OBJECTIVE: To explore the value of middle cerebral artery (MCA) plaque characteristics in predicting the outcomes of subacute ischemic stroke and the incremental value of the previous diet on predictive performance.
METHODS: One hundred and thirty-seven subacute ischemic stroke patients attributed to MCA plaques were included and analyzed in this prospective study. The National Institute of Health Stroke Scale (NIHSS) score, Mediterranean Diet Adherence Screener (MEDAS) score, and other clinical data were assessed. The plaque area, degree of stenosis, plaque burden, enhancement ratio, remodeling type, and intraplaque hemorrhage were measured using high-resolution MR vessel wall imaging (HR-VWI). Multivariable logistic regression analysis and receiver operating characteristic curve analysis were performed to assess the predictive performance of clinical and plaque characteristics for subacute ischemic stroke outcomes at 3 months.
RESULTS: Patients with poor outcomes exhibited high NIHSS scores, and low MEDAS scores (P<0.001). Plaque burden, enhancement ratio, and degree of stenosis were significantly higher in patients with poor outcomes (P<0.001). Multivariate analyses further indicated that NIHSS score (P=0.001), MEDAS score (P=0.013), and enhancement ratio (P=0.011) were independent predictors of subacute ischemic stroke outcomes. The three models\' area under the curve (AUC) values were 0.811, 0.844, and 0.794. Combining these three factors resulted in an AUC of 0.908 (P<0.001).
CONCLUSIONS: The combination of NIHSS score, MEDAS score, and enhancement ratio showed significant superiority in the prognostic evaluation of subacute ischemic stroke. Clinical data combined with plaque characteristics improves the accuracy of 3-month outcome prediction on subacute ischemic stroke.

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The long-term consequences of electronic cigarette (Ecig) use in humans are not yet known, but it is known that Ecig aerosols contain many toxic compounds of concern. We have recently shown that Ecig exposure impairs middle cerebral artery (MCA) endothelial function and that it takes 3 days for MCA reactivity to return to normal. However, the sources contributing to impairment of the endothelium were not investigated. We hypothesized that the increased levels of oxidative stress markers in the blood are correlated with impaired MCA reactivity. We used electron paramagnetic resonance (EPR) spectroscopy to examine plasma from 4-month-old male Sprague-Dawley rats that were exposed to either air (n = 5) or 1 h Ecig exposure, after which blood samples were collected at varying times after exposure (i.e., 1-4, 24, 48 and 72 h postexposure, n = 4 or 5 in each time group). The EPR analyses were performed using the redox-sensitive hydroxylamine spin probe 1-hydroxy-3-carboxymethyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) to measure the level of reactive oxidant species in the plasma samples. We found that EPR signal intensity from the CM• radical was significantly increased in plasma at 1-4, 24 and 48 h (P < 0.05, respectively) and returned to control (air) levels by 72 h. When evaluating the EPR results with MCA reactivity, we found a significant negative correlation (Pearson\'s P = 0.0027). These data indicate that impaired cerebrovascular reactivity resulting from vaping is associated with the oxidative stress level (measured by EPR from plasma) and indicate that a single 1 h vaping session can negatively influence vascular health for up to 3 days after vaping. HIGHLIGHTS: What is the central question of this study? Does the time course of oxidative stress triggered by electronic cigarette exposure follow the cerebral vascular dysfunction? What is the main finding and its importance? Electron paramagnetic resonance analysis shows that the oxidative stress induced after a single 1 h exposure to electronic cigarette aerosol takes ≤72 h to return to normal, which mirrors the time course for vascular dysfunction in the middle cerebral artery that we have reported previously.

The pterional approach has traditionally been employed for managing middle cerebral artery (MCA) aneurysms. With potential benefits like reduced surgical morbidity and improved postoperative recovery, the lateral supraorbital approach (LSO) should be considered individually based on aneurysm morphology, location and patient-specific variations of the MCA anatomy, which requires considerable technical expertise traditionally acquired through years of experience. The goal of this study was the development and evaluation of a novel phantom simulator in the context of clinical decision-making in the managmement of MCA aneurysms. For this purpose, high-fidelity simulators inclusive of MCA models with identical M1- and bifurcation aneurysms were manufactured employing 3D reconstruction techniques, additive manufacturing and rheological testings. Medical students, neurosurgical residents, and seasoned neurosurgeons (n = 22) tested and evaluated both approaches. Participants\' performances and progress over time were assessed based on objective metrics. The simulator received positive ratings in face and content validity, with mean scores of 4.9 out of 5, respectively. Objective evaluation demonstrated the model\'s efficacy as a practical training tool, particularly among inexperienced participants. While requiring more technical expertise, results of the comparative analysis suggest that the LSO approach can improve clipping precision and outcome particularly in patients with shorter than average M1-segments. In conclusion, the employed methodology allowed a direct comparison of the pterional and LSO approaches, revealing comparable success rates via the LSO approach while reducing operation time and complication rate. Future research should aim to establish simulators in the context of clinical decision making.

OBJECTIVE: Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes in patients with acute non-disabling stroke/Transient Ischemic Attack (TIA) to understand its implication in stroke ethiopatogenesis.
METHODS: VMR by Transcranial Doppler Breath Holding test was performed at 48-72 h from stroke onset (T1) and after 6 months (T2) on MCA of the non-affected hemisphere and PCA of the affected hemisphere.
RESULTS: We consecutively enrolled 124 patients with a median age of 66.0 (IQR 54.75-74.25) years with a median NIHSS 2 (IQR 1-3). Both MCA (1.38 %/s SD 0.58) and PCA (1.35 %/s SD 0.75) BHI at T1 did not differ among different stroke subtypes (p=0.067 and p=0.350; N=124). MCA and PCA BHI decreased from T1 to T2 (respectively 1.39 %/s SD 0.56 vs 1.18%/s SD 0.44 and 1.30 %/s SD 0.69 vs 1.20 %/s SD 0.51; N=109) regardless of ethiopatogenesis (respectively p<0.0001 and p=0.111).
CONCLUSIONS: The VMR is higher in acute phase than at 6 months in patients with non-disabling stroke/TIA, regardless of etiopathogenesis. The higher VMR in acute phase could be sustained by an increased Cerebral Blood Flow due to collateral circulation activation supporting the ischemic zone.

Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure with simultaneous fluctuations in middle cerebral artery blood velocity (MCAv). Some evidence indicates that RE may alter cerebrovascular function. This study aimed to examine the effects of habitual RE training on the within-RE cerebrovascular responses. RE-trained (n = 15, Female = 4) and healthy untrained individuals (n = 15, Female = 12) completed four sets of 10 paced repetitions (15 repetitions per minute) of unilateral leg extension exercise at 60% of predicted 1 repetition maximum. Beat-to-beat blood pressure, MCAv and end-tidal carbon dioxide were measured throughout. Zenith, nadir and zenith-to-nadir difference in mean arterial blood pressure (MAP) and mean MCAv (MCAvmean) for each repetition were averaged across each set. Two-way ANOVA was used to analyse dependent variables (training × sets), Bonferroni corrected t-tests were used for post hoc pairwise comparisons. Group age (26 ± 7 trained vs. 25 ± 6 years untrained, P = 0.683) and weight (78 ± 15 vs. 71 ± 15 kg, P = 0.683) were not different. During exercise average MAP was greater for the RE-trained group in sets 2, 3 and 4 (e.g., set 4: 101 ± 11 vs. 92 ± 7 mmHg for RE trained and untrained, respectively, post hoc tests all P = < 0.012). Zenith MAP and zenith-to-nadir MAP difference demonstrated a training effect (P < 0.039). Average MCAvmean and MCAvmean zenith-to-nadir difference was not different between groups (interaction effect P = 0.166 and P = 0.459, respectively). Despite RE-trained individuals demonstrating greater fluctuations in MAP during RE compared to untrained, there were no differences in MCAvmean. Regular RE may lead to vascular adaptations that stabilise MCAv during RE.

UNASSIGNED: Vascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown.
UNASSIGNED: OxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent-magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q.
UNASSIGNED: In 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, -0.01 to 0.05; P=0.18), or versus cilostazol (-0.01, -0.04 to 0.02; P=0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5-9.07; P<0.001; ∆ end-diastolic velocity, 1.98, 0.66-3.29; P=0.004). Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23-1.42; P=0.007), CVR-WMH (0.07, 0-0.14; P=0.043), CVR-normal-appearing white matter (0.06, 0.00-0.12; P=0.048), perfusion (WMH: 1.82 mL/100 g per minute, 0.5-3.15; P=0.008; and normal-appearing white matter, 2.12, 0.66-3.6; P=0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05-0.10; P=4.9×10-8; cilostazol-placebo, 0.06, 0.03-0.09; P=5.1×10-5). Both drugs increased headaches (P=1.1×10-4), while cilostazol increased moderate-severe diarrhea (P=0.013).
UNASSIGNED: Sildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease.
UNASSIGNED: URL: https://www.clinicaltrials.gov/study/NCT03855332; Unique identifier: NCT03855332.

UNASSIGNED: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions.
UNASSIGNED: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality.
UNASSIGNED: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group.
UNASSIGNED: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

BACKGROUND: We aimed to investigate the association of characteristics of lenticulostriate artery (LSA) morphology and parental atheromatous disease (PAD) with single subcortical infarction (SSI) and to explore whether the LSA morphology is correlated with proximal plaque features in asymptomatic PAD.
RESULTS: Patients with acute SSI were prospectively enrolled and classified as large- and small-SSI groups. The clinical data and imaging features of LSA morphology (branches, length, dilation, and tortuosity) and middle cerebral artery plaques (normalized wall index, remodeling index, enhancement degree, and hyperintense plaques) were evaluated. Logistic regression was performed to determine the association of large SSIs with morphologic features of LSAs and plaques. The Spearman correlation between the morphologic characteristics of LSAs and plaque features in asymptomatic PAD was analyzed. Of the 121 patients recruited with symptomatic PAD, 102 had coexisting asymptomatic contralateral PAD. The mean length of LSAs (odds ratio, 0.84 [95% CI, 0.73-0.95]; P=0.007), mean tortuosity of LSAs (odds ratio, 1.13 [95% CI, 1.05-1.22]; P=0.002), dilated LSAs (odds ratio, 22.59 [95% CI, 2.46-207.74]; P=0.006), and normalized wall index (odds ratio, 1.08 [95% CI, 1.01-1.15]; P=0.022) were significantly associated with large SSIs. Moreover, the normalized wall index was negatively correlated with the mean length of LSAs (r=-0.348, P<0.001), and the remodeling index was negatively correlated with the mean tortuosity of LSAs (r=-0.348, P<0.001) in asymptomatic PAD.
CONCLUSIONS: Our findings suggest that mean length of LSAs, mean tortuosity of LSAs, dilated LSAs, and normalized wall index are associated with large SSIs. Moreover, plaque features in asymptomatic PAD are correlated with morphologic features of LSAs.

Resistance breathing may restore cardiac output (CO) and cerebral blood flow (CBF) during hypovolemia. We assessed CBF and cerebral autoregulation (CA) during tilt, resistance breathing, and paced breathing in 10 healthy subjects. Blood velocities in the internal carotid artery (ICA), middle cerebral arteries (MCA, four subjects), and aorta were measured by Doppler ultrasound in 30° and 60° semi-recumbent positions. ICA blood flow and CO were calculated. Arterial blood pressure (ABP, Finometer), and end-tidal CO2 (ETCO2) were recorded. ICA blood flow response was assessed by mixed-models regression analysis. The synchronization index (SI) for the variable pairs ABP-ICA blood velocity, ABP-MCA velocities in 0.005-0.08 Hz frequency interval was calculated as a measure of CA. Passive tilting from 30° to 60° resulted in 12% decrease in CO (p = 0.001); ICA blood flow tended to fall (p = 0.04); Resistance breathing restored CO and ICA blood flow despite a 10% ETCO2 drop. ETCO2 and CO contributed to ICA blood flow variance (adjusted R2: 0.9, p < 0.0001). The median SI was low (<0.2) indicating intact CA, confirmed by surrogate date testing. The peak SI was transiently elevated during resistance breathing in the 60° position. Resistance breathing may transiently reduce CA efficiency. Paced breathing did not restore CO or ICA blood flow.