Interpretable CNN for ischemic stroke subtype classification with active model adaptation

Background TOAST subtype classification is important for diagnosis and research of ischemic stroke. Limited by experience of neurologist and time-consuming manual adjudication, it is a big challenge to finish TOAST classification effectively. We propose a novel active deep learning architecture to classify TOAST. Methods To simulate the diagnosis process of neurologists, we drop the valueless features by XGB algorithm and rank the remaining ones. Utilizing active learning framework, we propose a novel causal CNN, in which it combines with a mixed active selection criterion to optimize the uncertainty of samples adaptively. Meanwhile, KL-focal loss derived from the enhancement of Focal loss by KL regularization is introduced to accelerate the iterative fine-tuning of the model. Results To evaluate the proposed method, we construct a dataset which consists of totally 2310 patients. In a series of sequential experiments, we verify the effectiveness of each contribution by different evaluation metrics. Experimental results show that the proposed method achieves competitive results on each evaluation metric. In this task, the improvement of AUC is the most obvious, reaching 77.4. Conclusions We construct a backbone causal CNN to simulate the neurologist process of that could enhance the internal interpretability. The research on clinical data also indicates the potential application value of this model in stroke medicine. Future work we would consider various data types and more comprehensive patient types to achieve fully automated subtype classification.

Prevalence of the Frank’s sign by aetiopathogenic stroke subtype: A prospective analysis

Background and purpose The Frank’s sign is a diagonal earlobe crease running from the tragus to the edge of the auricle at an angle of 45°. Many studies have associated this sign with coronary artery disease and some with cerebrovascular disease. The objective of this study was to analyse the prevalence of the Frank’s sign in patients suffering from acute stroke with a particular focus on its prevalence in each of the five aetiopathogenic stroke subtypes. Special interest is given to embolic stroke of undetermined source (ESUS), correlating the sign with clinical and radiological markers that support an underlying causal profile in this subgroup. Methods Cross-sectional descriptive study including 124 patients admitted consecutively to a stroke unit after suffering an acute stroke. The Frank’s sign was evaluated by the same blinded member of the research team from photographs taken of the patients. The stroke subtype was classified following SSS-TOAST criteria and the aetiological study was performed following the ESO guidelines. Results The Frank’s sign was present in 75 patients and was more prevalent in patients with an ischaemic stroke in comparison with haemorrhagic stroke (63.9 vs. 37.5, p<0.05). A similar prevalence was found in the different ischaemic stroke subtypes. The Frank’s sign was significantly associated with age, particularly in patients older than 70 who had vascular risk factors. Atherosclerotic plaques found in carotid ultrasonography were significantly more frequent in patients with the Frank’s sign (63.6%, p<0.05). Analysing the ESUS, we also found an association with age and a higher prevalence of the Frank’s sign in patients with vascular risk factors and a tendency to a high prevalence of atherosclerosis markers. Conclusion The Frank’s sign is prevalent in all aetiopathogenic ischaemic stroke subtypes, including ESUS, where it could be helpful in suspecting the underlying cardioembolic or atherothrombotic origin and guiding the investigation of atherosclerosis in patients with ESUS and the Frank’s sign.

Stroke subtype-dependent synapse elimination by reactive gliosis in mice

The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.

P.076 Hypertensive disorders in pregnancy are strongly associated with future stroke and hypertension: A systematic review and meta-analysis

Background: We aimed to evaluate the association between hypertensive disorders in pregnancy (HDP) and future risk of stroke, stroke death, and hypertension. Methods: Systematic searches were performed in MEDLINE and EMBASE up to April 27th, 2020. Exposure of interest included the different types of HDP. Outcomes of interest included hypertension incidence, stroke incidence, stroke subtype, and stroke mortality. Results: Eighteen cohort and 1 case-control studies involving >10 million women were included in the meta-analysis. Pooled hazard ratios with 95% confidence interval generally adjusted for age at delivery, ethnicity, and vascular risk factors are listed in table 1. Conclusions: Increasing severities of HDP carry higher hazards of hypertension and stroke years later. HDP, including gestational hypertension alone, are also associated with future stroke mortality.

Ischemic Stroke Subtypes: Socio-demographic Factors, Risk Factors, and Outcomes in Southern Sri Lanka

Background: Stroke is a heterogeneous, catastrophic disease. A comprehensive clinical analysis of ischemic stroke (IS) risk factors and outcomes is crucial for optimum management in resource-poor settings.Methods: A prospective cross-sectional study of acute cerebrovascular disease (ACVD) involving 592 patients was con­ducted in a tertiary care center in Sri Lanka from November 2018 to May 2019. We aimed to describe the ACVD subtypes and the relationship of IS subtypes and subtype-categories (as defined by the Oxfordshire Community Stroke Project clinical clas­sification) with risk factors, severity, and outcome.Results: The majority (63.3%) had IS. Partial anterior circulation syndromes (PACS), total anterior circulation syndrome (TACS), posterior circulation syndromes (POCS), and lacunar syndromes (LACS) accounted for 102 (29.7%), 58 (16.9%), 88 (25.7%) and 95 (27.7%) of the cases, respectively. The most common PACS sub-category was higher-cerebral-dysfunction-with-homonymous-hemianopia (HCD+HH,39 cases;38.2%). Cerebellar-signs-without-long-tract-signs (CS-LTS) sub-category constituted the highest among POCS (47 cases; 53.4%). The leading sub-category within LACS was pure-motor (PM) strokes (43 cases; 45.3%).Patients aged ≥50 years (adjusted-OR [AOR]2.439; 95%CI,1.163-5.116;P=.018), IHD(AOR 2.520; 95%CI,1.347-4.713; P=.004) and BMI>23kg/m2(AOR 2.607; 95% CI,1.420-4.784; P=.002) were 2.5 times more likely to associate with TACS. Patients with a history of TIA (AOR 1.910; 95%CI,1.036-3.524; P=.038) and arrhyth­mias (AOR 5.933; 95%CI,3.294-10.684; P<.001) were 1.9 and 5.9 times more likely to be associated with POCS respectively. Those with hypertension were 2.3 times more likely to associate with LACS (AOR 2.233; 95%CI,1.270-3.926; P=.005).NIHSS(P<.001), mRS on admission (P=.001) and in 3 months (P<.001), deaths during hospital stay (P=.003) and within 28 days (P<.001) had a stronger relationship with individual stroke subtypes.Conclusion: The comparative risk of different IS subtypes depends on differ­ent risk factors. The findings of this study demonstrate that sub-categories within each stroke subtype may behave independently with regard to risk factors and outcomes, thus warranting the need for individual assessment. Ethn Dis. 2021;31(4):509-518; doi:10.18865/ed.31.4.509

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke

Background and Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02072681.

Women and Stroke: Different, yet Similar

<b><i>Background:</i></b> The impact of gender on acute ischemic stroke, in terms of presentation, severity, etiology, and outcome, is increasingly getting recognized. Here, we analyzed the gender-related differences in etiology and outcome of ischemic stroke in South India. <b><i>Methods:</i></b> Patients with first ever ischemic stroke within 1 week of onset presenting to the Comprehensive Stroke Care Centre, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India, were included in our study. Clinical and risk factor profile was documented. The stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) at onset, and stroke subtype classification was done using Trial of Org 10172 in Acute Ischemic Stroke criteria. The 3-month functional outcome was assessed using the modified Rankin Scale (mRS) with excellent outcome defined as an mRS ≤2. <b><i>Results:</i></b> Of the 742 patients, 250 (33.7%) were females. The age, clinical profile, and rate of reperfusion therapies did not differ between the genders. Women suffered more severe strokes (mean NIHSS 9.5 vs. 8.4, <i>p</i> = 0.03). While large artery atherosclerosis was more common in men (21.3% vs. 14.8%, <i>p</i> = 0.03), cardioembolic strokes secondary to rheumatic heart disease were more common in women (27.2% vs. 19.7%, <i>p</i> = 0.02). Men had a better 3-month functional outcome compared to women (68.6% vs. 61.2%, <i>p</i> = 0.04), but was not statistically significant after adjusting for confounders. <b><i>Conclusion:</i></b> Our data, from a single comprehensive stroke unit from South India, suggest that stroke in women are different, yet similar in many ways to men. Guideline-based treatment can result in comparable short-term outcomes, irrespective of admission stroke severity.

Association of Prestroke Glycemic Control With Vascular Events During 1-Year Follow-up

ObjectiveWe evaluated the association between admission HbA1c and subsequent risk of composite vascular events, including stroke, myocardial infarction, and vascular death, in patients with acute ischemic stroke and diabetes.MethodsPatients who had a transient ischemic attack or an acute ischemic stroke within 7 days of symptom onset, and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, myocardial infarction (MI), and vascular death, during one-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models.ResultsOf the 18567 patients, 1437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%–7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of the HbA1c associated with minimal risks for composite vascular events was the lowest for the small vessel occlusion subtype (6.6, [95% confidence internal [CI], 6.3–6.9]), compared to the large artery atherosclerosis (7.3 [95% CI, 6.8–7.9]) or the cardioembolic subtype (7.4[95% CI, 6.3–8.5]).ConclusionIn patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of the admission HbA1c was below 6.8%–7.0%, and were different according to the ischemic stroke subtype.

Low Diastolic Blood Pressure Predicts Good Clinical Outcome in Patients With Cerebral Venous Thrombosis

Background: Cerebral venous thrombosis (CVT) refers to a stroke subtype characterized by the disturbance of cerebral venous outflow caused by venous thrombosis. Previous studies have reported a range of factors that predict the prognosis of CVT. This study is aimed to find out whether systolic blood pressure (SBP) and diastolic blood pressure (DBP) are suitable as potential indicators of the severity and clinical outcome in CVT patients.Methods: The CVT patients admitted to Xuanwu Hospital from January 2014 to December 2019 were enrolled. The severity of CVT was assessed by the National Institute of Health Stroke Scale (NIHSS) and intracranial pressure (ICP) at the time of admission. The modified Rankin score (mRS) was assessed at 6 months of follow-up.Results: One hundred fifty-six CVT patients were enrolled with a mean age of 35.8 ± 12.8 years. A percentage of 55.8% of the CVT patients recruited were female, and 17.3% were either pregnant or in perinatal period. Headache was the most common symptom. SBP and DBP were not correlated with NIHSS at admission. Furthermore, SBP and DBP had no impact on the disturbance of consciousness, epilepsy, intracranial hemorrhage, and mental disorders. However, SBP and DBP were positively correlated with ICP at admission. SBP &gt; 129.5 mmHg and/or DBP &gt; 77.5 mmHg suggested the presence of intracranial hypertension (IH). Based on current results, SBP was not correlated with mRS at 6 months of follow-up. However, DBP was found to be positively correlated with mRS at 6 months of follow-up. DBP in CVT patients with good prognosis was significantly lower than in those with poor prognosis. DBP &gt; 79.5 mmHg was identified as a cutoff value to predict a poor clinical outcome. A higher mRS and a higher rate of poor clinical outcome were found in CVT patients with SBP &gt; 146 mmHg or DBP &gt; 79.5 mmHg compared to those with SBP ≤ 146 mmHg or DBP ≤ 79.5 mmHg.Conclusion: SBP &gt; 129.5 mmHg and DBP &gt; 77.5 mmHg suggested the presence of IH in CVT patients. DBP &gt; 79.5 mmHg predicted a poor clinical outcome.

Medical Costs of Stroke Care Between Women With and Without Dysmenorrhea: A Population-Based Comparison

Objective: This study investigated the medical care costs of stroke type between age-matched cohorts with and without dysmenorrhea using the National Health Insurance Research Database (NHIRD).Methods: We collected all 66,048 women with dysmenorrhea and 66,048 women without dysmenorrhea whose age (15-44-year-old) and index year (from 1997 to 2013) were matched for comparison. We assessed the incidence and compared the risk of stroke and stroke subtype in two cohorts. The proportional distributions of stroke subtypes by age between the two cohorts were compared among the women with stroke, and their hospitalization rate was also estimated. In addition, medical cost, length of stay, and the medical cost within 30 days after stroke were compared between the two cohorts.Results: The stroke risk in dysmenorrhea was greater than comparisons (HR = 1.26, 95% CI = 1.11–1.42). Proportionally, hemorrhagic stroke (HS) significantly decreased with age in both cohorts, whereas ischemic stroke (IS) significantly increased with age when both cohorts were combined. The dysmenorrhea cohort had a higher portion of transient cerebral ischemia (TIA) stroke than comparisons (31.3 vs. 24.2%, p = 0.01) and a lower risk of hospitalization for IS (OR = 0.48, 95% CI = 0.21–0.69). Among the four-stroke subtypes, the cost of care for TIA was the least (US$157 ± 254). The average cost for stroke care was not significantly different between women with and without dysmenorrhea.Conclusion: The hospitalization rate and medical costs of TIA are lower than other types. All women should prevent and treat TIA as soon as possible to avoid recurrence or progression to major stroke events and reduce medical costs, regardless of whether they have dysmenorrhea.