Healthcare data provides a unique opportunity to learn causal relationships but the largest datasets, such as from hospitals or intensive care units, are often observational and do not standardize variables collected for all patients. Rather, the variables depend on a patient's health status, treatment plan, and differences between providers. This poses major challenges for causal inference, which either must restrict analysis to patients with complete data (reducing power) or learn patient-specific models (making it difficult to generalize). While missing variables can lead to confounding, variables absent for one individual are often measured in another.

We propose a novel method, called Causal Model Combination for Time Series (CMC-TS), to learn causal relationships from time series with partially overlapping variable sets. CMC-TS overcomes errors by specifically leveraging partial overlap between datasets (e.g., patients) to iteratively reconstruct missing variables and correct errors by reweighting inferences using shared information across datasets. We evaluated CMC-TS and compared it to the state of the art on both simulated data and real-world data from stroke patients admitted to a neurological intensive care unit.

On simulated data, CMC-TS had the fewest false discoveries and highest F1-score compared to baselines. On real data from stroke patients in a neurological intensive care unit, we found fewer implausible and more highly ranked plausible causes of a clinically important adverse event.

Our approach may lead to better use of observational healthcare data for causal inference, by enabling causal inference from patient data with partially overlapping variable sets.

Mitral valve replacement, or any major cardiac surgery, is usually delayed for a minimum of 6 weeks after a previous stroke, mainly to avoid recurrence, if not associated with infective endocarditis or aortic dissection. A 50-year-old lady, diagnosed with severe mitral stenosis with a large left atrial clot, had a sudden onset cerebrovascular accident (CVA) while awaiting surgery. Mechanical thrombectomy (MT) of large vessel M1 middle cerebral artery (MCA) occlusion was done, and after adequate neurological improvement, she was taken up for emergency mitral valve replacement within 12 h, because of hemodynamic instability leading to low cardiac output syndrome and to avoid the chance of future CVA due to large clot burden. A 23-mm mechanical mitral valve prosthesis was implanted, and the postoperative course was uneventful. She was discharged on the fifth postoperative day, with stable hemodynamics and no residual neurological deficit. She was asymptomatic with normal echocardiographic findings on 12 months' follow-up. Major cardiac surgery after MT for ischemic CVA may be a viable option, if indicated, provided post-MT neurological improvement is adequate.

Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials.

We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA.

We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0-5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders.

From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%-4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%-3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%-2.14%); p = 0.004 and 6.18% (95% CI 4.19%-8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%-2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively).

In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

This study aimed to investigate whether late neurological improvement (LNI) during hospitalization serves as a favorable prognostic indicator in patients with acute ischemic stroke (AIS) and to identify the predictors of LNI.

We retrospectively analyzed data from the Safe Implementation of Treatments in Stroke (SITS) registry at two stroke centers in Egypt. LNI was defined as the lack of early neurological improvement (ENI) within 24 h after admission, accompanied by neurological improvement within 7 days of hospitalization. Multivariate logistic regression was employed to analyze the factors influencing favorable prognosis (modified Rankin Scale score 0-2) and LNI.

A total of 834 patients with AIS were included in this study, of which 130 (15.6%) exhibited LNI. Among these, 99 (76.2%) achieved favorable outcomes. Both ENI (OR = 6.756, 95% CI 3.355-13.603, P < 0.001) and LNI (OR = 5.760, 95% CI 3.146-10.545, P < 0.001) were independently associated with favorable prognosis after adjustment. Predictors of LNI in multivariable-adjusted logistic regression included younger age (OR = 0.973, 95% CI 0.957-0.990, P = 0.001), higher baseline National Institutes of Health Scale (NIHSS) score (OR = 1.196, 95% CI 1.146-1.248, P < 0.001), and rt-PA treatment (OR = 1.953, 95% CI 1.206-3.163, P = 0.006).

Approximately three-quarters of patients with LNI are expected to achieve good outcome. LNI was a favorable prognostic indicator in patients with AIS and younger age, higher baseline NIHSS score and rt-PA treatment predicted LNI.

Systolic blood pressure (SBP) affects the risk of early neurological deterioration (END). This subgroup analysis of Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial aimed to explore whether SBP at admission affected the efficacy of different antiplatelet therapies in preventing END.

Based on the modified intention-to-treat analysis set of the ATAMIS trial, patients were divided into two subgroups according to whether SBP at admission was equal to or higher than 140 mm Hg, which were further subdivided into clopidogrel plus aspirin and aspirin alone treatments according to the randomised assignment. We conducted multivariable regression analyses to detect relationship between SBP at admission and END, as well as efficacy of different antiplatelet therapies in each SBP subgroup. Primary endpoint was END defined as ≥2-point increase in 7-day National Institutes of Health Stroke Scale score. Safety endpoints included intracranial haemorrhage and bleeding events during the trial.

This study included 2915 patients. Risk of END raised by 16% as SBP at admission increased by every 10 mm Hg (p<0.001). Clopidogrel plus aspirin resulted in significantly lower risk of END than aspirin alone in patients with SBP≥140 mm Hg (5.5% vs 7.9%; adjusted risk difference (RD) and 95% CI -2.5% (-4.1% to -1.0%)), but not in those with SBP<140 mm Hg (3.4% vs 4.2%; adjusted RD and 95% CI -0.8% (-3.2% to 1.7%)). Efficacy of different antiplatelet therapies and SBP did not show significant interaction (p=0.50). Safety endpoints were similar between treatments in SBP subgroups.

The risk of END increases with elevated SBP at admission among patients with acute mild-to-moderate ischaemic stroke who are not suitable for reperfusion treatments. Fewer END occurred following clopidogrel plus aspirin compared with aspirin alone across different SBP levels. The finding should be interpreted cautiously.

Leptomeningeal collaterals (LMCs) are crucial in mitigating the impact of acute ischemic stroke (AIS) by providing alternate blood flow routes when primary arteries are obstructed. This article explores the evolutionary pathophysiology of LMCs, highlighting their critical function in stroke and the genetic and molecular mechanisms governing their development and remodelling. We address the translational challenges of applying animal model findings to human clinical scenarios, emphasizing the need for further research to validate emerging therapies-such as pharmacological agents, gene therapy and mechanical interventions-in clinical settings, aimed at enhancing collateral perfusion. Computational modelling emerges as a promising method for integrating experimental data, which requires precise parameterization and empirical validation. We introduce the 'Evolucollateral Dynamics' hypothesis, proposing a novel framework that incorporates evolutionary biology principles into therapeutic strategies, offering new perspectives on enhancing collateral circulation. This hypothesis emphasizes the role of genetic predispositions and environmental influences on collateral circulation, which may impact therapeutic strategies and optimize treatment outcomes. Future research must incorporate human clinical data to create robust treatment protocols, thereby maximizing the therapeutic potential of LMCs and improving outcomes for stroke patients.

During unilateral static and rhythmic handgrip exercise, middle cerebral artery blood velocity (MCAv) increases in the contralateral side to the exercising limb. However, whether this neurovascular coupling-mediated increase in contralateral MCAv is apparent against a background of fluctuating perfusion pressure produced by dynamic resistance exercise (RE) is unclear. We examined the cerebral haemodynamic response to unilateral dynamic RE in 30 healthy individuals (female = 16, mean ± SD: age, 26 ± 6 years; height, 175 ± 10 cm; weight, 74 ± 15 kg; body mass index, 24 ± 5 kg m-2). Participants completed four sets of 10 paced repetitions (15 repetitions min-1) of unilateral bicep curl exercise at 60% of the predicted one-repetition maximum (7 ± 3 kg). Beat-to-beat blood pressure, bilateral MCAv and end-tidal carbon dioxide were measured throughout. One-way ANOVA was used to analyse cardiovascular variables and two-way ANOVA to analyse dependent cerebrovascular variables (side × sets, 2 × 5). A linear mixed model analysis was also performed to investigate the effects of end-tidal carbon dioxide and mean arterial blood pressure on MCAv. In comparison to baseline, within-exercise mean arterial blood pressure increased (P < 0.001) across the sets, whereas bilateral MCAv decreased (P < 0.001). However, no significant interaction effect was observed for any dependent variables (all P > 0.787). The linear mixed model revealed that end-tidal carbon dioxide had the greatest effect on MCAv (estimate = 1.019, t = 8.490, P < 0.001). No differences were seen in contralateral and ipsilateral MCAv during dynamic RE, suggesting that neurovascular coupling contributions during dynamic RE might be masked by other regulators, such as blood pressure.

This study measured the relationship between pial collateral (leptomeningeal anastomoses, LMA) flow, intraparenchymal cortical cerebral blood flow (cCBF) and brain tissue oxygenation (btO2) during acute ischemic stroke to investigate how pial flow translates to downstream cCBF and btO2 and examined how this relationship is altered in hypertension. Proximal transient middle cerebral artery occlusion (tMCAO) was performed in male Wistar (n = 8/group) and Spontaneously Hypertensive Rats (SHR, n = 8/group). A combination laser Doppler-oxygen probe was placed within the expected cortical peri-infarct in addition to a surface laser doppler probe which measured LMA flow. Phenylephrine (PE) was infused 30 minutes into tMCAO to increase blood pressure (BP) by 30% for 10 minutes and assessed CBF autoregulation. During the initial 30-minute period of tMCAO, btO2 and cCBF were lower in SHR compared to Wistar rats (btO2: 11.5 ± 10.5 vs 17.5 ± 10.8 mmHg and cCBF: -29.7 ± 23.3% vs -17.8 ± 41.9%); however, LMA flow was similar between groups. The relationship between LMA flow, cCBF and btO2 were interdependent in Wistar rats. However, this relationship was disrupted in SHR rats and partially restored by induced hypertension. This study provides evidence that cCBF and btO2 were diminished during tMCAO in chronic hypertension, and that induced hypertension was beneficial regardless of hypertensive status.

To systematically review and perform a meta-analysis of published literature regarding postoperative stroke and mortality in patients with a history of stroke and to provide a framework for preoperative, intraoperative, and postoperative care in an elective setting.

Patients with nonneurological, noncardiac, and nonvascular surgery within three months after stroke have a 153-fold risk, those within 6 months have a 50-fold risk, and those within 12 months have a 20-fold risk of postoperative stroke. There is a 12-fold risk of in-hospital mortality within three months and a three-to-four-fold risk of mortality for more than 12 months after stroke. The risk of stroke and mortality continues to persist years after stroke. Recurrent stroke is common in patients in whom anticoagulation/antiplatelet therapy is discontinued. Stroke and time elapsed after stroke should be included in the preoperative assessment questionnaire, and a stroke-specific risk assessment should be performed before surgical planning is pursued.

In patients with a history of a recent stroke, anesthesiology, surgery, and neurology experts should create a shared mental model in which the patient/surrogate decision-maker is informed about the risks and benefits of the proposed surgical procedure; secondary-stroke-prevention medications are reviewed; plans are made for interruptions and resumption; and intraoperative care is individualized to reduce the likelihood of postoperative stroke or death.

Arterial carbon dioxide ([Formula: see text]) and posture influence the middle (MCAv) and posterior (PCAv) cerebral artery blood velocities, but there is paucity of data about their interaction and need for an integrated model of their effects, including dynamic cerebral autoregulation (dCA). In 22 participants (11 males, age 30.2 ± 14.3 yr), blood pressure (BP, Finometer), dominant MCAv and nondominant PCAv (transcranial Doppler ultrasound), end-tidal CO2 (EtCO2, capnography), and heart rate (HR, ECG) were recorded continuously. Two recordings (R) were taken when the participant was supine (R1, R2), two taken when the participant was sitting (R3, R4), and two taken when the participant was standing (R5, R6). R1, R3, and R5 consisted of 3 min of 5% CO2 through a mask and R2, R4, and R6 consisted of 3 min of paced hyperventilation. The effects of [Formula: see text] were expressed with a logistic curve model (LCM) for each parameter. dCA was expressed by the autoregulation index (ARI), derived by transfer function analysis. Standing shifted LCM to the left for MCAv (P < 0.001), PCAv (P < 0.001), BP (P = 0.03), and ARI (P = 0.001); downward for MCAv and PCAv (both P < 0.001), and upward for HR (P < 0.001). For BP, LCM was shifted downward by sitting and standing (P = 0.024). For ARI, the hypercapnic range of LCM was shifted upward during standing (P < 0.001). A more complete mapping of the combined effects of posture and arterial CO2 on the cerebral circulation and peripheral variables can be obtained with the LCM over a broad physiological range of EtCO2 values.NEW & NOTEWORTHY Data from supine, sitting, and standing postures were measured. Modeling the data with logistic curves to express the effects of CO2 reactivity on middle cerebral artery blood velocity (MCAv), posterior cerebral artery blood velocity (PCAv), heart rate, blood pressure (BP), and the autoregulation index (ARI), provided a more comprehensive approach to study the interaction of arterial CO2 with posture than in previous studies. Above all, shifts of the logistic curve model with changes in posture have shown interactions with [Formula: see text] that have not been previously demonstrated.

Cerebral autoregulation is an intrinsic myogenic response of cerebral vasculature that allows for preservation of stable cerebral blood flow levels in response to changing systemic blood pressure. It is effective across a broad range of blood pressure levels through precapillary vasoconstriction and dilation. Autoregulation is difficult to directly measure and methods to indirectly ascertain cerebral autoregulation status inherently require certain assumptions. Patients with impaired cerebral autoregulation may be at risk of brain ischemia. One of the central mechanisms of ischemia in patients with metabolically compromised states is likely the triggering of spreading depolarization (SD) events and ultimately, terminal (or anoxic) depolarization. Cerebral autoregulation and SD are therefore linked when considering the risk of ischemia. In this scoping review, we will discuss the range of methods to measure cerebral autoregulation, their theoretical strengths and weaknesses, and the available clinical evidence to support their utility. We will then discuss the emerging link between impaired cerebral autoregulation and the occurrence of SD events. Such an approach offers the opportunity to better understand an individual patient's physiology and provide targeted treatments.

Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI.

We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis.

We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; ptrend<0.001).

Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies.

Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated.

Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]).

Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy.

Fonds NutsOhra.

 There is limited data available regarding the prevalence of intracranial arterial stenosis (ICAS) among acute ischemic stroke (AIS) patients in Brazil and Latin America.

 The present study sought to investigate the frequency and predictors of ICAS among patients with AIS or transient ischemic attack (TIA) in a Brazilian center, with transcranial color-coded duplex sonography (TCCS) technique.

 Consecutive AIS and TIA patients, admitted to an academic public comprehensive stroke center in Brazil from February to December 2014, evaluated by TCCS were prospectively selected. Vascular narrowings > 50% were considered as ICAS, based on ultrasound criteria previously defined in the literature.

 We assessed 170 consecutive patients with AIS or TIA, of whom 27 (15.9%) were excluded due to an inadequate transtemporal acoustic bone window. We confirmed ICAS in 55 patients (38.5%). The most common location was the proximal segment of the middle cerebral artery (28.2%), followed by the vertebral (15.4%), posterior cerebral (13.6%), terminal internal carotid (9.1%) and basilar (8.2%) arteries. On multivariate models adjusting for potential confounders, systolic blood pressure (OR: 1.03, 95%CI: 1.01-1.04; p = 0.008) was independently associated with ICAS.

 We found significant ICAS in approximately ⅓ of patients admitted with symptoms of AIS or TIA in a public tertiary academic stroke center in Brazil. The TCCS is an accessible and noninvasive technique that can be used to investigate the presence of moderate and severe ICAS, especially in patients who cannot be exposed to more invasive exams, such as the use of intravenous contrast agents.

Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP).

Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients.

Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 s) peak in CrCP dynamic response that was not influenced by age.

These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature.

Blood brain barrier disruption (BBBD) can be visualized by contrast extravasation (CE) after endovascular treatment (EVT) in patients with acute ischemic stroke. Elevated blood pressure is a risk factor for BBBD. However, the association between procedural blood pressure and CE post-EVT is unknown.

In this single-center retrospective study, we analyzed 501 eligible patients who received a dual energy CT (DECT) immediately post-EVT for acute ischemic stroke. Procedural blood pressure values (SBPmean, SBPmax, SBPmax-min, and MAPmean) were collected. CE was quantified by measuring the maximum parenchymal iodine concentration on DECT iodine overlay map reconstructions. As a measure for the extent of BBBD, we created CE-ASPECTS by deducting one point per hyperdense ASPECTS region on iodine overlay maps. The association between blood pressure and CE was assessed using multivariable linear regression.

The procedural SBPmean, SBPmax, and MAPmean were 150 ± 26 mmHg, 173 ± 29 mmHg, and 101 ± 17 mmHg, respectively. The median maximum iodine concentration on post-EVT DECT was 1.2 mg/ml (IQR 0.7-2.0), and median CE-ASPECTS was 8 (IQR 5-11). The maximum iodine concentration was not associated with blood pressure. SBPmean, SBPmax, and MAPmean were significantly associated with CE-ASPECTS (per 10 mmHg, β = -0.2, 95 % CI -0.31 to -0.09, β = -0.15, 95 % CI -0.25 to -0.06, β = -0.33, 95 % CI -0.49 to -0.17, respectively).

In acute ischemic stroke patients undergoing EVT, particularly in patients achieving successful recanalization, SBPmean, SBPmax, and MAPmean are associated with the extent of BBBD on immediate post-EVT DECT, but not with maximum iodine concentration.

Ischemic stroke is the primary reason for human disability and death, but the available treatment options are limited. Hence, it is imperative to explore novel and efficient therapies. In recent years, pyroptosis (a pro-inflammatory cell death characterized by inflammation) has emerged as an important pathological mechanism in ischemic stroke that can cause cell death through plasma membrane rupture and release of inflammatory cytokines. Pyroptosis is closely associated with inflammation, which exacerbates the inflammatory response in ischemic stroke. The level of inflammasomes, GSDMD, Caspases, and inflammatory factors is increased after ischemic stroke, exacerbating brain injury by mediating pyroptosis. Hence, inhibition of pyroptosis can be a therapeutic strategy for ischemic stroke. In this review, we have summarized the relationship between pyroptosis and ischemic stroke, as well as a series of treatments to attenuate pyroptosis, intending to provide insights for new therapeutic targets on ischemic stroke.

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short-term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data-driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data-driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. KEY POINTS: Dynamic cerebral autoregulation is governed by two time constants. The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models. This arterial transit time is approximately 1 s in the brain. The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time. The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model.

The 70 recommendations summarize the current status of preoperative risk evaluation of adult patients prior to elective non-cardiothoracic surgery. Based on the joint publications of the German scientific societies for anesthesiology and intensive care medicine (DGAI), surgery (DGCH), and internal medicine (DGIM), which were first published in 2010 and updated in 2017, as well as the European guideline on preoperative cardiac risk evaluation published in 2022, a comprehensive re-evaluation of the recommendation takes place, taking into account new findings, the current literature, and current guidelines of international professional societies. The revised multidisciplinary recommendation is intended to facilitate a structured and common approach to the preoperative evaluation of patients. The aim is to ensure individualized preparation for the patient prior to surgery and thus to increase patient safety. Taking into account intervention- and patient-specific factors, which are indispensable in the preoperative risk evaluation, the perioperative risk for the patient should be minimized and safety increased. The recommendations for action are summarized under "General Principles (A)," "Advanced Diagnostics (B)," and the "Preoperative Management of Continuous Medication (C)." For the first time, a rating of the individual measures with regard to their clinical relevance has been given in the present recommendation. A joint and transparent agreement is intended to ensure a high level of patient orientation while avoiding unnecessary preliminary examinations, to shorten preoperative examination procedures, and ultimately to save costs. The joint recommendation of DGAI, DGCH and DGIM reflects the current state of knowledge as well as the opinion of experts. The recommendation does not replace the individualized decision between patient and physician about the best preoperative strategy and treatment.

Cerebral collateral circulation is a dynamic and adaptive process by which alternative vascular pathways supply perfusion to ischemic brain tissue in the event of an arterial occlusion. This complicated network of blood vessels that acts as a natural bypass plays a pivotal role in stroke pathophysiology and has become a key area of study given its significance in stroke treatment and patient outcomes. In this review, we will study the factors influencing the formation, recruitment, and endurance of collateral vessels; discuss imaging modalities for quantitative and qualitative assessment of this network; explore the role of collaterals in stroke management; and highlight several cardiovascular strategies to minimize damage to collaterals and optimize stroke outcomes.

Blood-brain barrier damage has traditionally been considered to determine the occurrence and development of poststroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting blood-brain barrier damage has been proven clinically effective in ameliorating brain edema.

In mice with stroke models induced by transient middle cerebral artery occlusion (MCAO), the changes in glymphatic system (GS) function impairment were detected by ex vivo fluorescence imaging, 2-photon in vivo imaging, and magnetic resonance imaging within 1 week after MCAO, and the effects of GS impairment and recovery on the formation and resolution of brain edema were evaluated. In addition, in patients with ischemic stroke within 1 week after onset, changes in GS function and brain edema were also observed by magnetic resonance imaging.

We found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after MCAO in mice, as brain edema reabsorption preceded blood-brain barrier closure. Strikingly, the time course of edema progression matched well with the GS dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aβ (amyloid-β) and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes.

GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for treating brain edema in ischemic stroke.

URL: https://www.chictr.org.cn/showproj.html?proj=162857; Unique identifier: NFEC-2019-189.

Restless legs syndrome (RLS) is a prevalent sensorimotor nervous system disorder in patients accompanied with insomnia, blood pressure fluctuation, and sympathetic dysfunction. These symptoms may disrupt cerebral hemodynamics. Dynamic cerebral autoregulation (dCA) describes the temporary response of cerebrovascular system to abrupt fluctuations in blood pressure, which keep cerebral blood flow stable and serve as a marker of cerebrovascular system ability.

This research aimed to assess dCA in RLS patients.

In this study, RLS patients were recruited and subsequently classified into four groups (mild, moderate, severe, and very severe) based on the International RLS Rating Scale (IRLS). Healthy controls matched for age and sex were enrolled. All participants were evaluated dCA by assessing phase difference (PD). A portion of patients with RLS was reassessed for dCA after one month of medication therapy (pramipexole [0.125 mg/day] and gabapentin [300 mg/day]).

There were altogether 120 patients with RLS and 30 controls completed the polysomnography and dCA assessment. PD was lower in the moderate, severe, and very severe RLS groups than that in the controls and mild RLS groups. Periodic limb movement index (PLMI), arousal index, and IRLS all showed a linear correlation with PD in RLS patients. Additionally, PD increased in RLS patients after therapy.

The dCA was compromised in moderate, severe, and very severe RLS patients and was negatively correlated with the IRLS, arousal index, and PLMI. After 1 month of therapy, dCA improved in RLS patients.

Fluctuating arterial blood pressure during high-intensity interval exercise (HIIE) may challenge dynamic cerebral autoregulation (dCA), specifically after stroke after an injury to the cerebrovasculature. We hypothesized that dCA would be attenuated at rest and during a sit-to-stand transition immediately after and 30 min after HIIE in individuals poststroke compared with age- and sex-matched control subjects (CON). HIIE switched every minute between 70% and 10% estimated maximal watts for 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were recorded. dCA was quantified during spontaneous fluctuations in MAP and MCAv via transfer function analysis. For sit-to-stand, time delay before an increase in cerebrovascular conductance index (CVCi = MCAv/MAP), rate of regulation, and % change in MCAv and MAP were measured. Twenty-two individuals poststroke (age 60 ± 12 yr, 31 ± 16 mo) and twenty-four CON (age 60 ± 13 yr) completed the study. Very low frequency (VLF) gain (P = 0.02, η2 = 0.18) and normalized gain (P = 0.01, η2 = 0.43) had a group × time interaction, with CON improving after HIIE whereas individuals poststroke did not. Individuals poststroke had lower VLF phase (P = 0.03, η2 = 0.22) after HIIE compared with CON. We found no differences in the sit-to-stand measurement of dCA. Our study showed lower dCA during spontaneous fluctuations in MCAv and MAP following HIIE in individuals poststroke compared with CON, whereas the sit-to-stand response was maintained.NEW & NOTEWORTHY This study provides novel insights into poststroke dynamic cerebral autoregulation (dCA) following an acute bout of high-intensity interval exercise (HIIE). In people after stroke, dCA appears attenuated during spontaneous fluctuations in mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) following HIIE. However, the dCA response during a single sit-to-stand transition after HIIE showed no significant difference from controls. These findings suggest that HIIE may temporarily challenge dCA after exercise in individuals with stroke.

Stroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats.

The change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs).

Pressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group.

Thus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Ischaemic or haemorrhagic perioperative stroke (that is, stroke occurring during or within 30 days following surgery) can be a devastating complication following surgery. Incidence is reported in the 0.1-0.7% range in adults undergoing non-cardiac and non-neurological surgery, in the 1-5% range in patients undergoing cardiac surgery and in the 1-10% range following neurological surgery. However, higher rates have been reported when patients are actively assessed and in high-risk populations. Prognosis is significantly worse than stroke occurring in the community, with double the 30-day mortality, greater disability and diminished quality of life among survivors. Considering the annual volume of surgeries performed worldwide, perioperative stroke represents a substantial burden. Despite notable differences in aetiology, patient populations and clinical settings, existing clinical recommendations for perioperative stroke are extrapolated mainly from stroke in the community. Perioperative in-hospital stroke is unique with respect to the stroke occurring in other settings, and it is essential to apply evidence from other settings with caution and to identify existing knowledge gaps in order to effectively guide patient care and future research.

The optimal general anesthetic (GA) technique for stroke patients undergoing endovascular thrombectomy (ET) is unclear. We compared favorable outcomes and mortality in patients receiving propofol or volatile GA during ET and assessed associations between mean arterial pressure (MAP) and outcome.

Ninety-three patients with anterior circulation stroke who received propofol or volatile GA during ET between February 2015 and February 2018 were included in this retrospective study. Ninety-day modified Rankin scores were compared and mortality was adjusted for intravenous thrombolysis and diabetes. We performed ordinal logistic regression analyses containing MAP time/exposure thresholds.

There was no difference in the rate of favorable outcome (modified Rankin scores 0-2) in the volatile and propofol groups (48.8% vs. 55.8%, respectively; P =0.5). Ninety-day mortality was lower in patients receiving propofol (11.5%) than in those receiving volatile GA (29.3%) (odds ratio, 0.32; 95% confidence interval, 0.11 to 0.94; P =0.03); this mortality benefit was greater in patients that did not receive intravenous thrombolysis before ET (odds ratio for survival, 6; 95% confidence interval, 1.13 to 31.74). There was no difference in MAP between groups and a (nonsignificant) trend towards the benefit of MAP <90 mm Hg but not <70 mm Hg.

Favorable outcome rates were similar in stroke patients receiving propofol or volatile GA during ET. Propofol was associated with lower mortality, an effect magnified in patients that did not receive intravenous thrombolysis. MAP time/exposure thresholds were associated with outcome but independent of the anesthetic agent. Our data suggest that a difference in outcome related to an anesthetic agent may exist; this hypothesis needs to be tested in a prospective study.

Transient neurological events (TNEs) occur after bypass surgery in Moyamoya disease (MMD); however, their pathology remains unknown. To elucidate the pathophysiology of TNEs, we investigated their relationship with perioperative superficial temporal artery (STA) blood flow volume, which was evaluated using ultrasonography. Forty-nine patients with MMD, who underwent direct bypass surgery, were included and stratified into TNE and non-TNE groups, respectively. The STA blood flow volume was evaluated at four time points (preoperatively and 2-4, 7, and 10-14 days postoperatively), and a change in volume during the postoperative period was defined as a flow volume mismatch. We investigated the association between ultrasonographic findings of flow volume mismatch and TNEs and magnetic resonance imaging findings, such as the cortical hyperintensity belt (CHB) sign, using univariate and path analyses. The STA blood flow volume increased immediately postoperatively, gradually decreasing over time, in both groups. The TNE group showed a significant increase in blood flow volume 2-4 days postoperatively (P = 0.042). Flow volume mismatch was significantly larger in the TNE group than in the non-TNE group (P = 0.020). In the path analysis, STA flow volume mismatch showed a positive association with the CHB sign (P = 0.023) and TNEs (P = 0.000). Additionally, the CHB sign partially mediated the association between STA flow volume mismatch and TNEs. These results suggest that significantly high STA blood flow volume changes occurring during the acute postoperative period after direct bypass surgery in MMD are correlated with TNEs and the CHB sign, suggesting involvement in the pathophysiology of TNEs.

Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel in silico approach that incorporates case-specific in vivo data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with in vivo data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke.

We aimed to characterize the cerebral hemodynamic response to obstructive sleep apnea/hypopnea events, and evaluate their association to polysomnographic parameters. The characterization of the cerebral hemodynamics in obstructive sleep apnea (OSA) may add complementary information to further the understanding of the severity of the syndrome beyond the conventional polysomnography.

Severe OSA patients were studied during night sleep while monitored by polysomnography. Transcranial, bed-side diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared diffuse correlation spectroscopy (NIRS-DOS) were used to follow microvascular cerebral hemodynamics in the frontal lobes of the cerebral cortex. Changes in cerebral blood flow (CBF), total hemoglobin concentration (THC), and cerebral blood oxygen saturation (StO2) were analyzed.

We considered 3283 obstructive apnea/hypopnea events from sixteen OSA patients (Age (median, interquartile range) 57 (52-64.5); females 25%; AHI (apnea-hypopnea index) 84.4 (76.1-93.7)). A biphasic response (maximum/minimum followed by a minimum/maximum) was observed for each cerebral hemodynamic variable (CBF, THC, StO2), heart rate and peripheral arterial oxygen saturation (SpO2). Changes of the StO2 followed the dynamics of the SpO2, and were out of phase from the THC and CBF. Longer events were associated with larger CBF changes, faster responses and slower recoveries. Moreover, the extrema of the response to obstructive hypopneas were lower compared to apneas (p < .001).

Obstructive apneas/hypopneas cause profound, periodic changes in cerebral hemodynamics, including periods of hyper- and hypo-perfusion and intermittent cerebral hypoxia. The duration of the events is a strong determinant of the cerebral hemodynamic response, which is more pronounced in apnea than hypopnea events.

Human stroke serum (HSS) has been shown to impair cerebrovascular function, likely by factors released into the circulation after ischemia. 20 nm gold nanoparticles (GNPs) have demonstrated anti-inflammatory properties, with evidence that they decrease pathologic markers of ischemic severity. Whether GNPs affect cerebrovascular function, and potentially protect against the damaging effects of HSS on the cerebral circulation remains unclear. HSS obtained 24 h poststroke was perfused through the lumen of isolated and pressurized third-order posterior cerebral arteries (PCAs) from male Wistar rats with and without GNPs (~2 × 109 GNP/ml), or GNPs in vehicle, in an arteriograph chamber (n = 8/group). All vessels were myogenically reactive ≥60 mmHg intravascular pressure; however, vessels containing GNPs had significantly less myogenic tone. GNPs increased vasoreactivity to small and intermediate conductance calcium activated potassium channel activation via NS309; however, reduced vasoconstriction to nitric oxide synthase inhibition. Hydraulic conductivity and transvascular filtration, were decreased by GNPs, suggesting a protective effect on the blood-brain barrier. The stress-strain curves of PCAs exposed to GNPs were shifted leftward, indicating increased vessel stiffness. This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications.

Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related cognitive decline. Severe VCID includes post-stroke dementia, subcortical ischemic vascular dementia, multi-infarct dementia, and mixed dementia. While VCID is acknowledged as the second most common form of dementia after Alzheimer's disease (AD) accounting for 20% of dementia cases, VCID and AD frequently coexist. In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent small subcortical infarcts, lacunes of presumed vascular origin, enlarged perivascular space, microbleeds, and brain atrophy are neuroimaging hallmarks of cSVD. The current primary approach to cSVD treatment is to control vascular risk factors such as hypertension, dyslipidemia, diabetes, and smoking. However, causal therapeutic strategies have not been established partly due to the heterogeneous pathogenesis of cSVD. In this review, we summarize the pathophysiology of cSVD and discuss the probable etiological pathways by focusing on hypoperfusion/hypoxia, blood-brain barriers (BBB) dysregulation, brain fluid drainage disturbances, and vascular inflammation to define potential diagnostic and therapeutic targets for cSVD.

The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.