The easy-to-use max-ICH score is a reliable tool to predict unfavorable long-term (12-month) functional outcome and death after intracerebral hemorrhage in the Chinese population.

Background and purposeThe Trial of Org 10 172 in Acute Stroke Treatment (TOAST) system is the most widely used aetiological categorisation system in clinical practice and research. Limited studies have validated the accuracy of routine aetiological diagnosis of patients with ischaemic stroke according to the TOAST criteria when the reported subtype is assumed to be correct. We investigated the agreement between centralised and non-centralised (site-reported, at discharge) stroke subtypes in the Third China National Stroke Registry (CNSR-III), and analysed the influence of classification consistency on evaluation during hospitalisation and for secondary prevention strategy.MethodsAll patients with ischaemic stroke from the CNSR-III study with complete diffusion-weighted imaging data were included. We used multivariable Cox proportional-hazard regression models to evaluate the factors associated with consistency between centralised and non-centralised stroke subtypes. Sensitivity analyses were conducted of the subgroup of patients with complete information.ResultsThis study included 12 180 patients (mean age, 62.3 years; and women, 31.4%). Agreement between centralised and non-centralised subtype was the highest for the large-artery atherosclerosis subtype stroke (77.4% of centralised patients), followed by the small-vessel occlusion subtype (40.6% of centralised patients). Agreements for cardioembolism and stroke of other determined aetiology subtypes were 38.7% and 12.2%, respectively. Patient-level and hospital-level factors were associated with the inconsistency between centralised/non-centralised aetiological subtyping. This inconsistency was related to differences in secondary prevention strategies. Only 15.3% of the newly diagnosed patients with cardioembolism underwent centralised subtyping with indications to receive oral anticoagulants at discharge. In comparison, 51.3% of the consistent cardioembolism group and 42.0% of the centrally reassigned cardioembolism group with anticoagulation indications were prescribed oral anticoagulants.ConclusionsSubstantial inconsistency exists between centralised and non-centralised subtyping in China. Inaccurate aetiological subtyping could lead to inadequate secondary prevention, especially in patients with cardioembolic stroke.

BackgroundMendelian stroke causes nearly 7% of ischaemic strokes and is also an important aetiology of cryptogenic stroke. Identifying the genetic abnormalities in Mendelian strokes is important as it would facilitate therapeutic management and genetic counselling. Next-generation sequencing makes large-scale sequencing and genetic testing possible.MethodsA systematic literature search was conducted to identify causal genes of Mendelian strokes, which were used to construct a hybridization-based gene capture panel. Genetic variants for target genes were detected using Illumina HiSeq X10 and the Novaseq platform. The sensitivity and specificity were evaluated by comparing the results with Sanger sequencing.Results53 suspected patients of Mendelian strokes were analysed using the panel of 181 causal genes. According to the American College of Medical Genetics and Genomics standard, 16 likely pathogenic/variants of uncertain significance genetic variants were identified. Diagnostic testing was conducted by comparing the consistency between the results of panel and Sanger sequencing. Both the sensitivity and specificity were 100% for the panel.ConclusionThis panel provides an economical, time-saving and labour-saving method to detect causal mutations of Mendelian strokes.

Background and Purpose: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687]) but not in the high-risk group ( P >0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.

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Background and purposePrevious studies have reported conflicting results as to whether women have poorer functional outcome than men after thrombolytic therapy. This study aims to investigate the relationship between sex differences and the prognosis of intravenous thrombolysis in Chinese patients with acute ischaemic stroke.MethodsThe patients enrolled in this study were from the Chinese Acute Ischemic Stroke Thrombolysis Monitoring and Registration study. The primary outcome was poor functional outcome, defined as a 3-month modified Rankin score of 3–6. The safe outcome was symptomatic intracranial haemorrhage (SICH) and mortality within 7 days and 90 days. Multiple Cox regression model was used to correct the potential covariates to evaluate the association between sex disparities and prognosis. Furthermore, the interaction of preonset Rankin scores, baseline National Institute of Health Stroke Scale (NIHSS) scores and Trial of Org 10172 in Acute Stroke Treatment (TOAST) types was statistically analysed.ResultsA total of 1440 patients were recruited, including 541 women and 899 men. The baseline information indicated that women were older at the time of onset (66.2±11.2 years vs 61.0±11.3 years, p<0.001), and more likely to have a history of atrial fibrillation (25.3% vs 11.2%, p<0.001), and had a higher NIHSS score on admission (12.3±6.8 vs 11.6±6.7, p=0.04). According to the prognosis analysis of unsatisfactory functional recovery, there was no significant difference between women and men (45.9% vs 37.1%; adjusted OR 1.01, 95% CI 0.75 to 1.37). As for the safe outcome, the proportion of SICH and mortality in women is relatively high but did not reach statistical significance. There was no significant interaction with sex, age, preonset Rankin score, NIHSS score, TOAST classification and the prognosis of intravenous thrombolysis.ConclusionsFor Chinese patients with ischaemic stroke, although women are older and more severe at the time of onset, the prognosis after intravenous thrombolysis is not significantly different from men.

Familial cerebral cavernous malformation (FCCM) is a vascular malformation disorder that closely associated with three identified genes: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Here, we present a Chinese family affected by FCCM due to a novel KRIT1/CCM1 insertion mutation. The proband was hospitalized for sudden unconsciousness and underwent surgical treatment. The section of lesions showed classical cavernous-dilated vessels without intervening brain parenchyma, and hemosiderin-laden macrophages were accumulated in the surrounding tissue. In addition, magnetic resonance imaging (MRI) showed severe multiple cerebral cavernous malformation (CCM) lesions in cerebrum, brainstem, and cerebellum in other affected subjects. Especially, for the proband's mother, hundreds of lesions were presented, and a few lesions were found in the expanded lateral ventricle (Evans' index =0.33). Moreover, she showed the similar symptoms of hydrocephalus, including headache, dizziness, and diplopia. It was extremely rare in previous reports. To date, the genetic alterations leading to FCCM in Chinese population remain largely unknown. We investigated genetic defects of this family. Sequence analyses disclosed a novel heterozygous insertion mutation (c.1896_1897insT; p.Pro633SerfsTer22) in KRIT1/CCM1. Moreover, our real-time PCR results revealed that the mRNA level of KRIT1/CCM1 were significantly decreased in FCCM subjects (CCM family =0.42 ± 0.20 vs. healthy control =1.01 ± 0.16, P = 0.004). It indicated that this mutation could cause KRIT1/CCM1 functional mRNA deficiency. It may be closely related with the pathogenesis of FCCM. Our findings provided a new gene mutation profile which will be of great significance in early diagnosis and appropriate clinical surveillance of FCCM patients.

Background and purposeTransient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.MethodsClinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or <50% ICAS and no ECAS; ≥50% ICAS but no ECAS; no or <50% ICAS with ECAS; and concurrent ≥50% ICAS and ECAS. Using multivariable Cox regression models, we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA, TSI and DWI-negative AIS.ResultsA total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).ConclusionsConcurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.