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Parkinson's Disease (PD) patients experience sleeping disorders in addition to the disease-defining symptomology of movement dysfunctions. The prevalence of PD is sex-based and presence of sleeping disorders in PD also shows sex bias with a stronger phenotype in males. In addition to loss of dopamine-containing neurons in the striatum, arousal-related, orexin-containing neurons in the lateral hypothalamus (LH) are lost in PD, which could contribute to state-related disorders. As orexin has been shown to be involved in sleeping disorders and to have neuroprotective effects, we asked whether orexin could protect sleep-related LH neurons from damage putatively from the protein α-synuclein (α-syn), which is found at high levels in the PD brain and that we have shown is associated with putatively excitotoxic rises in intracellular calcium in brainstem sleep-controlling nuclei, especially in males. Accordingly, we monitored intracellular calcium transients induced by α-syn and whether concurrent exposure to orexin affected those transients in LH cells of the mouse brain slice using calcium imaging. Further, we used an assay of cell death to determine whether LH cell viability was influenced when α-syn and orexin were co-applied when compared to exposure to α-syn alone. We found that excitatory calcium events induced by α-syn were reduced in amplitude and frequency when orexin was co-applied, and when data were evaluated by sex, this effect was found to be greater in females. In addition, α-syn exposure was associated with cell death that was higher in males, and interestingly, reduced cell death was noted when orexin was present, which did not show a sex bias. We interpret our findings to indicate that orexin is protective to α-syn-mediated damage to hypothalamic neurons, and the actions of orexin on α-syn-induced cellular effects differ between sexes, which could underlie sex-based differences in sleeping disorders in PD., Competing Interests: Declaration of competing interest All authors disclose that they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sleep disorders (SDs) are a symptom of the prodromal phase of neurodegenerative disorders that are mechanistically linked to the protein α-synuclein (α-syn) including Parkinson's disease (PD). SDs during the prodromal phase could result from neurodegeneration induced in state-controlling neurons by accumulation of α-syn predominant early in the disease, and consistent with this, we reported the monomeric form of α-syn (monomeric α-syn; α-syn M ) caused cell death in the laterodorsal tegmental nucleus (LDT), which controls arousal as well as the sleep and wakefulness state. However, we only examined the male LDT, and since sex is considered a risk factor for the development of α-syn-related diseases including prodromal SDs, the possibility exists of sex-based differences in α-syn M effects. Accordingly, we examined the hypothesis that α-syn M exerts differential effects on membrane excitability, intracellular calcium, and cell viability in the LDT of females compared to males., Methods: Patch clamp electrophysiology, bulk load calcium imaging, and cell death histochemistry were used in LDT brain slices to monitor responses to α-syn M and effects of GABA receptor acting agents., Results: Consistent with our hypothesis, we found differing effects of α-syn M on female LDT neurons when compared to male. In females, α-syn M induced a decrease in membrane excitability and heightened reductions in intracellular calcium, which were reliant on functional inhibitory acid transmission, as well as decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) with a concurrent reduction in action potential firing rate. Cell viability studies showed higher α-syn M -mediated neurodegeneration in males compared to females that depended on inhibitory amino acid transmission. Further, presence of GABA receptor agonists was associated with reduced cell death in males., Conclusions: When taken together, we conclude that α-syn M induces a sex-dependent effect on LDT neurons involving a GABA receptor-mediated mechanism that is neuroprotective. Understanding the potential sex differences in neurodegenerative processes, especially those occurring early in the disease, could enable implementation of sex-based strategies to identify prodromal PD cases, and promote efforts to illuminate new directions for tailored treatment and management of PD., (© 2023. Society of Chinese Bioscientists in America (SCBA).)

Background: A common dilemma in acute ischemic stroke management is whether to pursue recanalization therapy in patients with large vessel occlusions but minimal neurologic deficits. We describe and report preliminary experience with a provocative maneuver, i.e. 90-degree elevation of the head of bed for 30 min, which stresses collaterals and facilitates decision-making., Methods: A prospective cohort study of <7.5 h of acute anterior circulation territory ischemia patients with minimal deficits despite middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease., Results: Five patients met the study entry criteria. Their mean age was 78.4 years (range 65-93). All presented with substantial deficits (median NIHSS score 11, range 5-22), but improved while in supine position during initial imaging to normal or near-normal (NIHSS score 0-2). MRA showed persistent M1 MCA occlusions in 4, critical ICA stenosis or occlusion in 1, and substantial perfusion-diffusion mismatch in all. To evaluate the potential for eventual collateral failure, patients were placed in a head of bed upright posture. Mean arterial pressure and heart rate were unchanged. Two showed no neurologic worsening and were treated with supportive care with excellent final outcome. Three showed worsening, including recurrent hemiparesis and aphasia at the 6th, recurrent aphasia at the 23rd, and recurrent hemineglect at the 15th upright minute. These 3 underwent endovascular recanalization therapies with successful reperfusion and excellent final outcome., Conclusion: The 'Heads Up' test may be a useful, simple maneuver to assess the risk of collateral failure and guide the decision to pursue recanalization therapy in acute cerebral ischemia patients with minimal deficits despite persisting large cerebral artery occlusion.

Background and Purpose: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory., Materials and Methods: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared., Results: Fifty-five AIS patients with unilateral MCA stroke (mean 73.95±14.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.01±2.11 vs. 1.82±1.51, p=0.024) but no differences on scores on CBF (2.31±1.61 vs. 1.66±1.32, p=0.231) and ATT (2.67±2.33 vs. 3.42±3.37, p=0.593)., Conclusions: Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.

Background and Purpose: In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment., Methods: We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography., Results: Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019)., Conclusions: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion., (© 2016 American Heart Association, Inc.)

Background: The influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial., Objective: To investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy., Methods: We analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome., Results: CMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy., Conclusions: Patients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Selection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution., Methods: Demographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012., Results: Among patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs. 74 years; p<0.05), more often treated with intravenous tissue plasminogen activator (53% vs. 34%; p<0.01), and had shorter last known well to puncture times (328 vs. 367 min; p<0.05). Focusing on the largest trial with a non-interventional control arm, compared with trial eligible patients treated with EST outside the trial, enrolled patients presented later (274 vs. 163 min; p<0.001), had higher National Institutes of Health Stroke Scale scores (20 vs. 17; p<0.05), and larger strokes (diffusion weighted imaging volumes 49 vs. 18; p<0.001)., Conclusions: The majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The recent development of revascularization devices, including stent retrievers, has enabled increasingly higher revascularization rates for arterial occlusions in acute ischemic stroke. Patient-specific factors such as anatomy, however, may occasionally limit endovascular deployment of these new devices via the conventional transfemoral approach. We report three cases of acute ischemic stroke where a transbrachial endovascular approach to revascularization was used, resulting in successful recanalization. These examples suggest that a transbrachial approach may be considered as an alternative in the endovascular treatment of acute ischemic stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Purpose: The enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated., Methods: The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process-paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded., Results: From 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%)., Conclusions: In this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332., (© 2015 American Heart Association, Inc.)

Background: Endovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome., Methods: Demographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010., Results: Higher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival., Conclusions: Improved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions., Objective and Methods: To examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data., Results: We found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0-2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale., Conclusions: If suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis., Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns., Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days., Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047)., Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients., (© 2015 S. Karger AG, Basel.)

Plants have been one of the important sources of medicine even since the-dawn of human civilization. Curcumin has been found to possess tremendous therapeutic potency as antiinflammatory, antioxidant and antimicrobial agent. The present study was designed to examine possible potential therapeutic and protective effect of curcumin from oxidative stress and on total antioxidant capacity in liver damage. The study was conducted using H2O2 as inducing agent of oxidative stress in vivo. Rats were randomly divided into five groups, where n = 20 for each group. Group 1 (G1) rats served as control group. Group 2 (G2) rats subjected to experimentally induced oxidative stress by the ad libitum supply of drinking water containing 0.5% H2O2(v/v) was prepared daily over entire 60 days. Group 3 (G3) rats received H2O2 for sixty days followed by giving 200 mg kg(-1) of curcumin for 30 days. Group 4 (G4) was simultaneously given curcumin (200 mg kg(-1)) for 15 days then followed by receiving H2O2 with curcumin for sixty days. Group 5 (G5) rats was received H2O2 for sixty days followed by giving 200 mg kg(-1) of N-acetyl 1-cystine as standard drug for 30 days. Levels of marker enzymes (ALT, AST and ALP), uric acid, Total Protein (TP) and tumor necrosis factor (α-TNF) were assessed in serum for all studied groups. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguinosine, Total Antioxidant Capacity (TAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) were assayed in liver homogenates for all studied groups. The results revealed significant increase (p < 0.05) in levels of ALT, AST, ALP, uric acid and α-TNF while there are significant decrease (p < 0.05) in levels of TP in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5 which curcumin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation. The results also revealed a significant increase (p < 0.05) in levels of MDA and 8-H-2-deoxy guinosine while there was significant reduction (p < 0.05) in TAC, GSH, SOD and catalase in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5. The conclusion could be drown from this study that the ability of curcumin as therapeutic agent and hepatoprotective against liver damage from oxidative damage and on TAC more than N-acetyl 1-cystine related to its antioxidant and free radical scavenger activity.

Background and Purpose: Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH., Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region., Results: As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation., Conclusions: The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.

Background: Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers., Methods: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator-treated patients in the NIHSS categories (0-3, 4-5, or ≥ 6) and associated outcomes., Results: A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P < .001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001)., Conclusions: There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes., (Copyright © 2013 National Stroke Association. All rights reserved.)

Background and Purpose: Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA)., Methods: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed., Results: A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60-2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60-1.49), bridging therapy (OR, 0.82; 95% CI, 0.47-1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64-2.08) versus IV rtPA were not associated with increased in-hospital mortality., Conclusions: IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.

Background and Purpose: The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy., Methods: We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome., Results: Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale≤2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001)., Conclusions: Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.

Background: The influence of lesion size and laterality on each component of the National Institutes of Health Stroke Scale has not been delineated. The objective of this study was to use perfusion-weighted imaging to characterize the association of ischaemic volume and laterality on each component item and the total score of the  10 s. Ordinal regression was used to clarify the relationship between ischaemic volume, laterality, and

Objective: To investigate whether anterior choroidal artery (AChA) territory sparing or AChA infarction restricted to the medial temporal lobe (MT), implying good collateral status, predicts good outcome, defined as modified Rankin Scale 0-2, at discharge in acute internal carotid artery (ICA) occlusion., Methods: The authors studied consecutive patients with acute ICA occlusion admitted to an academic medical centre between January 2002 and August 2010, who underwent MRI followed by conventional angiography. The pattern of AChA involvement on initial diffusion-weighted imaging was dichotomised as spared or MT only versus other partial or full. The association of AChA infarct patterns and good outcome at discharge was calculated by multivariate logistic regression with adjustment., Results: For the 60 patients meeting entry criteria, mean age was 68.3 years and median admission NIH Stroke Scale score was 19. AChA territory was spared or restricted to the MT in 27 patients and other partially involved or fully involved in 33 patients. AChA territory spared or ischaemia restricted to MT only, compared with other partial infarct patterns or full infarct, was independently associated with good discharge outcome (44.4% vs 12.1%, OR 7.24, 95% CI 1.32 to 39.89, p=0.023)., Conclusion: In acute ICA occlusion, the absence of AChA infarction or restriction to the MT is an independent predictor of good discharge outcome. Analysis of AChA infarct patterns may improve early prognostication and decision-making.

Background and Purpose: Determinants of successful recanalization likely differ for Merci thrombectomy and intra-arterial pharmacological fibrinolysis interventions. Although the amount of thrombotic material to be digested is an important consideration for chemical lysis, mechanical debulking may be more greatly influenced by other target lesion characteristics., Methods: In consecutive patients with acute ischemic stroke treated with Merci thrombectomy for middle cerebral artery M1 occlusions, we analyzed the influence on recanalization success and clinical outcome of target thrombus size (length) and shape (curvature and branching) on pretreatment T2* gradient echo MRI., Results: Among 65 patients, pretreatment MRI showed susceptibility vessel signs in 45 (69%). Thrombus length averaged 13.03 mm (range, 5.56-34.91) and irregular shape (curvature or branching) was present in 17 of 45 (38%). Presence and length of susceptibility vessel signs did not predict recanalization or good clinical outcome. Substantial recanalization (Thrombolysis In Cerebral Infarction 2b or 3) and good clinical outcome (modified Rankin Scale score ≤2) were more frequent with regular than irregular susceptibility vessel signs shape (57% versus 18%, P=0.013; 39% versus 6%, P=0.017). On multiple regression analysis, the only independent predictor of substantial recanalization was irregular susceptibility vessel signs (OR, 0.16; 95% CI, 0.04-0.69; P=0.014); and leading predictors of good clinical outcome were baseline National Institutes of Health Stroke Scale (OR, 1.20; 95% CI, 1.03-1.40; P= 0.019) and irregular susceptibility vessel signs (OR, 9.36; 95% CI, 0.98-89.4; P=0.052)., Conclusions: Extension of thrombus into middle cerebral artery division branches and curving shape of the middle cerebral artery stem, but not thrombus length, decrease technical and clinical success of Merci thrombectomy in M1 occlusions.

Background: Early disruption of the blood-brain barrier (BBB) due to severe ischemia can be detected by MRI T2* permeability imaging. In middle cerebral artery (MCA) infarction, pretreatment T2* permeability derangements have been found in 22% of patients and are powerful predictors of hemorrhagic transformation after revascularization therapy. The frequency, clinical correlates, and relation to hemorrhagic transformation of permeability derangements in posterior circulation have not been previously explored, and may differ as ischemia volume and collateral status are different between vertebrobasilar and MCA infarcts., Methods: We analyzed clinical and pretreatment MRI data on consecutive patients undergoing recanalization therapy for acute vertebrobasilar ischemia at a medical center November 2001 through September 2009. Pretreatment MRI permeability images were derived from perfusion source imaging acquisitions. Permeability abnormality was detected as persisting increased signal intensity at later time points in perfusion MRI acquisition, indicating local accumulation of contrast caused by BBB leakage., Results: Among the 14 patients meeting study entry criteria, mean age was 71.1 years and median pretreatment NIHSS was 20.5. Permeability imaging abnormality was present in 1 of the 14 patients (7%). Among 14 patients, post-treatment parenchymal hematoma occurred in one and more minor degrees of hemorrhagic transformation in four. The one patient with pretreatment permeability abnormality was the patient to develop post-treatment parenchymal hematoma (Fisher's exact test, P=0.07)., Conclusion: Pretreatment permeability abnormality, an indicator of BBB derangements, is an infrequent finding in acute posterior circulation ischemic stroke and may be associated with an increased risk of parenchymal hematoma development undergoing recanalization therapy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Stenting of symptomatic intracranial atherosclerosis remains under investigation, yet this option to potentially avert subsequent stroke has been offered at select centers under humanitarian device exemption and off-label use for several years., Methods: Retrospective case series of consecutive patients undergoing stenting with Wingspan and balloon mounted coronary stents for symptomatic intracranial atherosclerosis at a single institution. Recurrent symptomatic ischemia in the territory of the stented artery was ascertained. Rates of recurrent ischemic stroke were calculated per patient-year of follow-up and were compared with medically treated patients in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial., Results: During the 10 year study period, 41 cases of intracranial stenting were identified. Stenoses were severe (>70%) in 88% of patients. Stenting procedures occurred a median of 14 days from the most recent symptomatic event. 19 Wingspan stents and 22 balloon mounted coronary stents were deployed. Four strokes occurred within 24 h of stenting, seven within 1 month and eight within 3 months. By 3 months after stenting, no further strokes occurred during up to 2 years of follow-up. Patients had 0.194 ischemic strokes per person-year of follow-up, compared with 0.083 ischemic strokes per person-year of follow-up in the aspirin arm of WASID and 0.065 ischemic strokes per person-year of follow-up in the warfarin arm of WASID., Conclusions: Stenting of symptomatic intracranial atherosclerosis in a high risk subset of cases with advanced degree of luminal stenosis may be associated with an increased early risk of recurrent ischemic stroke.

Background: We examined the correlation of angiographic collaterals in acute stroke with the presence, extent, and distribution of white matter changes, so-called Leukoaraiosis, in an effort to determine if Leukoaraiosis indicates chronic cerebral hypoperfusion and/or is associated with the development of cerebral collateral circulation., Methods: Consecutive acute strokes due to large-vessel occlusion on angiography had preprocedure CT or MRI white matter changes graded utilizing the Fazekas scale incorporating deep and periventricular components. Angiographic collaterals evaluated with a 5-point scale were correlated with leukoaraiosis., Results: Collaterals were evaluated in 102 cases (51 men, 51 women; mean age 66 (SD 18) years with acute occlusions of the proximal middle cerebral artery (MCA) (47%), distal internal carotid artery (ICA) (28%), distal MCA (9%), basilar (7%), proximal ICA (7%), vertebral (1%), posterior cerebral artery (PCA) (1%), and common carotid artery (CCA) (1%). Collateral grade was well distributed across the scale. Periventricular and deep white matter changes were evident in 34% and 51% of cases, respectively. Collateral grade exhibited no relationship with either the presence or extent of periventricular disease (P= .772, r= .029) or deep white matter changes (P= .559, r=-.059)., Conclusions: Leukoaraisosis exhibits no overt relationship with the extent of collaterals measured at angiography in acute ischemic stroke. Chronic small-vessel disease may be a distinct pathophysiologic entity unrelated to arteriogenesis and compensatory aspects of collateral flow., (© 2010 by the American Society of Neuroimaging.)

Background and Purpose: Conventional analysis of vascular prevention trials assigns equal weight to disparate vascular events in a composite end point at variance with the public's perception of their differential impact on health outcome. This study sought to apply the disability-adjusted life-year (DALY) metric to differential weighting individual vascular end points in trial analyses., Methods: DALY values for the most common major end points in vascular prevention trials (nonfatal myocardial infarction, nonfatal stroke, and vascular death), were derived by using World Health Organization Global Burden of Disease Project methodology. The standardized DALYs for each event were applied to recent major primary and secondary vascular prevention trials and to hypothetical model trials., Results: Standardized DALYs lost were 7.63 for nonfatal stroke, 5.14 for nonfatal myocardial infarction, and 11.59 for vascular death. In the published trials analyses, the direction of treatment effects was consistent between DALY and standard event analysis, but the rank order of treatment effect changed for 10 of 18 trials. The DALY analysis also permitted derivation of number-needed-to-treat values to gain 1 DALY: 2.1 for anticoagulation in atrial fibrillation, 2.7 for carotid endarterectomy in symptomatic stenosis, and 4.7 for clopidogrel added to aspirin in acute coronary syndrome. Hypothetical trial analyses demonstrated that the DALY metric more finely discriminates treatment effects., Conclusions: Compared with a nonfatal myocardial infarction, a nonfatal stroke causes a 1.48-fold greater loss and vascular death a 2.25-fold greater loss of DALY. DALY analysis integrates these valuations in a summary metric reflecting the net impact of therapy on patient and societal health, complementing conventional end point analyses.

The Framingham Coronary Risk Score (FCRS) is based on several factors, including age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, presence of diabetes, and cigarette smoking. Some of these factors are individually linked with acute stroke outcomes. We explored whether FCRS could predict outcome in patients hospitalized with recent stroke. We collected data on consecutive patients hospitalized for ischemic stroke over a 3-year period. Patients with known coronary artery disease were excluded. Discharge outcomes assessed were neurologic deficit (National Institutes of Health Stroke Scale [NIHSS] score), death or disability (modified Rankin Scale [mRS] score ≥2), and discharge to home directly from the hospital. The independent effect of FCRS on these outcomes was evaluated using multivariate regression analysis. During the study period, 434 patients with ischemic stroke met entry criteria (mean age, 64.5 years; 54% females). Median FCRS score was 8%. After adjusting for confounders, higher FCRS score was associated with an increased likelihood of death or being disabled at discharge (odds ratio [OR]=4.9; 95% confidence interval [CI]=0.98-24.1; P=.05), and a decreased likelihood of being discharged directly to home (OR=0.18; 95% CI=0.04-0.86; P=.032), but not with discharge NIHSS score. Higher FCRS in hospitalized ischemic stroke patients is associated with death or disability at discharge and a lower likelihood of being discharged directly to home. Along with indexing the long-term risk of cardiovascular events, this widely known, easily calculable score provides clinically relevant short-term prognostic information following ischemic stroke., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke., Methods: Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi., Results: Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P=0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P=0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P=0.002). Mean percent RBC was greater with BA (42% versus 23%, P=0.011)., Conclusions: CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

Background: large, long-term population data indicate an inverse association for adult height with stroke incidence and mortality, whereas the risk of atrial fibrillation appears greater in taller individuals. However, it is unclear whether knowledge of an individual's stature is an important clinical factor to consider when assessing hospitalized patients with ischemic stroke. We determined the relation of body height with clinical characteristics and discharge outcomes among persons with ischemic stroke., Methods: we analyzed prospectively collected data in 881 consecutive patients with ischemic stroke admitted to a university hospital stroke service during a 5-year period starting September 2002. Stroke subtyping was performed per modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Stroke severity was assessed with the National Institutes of Health Stroke Scale. All patients were assessed at discharge using the modified Rankin scale. Mean adjusted height was compared using linear regression models with height as outcome, and stroke subtype, modified Rankin scale, and potential confounders as covariates., Results: mean age was 67.4 years, 48% were women. Mean height was 169 cm (SD ± 11). In multivariable analysis, height decreased per year of age (P=0.003), those with a previous stroke were shorter than those without a previous stroke (P=0.04), and females were shorter than males (P<0.001). Height was not associated with stroke subtype or discharge outcomes in unadjusted or adjusted analyses., Conclusions: Body height at hospital admission has no relation to ischemic stroke subtype or discharge outcome. However, patients with history of previous stroke were significantly shorter than those without a previous stroke, which may be because of greater stroke occurrence in shorter individuals or taller people with relatively larger atrial fibrillation-related strokes dying earlier.

Background and Purpose: Subarachnoid hemorrhage (SAH) is a potential hemorrhagic complication after endovascular intracranial recanalization. The purpose of this study was to describe the frequency and predictors of SAH in acute ischemic stroke patients treated endovascularly and its impact on clinical outcome., Methods: Acute ischemic stroke patients treated with primary mechanical thrombectomy, intra-arterial thrombolysis, or both were analyzed. Postprocedural computed tomography and magnetic resonance images were reviewed to identify the presence of SAH. We assessed any decline in the National Institutes of Health Stroke Scale score 3 hours after intervention and in the outcomes at discharge., Results: One hundred twenty-eight patients were treated by primary thrombectomy with MERCI Retriever devices, whereas 31 were treated by primary intra-arterial thrombolysis. Twenty patients experienced SAH, 8 with pure SAH and 12 with coexisting parenchymal hemorrhages. SAH was numerically more frequent with primary thrombectomy than in the intra-arterial thrombolysis groups (14.1% vs 6.5%, P = 0.37). On multivariate analysis, independent predictors of SAH were hypertension (odds ratio = 5.39, P = 0.035), distal middle cerebral artery occlusion (odds ratio = 3.53, P = 0.027), use of rescue angioplasty after thrombectomy (odds ratio = 12.49, P = 0.004), and procedure-related vessel perforation (odds ratio = 30.72, P < 0.001). Patients with extensive SAH or coexisting parenchymal hematomas tended to have more neurologic deterioration at 3 hours (28.6% vs 0%, P = 0.11), to be less independent at discharge (modified Rankin Scale ≤ 2; 0% vs 15.4%, P = 0.5), and to experience higher mortality during hospitalization (42.9% vs 15.4%, P = 0.29)., Conclusions: Procedure-related vessel perforation, rescue angioplasty after thrombectomy with MERCI devices, distal middle cerebral artery occlusion, and hypertension were independent predictors of SAH after endovascular therapy for acute ischemic stroke. Only extensive SAH or SAH accompanied by severe parenchymal hematomas may worsen clinical outcome at discharge.

Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials., Methods: The NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively., Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and unconsentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean +/- SD: 8.4 +/- 2.5 min, range 6-14) was longer than non-enrollment calls (5.5 +/- 3.5, range 2-13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset., Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials., (Copyright (c) 2009 S. Karger AG, Basel.)

Background: Although influenza-related morbidity and mortality is high, and influenza can be a trigger for recurrent stroke, only about half of stroke survivors receive yearly influenza vaccination. Identifying new avenues through which to optimize influenza vaccination among stroke survivors is a public health need. We assessed the feasibility of integrating influenza vaccination into routine inpatient stroke care., Methods: We designed a quality improvement project incorporating influenza vaccination into care administered to hospitalized patients with ischemic stroke and transient ischemic attack that included a standardized order and discharge checklist. Data were then prospectively collected on consecutively encountered patients with ischemic stroke and transient ischemic attack admitted to a university hospital stroke service during the influenza season of October 2007 to February 2008. Successful influenza treatment use was based on optimal rather than actual treatment, with credit for optimal treatment given if an acceptable reason for nonadministration of the vaccine was documented., Results: Of 103 patients admitted during the study period, 75 (73%) were eligible for influenza vaccination (mean age 72.8 years; 51% women). Among vaccination-eligible patients, 65 (87%) received optimal influenza vaccination treatment, whereas 14 (21%) actually received the vaccination during hospitalization. Leading reason (90%) for suboptimal influenza vaccination treatment among eligible patients was that the vaccination was inadvertently not ordered on admission or at discharge., Conclusions: Influenza vaccination can be systematically incorporated into stroke hospitalization and may be a viable avenue for promptly enhancing short-term clinical outcomes among hospitalized patients with stroke during peak influenza season.

Background: The utility of clinical measurements of impairments in glomerular barrier or filtration rate among hospitalized stroke patients without known chronic kidney disease (CKD) has not been well studied. We determined whether various indices of CKD would predict discharge outcomes in persons hospitalized with a recent ischemic stroke., Methods: Presence of proteinuria and estimated low glomerular filtration rate (GFR) <60 ml/min per 1.73 m(2) on admission were assessed in consecutive ischemic stroke and transient ischemic attack patients admitted to a university hospital over 18 months, who had no history of CKD. The primary discharge outcomes assessed (among stroke patients only) were death or disability (modified Rankin Scale score > or =2) and being discharged home directly from hospital. Independent effects of CKD indices on the outcomes were evaluated using multivariable regression modeling., Results: Of 251 patients with recent ischemic cerebrovascular events, 198 ischemic stroke patients (79%), met the study criteria. In crude analyses, persons with proteinuria or low GFR were significantly more likely to die in the hospital (p < 0.05). After adjusting for confounders, proteinuria was independently linked with lower odds of going home directly from the hospital (OR = 0.38, 95% CI = 0.16-0.92) and poorer discharge functional status (OR = 3.19, 95% CI = 1.37-7.46), but low GFR was not independently related to either of these outcomes., Conclusions: Among hospitalized ischemic stroke patients without known CKD, presence of proteinuria on admission is independently associated with poorer discharge functional activity and lower likelihood of being discharged home directly. Low GFR was not related to either outcome in these patients without known CKD., (Copyright (c) 2009 S. Karger AG, Basel.)

Sleep and stroke have an important and fascinating interaction. Patients with sleep-disordered breathing present with cardiovascular heart disease, cognitive decline, and increased risk of stroke. Stroke adversely affects sleep and factors such as prolonged immobilization, chronic pain, nocturnal hypoxia, and depression, which can also adversely impact sleep quality. Obstructive sleep apnea (OSA), one of the most common and serious sleep disturbances, manifests itself in almost 50% of all stroke patients. Sleep apnea patients who experience a stroke may be at a greater impairment in their rehabilitation potential and have increased risk of secondary stroke and mortality. Given these factors, the practicing neurologist should possess the skills to appropriately recognize, rapidly diagnose, and properly manage stroke patients with OSA.

Background: Higher levels of serum bilirubin may offer a therapeutic advantage in oxidative stress-mediated diseases, but may also simply reflect intensity of oxidative stress. Little is known about the role of bilirubin in stroke. We assessed the relation of serum bilirubin levels with clinical presentation and outcomes among patients hospitalized with ischemic stroke., Methods: Data were collected prospectively during a 5-year period on consecutive ischemic stroke admissions to a university hospital. Serum bilirubin levels, total (Tbil) and direct (Dbil), were measured on admission. Presenting stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Functional outcome at discharge was assessed using the modified Rankin scale., Results: Among 743 patients, mean age was 67.3 years and 47.5% were women. Median presenting NIHSS score was 4, and 24% had a poor (modified Rankin scale 4-6) functional outcome at discharge. Higher Dbil levels were associated with greater stroke severity (P = .001) and poorer discharge outcome (P = .034). Multivariable regression analyses showed that those with higher Dbil levels (> or =0.4 mg/dL) had significantly greater admission NIHSS scores compared with those with lower levels (< or =0.1 mg/dL) (odds ratio 2.79, 95% confidence interval 1.25-6.20, P = .012), but no independent relationship was confirmed between Dbil and discharge outcome. Although higher admission Tbil was associated with greater stroke severity in crude analyses (P = .003), no independent relationship between Tbil versus stroke severity or outcome was noted after adjusting for confounders., Conclusions: Higher Dbil level is associated with greater stroke severity but not outcome among ischemic stroke patients, possibly reflecting the intensity of initial oxidative stress. Further study into the underlying pathophysiology of this relationship is needed.

Background and Purpose: Few data exist on the relationship between differential subpopulations of peripheral leukocytes and early cerebral infarct size in ischemic stroke. Using diffusion-weighted MR imaging (DWI), we assessed the relationship of early total and differential peripheral leukocyte counts and volume of ischemic tissue in acute stroke., Methods: All included patents had laboratory investigations and neuroimaging collected within 24 hours of stroke onset. Total peripheral leukocyte counts and differential counts were analyzed individually and by quartiles. DWI lesions were outlined using a semiautomated threshold technique. The relationship between leukocyte quartiles and DWI infarct volumes was examined using multivariate quartile regression., Results: 173 patients met study inclusion criteria. Median age was 73 years. Total leukocyte counts and DWI volumes showed a strong correlation (Spearman rho=0.371, P<000.1). Median DWI volumes (mL) for successive neutrophil quartiles were: 1.3, 1.3, 3.2, and 20.4 (P for trend <0.001). Median DWI volumes (mL) for successive lymphocyte quartiles were: 3.2, 8.1, 1.3, and 1.5 (P=0.004). After multivariate analysis, larger DWI volume remained strongly associated with higher total leukocyte and neutrophil counts (both probability values <0.001), but not with lymphocyte count (P=0.4971). Compared with the lowest quartiles, DWI volumes were 8.7 mL and 12.9 mL larger in the highest quartiles of leukocyte and neutrophil counts, respectively., Conclusions: Higher peripheral leukocyte and neutrophil counts, but not lymphocyte counts, are associated with larger infarct volumes in acute ischemic stroke. Attenuating neutrophilic response early after ischemic stroke may be a viable therapeutic strategy and warrants further study.

Background: Conflicting data exist on the role of antiplatelet agents in reducing incident ischemic stroke magnitude, but most prior studies used clinically-assessed neurologic deficit as the index of stroke extent rather than more precise volumetric measurements of infarct size. We assessed the relation of premorbid antiplatelet use to initial diffusion-weighted MRI (DWI) lesion volumes among acute ischemic stroke patients., Methods: Consecutive patients presenting within 24 h of ischemic stroke over an 18-month period were studied. DWI lesions were outlined using a semi-automated threshold technique. Subjects were categorized into two groups: antiplatelet (AP) or no antithrombotic (NA). The relationship between prestroke antithrombotic status and DWI infarct volumes was examined using multivariate quantile regression., Results: One hundred sixty-six individuals met study criteria: 75 AP and 91 NA patients. Median DWI volume was lower in the AP group than in the NA group (1.5 cc vs. 5.4 cc, p=0.031). A multivariable model (adjusting for age, history of transient ischemic attack, admission temperature, admission blood pressure, admission serum glucose, stroke onset to imaging interval, stroke mechanism, premorbid statin and antihypertensive use) demonstrated smaller infarcts in the AP vs. NA group (adjusted volume difference: -1.3 cc, 95% CI=-0.09, -2.5, p=0.037). Prior statin use, no history of TIA, large vessel atherosclerosis and microvascular ischemic disease stroke mechanism were also independently associated with reduced infarct volume., Conclusions: Prior antiplatelet treatment is independently associated with reduced cerebral infarct volume among acute ischemic stroke patients. Premorbid statin use, TIA history and stroke mechanism also predict infarct volume in ischemic stroke.

Background: Elevated serum calcium levels at admission in patients with stroke have been associated with less severe clinical deficits and with better outcomes; however, the relationship between serum calcium levels and volumetric measurement of cerebral infarct size on neuroimaging has not been studied, to our knowledge., Objective: To assess the relationship between serum calcium levels at admission and initial diffusion-weighted magnetic resonance imaging (DWI) infarct volumes among patients with acute ischemic stroke., Design: Secondary analysis of prospectively collected hospital quality improvement data., Setting: Tertiary university hospital., Patients: One hundred seventy-three consecutive patients with acute ischemic stroke initially seen within 24 hours of the last known well time., Main Outcome Measures: Total serum calcium levels were measured on admission and were collapsed into quartiles. The DWI lesions were outlined using a semiautomated threshold technique. The relationship between serum calcium level quartiles and DWI infarct volumes was examined using multivariate quartile regression analysis., Results: One hundred seventy-three patients (mean age, 70.3 years [age range, 24-100 years]; median National Institutes of Health Stroke Scale score, 4 [range, 0-38]) met the study criteria. The median DWI infarct volumes for the serum calcium level quartiles (lowest to highest quartile) were 9.42, 2.11, 1.03, and 3.68 mL. The median DWI infarct volume in the lowest serum calcium level quartile was larger than that in the other 3 quartiles (P < .005). After multivariate analysis, the median adjusted DWI infarct volumes for the serum calcium level quartiles (lowest to highest) were 8.9, 5.8, 4.5, and 3.8 mL. The median adjusted DWI infarct volume in the lowest serum calcium level quartile was statistically significantly larger than that in the other 3 quartiles (P < .05)., Conclusions: Higher serum calcium levels at admission are associated with smaller cerebral infarct volumes among patients with acute ischemic stroke. These results suggest that serum calcium level may serve as a clinical prognosticator following stroke and may be a potential therapeutic target for improving stroke outcome.

Objective: Predicting hemorrhagic transformation (HT) is critical in the setting of recanalization therapy for acute stroke. Dedicated magnetic resonance imaging (MRI) sequences for detection of increased blood-brain barrier (BBB) permeability recently have been developed. We evaluated the ability of a novel MRI permeability technique to detect baseline derangements predictive of various forms of HT after recanalization therapy., Methods: We retrospectively analyzed the clinical and pretreatment MRI data on patients undergoing recanalization therapy for acute cerebral ischemia at a university medical center from January 2004 to November 2006. Pretreatment MRI permeability images derived from perfusion source data were compared with posttreatment imaging to evaluate whether baseline BBB permeability derangements may predict HT after recanalization therapy. The use of a novel permeability technique to illustrate BBB derangements was based on the detection of decreased signal intensity at later time points in perfusion MRI acquisition, signifying continued local accumulation of contrast caused by leakage., Results: Among 32 patients, some degree of HT occurred in 12. Permeability image abnormalities at baseline were present in 7 of 12 patients with HT and none of the 20 patients without HT on follow-up images. The sensitivity of permeability abnormality for parenchymal hematoma was 83%. False-negative findings were noted in five cases, most commonly asymptomatic or minor HT after mechanical clot retrieval., Interpretation: Permeability images derived from pretreatment perfusion MRI source data may identify patients at risk for HT with high specificity. Our preliminary demonstration of permeability imaging based on standard perfusion data for prediction of hemorrhage merits further study with dedicated MRI BBB permeability acquisitions and multicenter validation.

Collateral circulation influences cerebral infarction occurrence and size. Statins may improve ischemic stroke outcomes. We evaluated the relationship between prestroke statin use and pretreatment angiographic collateral grade among acute ischemic stroke patients presenting with occlusion of a major cerebral artery. After adjusting for covariates, the statin-treated group had significantly higher collateral scores than non-statin users, suggesting an association between statin use and better collateralization during acute stroke.

Objective: To determine whether elevated urine erythrocyte (red blood cell) and leukocyte (white blood cell) counts, reflecting concomitant renal and cerebral emboli of cardiac origin, would be useful in discriminating cardioembolic (CE) from non-CE stroke in acute ischemic stroke., Design: Consecutive patients presenting within 24 hours of ischemic stroke over 3(3/4) years were studied. Patient medical history and urinalysis data, including white blood cell count, red blood cell count, specific gravity, and glucose and protein levels at admission, were analyzed and compared with the final determination of stroke subtype. Multivariate analysis (CE vs non-CE stroke) was performed using a classification and regression tree that included all 5 urine variables as potential predictors. Additional predictors entered into the classification and regression tree model were age, presence of urinary tract infection at admission, history of hypertension, history of diabetes mellitus, and serum creatinine level., Results: A total of 341 individuals met the study criteria. Their mean age was 68.6 years; 49.8% were female, 70.9% were white, and 38.7% had the CE stroke subtype. In bivariate analysis, age (P = .009), urine white blood cell count (P = .02), urine red blood cell count (P = .005), urine specific gravity (P = .02), and serum creatinine level (P = .02) were significantly higher in those with the CE vs the non-CE stroke subtype. In the classification and regression tree, 58.3% of those with CE stroke were correctly classified and 84.7% of those with non-CE stroke were correctly classified, for an overall accuracy of 71.5%. The best single predictor for the CE stroke subtype was a white blood cell count of greater than 14.5/microL, followed by a red blood cell count of greater than 41.7/microL and a serum creatinine level greater than 1.08 mg/dL (>95.5 micromol/L). Based on the distribution in the first 2 divisions in the tree, a patient could be placed into 1 of 4 categories that corresponded to 3 levels of CE stroke likelihood: low (25%), moderate (50%), and high (80%)., Conclusion: Urinalysis may have utility in the early identification of the CE stroke subtype in patients with acute ischemic stroke.

The stroke patient who deteriorates presents a common and rewarding diagnostic challenge. Up to one third of ischemic stroke patients worsen after admission, though the frequency of deterioration is declining with modern supportive care. The causes of clinical worsening are diverse; common etiologies include collateral failure, brain edema, seizures, reocclusion after successful initial therapeutic recanalization, and systemic medical complications. Clot propagation and recurrent embolization are only infrequent mechanisms of worsening. The advent of multimodal computed tomography and magnetic resonance imaging has transformed the evaluation of the deteriorating stroke patient. History, physical examination, screening blood work, and emergent reassessment of the cervical and cerebral vasculatures, regional hypoperfusion, and infarct core will yield a firm diagnosis of the cause of clinical worsening in the majority of patients. The therapeutic armamentarium for the worsening stroke patient has expanded greatly. Treatment options now include rescue late endovascular recanalization therapy, pressor collateral enhancement therapy, hemicraniectomy, and additional novel interventions in addition to enhanced supportive care. Because most causes of worsening can be treated effectively, the deteriorating stroke patient merits a swift and incisive diagnostic and therapeutic response.

Background: Obesity is a risk factor for vascular disease and has been associated with poorer outcomes in hospitalized patients., Objective: To evaluate the relationship between body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and discharge outcomes among persons hospitalized for ischemic stroke., Methods: The relationship between BMI and discharge outcomes was analyzed in 805 consecutive patients with ischemic stroke admitted to a university hospital stroke service. Patients were categorized into 4 BMI categories representing lean, overweight, and class I and class II obesity. Outcome measures analyzed included discharge functional activity, direct discharge to home, and length of hospital stay. The independent effect of BMI on outcome was evaluated with regression analysis, adjusting for other variables known to predict outcome after ischemic stroke., Results: Four hundred fifty-one individuals (56.0%) met study criteria. Mean age was 65 years, and 28.0% were men. In multivariate analysis, the highest BMI category (compared with lowest BMI category) was associated with the least likelihood of being discharged directly home from the hospital stroke service (26% vs 45%, P = .04), and the upper 2 BMI categories (compared with lowest BMI category) were associated with a trend toward extended length of hospital stay (6.3 vs 5.2 days, P = .08). No significant differences in the functional activity outcome were noted across BMI categories., Conclusions: Elevated BMI is associated with a lower likelihood of being discharged home and a trend toward extended hospital stay among patients hospitalized for ischemic stroke. Body mass index at hospital admission had no relation to discharge functional activity after stroke.