Ramin Zand

FABS: An Intuitive Tool for Screening of Stroke Mimics in the Emergency Department

Background and Purpose— A large number of patients with symptoms of acute cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a scoring system (FABS) for screening and stratifying SM from acute cerebral ischemia and to identify patients who may require magnetic resonance imaging to confirm or refute a diagnosis of stroke in the emergency setting. Methods— We designed a scoring system: FABS (6 variables with 1 point for each variable present): absence of Facial droop, negative history of Atrial fibrillation, Age <50 years, systolic Blood pressure <150 mm Hg at presentation, history of Seizures, and isolated Sensory symptoms without weakness at presentation. We evaluated consecutive patients with symptoms of acute cerebral ischemia and a negative head computed tomography for any acute finding within 4.5 hours after symptom onset in 2 tertiary care stroke centers for validation of FABS. Results— A total of 784 patients (41% SMs) were evaluated. Receiver operating characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93–0.98) indicated that FABS≥3 could identify patients with SM with 90% sensitivity (95% CI, 86%–93%) and 91% specificity (95% CI, 88%–93%). The negative predictive value and positive predictive value were 93% (95% CI, 90%–95%) and 87% (95% CI, 83%–91%), respectively. Conclusions— FABS seems to be reliable in stratifying SM from acute cerebral ischemia cases among patients in whom the head computed tomography was negative for any acute findings. It can help clinicians consider advanced imaging for further diagnosis.

Cerebral Microbleeds and Risk of Intracerebral Hemorrhage Post Intravenous Thrombolysis

BACKGROUND Stroke patients who have cerebral micro bleeds (CMBs) could be potentially at a greater risk for symptomatic intracerebral hemorrhage (sICH) than those patients without CMBs. The aim of our study was to investigate whether the presence and burden of CMBs are associated with post IVT sICH. METHODS In this multicenter study, consecutive patients treated with intravenous tissue plasminogen activator were prospectively identified and analyzed. Patients without magnetic resonance imaging (MRI) within 24 hours of treatment were excluded. CMBs were defined as round or oval, hypointense lesions with associated blooming on T2*-weighted MRI up to 10 mm in diameter. Outcome measures included the occurrence of sICH or death. RESULTS Of 672 patients with IVT (mean age 62 ± 14 years, 52% men, median admission NIHSS: 7 points), 103 patients had CMBs on T2*-MRI. Ten patients had more than 10, whereas the remaining 93 patients had 1-10 CMBs on T2*-MRI. The rates of sICH did not differ between patients with and patients without 1-10 CMBs (5.8% versus 3.5%; P = .27). However, sICH occurred more frequently (P = .0009) in patients with > 10 CMBs (30%, 95% confidence interval [CI] by the adjusted Wald method: 10%-61%). After adjusting for potential confounders, the presence of >10 CMBs on T2*-MRI was independently (P = .0004) associated with a higher likelihood for sICH (odds ratio [OR]:13.4, 95%CI:3.2-55.9). CONCLUSIONS Our findings indicate an increased risk of sICH after IVT when more than 10 CMBs are present.

Novel Screening Tool for Stroke Using Artificial Neural Network

Background and Purpose— The timely diagnosis of stroke at the initial examination is extremely important given the disease morbidity and narrow time window for intervention. The goal of this study was to develop a supervised learning method to recognize acute cerebral ischemia (ACI) and differentiate that from stroke mimics in an emergency setting. Methods— Consecutive patients presenting to the emergency department with stroke-like symptoms, within 4.5 hours of symptoms onset, in 2 tertiary care stroke centers were randomized for inclusion in the model. We developed an artificial neural network (ANN) model. The learning algorithm was based on backpropagation. To validate the model, we used a 10-fold cross-validation method. Results— A total of 260 patients (equal number of stroke mimics and ACIs) were enrolled for the development and validation of our ANN model. Our analysis indicated that the average sensitivity and specificity of ANN for the diagnosis of ACI based on the 10-fold cross-validation analysis was 80.0% (95% confidence interval, 71.8–86.3) and 86.2% (95% confidence interval, 78.7–91.4), respectively. The median precision of ANN for the diagnosis of ACI was 92% (95% confidence interval, 88.7–95.3). Conclusions— Our results show that ANN can be an effective tool for the recognition of ACI and differentiation of ACI from stroke mimics at the initial examination.

Potential Roles of Adropin in Central Nervous System: Review of Current Literature

Adropin is a 4.9 kDa peptide that is important for maintenance of metabolic and non-metabolic homeostasis. It regulates glucose and fatty acid metabolism and is involved in endothelial cell function and endothelial nitric oxide (NO) synthase bioactivity as well as physical activity and motor coordination. Adropin is expressed in many tissues and organs including central nervous system (CNS). This peptide plays a crucial role in the development of various CNS disorders such as stroke, schizophrenia, bipolar disorder as well as Alzheimers, Parkinsons, and Huntingtons diseases. In this comprehensive review, the potential roles of adropin in cellular signaling pathways that lead to pathogenesis and/or treatment of CNS disorders will be discussed.

Fluid-Attenuated Inversion Recovery (FLAIR) Signal Intensity Can Identify Stroke Within 6 and 8 Hours

BACKGROUND Patients with wake-up or unknown time of onset stroke are usually excluded from recanalization. However, a few studies indicate that some magnetic resonance sequences can help predict time from symptom onset (SxO). Our goal was to assess the value of fluid-attenuated inversion recovery (FLAIR) signal intensity ratio (SIR) in identifying patients within 6 and 8 hours of stroke onset. MATERIALS AND METHODS We studied consecutive acute stroke patients with known time of onset who underwent magnetic resonance imaging (MRI) within 48 hours of SxO. SIR was calculated as the value of the FLAIR signal intensity of the identified area of infarction divided by the signal intensity in the homologous contralateral side of the brain. RESULTS Out of 160 patients included in this study, 72 and 80 patients had MRI within 6 and 8 hours of SxO, respectively. We found a positive correlation between SIR and time from SxO (Pearson coefficient, .63). Receiver operating characteristic curves indicated that SIR ≤ 1.18 could accurately identify patients within 6 hours of SxO (86% sensitivity, 79% specificity) and a SIR ≤ 1.20 can be identified within 8 hours (89% sensitivity, 76% specificity). Among patients with no visible FLAIR hyperintensity, 83% (95% CI, 77%-89%) were within the 6-hour window. CONCLUSION Quantitative assessment of FLAIR sequence can be used to identify patients within 6 and 8 hours of stroke onset.

Thrombotic Thrombocytopenic Purpura with Concomitant Progressive Cerebral Microbleeds

Thrombotic thrombocytopenic purpura (TTP) is a disease caused by excessive platelet thrombi and multisystem vasculopathy. We report a young patient with refractory TTP who has developed multiple multifocal cerebral microbleeds on his brain magnetic resonance imaging scans. TTP-associated thrombotic microangiopathy resulting in diffuse microthrombi formation in the microcirculation and hypoperfusion might be an underlying etiology.

Development of Synthetic Patient Populations and In Silico Clinical Trials

Drug development, which includes clinical trials, is a lengthy and expensive process that could significantly benefit from predictive modeling and in silico testing. Additionally, current treatments were designed based on the average patient using the “one size fits all” protocol. Therefore, they can be effective on some patients but not for others. There is an urgent need to replace such generalized approaches with personalized and predictive strategies that capture and analyze human diversity and variation at a resolution sufficient to identify and clinically validate personalized treatment paradigms. Utilization of heterogenous datasets, such as Electronic Health Records (EHRs), to build synthetic populations of patients and personalized, predictive models of response to therapy holds enormous promise in precipitating a revolution in precision medicine for IBD. In silico trials can be designed to include multi-modal data sources, including clinical trial data at the individual and aggregated levels, pre-clinical data from animal studies, as well as data from EHR. In silico clinical trials can help inform the design of clinical trials and make prediction at the population and individual level to increase the chances of success. This chapter discusses pioneering work on the use of in silico clinical trials to accelerate the development of new drugs.

The association of adult vaccination with the risk of cerebrovascular ischemia: A systematic review and meta-analysis

There is mounting evidence supporting infection as an independent risk factor for ischemic stroke (IS), while preliminary data indicate that vaccination may prevent IS. We performed a systematic review and meta-analysis of available randomized clinical trials (RCTs) or prospective observational cohorts reporting associations of influenza vaccination (IV) and/or pneumococcal vaccination (PV) with IS. We identified a total of 12 studies (543,311 patients; 47.4% vaccinated). Vaccination was not related to the risk of IS (RR=1.06, 95%CI: 0.74-1.51, p=0.77), with no significant differences (p=0.26) among RCTs (RR=0.66, 95%CI: 0.30-1.47) and observational studies (RR=1.11, 95%CI: 0.76-1.61). Evidence of considerable heterogeneity was identified within observational studies (I2=98%), but not within RCTs (I2=0%). In subgroup analyses according to vaccination type, IV was associated with a significantly lower risk of IS (RR=0.87, 95%CI: 0.79-0.96, p=0.004) with moderate evidence of heterogeneity (I2=53%). No association was seen for PV (RR=1.38, 95%CI: 0.60-3.16, p=0.45), where considerable heterogeneity was identified (I2=97%). In the additional adjusted analyses of observational studies, vaccination tended to be associated with lower risk of IS (HRadjusted=0.87; 95%CI: 0.75-1.01; p=0.07). The findings of this meta-analysis indicate that IV may be associated with a lower risk of IS. This association was not reproduced for PV or the combination of two vaccines. Substantial heterogeneity was detected across observational studies for all outcome events, while moderate to low heterogeneity was identified across included RCTs. These preliminary findings require independent validation in large RCTs.

Hemicraniectomy for Malignant Middle Cerebral Artery Syndrome: A Review of Functional Outcomes in Two High-Volume Stroke Centers

BACKGROUND AND PURPOSE Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). METHODS We retrospectively evaluated consecutive patients with acute MMCAI treated in 2 tertiary care centers during a 7-year period. Pretreatment National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 3 months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4, respectively. RESULTS A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria (mean age 59 ± 15 years, 52% men, median admission NIHSS score: 19 points [interquartile range {IQR}: 16-22]). Cases were younger (51 ± 11 versus 68 ± 13 years; P < .001) and tended to have lower median admission NIHSS than controls (18 [IQR:16-20] versus 20 [IQR:18-23]; P = .072). The rates of FI and SWSD at 3 months were higher in cases than controls (16% versus 0% [P = .031] and 62% versus 0% [P < .001]), while 3-month mortality was lower (24% versus 77%; P < .001). Multivariable Cox regression analyses adjusting for potential confounders identified HCT as the most important predictor of lower risk of 3-month mortality (hazard ratio: .02, 95% confidence interval: .01-0.10; P < .001). CONCLUSIONS HCT is a critical and effective therapy for patients with MMCAI but cannot provide a guarantee of functional recovery.

Cerebral Microbleeds are Associated with Higher Mortality Among Ischemic Stroke Patients

BACKGROUND Several studies have shown that cerebral microbleeds (CMBs) increase the risk of long-term stroke-related mortality. The purpose of this study was to determine if the existence and burden of CMBs are a predictor of in-hospital death among patients with acute ischemic stroke (AIS). METHODS We studied consecutive ischemic stroke patients who admitted to our tertiary center over a 2-year period (2013-2014). Patients who underwent thrombolysis were excluded. Baseline characteristics of patients, number and topography of CMBs, white matter lesions, and spontaneous symptomatic hemorrhagic transformation were recorded. Outcome measure in our study was in-hospital death. RESULTS Out of 1126 consecutive AIS patients evaluated in this study, 772 patients included in the study (mean age 61.9 ± 14.2years [18-95 years], 51.6% men, and 58.2% African American). CMBs were present on the magnetic resonance imaging (MRI) sequences of 124 (16.1%) patients. The overall rate of in-hospital mortality was 4.1%. The presence or absence of CMBs was not predictive of in-hospital mortality (P = .058). After adjusting for potential confounders, the presence of ≥4 CMBs on T2*-weighted MRI was independently (P = .004) associated with a higher likelihood of in-hospital death (odds ratio: 6.6, 95% confidential interval: 2.50 and 17.46) in multivariable logistic regression analyses. Older age, higher National Institute of Health stroke scale, and history of atrial fibrillation were also associated with greater chance of in-hospital death. CONCLUSIONS The presence or absence of CMBs was not predictive of in-hospital mortality. However, the presence of multiple CMBs was associated with a higher in-hospital mortality rate among AIS patients.