Stroke Of Unknown Etiology Research Articles

Diagnosis and treatment of acute ischemic insults

In cases of stroke adistinction is made between a transient ischemic attack (TIA), a manifest ischemic infarction and cerebral hemorrhage. Cerebral ischemia can be caused by large vessel disease, small vessel disease, embolic causes, rare causes or stroke of unknown etiology. Acute diagnostic tests include a neurological examination, computed tomography (CT) and/or magnetic resonance imaging (MRI) with angiography, electrocardiography (ECG), and laboratory tests. The basic treatment of patients with TIA or acute ischemic infarction is performed in the stroke unit and includes monitoring of respiratory function, cardiac function, treatment of potential heart failure, detection of swallowing disorders, prophylaxis of thromboembolism, control of blood pressure and elevated blood sugar levels, and lowering of elevated body temperature. In patients with cardioembolic infarction, oral anticoagulation is initiated depending on the severity of the stroke and the size of the stroke on imaging.

Rationale, design, and baseline characteristics of the Cardiovascular Prognostic COUPLING Study in Japan (the COUPLING Registry).

Vascular biomarkers, including the cardio-ankle vascular index (CAVI), are increasingly being recognized as important indicators of cardiovascular risk. CAVI has been shown to have good discriminative ability for detecting new-onset hypertension, but results of studies investigating cardiovascular risk prediction are inconsistent. Furthermore, there is a lack of data on the prognostic value of changes in CAVI over time. The Cardiovascular Prognostic Coupling study was designed to determine the impact of baseline CAVI and changes in CAVI on cardiovascular events in a Japanese cohort. The design of the ongoing, multicenter, prospective, observational registry and baseline characteristics of the enrolled population are reported. Eligible consecutive patients were aged ≥30years, had ≥1 cardiovascular risk factor, and were being treated according to relevant Japanese guidelines. The primary outcome is time to onset of a major cardiovascular event (a composite of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of unknown etiology, myocardial infarction, cardiovascular intervention for angina pectoris, and sudden death). Screening and enrollment occurred over a period of 3years, followed by ≥7years of follow-up, with CAVI determined annually. A total of 5279 patients were registered, of whom 5109 had baseline data available and will be included in future analyses. Mean CAVI at baseline was 8.8±1.4. The proportion of patients with CAVI of <8, 8-10 or >10 was 25.3%, 57.0%, and 17.7%, respectively. Data from this registry should provide information on the significance of baseline CAVI and change in CAVI as indicators of cardiovascular prognosis in a representative patient population.

Clinical case of meningovascular syphilis in combination with HIV infection

Purpose: to study the features of clinical course, diagnosis and treatment of meningovacular syphilis associated with HIV infection. Materials and methods. Clinical case of meningovascular syphilis in the context of HIV infection in a 55-year-old man, methods of diagnosis and treatment. Results. The article deals with a special case of meningovascular syphilis associated with HIV in the man of 55 years, as well as the features of the clinical course and treatment of this pathology are discussed based on the analysis of the professional literature data. The data of anamnesis, objective, laboratory and instrumental examination, results of patient's treatment are presented. It is noted that a stroke may be the first manifestation of neurosyphilis and HIV infection. Changes in the cerebrospinal fluid were accompanied by a slight increase in lymphocytes. Specific immunological examination of blood and liquor was the key to the diagnosis. Treatment with ceftriaxone has resulted in improvement of the patient's health condition and a regression of motor neurologic deficit. Conclusions. Patients with HIV infection are vulnerable to cerebrovascular diseases due to various etiological factors. Meningovascular form of neurosyphilis may be the initial manifestation of syphilis in both HIV-positive and HIV-negative individuals. Due to the increased incidence of syphilis, as well as co-infection with HIV, it is recommended to examine young patients with a stroke of unknown etiology with a presence of undetermined neurological symptoms and changes in the cerebrospinal fluid for HIV and syphilis. Clinical manifestations of neurovascular syphilis tend to be regressed in the course of specific antibiotic therapy.

Neuropsychological outcome following thalamic stroke in adolescence: an identical twin comparison

Objective: Medial thalamic stroke in adults commonly results in severe learning and memory impairments and executive dysfunction, particularly during the acute phase. However, there is limited research on the cognitive recovery from thalamic stroke in physically healthy adolescents. This study aimed to fill this gap in the literature by utilizing a monozygotic twin control to investigate the neuropsychological outcomes of bilateral thalamic stroke in adolescence.Method: We evaluated an otherwise healthy 17-year-old male with a history of premature birth, developmental delay, and learning disability 2 and 7 months after he sustained a bilateral medial/anterior thalamic stroke of unknown etiology. His identical twin brother served as a case control.Results: The patient presented with improvements in many cognitive skills between assessments, most notably processing speed. Despite some mild improvement, however, he presented with significant deficits in fine motor speed/coordination, spatial perception, and rapid naming. Additionally, he exhibited persistent, severe deficits in verbal learning and memory. Relative sparing of executive functions (i.e., planning and set-shifting) and attention on standardized measures in this case may be explained by good underlying health, limited extra-thalamic damage, and/or recovery of function. The effects of thalamic injury resulted in minimal adaptive dysfunction or deterrence from academic or athletic success for the presented case.Conclusions: These results suggest risk for deficits in encoding of new verbal information following bilateral thalamic stroke in adolescence, as well as risk for persistent cognitive deficits despite initial improvements. This is consistent with descriptions of anterograde memory impairments in adults with similar lesions.

Thirty-day recurrence after ischemic stroke or TIA.

BackgroundIncidence of recurrent stroke is highest within 30 days after the initial ischemic stroke (IS) or TIA, but knowledge about early recurrence is lacking. We aimed to identify etiological groups with highest risk of early recurrence and assess how the TOAST classification identified index stroke etiology.MethodsMedical records of 1874 IS and TIA patients in the Bergen NORSTROKE registry were retrospectively reviewed for identification of recurrent IS or TIA within 30 days after index IS or TIA. Stroke etiology was determined by review of electronical medical journals. Logistic regression was used to calculate odds ratios (OR) for 30‐day recurrence.ResultsThirty‐three patients (1.8%) were readmitted with recurrent IS or TIA within 30 days after index stroke. By using TOAST, 12 patients were initially classified with stroke of unknown etiology (SUE). Etiologies behind recurrent IS or TIA were after the recurrent episode identified as extracranial large artery atherosclerosis (LAA) in 14 patients (42.4%), intracranial arterial pathology in seven patients (21.2%), active malignancy in six patients (18.2%), and cardio embolism in four patients (12.1%). Small vessel occlusion and SUE were the causes in one patient each. Logistic regression showed that patients with stroke of other determined etiology (SOE) and LAA had increased risk of 30‐day recurrence (OR = 9.72, 95% CI 1.84–51.3, p < 0.01 and OR = 4.36, 95% CI 2.01–9.47, p < 0.01, respectively).ConclusionPatients with LAA and SOE had increased risk of recurrent IS or TIA within 30 days. TOAST was inadequate at identifying exact etiologies behind recurrent stroke at index event.

Practice Patterns for Acute Ischemic Stroke Workup: A Longitudinal Population-Based Study.

BackgroundWe examined practice patterns of inpatient testing to identify stroke etiologies and treatable risk factors for acute ischemic stroke recurrence.Methods and ResultsWe identified stroke cases and related diagnostic testing from four 1‐year study periods (July 1993 to June 1994, 1999, 2005, and 2010) of the Greater Cincinnati/Northern Kentucky Stroke Study. Patients aged ≥18 years were included. We focused on evaluation of extracranial arteries for carotid stenosis and assessment of atrial fibrillation because randomized controlled trials supported treatment of these conditions for stroke prevention across all 4 study periods. In each study period, we also recorded stroke etiology, as determined by diagnostic testing and physician adjudication. An increasing proportion of stroke patients received assessment of both extracranial arteries and the heart over time (50%, 58%, 74%, and 78% in the 1993–1994, 1999, 2005, and 2010 periods, respectively; P<0.0001 for trend), with the most dramatic individual increases in echocardiography (57%, 63%, 77%, and 83%, respectively). Concurrently, we observed a decrease in strokes of unknown etiology (47%, 48%, 41%, and 38%, respectively; P<0.0001 for trend). We also found a significant increase in strokes of other known causes (32%, 25%, 45% and 59%, respectively; P<0.0001 for trend).ConclusionsStroke workup for treatable causes of stroke are being used more frequently over time, and this is associated with a decrease in cryptogenic strokes. Future study of whether better determination of treatable stroke etiologies translates to a decrease in stroke recurrence at the population level will be essential.

Risk factors and mechanisms of stroke in young adults: The FUTURE study

Incidence of ischemic stroke and transient ischemic attack in young adults is rising. However, etiology remains unknown in 30–40% of these patients when current classification systems designed for the elderly are used. Our aim was to identify risk factors according to a pediatric approach, which might lead to both better identification of risk factors and provide a stepping stone for the understanding of disease mechanism, particularly in patients currently classified as “unknown etiology”. Risk factors of 656 young stroke patients (aged 18–50) of the FUTURE study were categorized according to the “International Pediatric Stroke Study” (IPSS), with stratification on gender, age and stroke of “unknown etiology”. Categorization of risk factors into ≥1 IPSS category was possible in 94% of young stroke patients. Chronic systemic conditions were more present in patients aged <35 compared to patients ≥35 (32.6% vs. 15.6%, p < 0.05). Among 226 patients classified as “stroke of unknown etiology” using TOAST, we found risk factors in 199 patients (88%) with the IPSS approach. We identified multiple risk factors linked to other mechanisms of stroke in the young than in the elderly. This can be a valuable starting point to develop an etiologic classification system specifically designed for young stroke patients.

Age disparity in diagnostic evaluation of stroke patients: Embolic Stroke of Undetermined Source Global Registry Project.

Introduction: Incomplete evaluation of stroke patients may result in an unclear diagnosis. Our objective was to determine if older stroke patients more often undergo incomplete diagnostic evaluations versus younger patients in an international cohort. Patients and methods: The Embolic Stroke of Undetermined Source Global Registry was a retrospective cohort of consecutive stroke patients evaluated at 19 stroke centers in 19 countries. Diagnostic evaluation was considered as complete if the patient had, at a minimum, brain computed tomography or magnetic resonance imaging with evidence of infarction, extracranial and intracranial vascular imaging, electrocardiography, ≥24 h of cardiac rhythm monitoring, and echocardiography. Patients were diagnosed with Embolic Stroke of Undetermined Source if brain imaging confirmed a nonlacunar infarction and no stroke etiology was determined after complete evaluation. Completeness of evaluation was compared between patients ≥75 versus <75 years old. Results: The registry included 2132 patients with recent ischemic stroke during 2013-2014, of which 349 were diagnosed with Embolic Stroke of Undetermined Source. Embolic Stroke of Undetermined Source patients ≥75 years were less likely to undergo brain magnetic resonance imaging (74% versus 89%, p = 0.001), transesophageal echocardiography (22% versus 39%, p = 0.005), and combination transthoracic and transesophageal echocardiography (16% versus 32%, p = 0.005) compared with Embolic Stroke of Undetermined Source patients <75 years. Discussion: Our study has identified an international age disparity in fundamental diagnostic testing for older patients with stroke of unknown etiology. Some testing biases were affected by geographic location (e.g., brain MRI was less frequently used in European ESUS patients), whereas other testing was implemented less frequently in the elderly regardless of location (e.g., transesophageal echocardiogram). Conclusion: Older patients in this international cohort had less sophisticated diagnostic testing for stroke, despite advanced age being well established as an independent risk factor for recurrent stroke. This was a global problem and further investigations are warranted to explore the cause.

Early Neurologic Deterioration after Stroke Depends on Vascular Territory and Stroke Etiology.

Background and PurposeEarly neurologic deterioration (END) occurs in up to one-third of patients with ischemic stroke and is associated with poor outcomes. The purpose of the present study was to determine which stroke etiologies and vascular distributions pose a greater threat of END in stroke patients.MethodsUsing a single-center registry of prospectively maintained clinical data, adult ischemic stroke patients admitted (July 2008 to June 2014) within 48 hours of symptom onset were evaluated according to stroke etiology and vascular distribution using diffusion-weighted MRI. Major stroke etiologies were divided into cardioembolic, large vessel, small vessel, other, unknown source, and multiple possible etiologies. END was defined as a worsening of 2 or more points on the National Institutes of Health Stroke Scale during a 24-hour period of hospitalization. Crude and backward stepwise regression models were generated to associate stroke etiology and vascular distribution with END.ResultsOf the included 961 patients (median age 65 years, 47% female, 72% non-White), 323 (34%) experienced END. Strokes involving the internal carotid artery (ICA) were associated with a threefold higher odds of END in stepwise regression models (OR 3.0, 95% CI 1.4-6.6, P=0.006). Among stroke etiologies, those with unclear mechanisms had the lowest odds of END in the fully adjusted model (OR 0.6, 95% CI 0.4-1.0, P=0.029).ConclusionsIn our single-center cohort of patients, ICA infarctions were independently associated with END whereas strokes of unknown etiology were least often associated with END. Larger cohorts are necessary to determine which steps, if any, can be taken to prevent END in these vulnerable populations.

PFO Closure for Cryptogenic Stroke.

A patent foramen ovale (PFO) is a common finding in the general population and has been theorized to be a mechanism for ischemic stroke primarily due to a deep venous thrombus embolizing through the shunt into the arterial circulation. There has been much debate regarding the association between PFO and stroke, especially in the case of a cryptogenic stroke (i.e., stroke of unknown etiology) in a younger patient without other risk factors. Traditionally, when a PFO is detected, antithrombotic therapy to mitigate risk of a future ischemic event has been the mainstay of treatment. More recently, both surgical and transcatheter closure of a PFO have been widely utilized. However, there are only few randomized controlled trials assessing the efficacy of PFO closure for stroke prevention.

Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings: a decision analysis

Background: Seventy-one percent of worldwide stroke mortality and 77.5% of worldwide stroke disability-adjusted life years (DALYs) lost occur in lowand middle-income countries (LMIC). This disproportionate burden of stroke in LMIC is due to resource limitations in both prevention and treatment. In addition to risk factor modification, aspirin is an inexpensive and effective medication for secondary stroke prevention. However, only 3.8% of patients with prior stroke in low-income countries take antiplatelet agents, compared to 53.1% in high-income countries. One reason for this is that without access to CT to distinguish ischemic stroke (IS) from intracerebral hemorrhage (ICH), clinicians must balance presumed risks of aspirin administration in patients with potential ICH against potential benefits of secondary prevention in patients with possible IS. In order to assist clinicians practicing in resource-limited settings, we conducted a decision analysis to determine the impact of administering aspirin as long-term secondary preventive therapy to all patients after stroke when CT is not available to distinguish IS from ICH. Methods: We used a Markov state transition model to evaluate the potential outcomes of two strategies for long-term secondary prevention after stroke of undetermined etiology: administering aspirin to all patients versus not administering aspirin to any patients. Data on the risks and benefits of aspirin use after IS and ICH were obtained from meta-analyses and large series. Sensitivity analyses were performed across the worldwide reported range of the proportion of strokes due to ICH and the 95% confidence intervals of aspirin-associated relative risks in patients with ICH. Findings: For patients with stroke of unknown etiology, long-term aspirinwas the preferred treatment strategy across theworldwide reported range of the proportion of strokes due to ICH. At 34% of strokes due to ICH (the highest proportion reported in a large epidemiologic study), the benefit of aspirin remained beyond the upper bounds of the 95% confidence intervals of aspirin-associated post-ICH relative risks most concerning to clinicians (ICH recurrence risk andmortality risk if ICHrecurs on aspirin). Based on the estimated11,590,204 strokes inLMIC in2010, ourmodel predicts that aspirin therapy for secondary stroke prevention in all patients in these countries could lead to an estimated yearly decrease of 84,492 recurrent strokes and 4,056 stroke-related mortalities. Interpretation: The concern that the risks of aspirin in patients with stroke of unknown etiology could outweigh the benefits is not supported by our model, which predicts that aspirin for secondary prevention after stroke of undetermined etiology could lead to decreased stroke-related mortality and stroke recurrence. In the absence of a clinical trial to test this approach empirically, clinical decisions still require patient-specific assessment of risk and benefit. Funding: None. Abstract #: 01NCD001

Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings.

To analyze the potential impact of aspirin therapy for long-term secondary prevention after stroke of undetermined etiology in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). We conducted a decision analysis using a Markov state transition model. Sensitivity analyses were performed across the worldwide reported range of the proportion of strokes due to ICH and the 95% confidence intervals (CIs) of aspirin-associated relative risks in patients with ICH. For patients with stroke of undetermined etiology, long-term aspirin was the preferred treatment strategy across the worldwide reported range of the proportion of strokes due to ICH. At 34% of strokes due to ICH (the highest proportion reported in a large epidemiologic study), the benefit of aspirin remained beyond the upper bounds of the 95% CIs of aspirin-associated post-ICH relative risks most concerning to clinicians (ICH recurrence risk and mortality risk if ICH recurs on aspirin). Based on the estimated 11,590,204 strokes in low- and middle-income countries in 2010, our model predicts that aspirin therapy for secondary stroke prevention in all patients with stroke in these countries could lead to an estimated yearly decrease of 84,492 recurrent strokes and 4,056 stroke-related mortalities. The concern that the risks of aspirin in patients with stroke of unknown etiology could outweigh the benefits is not supported by our model, which predicts that aspirin for secondary prevention in patients with stroke of undetermined etiology in resource-limited settings could lead to decreased stroke-related mortality and stroke recurrence.

The incidence of new-onset atrial fibrillation in patients with stroke of unknown etiology is similar to the age- and gender-matched stroke-free population during 10-year follow up

Introduction: In patients with atrial fribrillation (AF), the leading cause of ischemic stroke is cardioembolism. In many patients with stroke, its cause remains unknown and may be due to underdiagnosis of AF, which may become apparent after stroke. We aimed to assess whether the incidence of new-onset AF in patients with unknown etiology stroke exceeds the one in stroke-free population during 10-year follow-up (FU). Methods: Patients with first-ever ischemic stroke (n=336, age 74±11 y, 200 men) and 1:1 age- and gender-matched control subjects without stroke were enrolled in Lund Stroke Register in 2001. AF history prior to admission and new-onset AF during FU were assessed using medical records, an electronic ECG archive and by record linkage with the Swedish Hospital Discharge Register. The mechanism of stroke was assessed using TOAST criteria. Results: By enrolment, 32% of stroke patients and 13% of controls had AF history (p<0.001) and were excluded from analysis. The cause of stroke could not be identified in 133 patients, of whom 122 did not have AF history and comprised study population (age 75±12 y, 54% men) that was compared with 292 controls without prior stroke (age 74±11 y, 61% men). During FU median number of available ECG was 3 (IQ 7) in patients vs 4 (IQ 7) in controls, p=0.708. In FU, AF was detected in 16 (13%) stroke patients and in 36 (12%) controls (HR for stroke 1.3 95% CI 0.70-2.29, p=0.430, Figure). ![Figure][1] Time to new-onset AF after stroke Conclusions: The incidence of AF during 10-year FU in patients with stroke of undetermined cause is similar to the stroke-free population, which suggest that underdiagnosed AF is unlikely to be a common cause of it. However, AF detection rate at baseline in our study exceeds earlier reported AF prevalence, which might have resulted in a low number of undiagnosed AF cases. [1]: pending:yes

Ambulatory blood pressure monitoring in acute stroke

Time rate of blood pressure (BP) variation is a measure of the speed of BP fluctuations derived from a computerized analysis of ambulatory BP monitoring. The aim of this study was to identify pathophysiological differences in the time rate of BP variation between stroke subtypes, on the basis of the Trial of Org 10172 in Acute Stroke Treatment criteria, in the acute phase and to examine the impact of time rate of BP variation on outcome at 1 year after stroke. A consecutive series of 109 first-ever stroke patients, who fulfilled our inclusion criteria, underwent 24 h ambulatory BP monitoring within 24 h after the onset of stroke. On the basis of the patients' Modified Rankin Scale score at 1 year after stroke, the study population was divided into two groups: patients with a positive (n=73) and those with a negative outcome (n=36). The 24-h rate of systolic BP variation is higher in patients with large artery atherosclerosis [0.692 mmHg/min; 95% confidence interval (CI) 0.627-0.757] compared with those with lacunar strokes (0.609 mmHg/min; 95% CI 0.579-0.640) or strokes of unknown etiology (0.586 mmHg/min; 95% CI 0.522-0.649). Moreover, patients with higher 24-h rates of systolic BP variation were more likely to have a negative outcome at 1 year (odds ratio 1.96; 95% CI 1.16-3.32). Moreover, each 0.1 mmHg/min increase in the 24-h rate of SBP variation was associated with a 1.96-fold increase in the odds of a negative outcome (95% CI 1.16-3.32). Time rate of BP variation shows significant differences between stroke subtypes in the acute phase of the event, and it is associated with outcome at 1 year. Lowering the time rate of BP variation, in the acute phase, might lead to better outcomes in patients who have had a cerebrovascular incident.

Abstract TP202: Atrial Fibrillation In Young Stroke Patients: Do We Underestimate Its Prevalence?

BACKGROUND: Our knowledge of the presence of atrial fibrillation (AF) in young stroke patients is scarce. Our objective was to analyze the frequency of AF in ischemic stroke (IS) patients up to 50 years of age and its relationship with stroke severity and outcomes. METHODS: Prospective observational study of consecutive IS patients up to 50 years of age admitted to a stroke center during a five-year period (2007-2011). A complete cardiology study was performed with daily electrocardiogram (ECG) and cardiac monitoring for 72 hours as well as echocardiography. In cases of stroke of unknown etiology, a 24-hour Holter monitoring was performed, which was repeated as necessary. We analyzed baseline data, previously or newly diagnosed AF, structural heart disease (SHD) (valvulopathy/cardiomyopathy), stroke severity on admission measured by the NIHSS (moderate-severe stroke if NIHSS≥5) and 3-month outcomes according to the mRS (good outcome if mRS ≤2). AF was classified as AF associated with SHD (AF-SHD) and AF not associated with SHD (AF-NSHD). RESULTS: One hundred fifty-seven patients were included (mean age 41.1 years, 58.6% male). Sixteen subjects (10.2%) presented AF, 5 with AF-NSHD and 11 with AF-SHD. AF was previously known in 10 patients (6.4%), 2 with AF-NSHD and 8 with AF-SHD. A multivariate analysis showed an independent association between AF and moderate-severe IS (OR 3.882, 95%CI: 1.277-11.799), but AF was not an independent prognostic factor. CONCLUSION: AF is present in up to 10% of young patients with IS and is associated with increased NIHSS scores.

Subclinical Atrial Fibrillation Is Associated with Increased Stroke Risk

Subclinical atrial fibrillation (AF) is thought to cause some strokes of unknown etiology. To investigate this issue, researchers enrolled 2580

Abstract 2278: Factors Associated with the Levels of Circulating Endothelial Progenitor Cells in Patients with Acute, Subacute and Chronic stroke.

Introduction In patients with ischemic stroke, the levels of circulating Endothelial Progenitor Cells (EPCs) have been infrequently studied. Our study was focused on investigating the EPC counts in patients with acute, subacute and chronic ischemic stroke and analyzing the associated variables. Methods We prospectively studied consecutive patients with ischemic stroke within the first 48 hours from symptoms onset. We evaluated demographic data (age, sex); classical vascular risk factors (high blood pressure, diabetes mellitus, hypercholesterolemia, coronary artery disease, peripheral vascular disease, previous ischemic stroke, smoking, alcohol abuse, obesity, number or risk factors); thrombolysis; treatment with statins before and after stroke; etiology (sss-TOAST criteria); severity of the neurological deficit (NIHSS score). Blood samples were collected at baseline (n=146), day 7 (n=121) and day 90 (n=92) after stroke onset. EPCs were measured by flow cytometry within 30 minutes after blood collection. We considered that a cell was an EPC when it was labeled for the following 3 markers: CD34, AC133 and KDR. EPC counts were adjusted for the lymphomonocytic population in each sample and expressed as %. Statistics: Non-parametric bivariate analyses, logistic regression analysis. Results We included 146 patients (mean age 70.8±12.2 y, 63% men). In the baseline sample, the following variables were associated with the EPCs count: alcohol abuse (p=0.08), hipercolesterolemia (p=0.029), pre-treatment with statins (p=0.015) and etiology (p=0.037). There were no variables associated with the EPCs count at 7 days. Variables associated with the EPCs count at 3 months were: treatment with statins after stroke (p=0.017), old cerebral infarction (p=0.059) and obesity (p=0.029). The multivariate analysis showed that pre-treatment with statins (OD 3.11, 95%CI 1.34-7.19, p=0.008) and stroke of unknown etiology (p=0.032) independently predicted higher EPC counts at baseline. No variables were independently associated with EPCs counts at 7 days. Finally, at day 90, treatment with statins after stroke was the only variable independently associated with higher EPC counts (OR 11.7, 95%CI 1.5-86, p=0.016). Conclusion In conclusion, prior treatment with statins and stroke etiology are predictors of EPC counts in patients with acute ischemic stroke, while treatment with statins after stroke is independently associated with EPC count at 3 months. The increase in EPCs may be one of the pleiotropic effects of statins that improve the outcome of patients with ischemic stroke.

虚血性脳血管障害発症前の抗血栓薬内服状況の検討

In clinical practice, secondary prevention in patients with ischemic stroke (IS) needs to be continued permanently; however, antithrombotic agents are sometimes stopped by clinicians or the patients themselves. The rate of non-taking oral antithrombotic agents was evaluated in IS patients. 266 consecutive patients (154 men and 112 women; age, 73.6 +/- 11.5 years) with first-ever acute IS were studied. Patients with transient ischemic attack (TIA) were also included. Emboligenic heart diseases, frequency of past stroke, oral antithrombotic agent use just before IS, and secondary prevention were evaluated. The number of past strokes was 0 in 182 cases (68.4%), 1 in 66 cases (24.8%), 2 in 14 cases (5.3%), 3 in 3 cases (1.1%), and 9 in 1 case (0.4%; 3 times with stroke, and 6 times with TIA). There were 42 cases (15.8%) with TIA, 47 (17.7%) with lacunar infarction, 69 (25.9%) with atherothrombotic infarction, 62 (23.3%) with cardioembolic infarction, 23 (8.7%) with other types of infarction, and 23 (8.7%) with stroke of unknown etiology. Although 15-26% of patients with their first IS had taken antithrombotic agents just before IS, about 40% of the patients with a previous IS history were not taking antithrombotic agents just before their recurrent IS. About 40% of the patients with recurrent IS were not taking antithrombotic agents at the time of their recurrent IS; had they been taking antithrombotic agents at the time, the recurrent IS might have been prevented. Clinicians must recognize the importance of antithrombotic agents in patients with IS, and patients must continue to take antithrombotic agents permanently.

Study Design of the CLOSURE I Trial

Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke. This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I. This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

Signatures of cardioembolic and large‐vessel ischemic stroke

The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group. A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large-vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross-validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors. A 40-gene profile differentiated cardioembolic stroke from large-vessel stroke with >95% sensitivity and specificity. A separate 37-gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large-vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation. Gene expression signatures distinguish cardioembolic from large-vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies.