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Background and purposeThe presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.MethodsWe examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in db/+ and db/db mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.ResultsAfter unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared with db/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with db/+ mice.ConclusionsType 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.

Background Despite thrombectomy having become the standard of care for large‐vessel occlusion strokes, acute endovascular management in tandem occlusions, especially of the cervical internal carotid artery lesion, remains uncertain. We aimed to compare efficacy and safety of acute carotid artery stenting to balloon angioplasty alone on treating the cervical lesion in tandem occlusions. Similarly, we aimed to explore those outcomes’ associations with technique approaches and use of thrombolysis. Methods and Results We performed a systematic review and meta‐analysis to compare functional outcomes (modified Rankin Scale), reperfusion, and symptomatic intracranial hemorrhage and 3‐month mortality. We explored the association of first approach (anterograde/retrograde) and use of thrombolysis with those outcomes as well. Two independent reviewers performed the screening, data extraction, and quality assessment. A random‐effects model was used for analysis. Thirty‐four studies were included in our systematic review and 9 in the meta‐analysis. Acute carotid artery stenting was associated with higher odds of modified Rankin Scale score ≤2 (odds ratio [OR], 1.95 [95% CI, 1.24–3.05]) and successful reperfusion (OR, 1.89 [95% CI, 1.26–2.83]), with no differences in mortality or symptomatic intracranial hemorrhage rates. Moreover, a retrograde approach was significantly associated with modified Rankin Scale score ≤2 (OR, 1.72 [95% CI, 1.05–2.83]), and no differences were found on thrombolysis status. Conclusions Carotid artery stenting and a retrograde approach had higher odds of successful reperfusion and good functional outcomes at 3 months than balloon angioplasty and an anterograde approach, respectively, in patients with tandem occlusions. A randomized controlled trial comparing these techniques with structured antithrombotic regimens and safety outcomes will offer definitive guidance in the optimal management of this complex disease.

Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease.21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume.CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00–0.16]; p = 0.053), but pulsatility was similar (0.07 [-0.04–0.18]; p = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32–0.88]; p = 0.34; pulsatility = 0.00 [-0.10–0.11]; p = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO (p = 0.06) and BG (p = 0.11) flow velocity related to larger WMH volume.Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations.

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.

Objective – to optimize imaging algorithms of preoperative evaluation and postoperative changes and complications in patients with occlusive carotid disease.Material and methods. Results of pre- and postoperative imaging of patients with occlusive carotid disease during 2012–2016 years were analyzed. Four groups were defined: assessment of CT-angiography (CTA) for preoperative planning (256 patients); the role of CTA for postoperative changes (51 patients); CT-perfusion (CTP) abilities in cerebral circulation assessment before and after surgery (103 and 76 patients); CT and MRI in diagnosis of postoperative neurologic complications (595 patients).Results. CTA employment in preoperative examination increased accuracy of occlusive process evaluation and changed management strategy in 6 patients. With CTA data we were able to define three variants of postoperative carotid changes: “expected” condition; changes that require further dynamic control studies; complications. The most reasonable was CTP employment for patients with combination of stenosis of one carotid artery and occlusion of contralateral artery. For diagnosis of neurologic complication first line examination was MRI, than for further assessment – CTA and CTP.Conclusion. Complex imaging algorithm for occlusive carotid disease assessment, defining of postoperative vascular status and possible neurologic complications provide necessary information for management strategy examination.

Abstract Introduction We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]). Methods We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi‐center Heart–Brain Study. We used pseudo‐continuous ASL to estimate whole‐brain and regional partial volume‐corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains. Results CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning. Discussion We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart–brain axis.

Cardiovascular disease is an important contributor to cognitive impairment. This likely involves prototypical vascular disease mechanisms like ischemia, but cardiovascular disease might also impact the brain by accelerating cerebral amyloid-β accumulation. We aimed to determine whether there is an association between heart disease or carotid occlusive disease (COD) and cerebral amyloid-β burden. We conducted a systematic review of studies investigating cerebral amyloid-β burden, measured with positron emission tomography, in adults with and without heart disease or COD. Where possible, we obtained standardized mean differences (SMD) of amyloid-β standardized uptake volume ratios (SUVr) for meta-analysis. Eight cross-sectional studies were identified (1478 participants, aged 60–81 years, 51% female). Three studies on heart disease (two on atrial fibrillation (AF) only, one on AF, coronary artery disease and heart failure) did not find a difference in amyloid-β burden between patients and controls. The pooled difference for 746 participants with and without AF did not reach significance (SMD SUVr 0.14, 95%CI -0.06–0.34). Of the five studies on COD (one on differences between participants with and without COD, four on differences between hemispheres in unilateral COD), four did not find a difference in amyloid-β between participants or hemispheres. The pooled difference in amyloid-β load between hemispheres in 24 patients with unilateral COD was not significant (SMD SUVr −0.13, 95%CI -0.70–0.43). Based on current studies, although limited and heterogeneous, there is insufficient evidence to support the hypothesis that heart disease or COD are associated with increased cerebral amyloid-β burden. • Cardiovascular disease is an important contributor to cognitive impairment. • Cardiovascular disease may impact the brain by accelerating amyloid-β accumulation. • We found no link between heart or carotid occlusive disease and amyloid-β load. [ABSTRACT FROM AUTHOR]

This study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in participants without or with either heart failure, carotid occlusive disease, or vascular cognitive impairment. Neighbourhood walkability at baseline was positively associated with global cognition and attention-psychomotor speed. These associations were stronger in patients with vascular cognitive impairment. Individuals who live in residential areas with higher walkability levels were less likely to have impairments in language and executive functioning at two-year follow-up. These findings highlight the importance of the built environment for cognitive functioning in healthy and vulnerable groups. • We assessed associations of neighbourhood walkability with cognitive functioning. • We did this in reference participants and various heart-brain axis patient groups. • Walkability was positively cross-sectionally associated with global cognition. • Higher walkability lowered the odds of impaired executive functioning at follow-up. • Some associations were stronger in patients with vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Ischaemic stroke is a major complication of cardiac surgery. The optimal strategies for operating on patients with obstructive carotid and/or intracranial artery disease (CIAD) are controversial. We aimed to clarify whether single-photon emission computed tomography (SPECT) with acetazolamide, to quantify the cerebral perfusion reserve, could predict the risk of haemodynamic ischaemic stroke during cardiac surgery. METHODS: The incidence of stroke related to obstructive CIAD and the corresponding autoregulatory reserve were prospectively assessed in 514 consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass (n = 484) and off-pump coronary artery bypass grafting (n = 30) between 2009 and 2013. Preoperative cerebral blood flow and its reactivity to acetazolamide were quantitatively determined in patients (n = 88) with obstructive CIAD, diagnosed by carotid ultrasonography and/or magnetic resonance angiography. RESULTS: An impaired cerebral perfusion reserve was identified in 1 (1.1%) of the 88 patients. This patient underwent prophylactic superficial temporal artery to middle cerebral artery anastomosis 1 month before coronary artery bypass surgery. Subsequently, the patient underwent conventional coronary artery bypass surgery, without experiencing perioperative stroke. Seven (1.4%) patients died in-hospital mortality and 5 (1.0%) experienced perioperative stroke. However, no patients experienced perioperative haemodynamic ischaemic stroke. CONCLUSIONS: It is unusual for CIAD to affect the incidence of haemodynamic ischaemic stroke during cardiac surgery. Brain perfusion SPECT with acetazolamide is effective for narrowing down patients at high risk of ischaemic stroke during cardiac surgery. Meanwhile, the application of brain perfusion single-photon emission tomography should be confined only to patients with obstructive CIAD because it is an expensive examination tool. [ABSTRACT FROM AUTHOR]

Background The optimal approach to treat the cervical carotid artery lesion during endovascular thrombectomy (EVT) for acute strokes with tandem occlusions is unclear. While carotid artery stenting (CAS) might be a more definitive recanalization method, the potential risk of intracranial hemorrhage (ICH) limits its routine usage. In this study, we aimed to evaluate the safety outcomes of CAS and carotid artery angioplasty (CAA) in patients with acute tandem occlusions. Methods In this retrospective cohort study, data were obtained from the Nationwide Readmissions Database 2016–2017. The primary safety outcome was a composite of ICH and all-cause in-hospital mortality. Logistic regression analysis was used to compare the in-hospital outcomes. Survival analysis was used to estimate the 30-day readmissions. Results We identified 2042 hospitalizations meeting the study inclusion criteria (median age: 66 years, female 31.3%). Of these, 1391 (68.1%) had undergone CAS and 651 (31.9%) CAA alone. Baseline characteristics between the two groups were similar, except patients with CAS were more likely to be on anti-thrombotic medications and were less likely to have received intravenous thrombolysis. There was no significant difference in the clinical outcomes including ICH, in-hospital mortality, gastrostomy tube placement, prolonged mechanical ventilation, length of stay, hospital charges, and 30-day readmissions between the two groups, however, patients with CAS were more likely to be discharged home after adjusting for the confounding variables [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.05–2.12, P 0.025]. Conclusion The emergent CAS-EVT approach appears to be safe with no adverse outcomes compared to CAA alone. • Acute carotid artery intervention in tandem occlusions involves stenting in most (68%) cases. • Carotid artery angioplasty and stenting for acute tandem occlusions have similar safety profile for in-hospital outcomes. • Patients with carotid artery stenting are more likely to be discharged home as compared to those with angioplasty alone. [ABSTRACT FROM AUTHOR]

Carotid revascularization has been recommended as the maximally beneficial treatment for stroke prevention in patients with recently symptomatic carotid stenosis (SCS). The appropriate timing for performing carotid endarterectomy (CEA) within the first 14 d after the occurrence of the index event remains controversial. We aim to provide a snapshot of the pertinent current literature related to the timing of CEA for patients with SCS. A systematic review of literature was conducted to study the timing of CEA for SCS. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) were followed. A total of 63 articles were identified as relevant to this topic. A summary of 15 articles favoring urgent CEA (within 48 h) for SCS within 48 h of index event and 9 articles not favoring urgent CEA is presented. A consensus is still to be achieved on the ideal timing of CEA for SCS within the 14-d window presently prescribed. The current literature suggests that patients who undergo urgent CEA (within 48 h) after nondisabling stroke as the index event have an increased periprocedural risk as compared to those who had transient ischemic attack (TIA) as the index event. Further prospective studies and clinical trials studying this question with separate groups classified as per the index event are required to shed more light on the subject. The current literature points to a changing paradigm towards early carotid surgery, specifically targeted within 48 h if the index event is TIA, and within 7 d if the index event is stroke., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Introduction: Symptomatic internal carotid artery occlusion (ICAO) can lead to neurologic decline, recurrent stroke, and mortality., Objective: We sought to evaluate the safety and feasibility of endovascular revascularization for ICAO without tandem intracranial large vessel occlusion (LVO)., Design, Setting, and Participants: This is a retrospective cohort analysis of all patients presenting to a single academic center with ischemic stroke and ipsilateral cervical ICAO from November 2003 through April 2016. Patients were excluded if pre-procedural angiography demonstrated tandem LVO or if patients were known to have chronic ICAO., Main Outcomes and Measures: Study endpoints included discharge neurologic examination, post-procedural infarct burden, 3-month functional outcomes, and treatment durability., Results: A total of 107 patients with symptomatic angiographically-confirmed cervical ICAO without tandem LVO were identified. Median admission NIH Stroke Scale (NIHSS) score was 8 (IQR 11). Baseline radiographic stroke severity was assessed by ASPECT score (median 9; IQR 2), perfusion mismatch (present in 93%), and clinical imaging mismatch (42%). Median time from symptom onset to treatment was 25 hours (IQR 61). Successful revascularization was achieved in 92% of patients. At discharge, 83% had stable/improved NIHSS score, while at 3 months 65% achieved independence (modified Rankin Scale score ≤2). The most common complication was distal embolization (22%) of which 16% required intra-arterial treatment. Rate of significant restenosis (≥70%) was 15% at 1 year., Conclusions: Stenting in selected patients at risk of neurologic deterioration due to symptomatic ICAO can be performed with high rates of technical success and good clinical outcomes. Because of significant peri-procedural risks and high rates of restenosis, randomized studies are necessary to understand the benefit of this approach., Competing Interests: Competing interests: TGJ has the following disclosures: Consultant, Neuravi (steering committee -modest), Codman Neurovascular (DSMB - modest), Stryker Neurovascular (PI DAWN - unpaid), Fundacio Ictus (PI REVASCAT unpaid); stock, Anaconda, Silk Road, Blockade Medical (modest). AFD has the following disclosure: Consultant, Medtronic (device proctor - modest)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Craniocervical fibromuscular dysplasia (FMD) is associated with dissections and with S-shaped curves in the internal carotid artery (ICA). We evaluated the occurrence of S-curves in patients presenting with acute strokes due to ICA steno-occlusive dissections., Methods: This was a retrospective review of the interventional databases of two academic tertiary-care institutions. The presence of ICA S-shaped curves, C-shaped curves, 360-degree loops, as well as classic FMD and atherosclerotic changes at the ICA bulb and curve/loop was determined. Cases of carotid dissections were compared with a control group (consecutive non-tandem anterior circulation strokes)., Results: Twenty-four patients with carotid dissections were compared to 92 controls. Baseline characteristics and procedural variables were similar, with the exception of younger age, less frequent history of hypertension, diabetes, atrial fibrillation and stent retriever use in patients with dissections. The rates of mTICI2b-3 reperfusion, parenchymal hematoma, good outcome and mortality were similar amongst groups. The frequency of S-curves (any side without superimposed atherosclerosis) was 29% in the dissection group versus 7% in controls (p < 0.01). S-curves were typically mirror images within the dissection group (85% had bilateral occurrence). The frequency of C-shaped and 360-degree curves was similar between groups. FMD changes within the craniocervical arteries were statistically more common in dissection patients. Ten patients (41%) of the dissection group had S-curves or classic FMD changes. Multivariate analysis indicated that S-curves were independently associated with the presence of dissections., Conclusion: S-shaped ICA curves are predictably bilateral, highly associated with carotid dissections in patients with moderate to severe strokes, and may suggest an underlying presence of FMD.