Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia.

BACKGROUND: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. METHODS: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. RESULTS: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction=0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction<0.01); no heterogeneity was observed for other stroke subtypes (P interaction>0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. CONCLUSIONS: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

The new Hematoma Maturity Score is highly associated with poor clinical outcome in spontaneous intracerebral hemorrhage.

OBJECTIVES: The purpose of this study was to analyze the new combined indicators on noncontrast computed tomography (NCCT) to predict functional outcome at discharge, compared to previously individual radiological NCCT signs. METHODS: Patients with spontaneous intracerebral hemorrhage (ICH) who underwent baseline CT scan were retrospectively analyzed. Black hole (BH) sign, blend sign (BS), island sign (IS), swirl sign (SwS), Barras classification, any hypodensity, any irregularity, and two combined novel indicators-Combined Barras Total Score (CBTS) and Hematoma Maturity Score-were assessed independently by two radiologists blinded to clinical information. Patients were trichotomized depending on the disability or dependency at discharge according to the Modified Rankin Scale (mRS): no symptoms or no significant/mild disability (mRS 0-2); moderate or severe disability (mRS 3-5); and mortality (mRS 6). RESULTS: One hundred fourteen patients with spontaneous ICH confirmed by NCCT were included in the analysis. Multivariable statistical analysis was adjusted for anticoagulation, hematoma volume, ventricular expansion, hypertension, blood glucose level at admission, age, and history of atrial fibrillation and demonstrated that any hypodensity (OR 4.768, p 0.006), any irregularity (OR 4.768, p 0.006), CBTS ≥ 4 (OR 3.205, p 0.025), and the new Hematoma Maturity Score (Immature) (OR 5.872, p 0.006) are independent predictors of functional outcome at discharge. CONCLUSIONS: The new concept of the Hematoma Maturity Score was the radiological sign on NCCT with the highest impact on clinical outcome in comparison with the rest of the evaluated radiological signs. KEY POINTS: • This is the first manuscript where density and shape characteristics of the ICH had been evaluated together and integrated in a new Hematoma Maturity Score. • The new Hematoma Maturity Score is the radiological sign on NCCT with the highest impact on clinical outcome at discharge.

The Role of Vascular Imaging atReferral Centers in the Drip and Ship Paradigm.

BACKGROUND: In drip-and-ship protocols, non-invasive vascular imaging (NIVI) at Referral Centers (RC), although recommended, is not consistently performed and its value is uncertain. We evaluated the role of NIVI at RC, comparing patients with (VI+) and without (VI-) vascular imaging in several outcomes. METHODS: Observational, multicenter study from a prospective government-mandated population-based registry of code stroke patients. We selected acute ischemic stroke patients, initially assessed at RC from January-2016 to June-2020. We compared and analyzed the rates of patients transferred to a Comprehensive Stroke Center (CSC) for Endovascular Treatment (EVT), rates of EVT and workflow times between VI+ and VI- patients. RESULTS: From 5128 ischemic code stroke patients admitted at RC; 3067 (59.8%) were VI+, 1822 (35.5%) were secondarily transferred to a CSC and 600 (11.7%) received EVT. Among all patients with severe stroke (NIHSS ≥16) at RC, a multivariate analysis showed that lower age, thrombolytic treatment, and VI+ (OR:1.479, CI95%: 1.117-1.960, p=0.006) were independent factors associated to EVT. The rate of secondary transfer to a CSC was lower in VI+ group (24.6% vs. 51.6%, p<0.001). Among transferred patients, EVT was more frequent in VI+ than VI- (48.6% vs. 21.7%, p<0.001). Interval times as door-in door-out (median-minutes 83.5 vs. 82, p= 0.13) and RC-Door to puncture (median-minutes 189 vs. 178, p= 0.47) did not show differences between both groups. CONCLUSION: In the present study, NIVI at RC improves selection for EVT, and is associated with receiving EVT in severe stroke patients. Time-metrics related to drip-and-ship model were not affected by NIVI.

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia.

INTRODUCTION: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. METHODS: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. RESULTS: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. CONCLUSION: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately.

Leukocytes, Collateral Circulation, and Reperfusion in Ischemic Stroke Patients Treated With Mechanical Thrombectomy.

Background and Purpose- Peripheral immune cells are activated after stroke and may in turn influence the fate of ischemic brain tissue, thus exerting a dual role in ischemic stroke. We evaluated the contribution of neutrophil and lymphocyte counts to hemorrhagic complications and functional outcome in stroke patients treated with mechanical thrombectomy (MT) with varying degrees of collateral circulation and reperfusion. Methods- We retrospectively analyzed 433 consecutive ischemic stroke patients treated with MT. Neutrophil and lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) were collected before MT and 1 day after symptom onset. Outcome measures included categories of hemorrhagic transformation, symptomatic intracerebral hemorrhage, 3-month functional dependence (modified Rankin Scale, 3-6), and mortality. Patients were categorized according to their baseline collateral status and the degree of reperfusion after MT. Results- Neutrophil counts and NLR increased, whereas lymphocyte counts decreased after MT (P<0.001), and changes in neutrophils and NLR at day 1 were significantly greater in patients with poor reperfusion. Neutrophil counts and NLR were significantly higher already at admission in patients with poor 3-month outcome. In adjusted analysis, the impact of neutrophilia on poor functional outcome was more substantial in patients with good collaterals achieving successful reperfusion (aOR, 3.09 per quartile; 95% CI, 1.95-4.90), whereas admission lymphopenia (aOR, 4.08 per decreasing quartile; 95% CI, 1.56-10.64) and higher NLR (aOR, 3.76 per quartile; 95% CI, 1.44-9.79) predicted subsequent symptomatic intracerebral hemorrhage in patients with poor collaterals and successful reperfusion. Conclusions- In patients treated with MT, neutrophil and lymphocyte counts are dynamic parameters associated with hemorrhagic complications and long-term outcome. The extent of collateral circulation and the success of brain reperfusion influence the strength of these associations and highlight the dual role of leukocytes in acute stroke.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. METHODS: Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. RESULTS: We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). CONCLUSIONS: This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

Clinical relevance of glucose metrics during the early brain injury period after aneurysmal subarachnoid hemorrhage: An opportunity for continuous glucose monitoring.

Hyperglycaemia, hypoglycaemia and higher glucose variability during the Early Brain Injury (EBI) period of aneurysmal subarachnoid hemorrhage (aSAH) have been associated with poor clinical outcome. However, it is unclear whether these associations are due to direct glucose-driven injury or if hyperglycaemia simply acts as a marker of initial severity. Actually, strict glucose control with intensive insulin therapy has not been demonstrated as an effective strategy for improving clinical outcomes after aSAH. Currently published studies describing an association between hyperglycaemia and prognosis in aSAH patients have been based on isolated glucose measurements and did not incorporate comprehensive dynamic evaluations, such as those derived from subcutaneous continuous glucose monitoring devices (CMG). Arguably, a more accurate knowledge on glycaemic patterns during the acute phase of aSAH could increase our understanding of the relevance of glycaemia as a prognostic factor in this disease as well as to underpin its contribution to secondary focal and diffuse brain injury. Herein, we have summarized the available evidence on the diagnostic and prognostic relevance of glucose metrics during the acute phase of cerebrovascular diseases, focusing in the EBI period after aSAH. Overall, obtaining a more precise scope of acute longitudinal glucose profiles could eventually be useful for improving glucose management protocols in the setting of acute aSAH and to advance toward a more personalized management of aSAH patients during the EBI phase.

Minimally Invasive Surgery for Spontaneous Intracerebral Hematoma. Real-Life Implementation Model and Economic Estimation.

Objective: Spontaneous intracerebral hemorrhage is characterized by high fatality outcomes, even under best medical treatment. Recently, minimally invasive surgical (MIS) evacuation of the hematoma has shown promising results and may soon be implemented in the clinical practice. Hereby, we intended to foresee the logistic requirements for an early hematoma evacuation protocol, as well as to evaluate in a real-life implementation model the cost-utility of the two main MIS techniques for hemorrhagic stroke (catheter evacuation plus thrombolysis and neuroendoscopic aspiration). Methods: Data were obtained from the pool of hemorrhagic-stroke patients admitted to our institution during an annual period (2020-2021) and contrasted to the reported results in published trials of MIS techniques. Potential candidates for surgical treatment were identified according to the inclusion/exclusion criteria established in these trials. Then, a cost-utility analysis was performed, which explored the incremental cost per unit of health gained with a given treatment. The treatment effect was measured by differences in modified Rankin Score, and subsequently converted to quality-adjusted life years (QALY). Results: Of the 137 patients admitted to our center with supratentorial spontaneous intracerebral hemorrhage in a 1-year period, 17 (12.4%) were potential candidates for the catheter evacuation plus thrombolysis technique (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, MISTIE III criteria) and 59 (43.0%) for the neuroendoscopic aspiration technique (Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study, DIST criteria). The incremental cost-utility ratio was € 76,533.13 per QALY for the catheter-based evacuation and € 60,703.89 per QALY for the endoscopic-based technique. Conclusion: Around 12-43% of patients admitted to hospital with spontaneous hemorrhagic stroke could be potential candidates to MIS early evacuation of the cerebral hematoma. In our real-life implementation model, the cost-utility analysis favored the neuroendoscopic evacuation over the catheter aspiration technique. Further studies are advisable as new data from the ongoing randomized trials becomes available.

Characterization of Subarachnoid Hyperdensities After Thrombectomy for Acute Stroke Using Dual-Energy CT.

BACKGROUND AND OBJECTIVES: The presence of postinterventional subarachnoid hyperdensities (SA-HD) is a relatively common finding after mechanical thrombectomy (MT). We aimed to assess the incidence, characteristics, clinical relevance, and predictors of SA-HD after MT as categorized through the use of postinterventional dual-energy CT (DE-CT). METHODS: A single-center consecutive series of patients with acute stroke treated with MT was retrospectively reviewed. Posttreatment SA-HD were defined as incident extraaxial hyperdensities in a follow-up DE-CT performed within a median of 8 hours after MT. SA-HD were further classified according to their content (isolated contrast extravasation vs blood extravasation) and extension (diffuse [hyperdensities in more than one extraparenchymal compartment] vs nondiffuse). Adjusted logistic regression models assessed the association of SA-HD with pretreatment and procedural variables and with poor clinical outcome (shift towards worse categories in the ordinal Rankin Scale at 90 days). RESULTS: SA-HD were observed in 120 (28%) of the 424 included patients (isolated contrast extravasation n = 22, blood extravasation n = 98). In this group, SA-HD were diffuse in 72 (60%) patients (isolated contrast extravasation n = 7, blood extravasation n = 65) and nondiffuse in 48 (40%) patients (isolated contrast extravasation n = 15, blood extravasation n = 33). Diffuse SA-HD were significantly associated with worse clinical outcome in adjusted models (common odds ratio [cOR] 2.3, 95% confidence interval [CI] 1.36-4.00, p = 0.002), unlike the specific SA-HD content alone. In contrast with the absence of SA-HD, only the diffuse pattern with blood extravasation was significantly associated with worse clinical outcome (cOR 2.4, 95% CI 1.36-4.15, p = 0.002). Diffuse SA-HD patterns were predicted by M2 occlusions, more thrombectomy passes, and concurrent parenchymal hematomas. DISCUSSION: In our cohort of patients imaged within a median of 8 hours after MT, postinterventional SA-HD showed a diffuse pattern in 17% of thrombectomies and were associated with more arduous procedures. Diffuse SA-HD but not local collections of blood or contrast extravasations were associated with an increased risk of poor outcome and death. These findings reinforce the need for improvement in reperfusion strategies. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in individuals with proximal carotid artery territory occlusions treated with MT, diffuse postinterventional SA-HD on imaging 8 hours postprocedure are associated with worse clinical outcomes at 90 days.

Intense long-term training impairs brain health compared with moderate exercise: Experimental evidence and mechanisms.

The consequences of extremely intense long-term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose-response relationship, and mechanisms in a rat model of endurance training. Five-week-old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sedentary (SED) group for 16 weeks. MOD rats showed the highest motivation and learning capacity in operant conditioning experiments; SED and INT presented similar results. In vivo MRI demonstrated enhanced global and regional connectivity efficiency and clustering as well as a higher cerebral blood flow (CBF) in MOD but not INT rats compared with SED. In the cortex, downregulation of oxidative phosphorylation complex IV and AMPK activation denoted mitochondrial dysfunction in INT rats. An imbalance in cortical antioxidant capacity was found between MOD and INT rats. The MOD group showed the lowest hippocampal brain-derived neurotrophic factor levels. The mRNA and protein levels of inflammatory markers were similar in all groups. In conclusion, strenuous long-term exercise yields a lesser improvement in learning ability than moderate exercise. Blunting of MOD-induced improvements in CBF and connectivity efficiency, accompanied by impaired mitochondrial energetics and, possibly, transient local oxidative stress, may underlie the findings in intensively trained rats.

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score.

BACKGROUND: Risk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding. METHODS: A retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort. RESULTS: 68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 . CONCLUSIONS: Venous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

Use of second generation supraglottic airway device for endovascular treatment of unruptured intracranial aneurysms: a retrospective cohort.

BACKGROUND: We aimed to assess the feasibility of using supraglottic devices as an alternative to orotracheal intubation for airway management during anesthesia for endovascular treatment of unruptured intracranial aneurisms in our department over a nine-year period. METHODS: Retrospective single center analysis of cases (2010-2018). Primary outcomes: airway management (supraglottic device repositioning, need for switch to orotracheal intubation, airway complications). SECONDARY OUTCOMES: aneurysm complexity, history of subarachnoid hemorrhage, hemodynamic monitoring, and perioperative complications. RESULTS: We included 187 patients in two groups: supraglottic device 130 (69.5%) and orotracheal intubation 57 (30.5%). No adverse incidents were recorded in 97% of the cases. Three supraglottic device patients required supraglottic device repositioning and 1 supraglottic device patient required orotracheal intubation due to inadequate ventilation. Three orotracheal intubation patients had a bronchospasm or laryngospasm during awakening. Forty-five patients (24.1%) had complex aneurysms or a history of subarachnoid hemorrhage. Thirty-three of them (73.3%) required orotracheal intubation compared to 24 of the 142 (16.9%) with non-complex aneurysms. Two patients in each group died during early postoperative recovery. Two in each group also had intraoperative bleeding. A post-hoc analysis showed that orotracheal intubation was used in 55 patients (44%) in 2010 through 2014 and 2 (3.2%) in 2015 through 2018, parallel to a trend toward less invasive blood pressure monitoring from the earlier to the later period from 34 (27.2%) cases to 5 (8.2%). CONCLUSION: Supraglottic device, like other less invasiveness protocols, can be considered a feasible alternative airway management approach in selected patients proposed for endovascular treatment of unruptured intracranial aneurisms.

Uric acid therapy for vasculoprotection in acute ischemic stroke.

Uric acid (UA) is a product of the catabolism of purine nucleotides, the principal constituents of DNA, RNA, and cellular energy stores, such as adenosine triphosphate. The main properties of UA include scavenging of hydroxyl radicals, superoxide anion, hydrogen peroxide, and peroxynitrite that make this compound to be the most potent antioxidant in the human plasma. As the result of two silencing mutations in the gene of the hepatic enzyme uricase which degrades UA to allantoin, humans have higher levels of UA than most mammals. However, these levels rapidly decrease following an acute ischemic stroke (AIS), and this decrement has been associated to worse stroke outcomes. This review highlights the safety and potential clinical value of UA therapy in AIS, particularly in patients more exposed to redox-mediated mechanism following the onset of ischemia, such as women, hyperglycemic patients, or patients treated with mechanical thrombectomy. The clinical findings are supported by preclinical data gathered in different laboratories, and in assorted animal species which include male and female individuals or animals harboring comorbidities frequently encountered in patients with AIS, such as hyperglycemia or hypertension. A remarkable finding in these studies is that UA targets its main effects in the brain vasculature since available evidence suggests that does not seem to cross the blood-brain barrier. Altogether, the available data with UA therapy extend the importance of vasculoprotection for effective neuroprotection at the bedside and reinforce the role of endothelial cells after brain ischemia for an increased survival of the whole neurovascular unit.

Uric acid treatment after stroke modulates the Krüppel-like factor 2-VEGF-A axis to protect brain endothelial cell functions: Impact of hypertension.

Uric acid (UA) is a promising protective treatment in ischaemic stroke, but the precise molecular targets underlying its in vivo beneficial actions remain unclear. High concentrations of UA inhibit angiogenesis of cultured endothelial cells via Krüppel-like factor 2 (KLF)-induced downregulation of vascular endothelial growth factor (VEGF), a pro-angiogenic mediator that is able to increase blood-brain barrier (BBB) permeability in acute stroke. Here, we investigated whether UA treatment after ischaemic stroke protects brain endothelial cell functions and modulates the KLF2-VEGF-A axis. Transient intraluminal middle cerebral artery (MCA) occlusion/reperfusion was induced in adult male spontaneously hypertensive (SHR) rats and corresponding normotensive Wistar-Kyoto (WKY) rats. Animals received UA (16 mg/kg) or vehicle (Locke's buffer) i.v. at reperfusion. BBB permeability was evaluated by Evans blue extravasation to the brain and in human cerebral endothelial hCMEC/D3 cells under oxygen-glucose deprivation/re-oxygenation. Circulating VEGF-A levels were measured in rats and acute ischaemic stroke patients from the URICO-ICTUS trial. Angiogenesis progression was assessed in Matrigel-cultured MCA. Worse post-stroke brain damage in SHR than WKY rats was associated with higher hyperaemia at reperfusion, increased Evans blue extravasation, exacerbated MCA angiogenic sprouting, and higher VEGF-A levels. UA treatment reduced infarct volume and Evans blue leakage in both rat strains, improved endothelial cell barrier integrity and KLF2 expression, and lowered VEGF-A levels in SHR rats. Hypertensive stroke patients treated with UA showed lower levels of VEGF-A than patients receiving vehicle. Consistently, UA prevented the enhanced MCA angiogenesis in SHR rats by a mechanism involving KLF2 activation. We conclude that UA treatment after ischaemic stroke upregulates KLF2, reduces VEGF-A signalling, and attenuates brain endothelial cell dysfunctions leading to neuroprotection.

Cerebral amyloid angiopathy-related atraumatic convexal subarachnoid hemorrhage: an ARIA before the tsunami.

Atraumatic convexal subarachnoid hemorrhage (cSAH) in elderly patients is a rare entity that has been associated with cerebral amyloid angiopathy (CAA) and intracerebral hematomas (ICH). To characterize this entity and to study these associations, 22 patients over 60 with cSAH were included in a multicenter ambispective cohort study. Clinical data, magnetic resonance imaging (MRI) studies, APOE genotyping, and cerebrospinal fluid (CSF) biomarkers were evaluated. Results were compared with data from healthy controls (HC), non-cSAH CAA patients (CAAo), and Alzheimer disease patients. Convexal subarachnoid hemorrhage presented with transient sensory or motor symptoms. At follow-up (median 30.7 months), 5 patients had died, 6 survivors showed functional disability (modified Rankins Scale (mRS)>2), and 12 cognitive impairment. Four patients had prior ICH and six had an ICH during follow-up. CSF-Aß40 and Aß42 levels were lower in cSAH and CAAo compared with HC. Convexal subarachnoid hemorrhage presented an APOE-ɛ2 overrepresentation and CAAo had an APOE-ɛ4 overrepresentation. On MRI, all patients fulfilled CAA-modified Boston criteria and 9 showed cortical ischemia in the surrounding cortex or the vicinity of superficial siderosis. The neuropathologic study, available in one patient, showed severe CAA and advanced Alzheimer-type pathology. Convexal subarachnoid hemorrhage in the elderly is associated with cognitive impairment and lobar ICH occurrence. Our findings support the existence of an underlying CAA pathology.