patients with severe neurological impairments and concomitant pathology. Properly selected patients and postoperative drug therapy helps prevent repeated ischemic cerebral circulatory disorders.Conflict of interest. The authors declare no conflict of interest.Informed consent. All patients gave written informed consent to participate in the study.

Transcranial Doppler ultrasonography in neurological surgery and neurocritical care.

Transcranial Doppler (TCD) ultrasonography is an inexpensive, noninvasive means of measuring blood flow within the arteries of the brain. In this review, the authors outline the technology underlying TCD ultrasonography and describe its uses in patients with neurosurgical diseases. One of the most common uses of TCD ultrasonography is monitoring for vasospasm following subarachnoid hemorrhage. In this setting, elevated blood flow velocities serve as a proxy for vasospasm and can herald the onset of ischemia. TCD ultrasonography is also useful in the evaluation and management of occlusive cerebrovascular disease. Monitoring for microembolic signals enables stratification of stroke risk due to carotid stenosis and can also be used to clarify stroke etiology. TCD ultrasonography can identify patients with exhausted cerebrovascular reserve, and after extracranial-intracranial bypass procedures it can be used to assess adequacy of flow through the graft. Finally, assessment of cerebral autoregulation can be performed using TCD ultrasonography, providing data important to the management of patients with severe traumatic brain injury. As the clinical applications of TCD ultrasonography have expanded over time, so has their importance in the management of neurosurgical patients. Familiarity with this diagnostic tool is crucial for the modern neurological surgeon.

Collateral and Cerebrovascular Reserve Predict the Developement of Hyperperfuson Syndome After Carotid Endarterectomy in Asymptomatic Patients

Collateral and Cerebrovascular Reserve Predict the Developement of Hyperperfuson Syndome After Carotid Endarterectomy in Asymptomatic Patients

Beneficial Effect of Carotid Artery Stenting on Cerebral Hemodynamic Impairment and Cognitive Function.

The aim of this study was to evaluate the effects of the carotid artery stenting (CAS) procedure on cerebral hemodynamics and cognitive performance in patients with internal carotid artery stenosis. In this prospective observational study, 16 consecutive patients in a single institute were treated with CAS from 2010 to 2011 (71.7 ± 7.3 years old, 12 males, and six left-sided procedures). Before and after the CAS procedure, all patients were evaluated with single photon emission computed tomography using 123 I-iodoamphetamine and acetazolamide as well as the Weschler Adult Intelligent Scale (WAIS) to assess three intelligent quotients and four indexes. Patients with decreased preprocedural cerebral blood flow (CBF) and cerebrovascular reserve (CVR) experienced significant increases in CBF and CVR (P = 0.01 and 0.03). Twelve (75%) patients experienced a significant increase in one or more WAIS scores, while two (13%) showed a significant decrease. The most frequently improved scores were the Working Memory Index and Processing Speed Index (seven patients/44%). Preprocedural CBF was significantly correlated with the Full-scale and Performance Intelligent Quotients (r = 0.51–0.56, P = 0.02–0.04), and patients who experienced a significant increase in these scores had larger increases in CVR than patients with unchanged scores (P = 0.0097–0.019). These results indicate that the CAS procedure improved impaired cerebral hemodynamics and might benefit the cognitive function of patients with internal carotid artery stenosis related to impaired cerebral hemodynamics.

Association of Endothelial Biomarkers with Cerebral MRI Perfusion Analysis in Patients with Sickle Cell Disease

Introduction Sickle cell disease (SCD) is associated with silent cerebral infarcts (SCI) which are related to neurocognitive damage. One of the major causes of SCI is the impaired cerebral oxygenation, which makes cerebral blood flow (CBF) an essential parameter to measure. Previous hemodynamic studies have shown elevated CBF and reduced cerebrovascular reserve (CVR) in patients with SCD (Helton 2015; Václavů 2018). CVR is known as the increase of CBF in response to vasoactive stimulus, relative to the baseline. The reduced CVR renders SCD patients susceptible to cerebral ischemia, especially under hypotensive or hypoxic conditions. Possible factors contributing to microvascular damage and thus reduced CVR include hemoglobin S polymerization, neutrophil activation and endothelial activation and adhesion. Previous studies examined the role of these factors in patients with SCD (Sins 2017; Al Najjar 2017). However, the association between the endothelial biomarkers and hemodynamic parameters is unknown in adult patients with SCD. In this study, we investigated the correlation between CBF and CVR and the adhesion molecules including sVCAM-1, sP-selectin, VWF-Ag and ADAMTS13. Additionally, we studied the association of these endothelial biomarkers with standard laboratory parameters. Methods This study was performed in accordance with the Declaration of Helsinki and was approved by the Review Board of Amsterdam UMC. For this study, 33 steady state patients with SCD (mean age 32.1 ± 10.7, 64% male, 29 HbSS, 4 HbSß) and 10 healthy volunteers (mean age 36,4 ± 15.9, 60% male, 2 HbAS, 8 HbAA) were included. Hematologic laboratory parameters were assessed using standard laboratory procedures. Plasma levels of sVCAM-1 and sP-selectin were determined using ELISA (R&amp;D Systems, USA) and ADAMTS13 and VWF-Ag were measured with the INNOVANCE assay (Siemens Healthcare Diagnostics). For the CBF measurements, pseudo-continuous arterial spin labelling (pCASL) was acquired at 3T MRI (Philips Healthcare, The Netherlands). CBF was measured before and after acetazolamide (vasoactive stimulus) administration and subsequently CVR was calculated using the following equation: CVR = (CBFafter - CBFbefore) / CBFbefore x 100% Plasma levels of endothelial biomarkers were compared between groups using ANOVA test. Correlation between the parameters were measured using single regression model where p&lt;0.05 was considered as statistically significant. Results sVCAM-1 levels and VWF-Ag were significantly higher in SCD patients compared to healthy controls (p &lt; 0.01 and p = 0.01). ADAMTS13 and sP-selectin were not significantly different between the two groups (p = 0.06 and p = 0.33). sVCAM-1 was significantly associated with CBF, and parameters of hemolysis LDH and bilirubin in SCD patients (Fig. 1A and 2C). Negative correlation was observed between sVCAM-1 and hemoglobin (Fig. 1B). The relationship between sVCAM-1 and hemodynamic and laboratory parameters are shown in Table 1. No significant correlation was found between sVCAM-1, hemodynamic and standard laboratory parameters in healthy controls. VWF-Ag, ADAMTS13 and sP-selectin were not significantly associated with hemodynamic MRI parameters. Discussion Our results show elevated sVCAM-1 levels in sickle cell patients, strongly related to CBF. sVCAM-1 is an adhesion molecule and elevated plasma levels are found in patients with endothelial activation due to inflammation or atherosclerosis (Cook-Mills 2013; Cybulsky 2001). Previous studies showed elevated levels in sickle cell disease but no correlation with parameters of cerebral perfusion have been demonstrated yet (Antwi-Boasiako 2018; Kato 2005). The strong correlation with CBF is mostly related to the chronic hemolysis given the association found with hemoglobin levels and markers of hemolysis like LDH and bilirubin. In contrast to sVCAM-1, no such relation was found with other markers of endothelial activation such as VWF activity and sP-selectin levels. No correlation between endothelial markers and the CVR was demonstrated, suggesting that endothelial damage itself may not related to the impaired cerebral vasodilatation in response to a vasoactive stimulus. Conclusion Endothelial adhesion molecule sVCAM-1 showed a strong correlation with CBF and parameters of hemolysis, suggesting a relation between the hemolytic damage of endothelial cells and impaired cerebral perfusion. Disclosures Nur: Novartis Pharmaceuticals: Consultancy.

Using postoperative remodeling of donor arteries on MR angiography to predict the development of surgical collaterals in moyamoya disease.

The calibers of donor arteries can change dynamically after bypass surgery in patients with moyamoya disease (MMD). The present study aimed to evaluate the cutoffs of caliber changes in donor arteries associated with good surgical revascularization and to assess the impact of clinical factors potentially related to bypass development. The authors studied 71 hemispheres of 30 adults and 16 children with MMD who underwent combined direct and indirect revascularization. They quantitatively measured the calibers of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) with MR angiography (MRA) source images and calculated the postoperative caliber change ratios (CCRs) to assess direct and indirect bypass development. These values were compared with the findings of digital subtraction angiography, in which revascularization areas were categorized into 3 groups (poor, good, and excellent). In both adult and pediatric hemispheres, the median STA and DTA CCRs were higher in better-revascularization groups (p < 0.05), while MMA CCRs were not significantly different among the groups. Receiver operating characteristic analysis revealed that the cutoff STA CCRs of > 1.1 and > 1.3 were associated with good direct revascularization in adult and pediatric hemispheres, respectively. Cutoff DTA CCRs of > 1.6 and > 1.2 were associated with good indirect revascularization in adult and pediatric hemispheres, respectively. Considering these cutoff values, STA and DTA CCRs showed high median values, irrespective of age, severity of cerebrovascular reserve, disease stage, and disease-onset type. Caliber changes in STAs and DTAs can be easily measured using MRA, and they could be indicators of direct and indirect bypass development. The dual development of a direct and indirect bypass was most frequently observed in the context of a combined bypass procedure in both adults and children with MMD.

Acute symptomatic extracranial internal carotid occlusion - natural course and clinical impact.

Background: To assess the vascular and clinical course of acute symptomatic extracranial internal carotid artery (ICA) occlusion. Patients and methods: Patients with an acute ischemic event in the anterior circulation and corresponding extracranial ICA occlusion at CT angiography and/or color-coded duplex sonography underwent recurrent duplex follow-up for detection of spontaneous recanalization. Stroke recurrence and functional outcome 4.5 months after the ischemic index event assessed by modified Rankin scale served as secondary outcome parameters. Results: 133 patients (91 men, mean age 62.3years, SD 10.8) demonstrated symptomatic occlusion of the extracranial ICA with open intracranial ICA and open middle cerebral artery and were followed-up for spontaneous recanalization. Twenty-eight recanalized spontaneously, 25 to high-grade focal stenosis within 12 days, revealing an early cumulative recanalization rate of 23%. Detection of recanalization was independently associated with de novo dual anti-platelet therapy (adjusted odds ratio [OR], 3.24; 95% confidence interval [CI], 1.34 to 7.80). Ischemic recurrence occurred in 16 patients, of which 10 deemed to be embolic and 5 hemodynamic. Spontaneous ICA recanalization and an exhausted cerebrovascular reserve in the hemisphere distal to the occluded ICA were both independently associated with the occurrence of a recurrent ischemic event at Cox regression. An increasing NIHSS score at admission, a decreasing middle cerebral artery flow velocity and an ischemic recurrence independently predicted poor outcome (modified Rankin scale 3 to 6) in multivariate analysis. Conclusions: Acute symptomatic extracranial ICA occlusion is an unstable condition with frequent spontaneous recanalization to severe stenosis and early embolic stroke recurrence, demanding appropriate prevention especially in those patients with only mild deficit.

Quantification of cerebral perfusion and cerebrovascular reserve using Turbo-QUASAR arterial spin labeling MRI.

PurposeTo compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo‐QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post‐labeling delay pseudo‐continuous ASL (PCASL).MethodsA model‐based method was developed to quantify CBF and arterial transit time (ATT) from Turbo‐QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model‐based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo‐QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV).ResultsThe model‐based method for Turbo‐QUASAR was accurate for CBF estimation (relative error was 8% for signal‐to‐noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo‐QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre‐ and postacetazolamide conditions. The CoV of Turbo‐QUASAR data was significantly higher than PCASL.ConclusionBoth ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo‐QUASAR demonstrated a higher variability than PCASL, Turbo‐QUASAR offers the advantage of being able to measure and control for variation in ATT.

Neurologic Deterioration in Patients With Moyamoya Disease During Pregnancy, Delivery, and Puerperium

Abstract INTRODUCTION We reviewed our clinical experience of patients with moyamoya disease (MMD) who gave birth and assessed characteristics of those experiencing neurologic deterioration. METHODS The patients were classified into patients diagnosed with MMD during pregnancy and puerperium (group 1) and those diagnosed before pregnancy (group 2). We retrospectively reviewed patient characteristics, MMD treatment, neurologic symptoms before and during pregnancy and/after puerperium, obstetrical history, and delivery type in groups 1 and 2. RESULTS Group 1 included 2 patients with a deterioration of preexisting transient ischemic attacks (TIAs) and acute cerebral infarction and 1 patient with seizures and newly developed TIAs during pregnancy and/or puerperium. Group 2 included 20 patients with 23 pregnancies. In group 2, 4 patients had deterioration of TIAs during pregnancy and puerperium. There were significant differences between the cases without neurologic deterioration and with deterioration in group 2 (TIAs ! 10 before pregnancy, 0% vs 75%, P = .002; severely reduced regional cerebrovascular reserve on single-photon emission computed tomography, 10.5% vs 100%, P = .002; and surgical revascularization before pregnancy, 75% vs 15.8%, P = .04). In groups 1 and 2, 6 of the 7 cases in which TIAs occurred or worsened during pregnancy or puerperium recovered to prepregnancy TIA levels after puerperium. CONCLUSION Patients with severely reduced regional cerebrovascular reserve on single-photon emission computed tomography and frequent TIAs before pregnancy may experience neurologic deterioration during pregnancy, delivery, and puerperium. Surgical revascularization before pregnancy may decrease neurologic deterioration during these periods.

The role of ICP overnight monitoring (ONM) in children with suspected craniostenosis.

Secondary craniostenosis is a relevant problem pediatric neurosurgeons are confronted with and poses challenges regarding reliable diagnosis of raised ICP, especially in case of absent or questionable papilledema. How to identify children with elevated ICP is still controversial and diagnostics vary. We report on our experience with computerized ICP ONM in relation to imaging derived parameters. Thirty-four children with primary or secondary craniostenosis and clinical suspicion of raised ICP were investigated. We compared clinical signs, history, and radiographic assessment with the results of computerized ICP ONM. Differences were significant at a p < 0.05. Baseline ICP was significantly higher in patients with combined suture synostosis, who also had a higher rate of questionable papilledema. Children with narrowed external CSF spaces in MRI had significantly higher ICP levels during REM sleep. Mean RAP was significantly elevated in patients with multi-suture synostosis, indicating poor intracranial compensatory reserve. Syndromal craniostenosis was associated with elevated ICP, RAP was significantly lower, and skull X-rays showed more impressions (copper beaten skull). RAP increased with more severe impressions only to decline in most severe abnormalities, indicating exhaustion of cerebrovascular reserve at an upper ICP breakpoint of 23.9mmHg. Headaches correlated to lower ICP and were not associated with more severe X-ray abnormalities. Narrowed external CSF spaces in MRI seem to be associated to elevated ICP. Skull X-rays can help to identify patients at risk for chronically elevated ICP. Severe X-ray changes correlate with exhausted cerebrovascular reserve as indicated by RAP decline. Only ICP monitoring clearly identifies raised ICP and low brain compliance. Thus, in cases with ambiguous imaging, ONM constitutes an effective tool to acquire objective data for identification of surgical candidates.

Superficial temporal artery-middle cerebral artery anastomosis patency correlates with cerebrovascular reserve in adult moyamoya syndrome patients

ObjectivesTo evaluate the effectiveness of superficial temporal artery-middle cerebral artery (STA-MCA) bypass in improving cerebrovascular reserve (CVR) in Moyamoya syndrome. Patients and methodsThis prospective study included 10 consecutive patients treated for Moyamoya syndrome by STA-MCA bypass in our institution between June 2016 and January 2018. Perfusion MRI, transcranial Doppler and 99m Tc-HMPAO SPECT with acetazolamide challenge were performed before and after treatment to evaluate perfusion and cerebrovascular reserve. STA-MCA bypass was indicated for patients with history of ischemic or hemorrhagic stroke and when CVR was diminished on both transcranial Doppler and 99m Tc-HMPAO SPECT with acetazolamide challenge or brain perfusion was deteriorated on MRI. ResultsBypass anastomosis was patent in all patients at end of surgery. One patient presented partial postoperative sensorimotor deficit related to an ischemic lesion in the frontal cortical area. One patient presented regressive chronic subdural hematoma without neurological deficit. Three months after treatment, CVR was significantly improved in 8 patients and unchanged in 2, probably related to low flow. Further follow-up found CVR deterioration in 1 patient, with anastomosis occlusion at 1 year. ConclusionOur data suggest that improvement in cerebral perfusion and CVR depends on flow in the STA-MCA anastomosis in patients with Moyamoya syndrome. Systematic long-term follow-up of anastomosis flow, brain perfusion and CVR improves quantification of the benefit of STA-MCA anastomosis in terms of disease progression.