Sex and Hemisphere - A Neglected, Nature-Determined Relationship in Acute Ischemic Stroke

Background: Sex differences in the structural connectome of the brain are clinically highly relevant, but they have mostly been neglected in stroke trials. We investigated the impact of the interaction sex-by-hemisphere on outcome in stroke patients after intravenous thrombolysis (IVT). Methods: This is an observational study based on consecutively collected supratentorial stroke patients treated with IVT (n = 1,231). The 3-month modified Rankin scale (mRS) was estimated by adjusted binary (mRS 0-2 for good outcome) and ordinal regression analysis. As baseline characteristics differ substantially between the sexes, we aimed for better covariate balance by employing coarsened exact matching. Results: Sex-by-hemisphere predicted good outcome in the entire cohort (726 left, 505 right hemispheric strokes, p valueinteraction 0.032) and in the matched cohort (338 left, 273 right, p valueinteraction 0.003). Ordinal regression suggested a comparable estimate in the matched cohort (p valueinteraction 0.006). Further investigation revealed relevant between-sex and within-sex risk: right hemispheric strokes in men were 1.54 times (95% confidence intervals (CIs) 1.15-2.01) more likely than in women to achieve mRS 0-2. Women with right hemispheric strokes were 0.72 times (95% CI 0.54-0.92) less likely to reach mRS 0-2 than women with left hemispheric strokes. Conversely, men with right hemispheric strokes were 1.35 times (95% CI 1.06-1.70) more likely to achieve mRS 0-2 than men with left hemispheric strokes. Conclusion: This study suggests that outcomes are different in both sexes after IVT when different hemispheres are affected. Further consideration of this hypothesis in clinical trials might help in guiding individualized, injury-specific treatment approaches for acute ischemic stroke. © 2015 S. Karger AG, Base

Impact of statin use and lipid profile on symptomatic intracerebral haemorrhage, outcome and mortality after intravenous thrombolysis in acute stroke

Background: It is unclear if a certain lipid profile and/or statin use contribute to symptomatic intracerebral haemorrhage (sICH), poor outcome or mortality after intravenous thrombolysis for ischaemic stroke. The aim of the current study was to assess the impact of statin use and lipid profile on sICH, outcome and mortality following thrombolysis in acute stroke. Methods: From 2001 to 2010, all patients admitted to our hospital and undergoing intravenous thrombolysis for acute ischaemic stroke were included into an open, prospective database. Initial stroke severity was assessed using the National Institute of Health Stroke Scale. Demographics, vascular risk factors, admission blood pressure, glucose levels, previous medication including statin use, lipid profiles including low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were recorded. Outcome measures included sICH according to the European Cooperative Acute Stroke Study II criteria, modified Rankin scale and mortality at 3 months. Results: 1,066 patients were included in the analysis; 5.3% (57 patients) had sICH. Mortality at 3 months was 17.6% (188 patients). A favourable outcome (modified Rankin scale 0-1) at 3 months was attained by 35.6% (379 patients). Prior statin use was not associated with increased odds for sICH (OR 1.05, 95% CI 0.55–2.04, p = 0.864), mortality (OR 1.32, 95% CI 0.90–1.93, p = 0.152) or favourable outcome (OR 0.89, 95% CI 0.65–1.24, p = 0.507). Similar results were found for the different lipid variables: high LDL (OR 0.96, 95% CI 0.36–2.60, p = 0.942), high triglyceride (OR 1.74, 95% CI 0.84–3.56, p = 0.132) and low HDL (OR 1.78, 95% CI 0.68–4.65, p = 0.279) were not associated with increased odds for sICH. Likewise, neither mortality nor functional outcome at 3 months was significantly associated with any of the lipid variables in the univariable analysis following Bonferroni adjustment for multiple comparisons. The same results were found in the multivariable analysis adjusting for imbalances in baseline characteristics. Conclusions: In contrast to previous studies, we found that in stroke patients receiving thrombolysis therapy, neither the lipid profile nor prior statin use were associated with increased odds for sICH, functional outcome or mortality at 3 months

Blood pressure variability after intravenous thrombolysis in acute stroke does not predict intracerebral hemorrhage but poor outcome

Background: The relevance of blood pressure variability (BPV) in the development of intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) in acute stroke still remains uncertain. Methods: 427 consecutive patients treated with IVT in the years 2007-2009 were studied. Blood pressure (BP) values were analyzed from admission to follow-up imaging scan and described as mean, maximum, minimum, standard deviation (SD), difference between maximum and minimum, successive variation (SV) and maximum SV. ICH was categorized based on radiologic criteria and symptomatic ICH (sICH) was defined as ICH plus worsening of the National Institute of Health Stroke Scale by 6 4 points or leading to death. Three-month outcome was described by means of the modified Rankin Scale. Results: We observed any ICH in 51 (11.9%) and sICH in 10 (2.3%) patients. Systolic and diastolic BP profiles, including mean, maximum, minimum, SD, difference between maximum and minimum, SV and maximum SV, did not differ between ICH-negative, ICH-positive and sICH patients

in situ tracking of redox transitions and mode of catalysis

Water oxidation by amorphous oxides is of high interest in artificial photosynthesis and other routes towards non-fossil fuels, but the mode of catalysis in these materials is insufficiently understood. We tracked mechanistically relevant oxidation-state and structural changes of an amorphous Co-based catalyst film by in situ experiments combining directly synchrotron-based X-ray absorption spectroscopy (XAS) with electrocatalysis. Unlike a classical solid-state material, the bulk material is found to undergo chemical changes. Two redox transitions at midpoint potentials of about 1.0 V (CoII0.4CoIII0.6 ↔ all-CoIII) and 1.2 V (all-CoIII ↔ CoIII0.8CoIV0.2) vs. NHE at pH 7 are coupled to structural changes. These redox transitions can be induced by variation of either electric potential or pH; they are broader than predicted by a simple Nernstian model, suggesting interacting bridged cobalt ions. Tracking reaction kinetics by UV-Vis-absorption and time-resolved mass spectroscopy reveals that accumulated oxidizing equivalents facilitate dioxygen formation. On these grounds, a new framework model of catalysis in an amorphous, hydrated and volume-active oxide is proposed: Within the oxide film, cobalt ions at the margins of Co-oxo fragments undergo CoII ↔ CoIII ↔ CoIV oxidation-state changes coupled to structural modification and deprotonation of Co-oxo bridges. By the encounter of two (or more) CoIV ions, an active site is formed at which the O–O bond-formation step can take place. The Tafel slope is determined by both the interaction between cobalt ions (width of the redox transition) and their encounter probability. Our results represent a first step toward the development of new concepts that address the solid-molecular Janus nature of the amorphous oxide. Insights and concepts described herein for the Co-based catalyst film may be of general relevance also for other amorphous oxides with water-oxidation activity

Quantitative high-field diffusion tensor imaging of cerebral white matter in asymptomatic high-grade internal carotid artery stenosis

Background: Recently, several studies using diffusion-sensitized MRI reported changes in patients with high-grade internal carotid artery stenosis (ICAS) suggestive of subtle brain tissue damage. We used diffusion tensor imaging (DTI) to investigate the microstructural cerebral white matter integrity in asymptomatic patients with high-grade ICAS. Methods: In 15 asymptomatic patients with unilateral high grade (>70%) ICAS, we used 3T MRI including DTI. We used a region-of-interest approach comparing quantitative DTI metrics between both hemispheres including the so-called border zones. MR images were also assessed for periventricular white matter lesions (PWML) as well as collaterals via the circle of Willis. Results: There was no significant intraindividual difference of fractional anisotropy or mean diffusivity values between the hemispheres for any region. PWML was graded 0 degrees in 6 patients, I degrees in 9 and II degrees in 2. Conclusions: In clinically asymptomatic patients with high-grade unilateral ICAS, there was no difference between the DTI parameters of the affected and the unaffected hemisphere. These findings contrast with other studies in asymptomatic high-grade ICAS, which is likely due to patient selection. These findings argue against concomitant chronic tissue integrity changes and implicate the benignity of asymptomatic carotid artery disease in individual patients. Copyright (C) 2012 S. Karger AG, Base

Oral anticoagulants - a frequent challenge for the emergency management of acute ischemic stroke

Background: The emergency management of patients with acute ischemic stroke (IS) using oral anticoagulants (OAC) represents a great challenge. Effective anticoagulation predisposes to bleeding and represents a contraindication for systemic thrombolysis. However, patients on OAC can receive intravenous thrombolysis with recombinant tissue-type plasminogen activator if the international normalized ratio (INR) does not exceed 1.7, but data regarding the risk of hemorrhagic complications are highly controversial. Neurointerventional recanalization of intracranial artery occlusion represents an alternative option in OAC patients with acute IS. The proportion of OAC users among consecutive patients who suffer from acute IS or transient ichemic attacks (TIA) is unknown. Methods: A prospective observational study, consecutively enrolling all patients with IS or TIA admitted to our neurological emergency room (ER), was performed between August 2009 and February 2011. Basic demographic variables, present use of OAC, severity of stroke, cardiovascular risk factors, INR values and the symptom onset to presentation time were recorded. In IS patients on OAC presenting within 4.5 h after symptom onset, management was analyzed. In thrombolysed IS patients, bleeding events were documented. Outcome was assessed after 3 months

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year

Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy.

Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41-1.4) min-1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56-0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10-0.82]) compared to hyperperfusion (PPV = 0.93 [0.68-1.0]) or unaffected perfusion (PPV = 1.0 [0.75-1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression

Comparing Poor and Favorable Outcome Prediction With Machine Learning After Mechanical Thrombectomy in Acute Ischemic Stroke

Outcome prediction after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) is commonly performed by focusing on favorable outcome (modified Rankin Scale, mRS 0–2) after 3 months but poor outcome representing severe disability and mortality (mRS 5 and 6) might be of equal importance for clinical decision-making