scholarly journals FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction

Stroke ◽  
2021 ◽  
Author(s):  
Juliette Tennenbaum ◽  
Matthieu Groh ◽  
Laura Venditti ◽  
France Campos-Gazeau ◽  
Emilie Chalayer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hypereosinophilic Syndrome ◽  
Growth Factor Receptor ◽  
Clinical History ◽  
First Episode ◽  
Stroke Treatment ◽  
Cardiac Thrombus ◽  
Factor Receptor Alpha ◽  
Undetermined Etiology ◽  
Toast Classification

Background and Purpose: Ischemic stroke has been reported in various conditions associated with eosinophilia. FIP1L1-PDGFRA fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; F/P ) leads to the proliferation of the eosinophilic lineage and thus to a clonal hypereosinophilic syndrome that is highly responsive to imatinib. Methods: We previously reported on a nationwide retrospective study of 151 patients with F/P -associated clonal hypereosinophilic syndrome. Patients from this cohort with a clinical history of ischemic stroke (as well as 2 additional cases) were further analyzed to better define their clinical picture and outcomes. Results: Sixteen male patients (median age, 51 [43–59] years) with low-to-intermediate cardiovascular risk were included. Median National Institutes of Health Stroke Scale was 4 (range, 1–6). Most cerebral imaging disclosed multiple bilateral infarctions of watershed distribution (69%). Despite frequent cardiac involvement (50%), cardiac thrombus was evidenced in a single patient and, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of undetermined etiology. Among the 15 patients treated with imatinib, and after a median follow-up of 4.5 years, stroke recurred in only 3 patients (consisting of either cardio embolic or hemorrhagic events, unrelated to the first episode). Conclusions: F/P + clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.

Abstract 34: Improvement In Etiological Identification In Tia And Minor Stroke Using The Causative Classification Of Stroke.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jamsheed A Desai ◽  
Ahmad Abuzinadah ◽  
Oje Imoukhuede ◽  
Jayesh Modi ◽  
Manya L Bernbaum ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Relative Increase ◽  
Classification Systems ◽  
Minor Stroke ◽  
Large Artery ◽  
Stroke Treatment ◽  
Minor Ischemic Stroke ◽  
Undetermined Etiology ◽  
Toast Classification

Background: classification of Transient Ischemic attacks (TIA) and minor stroke is challenging, as there is no classification systems developed specifically for the TIA and minor stroke patient population. Hypothesis: We hypothesize that the newly developed Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other Source (ASCO) classification would reduce the proportion of patients classified as cause undetermined compared with The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in a large prospectively evaluated TIA and Minor stroke population. Methods: Using published algorithms for TOAST, CCS, and ASCO, a single rater classified the etiology in patients presenting with a high-risk TIA (weakness or speech disturbance lasting ≥ 5minutes) or minor ischemic stroke (National Institute of Health Stroke Scale score ≤ 3) who underwent CT/CTA and subsequent MRI as part of the CATCH study. Results: 419 patients with TIA or Minor stroke were classified using TOAST, CCS, and ASCO. The proportion of patients with an undetermined etiology was 51.3% (215/419) with TOAST. This was significantly reduced by both CCS 36% (151/419, p< 0.001) and ASCO 41% (172/419, p< 0.001). CCS was also less likely to have an undetermined etiology as compared to ASCO (36% versus 41%, p = 0.024). When compared with TOAST, there was a 23.9% (95%CI:18.1- 29.7, P< 0.001) and 17.4% (10.1- 24.7, P< 0.001) reduction in the proportion of patients assigned to the undetermined group using CCS and ASCO respectively. The 8.5 % reduction in the undetermined group between CCS and ASCO was also statistically different P=0.031). Compared with ASCO1, CCS increased the assignment of patients to large artery disease (relative increase 7.4% {4.3-10.4}, P< 0.001) and Cardio-embolism/cardio-aortic categories (relative increase 8.1% {4.6-11.5}, P< 0.001). Conclusions: Both CCS and ASCO were superior to TOAST in assigning fewer patients to an undetermined etiology category. CCS was superior to ASCO at reducing the proportion of patients with undetermined etiology. This was largely driven by increased assignment in the large artery and Cardio-aorto embolic categories.

scholarly journals DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2810-2816
Author(s):  
Lucas Di Meglio ◽  
Jean-Philippe Desilles ◽  
Mialitiana Solonomenjanahary ◽  
Julien Labreuche ◽  
Véronique Ollivier ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Dna Content ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Embolic Stroke ◽  
Unique Identifier ◽  
Stroke Treatment ◽  
Glycoprotein Vi ◽  
Biochemical Assays ◽  
Toast Classification

Background and Purpose: Identification of acute ischemic stroke (AIS) cause is crucial for guidance of secondary prevention. Previous studies have yielded inconsistent results regarding possible correlations between AIS cause and thrombus composition, as assessed by semiquantitative histological analysis. Here, we performed a correlation analysis between AIS cause and AIS thrombus cellular composition and content, as assessed using quantitative biochemical assays. Methods: Homogenates of 250 patients with AIS thrombi were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of AIS thrombi were estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. AIS cause was defined as cardioembolic, noncardioembolic, or embolic stroke of undetermined source, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment). Results: Cardioembolic thrombi were richer in DNA (35.8 versus 13.8 ng/mg, P <0.001) and poorer in GPVI (0.104 versus 0.117 ng/mg, P =0.045) than noncardioembolic ones. The area under the receiver operating characteristic curve of DNA content to discriminate cardioembolic thrombi from noncardioembolic was 0.72 (95% CI, 0.63–0.81). With a threshold of 44.7 ng DNA/mg thrombus, 47% of thrombi from undetermined cause would be classified as cardioembolic with a specificity of 90%. Conclusions: Thrombus DNA content may provide an accurate biomarker for identification of cardioembolic thrombi in patients with AIS with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03268668.

scholarly journals Young women’s stroke etiology differs from that in young men: an analysis of 511 patients

2013 ◽  
Vol 5 (3) ◽  
pp. 12 ◽  
Author(s):  
Emily Nakagawa ◽  
Michael Hoffmann
Keyword(s):  
Acute Stroke ◽  
Small Vessel Disease ◽  
Stroke Treatment ◽  
Stroke Registry ◽  
Stroke Etiology ◽  
Scale Scores ◽  
Acute Stroke Treatment ◽  
Undetermined Etiology ◽  
Toast Classification

Women are known to have particular heterogeneity in stroke etiology related to childbearing and hormonal factors. Although there are continued acute stroke treatment advances focusing on clot dissolution or extraction, effective secondary prevention of stroke, however, is dependent on an accurate etiological determination of the stroke. Otherwise, more strokes are likely to follow. Analysis of young women’s stroke etiology in a large stroke registry incorporating contemporary neurovascular and parenchymal imaging and cardiac imaging. Young people (18-49 years old) with stroke were consecutively accrued over a 4 year period and an investigative protocol prospectively applied that incorporated multimodality magnetic resonance imaging, angiography, cardiac echo and stroke relevant blood investigations. All patients were classified according to an expanded Trial of Org 10172 in Acute Stroke Treatment − TOAST − classification and neurological deficit by the National Institute of Health stroke admission scores. In 511 registry derived, young stroke patients (mean age 39.8 years, 95% confidence interval: 39.1; 40.7 years), gender (women n=269, 53%) the etiological categories (women; men) included: i) small vessel disease (30/55;25/55), ii) cardioembolic (16/42;26/42), iii) large vessel cervical and intracranial disease (24/43;19/43), the <em>other category</em> (132/226; 91/226), which included, iv) substance abuse (15/41; 26/41, 4.6), v) prothrombotic states (22/37;15/37), vi) dissection (11/30;19/30), vii) cerebral venous thrombosis (15/19; 4/19, 12.4), viii) vasculitis (8/12; 4/12), ix) migraine related (10/11, 1/11) and x) miscellaneous vasculopathy (38/52;14/52). The latter entities comprised of aortic arch atheroma, vessel redundancy syndrome, vertebrobasilar hypoplasia, arterial fenestrations and dolichoectasia. Some conditions occurred solely in women, such as eclampsia (5), Call Fleming syndrome (4), fibromuscular dysplasia (3) and Moya Moya syndrome (2). Categories aside from bland infarction included: ii) intracerebral hemorrhage (43/106; 63/106) and xiii) stroke of undetermined etiology (6/10; 4/10). Admission mean National Institute of Health Stroke Scale scores differed significantly between women and men (4.7; 6.0 t=1.8, P=0.03). Young women’s stroke is significantly different from men in 7/12 stroke etiological categories in addition to 4 unique subtypes that require specific management.

Abstract 2597: Centralized and Study-specific Phenotyping in a Large-scale Stroke Genetics Study: An Analysis from the NINDS Stroke Genetics Network (SiGN)

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Bradford B Worrall ◽  
Alejandro Rabinstein ◽  
Dale M Gamble ◽  
Kevin M Barrett ◽  
Shaneela Malik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Large Scale ◽  
Association Studies ◽  
Web Based ◽  
Stroke Treatment ◽  
Automated Algorithm ◽  
Genome Association ◽  
Whole Genome Association ◽  
Toast Classification ◽  
User Friendly

Background: The Stroke Genetics Network (SiGN) funded by the NINDS aims to identify genetic risk factors in ischemic stroke using whole-genome association studies (GWAS). High quality phenotyping is crucial to successful application of GWAS. As a heterogenous disorder, stroke poses specific challenges. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification is a broadly used, but its validity is challenged especially when performed by multiple investigators with differing interpretations of the system. The Causative Classification System for Ischemic Stroke (CCS) system is a new, web-based, and computerized algorithm that integrates clinical, diagnostic, and etiologic stroke characteristics in an evidence-based manner ( ccs.mgh.harvard.edu ) to generate subtypes. Methods: In planning the SiGN proposal, a sample of 20 coded charts were collected from a subset of participating studies to assess feasibility of central adjudication and comparability to study-specific TOAST. Two central adjudicators reviewed all records and generated TOAST and CCS subtypes. These were compared to study-specific TOAST subtype and the CCS phenotype generated for SiGN by local trained adjudicators. CCS data is now available for 7134 included cases using both a 5 and a 7 category system as defined in the table . Results: All 4 phenotypes were available for 115 ischemic stroke cases from 6 studies in SiGN. Basic demographics were 54% women, 63% white, and median age between 65-74. Table 1 provides the agreement between the various subtypes. Table 2 describes the types of disagreement. Conclusions: Central adjudication with only two adjudicators and curated medical records yielded more consistent subtyping independent of phenotyping system. The agreement for TOAST was higher than published rates by independent groups (∼0.50). In contrast, the agreement for CCS was lower than previously published (0.85-0.95). Site adjudicators' familiarity with TOAST and inexperience with CCS may contribute. Although CCS is an automated algorithm and has a number of user friendly features, our findings suggest that formal training and certification process before starting to use CCS may be worthwhile to achieve optimal benefit from the system.

scholarly journals TOAST Subtypes of Ischemic Stroke and Its Risk Factors: A Hospital-Based Study at Cipto Mangunkusumo Hospital, Indonesia

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Salim Harris ◽  
Saleha Sungkar ◽  
Al Rasyid ◽  
Mohammad Kurniawan ◽  
Taufik Mesiano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Significant Risk ◽  
Large Artery ◽  
Stroke Risk Factor ◽  
Stroke Subtypes ◽  
Undetermined Etiology ◽  
Toast Classification

Background and Purpose. Stroke is a leading cause of death and disability, with ischemic stroke as the highest prevalent cases in Indonesia. Ischemic stroke can be classified further into five subtypes according to TOAST classification. Numerous studies have revealed that stroke risk factor has variable correlation with different stroke subtype. Currently, there is no data regarding this phenomenon in Indonesia. The aim of study is to identify characteristic of ischemic stroke subtypes and the risk factors in TOAST classification. Methods. A retrospective, cross-sectional study of patients diagnosed with ischemic stroke at Cipto Mangunkusumo Hospital from January till December 2016. Demographic data, ischemic stroke subtypes, risk factors, and other relevant data were documented. Bivariate and multivariate analysis was done using SPSS 23. Results. 235 recorded data patients were included. Large artery atherosclerosis (LAA) was the most prevalent stroke subtypes at 59,6%, followed with small vessel disease (SVD) at 26,7%, undetermined etiology at 9,8%, cardioembolism (CE) at 2,1%, and other determined etiology at 0,9%. Hypertension was the most common vascular risk factor. However, it was only significant in SVD (p=0,023) and undetermined etiology subtypes (p<0,001). Significant risk factor in LAA was diabetes (55%; p=0,016) while in CE subtypes was atrial fibrillation (60%;p<0,001). In multivariate analyses, hypertension (OR 3; 95% CI 1,12-8,05) was the only variable that was related to SVD while in CE it was atrial fibrillation (OR 113,5; 95% CI 13,6-946,5). Conclusion. LAA was the most common stroke ischemic subtypes. Associated risk factor in LAA was diabetes while in SVD and undetermined etiology subtypes it was hypertension. Atrial fibrillation was associated with cardioembolism.

Comparison of acute ischemic stroke evaluation and the etiologic subtypes between university and nonuniversity hospitals in Isfahan, Iran

2019 ◽  
Vol 14 (6) ◽  
pp. 613-619 ◽  
Author(s):  
Fariborz Khorvash ◽  
Mabobeh Khalili ◽  
Roya Rezvani Habibabadi ◽  
Nizal Sarafzadegan ◽  
Mahshid Givi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
University Hospital ◽  
Large Artery ◽  
University Hospitals ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
Hospital Patients ◽  
Degree Of Disability ◽  
One Year ◽  
Undetermined Etiology

Background and purpose Performing a proper causative workup for ischemic stroke patients is essential as it guides the direction of primary and secondary preventions. We aim to investigate the etiological evaluation of these patients in university and nonuniversity hospitals. Method We enrolled subjects from the Persian Registry of Cardiovascular Disease–stroke. Stroke patients were categorized base on an etiological-based classification (Trial of Org 10172 in Acute Stroke Treatment or TOAST) into five groups. We also separated patients with ischemic stroke of undetermined etiology due to incomplete standard evaluation from ischemic stroke of undetermined etiology due to negative standard evaluation. The etiological subtypes and diagnostic evaluations were compared between the two hospital groups. Result Ischemic stroke of undetermined etiology was the most common subtype overall (43%). The prevalence of ischemic stroke of undetermined etiology (incomplete standard evaluation) was significantly higher in patients evaluated in nonuniversity hospitals versus university hospital (46.2% vs. 22.3%). Patients with ischemic stroke of undetermined etiology (negative standard evaluation) and large-artery atherosclerosis were significantly more prevalent in university hospitals (10.3% vs. 4.6% and 13.9% vs. 4.4%, respectively). All diagnostic workups were performed more significantly for university hospital patients. Patients with Ischemic stroke of undetermined etiology (negative standard evaluation). Patients were significantly younger (64.91 ± 14.44 vs. 71.42 ± 12.93) and had lower prevalence of risk factors such as hypertension (48.5% vs. 65.4%) and diabetes (19.4% vs. 33.1%) than patients in ischemic stroke of undetermined etiology (incomplete standard evaluation) subgroup. University hospital patients had better clinical outcomes in terms of mortality and degree of disability during one-year follow-up. Conclusion The high clinical burden of ischemic stroke of undetermined etiology especially in nonuniversity hospitals shows the rational for promoting ischemic stroke evaluation and providing specialized stroke centers for these hospitals in a developing country like Iran.

FIP1L1/PDGFRα synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2500-2507 ◽  
Author(s):  
Yoshiyuki Yamada ◽  
Abel Sanchez-Aguilera ◽  
Eric B. Brandt ◽  
Melissa McBride ◽  
Nabeel J. H. Al-Moamen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fusion Gene ◽  
Systemic Mastocytosis ◽  
Hypereosinophilic Syndrome ◽  
Growth Factor Receptor ◽  
Hematopoietic Stem ◽  
Chronic Eosinophilic Leukemia ◽  
Factor Receptor Alpha

Abstract Expression of the fusion gene FIP1-like 1/platelet-derived growth factor receptor alpha (FIP1L1/PDGFRα, F/P) and dysregulated c-kit tyrosine kinase activity are associated with systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES). We analyzed SM development and pathogenesis in a murine CEL model induced by F/P in hematopoietic stem cells and progenitors (HSCs/Ps) and T-cell overexpression of IL-5 (F/P-positive CEL mice). These mice had more mast cell (MC) infiltration in the bone marrow (BM), spleen, skin, and small intestine than control mice that received a transplant of IL-5 transgenic HSCs/Ps. Moreover, intestinal MC infiltration induced by F/P expression was severely diminished, but not abolished, in mice injected with neutralizing anti–c-kit antibody, suggesting that endogenous stem cell factor (SCF)/c-kit interaction synergizes with F/P expression to induce SM. F/P-expressing BM HSCs/Ps showed proliferation and MC differentiation in vitro in the absence of cytokines. SCF stimulated greater migration of F/P-expressing MCs than mock vector–transduced MCs. F/P-expressing bone marrow–derived mast cells (BMMCs) survived longer than mock vector control BMMCs in cytokine-deprived conditions. The increased proliferation and survival correlated with increased SCF-induced Akt activation. In summary, F/P synergistically promotes MC development, activation, and survival in vivo and in vitro in response to SCF.

Abstract TP375: Using Characteristics of Secondary Ischemic Stroke Events to Improve Stroke Education Initiatives

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Amanda Dirickson ◽  
Suzanne Stone
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Small Vessel Disease ◽  
Secondary Stroke Prevention ◽  
Stroke Treatment ◽  
Vessel Disease ◽  
Acute Stroke Treatment ◽  
Stroke Education ◽  
Toast Classification

Purpose: While it is common practice for nursing to perform the duty of stroke education,it is not common to use secondary stroke event data to determine what aspect of stroke education should be emphasized for the greatest impact on secondary stroke prevention. The purpose of this descriptive study is to exam the characteristics of secondary stroke events using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria so future educational initiatives can be customized to the needs of the local high risk population. Methods: The team collected data characteristics on all ischemic stroke admissions with previous admitting diagnosis of acute ischemic stroke. The strokes were further characterized using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification to determine any emerging patterns of both risk factors and etiological types. Conclusions: A total of n=51 admissions were previous adult stroke survivors, (M=30, F=21). Pre-morbid risk factors were as follows: hypertension=78%, type 2 diabetes=39%, hyperlipidemia =54%, smoking=8%, atrial fibrillation=24%. TOAST classification results: Large Vessel Atherosclerosis=14%, Cardioembolic =17%, Small Vessel Disease=3%, Other Known Cause=2%, Cryptogenic=15%. Summary: The results reveal a striking pattern of the presence of premorbid hypertension. While the TOAST classification did not have a single dominant type, but nearly equal distribution of large vessel atherosclerosis, cardioembolic, and small vessel disease etiologies. Not surprising, the decline in stroke mortality is felt to be due to improved blood pressure control, but in discharge stroke education, hypertension is not necessarily emphasized over other perhaps less impactful risk factors. Yet, the most recent acute ischemic stroke clinical guidelines gave providers a first-time recommendation to start or restart antihypertensive therapy in stable patients with BP > 140/90. Nursing has enough encouragement to take the lead on hypertension prevention education in appropriate stable patients ready for discharge. The next goal will be to develop a multimedia educational effort in patient stroke education on hypertension as a risk factor for secondary stroke prevention in this Comprehensive Stroke Center.

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