Multidisciplinary Approach to Patent Foramen Ovale Closure for Cryptogenic Stroke: Brain-Heart Board Experience.

Background and Objectives: Patent foramen ovale (PFO) is present in approximately 25% of adult population. The prevalence of PFO is high in patients with cryptogenic stroke suggesting paradoxical embolism. PFO closure in carefully selected patients is an effective secondary preventive strategy in these patients. We report predictors of management recommendations by the multidisciplinary Board and their impact on outcomes. Methods: Brain-Heart Board comprises vascular and interventional neurology and cardiology subspecialties (structural, electrophysiology, and cardiac imaging). Adult patients referred to the Board for consideration of PFO closure between October 2017 to March 2021 were included in this retrospective cohort analysis. Demographics, comorbid conditions, risk of paradoxical embolism (RoPE) score, event frequencies (transient ischemic attack [TIA] or stroke, intracranial hemorrhage [ICH], post-PFO closure cardiac arrhythmias), and modified Rankin Scale (mRS) at 1 year were compared between the groups (PFO closure vs medical management). Multivariable logistic regression was used to identify factors associated with management recommendation and chi-square tests to test differences in outcomes for patients according to management. Results: Two hundred seventy patients (229 stroke; 41 TIA) were discussed by the Board for PFO closure. 119 (44.0%) patients were recommended for PFO closure of which 117 (98.3%) had evidence of ischemic infarct on imaging. In univariate analysis, age was similar (50 ± 11.9 vs 52 ± 12.8, p = 0.17), but RoPE score was higher in closure as compared with the medical management group (6 [IQR 5-7] vs 5 [IQR 4-7], p < 0.05). In multivariable analysis, TIA as the index event was an independent predictor of Board recommendation against PFO closure (OR 0.05, 95% CI 0.01-0.19, p < 0.05). Event frequency was low in both cohorts (5.9% vs 4.8%, p > 0.05) and comprised cardiac arrhythmias (6 cases of atrial fibrillation and 1 ICH in closure group; 1 TIA and 1 recurrent stroke in medical management group). Excellent functional outcome (mRS 0-1) was similar in both cohorts (66.3% vs 70.7%, p > 0.05) at 1 year. Discussion: Multidisciplinary Brain-Heart Board provides a clinical practice model of collaborative care to ensure proper patient selection for PFO closure. TIA as the index event is associated with recommendation of medical management by the multidisciplinary Brain-Heart Board.

Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan.

Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan. Methods: A total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies. Results: All patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected. Discussion: All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.

Neurogenic cardiac outcome in patients after acute ischemic stroke: The brain and heart connection.

BACKGROUND: Neurogenic cardiac impairment can occur after acute ischemic stroke (AIS), but the mapping of the neuroanatomic correlation of stroke-related myocardial injury remains uncertain. This study aims to identify the association between cardiac outcomes and middle cerebral artery (MCA) ischemic stroke, with or without insular cortex involvement, as well as the impact of new-onset atrial fibrillation (AF) after AIS on recurrent stroke. METHODS: Serial measurements of high sensitivity troponin T (TnT), brain natriuretic peptide (BNP), electrocardiography (ECG), echocardiogram, and cardiac monitoring were performed on 415 patients with imaging confirmed MCA stroke, with or without insular involvement. Patients with renal failure, recent cardiovascular events, or congestive heart failure were excluded. RESULTS: One hundred fifteen patients (28%) had left MCA infarcts with insular involvement, 122 (29%) had right MCA infarcts involving insular cortex, and 178 (43%) had no insular involvement. Patients with left MCA stroke with insular involvement tended to exhibit higher BNP and TnI, and transient cardiac dysfunction, which mimicked Takotsubo cardiomyopathy in 10 patients with left ventricular ejection fraction (LVEF) of 20-40%. Incidence of new-onset AF was higher in right MCA stroke involving insula (39%) than left MCA involving insula (4%). Nine out of fifty-three patients with new-onset AF were not on anticoagulant therapy due to various reasons; none of them experienced recurrent AF or stroke during up to a 3-year follow-up period. Statistically significant correlations between BNP or TnT elevation and left insular infarcts, as well as the incidence of AF and right insular infarcts, were revealed using linear regression analysis. CONCLUSIONS: The present study demonstrated that acute left MCA stroke with insular involvement could cause transient cardiac dysfunction and elevated cardiac enzymes without persistent negative outcomes in the setting of health baseline cardiac condition. The incidence of new-onset AF was significantly higher in patients with right MCA stroke involving the insula. There was no increased risk of recurrent ischemic stroke in nine patients with newly developed AF who were not on anticoagulant therapy, which indicated a need for further research on presumed neurogenic AF and its management.

Shorter Intensive Care Unit Stay (12 Hours) Post Thrombolysis Is Safe and Reduces Length of Stay for Minor Stroke Patients.

The current standard of practice for patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator (tPA) requires critical monitoring for 24-hours post-treatment due to the risk of symptomatic intracranial hemorrhage (sICH). This is a costly and resource intensive practice. In this study, we evaluated the safety and efficacy of this standard 24-hour ICU monitoring period compared with a shorter 12-hour ICU monitoring period for minor stroke patients (NIHSS 0-5) treated with tPA only. Stroke mimics and those who underwent thrombectomy were excluded. The primary outcome was length of hospital stay. Secondary outcome measures included sICH, deep venous thrombosis (DVT), pulmonary embolism (PE), pneumonia, favorable discharge to home or acute rehabilitation, readmission within 30 days, and favorable functional outcome defined as modified Rankin scale (mRS) of 0-2 at 90 days. Of the 122 patients identified, 77 were in the 24-hour protocol and 45 were in 12-hour protocol. There was significant difference in length of hospital stay for the 24-hour ICU protocol (2.8 days) compared with the 12-hour ICU protocol (1.8 days) (P < 0.001). Although not statistically significant, the 12-hour group had favorable rates of sICH, 30-day readmission rates, favorable discharge disposition and favorable functional outcome. Rates of DVT, PE and aspiration pneumonia were identical between the groups. Compared with 24-hour ICU monitoring, 12-hour ICU monitoring after thrombolysis for minor acute ischemic stroke was not associated with any increase in adverse outcomes. A randomized trial is needed to verify these findings.

Novel Imaging Biomarker Prediction of Parenchymal Hemorrhage after Mechanical Thrombectomy in Patients with Large Ischemic Core.

BACKGROUND: Recently studies have shown that select acute ischemic stroke (AIS) patients with large ischemic core could be deemed as reasonable candidates to receive mechanical thrombectomy (MT) with low risk of developing parenchymal hemorrhage (PH) or symptomatic intracerebral hemorrhage (sICH); however, the selection criterion remains lacking. Our study aims to investigate the relationship between a novel imaging biomarker of largest core mass volume (LCMV) and development of PH in stroke patients with large ischemic core who have undergone MT. METHODS: A total of 26 AIS patients with large ischemic core (defined as ischemic core volume ≧ 50 ml) were enrolled in the study. Volume of ischemic core and the LCMV measured with Mistar software were measured in all patients. Fourteen patients with AIS developed PH while 12 patients showed no signs of PH based on CT imaging obtained between 24 h and 3 day after MT. We compared the volume of ischemic core and LCMV between two groups. RESULTS: Volume of ischemic core showed no significant difference between the PH and no PH group [105.5 (62.4-131.5) vs 75.0 (56.3-102.2), p = 0.105], whereas LCMV was significantly higher in the PH (14.80 ± 5.23) vs. no PH group (8.40 ± 2.61, p = 0.001). ROC analysis revealed that LCMV was positively correlated with PH (area under the curve = 0.905). The optimal LCMV associated with PH was ≧ 9.67 ml. CONCLUSION: LCMV is an effective and easy-to-use imaging biomarker to predict PH after MT in AIS patients with large ischemic core.

Jamestown Canyon Virus (JCV) Encephalitis Mimicking Acute Stroke in Michigan: A Case Report and Review of the Literature.

Jamestown canyon virus (JCV) is an arbovirus and is an under-recognized cause of mosquito-borne viral encephalitis. In this report we present a patient who presented with focal neurological deficits. Patient was initially evaluated for stroke. However, leptomeningeal enhancement on MRI and CSF studies were concerning for viral encephalitis. Brain biopsy and CSF sample from surgical site was positive for JCV IgM antibodies. Patients presenting with concern for viral encephalitis in endemic areas should undergo antibody testing for JCV to guide appropriate treatment.

A cost comparison of atrial fibrillation monitoring strategies after embolic stroke of undetermined source.

Background: Detection of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS) is challenging due to its paroxysmal nature. We sought to assess AF detection with an insertable cardiac monitor (ICM) and to perform cost analysis for various AF monitoring strategies post-ESUS We applied this cost analysis modeling to recently published Stroke AF and Per Diem trials. Methods: Retrospective chart review was performed in consecutive hospitalized patients with ESUS who had ICM placed prior to discharge. Utilizing rate of ICM-detected AF and Medicare average payments, we modeled 30-day per-patient diagnostic costs of Immediate ICM insertion prior to discharge versus using a wearable monitor followed by ICM in patients with ESUS, from Medicare and patient out-of-pocket perspectives. Similar modeling strategy and cost analysis was applied to the Stroke AF and Per Diem trials. Results: In 192 ESUS patients, AF detection increased with length of monitoring: 7.3 % at 14 days, 9.4 % at 30 days, and 17.2 % after a median ~ 6 months (189 days). Cost modeling predicted that immediate ICM leads to $3683-$4070 lower Medicare payments per-patient and $1425-$1503 lower patient out-of-pocket costs compared to Wearable-to-ICM strategies. Using similar modeling in the PER DIEM and STROKE AF trials, the additive costs of the 30-day ELR to ICM strategy ranged from $3786-$3946 from a payer perspective and $1472-$1503 from a patient out-of-pocket perspective. Conclusions: Use of ICM immediately after ESUS is cost-saving compared to Wearable-to-ICM strategies, due to the cost and low diagnostic yield of short-term wearable cardiac monitoring.

Impact of a Stay-at-Home Order on Stroke Admission, Subtype, and Metrics during the COVID-19 Pandemic.

OBJECTIVE: Our study aims to evaluate the impact of a stay-at-home order on stroke metrics during the 2019-novel coronavirus (COVID-19) pandemic. METHODS: Data on baseline characteristics, stroke subtype, initial National Institutes of Health Stroke Scale (NIHSS) score, the time between last known well (LKW) to emergency department (ED) arrival, tissue plasminogen activator (tPA) administration, the involvement of large vessel occlusion (LVO), and whether mechanical thrombectomy (MT) was pursued in patients with acute stroke were extracted from 24 March to 23 April 2020 (the time period of a stay-at-home order was placed due to the COVID-19 pandemic as the study group) at a tertiary care hospital in West Michigan, USA, compared with data from 24 March to 23 April 2019 (control group). RESULTS: Our study demonstrated a reduction in cases of acute ischemic stroke (AIS), although this did not reach statistical significance. However, there was an increase in hemorrhagic stroke (7.5% controls vs. 19.2% study group). The age of stroke patients was significantly younger during the period of the stay-at-home order compared to the control group. We identified a significant overall delay of ED arrivals from LKW in the study group. Additionally, an increased number of AIS patients with LVO in the study group (34.8%) was found compared to the control group (17.5%). A significantly increased number of patients received MT in the study group. Additionally, 11 patients were COVID-19 PCR-positive in the study group, 10 with AIS and only 1 with hemorrhagic stroke. Patients with COVID-19 had a high incidence of atrial fibrillation and hyperlipidemia. One AIS patient with COVID-19 rapidly developed cytotoxic edema with corresponding elevated inflammatory biomarkers. No statistical significance was noted when stroke subtype, LVO, and MT groups were compared. CONCLUSIONS: There was a trend of decreasing AIS admissions during the COVID-19 pandemic. There was also a significantly increased number of AIS patients with LVO who received MT, especially those with COVID-19. We conclude that cytokine storm resulting from SARS-CoV-2 infection might play a role in AIS patients with COVID-19.

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes.

BACKGROUND AND PURPOSE: Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP). METHODS: We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome. RESULTS: A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome. CONCLUSIONS: Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.

The Role of CT Perfusion in Defining the Clinically Relevant Core Infarction to Guide Thrombectomy Selection in Patients with Acute Stroke.

BACKGROUND AND PURPOSE: Infarct core assessment on presentation is important to evaluate salvageable tissue to select patients for thrombectomy. Our study aims to evaluate the correlation between infarct core volume measured by computed tomography (CT) perfusion (CTP) and magnetic resonance diffusion-weighted imaging (MR-DWI) in patients with acute large-vessel occlusion. METHODS: We studied patients who underwent CTP on presentation to the emergency department for stroke symptoms. National Institute of Health Stroke Scale (NIHSS), collateral status, symptomatic vessels, and modified Rankin scale (mRS) at 90 days were collected. Admission infarct core volume was measured on initial relative cerebral blood volume and final infarct core volume on follow-up DWI. The correlation between two measures was assessed using Pearson's correlation coefficient. RESULTS: Seventy-four patients were studied of which 41.9% were female. Median NIHSS was 13 (2-30). Middle cerebral artery occlusion was present in 53 (71.6%) patients and 54 (72.9%) had good collaterals. Good functional outcome of mRS 0-2 was achieved by 60.8% at 90 days. There was a strong correlation between CTP and MR-DWI (r = .94). There was no significant difference between volume (in milliliters) on CTP (54.1 ± 69.8) and volume on DWI (50.3 ± 59.7; P = .18) using the paired t-test. CONCLUSION: CTP provides a good estimation of the core infarct volume. It performs well within the clinically relevant thresholds for patient selection for thrombectomy.

An exploratory study of the electronic medical record and outpatient vascular neurology consultations.

We carried out a quality improvement project utilizing the electronic medical record (EMR) to determine (1) the quality of vascular neurologists' recommendations for recurrent stroke prevention and (2) primary care provider (PCP) acknowledgement of the vascular neurologists' recurrent stroke prevention recommendations and their frequency of meeting the recommended metrics for risk factor control and lifestyle modification. We conducted a retrospective EMR chart review on a convenience sample of ischemic stroke patients during two epochs. Data collected included risk factors, stroke subtype, and process and outcome guidance metrics for recurrent ischemic stroke prevention according to American Heart Association/American Stroke Association (AHA/ASA) recommendations. Overall, vascular neurologists commonly recommended appropriate AHA/ASA risk factor management standards, but were less likely to do so for lifestyle management. Improvements in the EMR system over time, including the establishment of guideline-driven importable recurrent stroke prevention templates, led to a high frequency of proper risk factor and lifestyle recommendations made by vascular neurologists. Statistical analysis provided further evidence that the EMR positively influenced the delivery of proper recurrent stroke prevention guidance. Although PCPs infrequently acknowledged receipt of vascular neurology consultations, there was a relatively high frequency of achieved risk factor control. The latter may be attributed at least in part to pre-existent quality improvement programs implemented at primary care offices. Our exploratory findings suggest that proper use of the EMR may heighten efforts to provide appropriate and consistent recurrent stroke prevention recommendations in a primary care setting.

Pharmacotherapy for Vascular Cognitive Impairment.

Vascular cognitive impairment (VCI) is the second most common type of dementia after Alzheimer's disease (AD). Stroke and cardiovascular risk factors have been linked to both AD and VCI and potentially can affect cognitive function in mid and later life. Various pharmacological agents, including donepezil, galantamine, and memantine, approved for the treatment of AD have shown modest cognitive benefits in patients with vascular dementia (VaD). However, their functional and global benefits have been inconsistent. Donepezil has shown some cognitive benefit in patients with VaD only, and galantamine has shown some benefit in mixed dementia (AD/VaD). The benefits of other drugs such as rivastigmine, memantine, nimodipine, and piracetam are not clear. Some other supplements and herbal therapies, such as citicoline, actovegin, huperzine A, and vinpocetine, have also been studied in patients with VaD, but their beneficial effects are not well established. Non-drug therapies and lifestyle modifications such as diet, exercise, and vascular risk factor control are important in the management of VCI and should not be ignored. However, there is a need for more robust clinical trials focusing on executive function and other cognitive measures and incorporation of newer imaging modalities to provide additional evidence about the utility of these strategies in patients with VCI.

The Value of the Score for the Targeting of Atrial Fibrillation (STAF) Screening in Acute Stroke Patients.

BACKGROUND AND PURPOSE: Recently, the score for the targeting of atrial fibrillation (STAF) was introduced to identify the risk of atrial fibrillation (AF) in stroke patients. In this study, we aim to evaluate the usefulness of the STAF score for AF screening in acute stroke patients. METHODS: Patients with acute ischemic stroke who were admitted to our stroke unit were prospectively enrolled from March 2011 to March 2013. Baseline National Institutes of Health Stroke Scale (NIHSS), left atrial dilatation, and vascular etiology were assessed to calculate the STAF score. Logistic regression analysis was used to examine the relationship between AF and STAF factors. Univariate analysis of AF and age, history of coronary heart disease and rheumatic heart disease, NIHSS, left atrial dilatation, and vascular etiology was performed. RESULTS: A total of 472 patients were enrolled in our analysis. AF was documented in 78 (16.53%) patients, of which 50% were paroxysmal. Multivariable analysis demonstrated that age, NIHSS, left atrial dilatation, and the absence of vascular etiology can each function as independent predictors for AF. In addition, all AF patients with a STAF ≥5 show a sensitivity of 76.92% and a specificity of 78.68%. The area under the receiver operating characteristic for all AF patients was .842 versus .763 for the paroxysmal AF (pAF) patients. In addition, a sensitivity of 81% (95% CI 73-92) and a ROC of .829 were for new-AF. CONCLUSIONS: The value of the STAF system for predicting the risk of pAF and new-AF in stroke patients is relatively limited.

Pathophysiology and management of reperfusion injury and hyperperfusion syndrome after carotid endarterectomy and carotid artery stenting.

Cerebral hyperperfusion is a relatively rare syndrome with significant and potentially preventable clinical consequences. The pathophysiology of cerebral hyperperfusion syndrome (CHS) may involve dysregulation of the cerebral vascular system and hypertension, in the setting of increase in cerebral blood flow. The early recognition of CHS is important to prevent complications such as intracerebral hemorrhage. This review will focus on CHS following carotid endarterectomy and carotid artery stenting. We will discuss the typical clinical features of CHS, risk factors, pathophysiology, diagnostic modalities for detection, identification of patients at risk, and prevention and treatment. Although currently there are no specific guidelines for the management of CHS, identification of patients at risk for CHS and aggressive treatment of hypertension are recommended.

Detecting nonvalvular atrial fibrillation and anticoagulant therapy in cardioembolic ischemic stroke.

Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed.

Population-based approaches for reducing stroke risk.

The global burden of stroke is particularly substantial in low- and middle-income countries. There are several risk factors or determinants of stroke and other cardiovascular diseases that are modifiable and have been shown to reduce the risk of stroke in at-risk persons. The high-risk or individual approach to prevention uses screening to identify such persons and medication is then usually required; however, to affect change in risk in a community, a population or mass approach is required to shift the community population to a lower risk profile. The community approach is usually accomplished through legislation, health education and wider economic means. In this review, the authors discuss the population approach to primary stroke prevention.

Reviving Intracranial Angioplasty and Stenting "SAMMPRIS and beyond".

We review the methods and results of Stenting and Aggressive Medical Management for Preventing Recurrent Stroke (SAMMPRIS) and provide a critical review of its strengths and limitations. In SAMMPRIS, the aggressive medical treatment arm (AMT arm) did substantially better than the Wingspan Stenting plus aggressive medical management arm (WS+ arm). Complications in the first 30 days post intervention led to the disparity between treatment arms. A major contribution of SAMMPRIS was the added value that AMT and lifestyle change may provide, when compared to a precursor trial, Warfarin-Aspirin Symptomatic Intracranial Disease (WASID), designed to prevent stroke in persons with high-grade symptomatic intracranial occlusive disease, however, the results of neither of these two trials have ever been reproduced. On the other hand, we argue that technical limitations of the Wingspan stent system (WS System) and lack of an angioplasty only intervention arm may have led to a premature launch of the trial and early termination of the study. Future randomized trials with different devices and modified patient selection criteria are warranted.

Lymphocyte cell kinase activation mediates neuroprotection during ischemic preconditioning.

The molecular mechanisms underlying preconditioning (PC), a powerful endogenous neuroprotective phenomenon, remain to be fully elucidated. Once identified, these endogenous mechanisms could be manipulated for therapeutic gain. We investigated whether lymphocyte cell kinase (Lck), a member of the Src kinases family, mediates PC. We used both in vitro primary cortical neurons and in vivo mouse cerebral focal ischemia models of preconditioning, cellular injury, and neuroprotection. Genetically engineered mice deficient in Lck, gene silencing using siRNA, and pharmacological approaches were used. Cortical neurons preconditioned with sublethal exposure to NMDA or oxygen glucose deprivation (OGD) exhibited enhanced Lck kinase activity, and were resistant to injury on subsequent exposure to lethal levels of NMDA or OGD. Lck gene silencing using siRNA abolished tolerance against both stimuli. Lck-/- mice or neurons isolated from Lck-/- mice did not exhibit PC-induced tolerance. An Lck antagonist administered to wild-type mice significantly attenuated the neuroprotective effect of PC in the mouse focal ischemia model. Using pharmacological and gene silencing strategies, we also showed that PKCε is an upstream regulator of Lck, and Fyn is a downstream target of Lck. We have discovered that Lck plays an essential role in PC in both cellular and animal models of stroke. Our data also show that the PKCε-Lck-Fyn axis is a key mediator of PC. These findings provide new opportunities for stroke therapy development.

Cerebral venous and sinus thrombosis associated with subcutaneous immunoglobulin injection and oral contraceptive use.

Although patients of cerebral sinus thrombosis after intravenous immunoglobulin (IVIG) has been previously reported; reports of cerebral venous thrombosis secondary to subcutaneous injection of immunoglobulin (SIG) in conjunction with oral contraceptives are nonexistent in the current literature. We describe here a patient of cerebral venous and sinus thrombosis occurring after the combination of SIG and oral contraceptive use. Furthermore, we shall explore proper clinical precautions for someone who receives IG therapy, especially in conjunction with the use of oral contraceptives.

Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia.

The present study sought to determine the neuroprotective effect of anthocyanin cyanidin-3-O-glucoside (CG), isolated and purified from tart cherries, against permanent middle cerebral artery occlusion (pMCAO) in mice and its potential mechanisms of neuroprotection. C57BL/6 mice subjected to pMCAO were treated with CG orally. Twenty-four hours after pMCAO, neurological scoring was used to evaluate functional outcome. The brains were then excised for measuring infarct volume and brain superoxide levels were determined. In a separate set of experiments, the influence of CG on cytochrome c (cyt c) and apoptosis-inducing factor (AIF) release from mitochondria under oxidative stress were assessed in isolated cortical neurons from adult mouse brains. Infarction volume was attenuated by 27% in mice pre-treated with 2mg/kg of CG compared to vehicle-treated mice. Delayed treatment with 2mg/kg of CG also showed 25% reduction in infarct size. Neurological functional outcome was significantly improved in mice pre- or post-treated with CG. Compared to vehicle treated mice CG treated mice had lower levels of brain superoxide. CG also blocked the release of AIF from mitochondria under oxidative stress, but did not inhibit the release of cyt c. Our data show that CG is neuroprotective against pMCAO in mice, and this beneficial effect may be mediated by attenuation of brain superoxide levels after ischemia. CG may also exert its neuroprotective effect by blocking AIF release in mitochondria.