Cerebral microbleeds in CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.     

Brain hemorrhage on 24h-CT and functional outcome in stroke patients with cerebral amyloid angiopathy features on pre-thrombolysis MRI treated with intravenous thrombolysis: A case series

Background and objectivesIn stroke patients treated with intravenous thrombolysis (IVT), presence and high number of strictly lobar cerebral microbleeds (compatible with cerebral amyloid angiopathy, CAA) seems to be associated with increased risk of hemorrhagic transformation, symptomatic hemorrhagic transformation, remote hemorrhage, and poor functional outcome. Some of these CAA patients with cerebral microbleeds also have chronic lobar intracerebral hemorrhage. Few data are available on IVT-treated CAA patients showing cortical superficial siderosis. There are no reports studying factors associated with brain hemorrhagic complication or functional outcome in IVT-treated CAA patients. We present a case series study of IVT-treated stroke patients with CAA features on pre-IVT MRI in whom we have evaluated brain hemorrhagic complications on 24 h-CT and functional outcome after IVT.Material and methodsIn our stroke center, IVT decision in patients with CAA MRI features is at the physician's discretion. We retrospectively screened our stroke database between January 2015 and July 2022 for pre-IVT imaging of 959 consecutive IVT-treated stroke patients without ongoing anticoagulation therapy for probable CAA MRI features defined by modified Boston criteria. After exclusion of 119 patients with missing MRI (n = 47), MRI showing motion artefacts (n = 49) or with alternative chronic brain hemorrhage cause on MRI (n = 23), 15 IVT-treated patients with probable CAA on pre-IVT MRI were identified. In these 15 patients, clinical, biological and MRI characteristics were compared between patients with vs. without post-IVT hemorrhage and between patients with poor (MRS 3–6) vs. good (MRS 0-2) functional outcome at discharge.ResultsTwo patients showed brain hemorrhage on 24 h-CT and both died after 40 and 31 days respectively. The remaining patients had no brain hemorrhage and showed very good outcome except one. Atrial fibrillation (p = 0.029) and Fazekas scale (p = 0.029) were associated with brain hemorrhage whereas atrial fibrillation (p = 0.0022), NIHSS (p = 0.027), blood glucose level (p = 0.024), CRP (p = 0.022) and DWI ASPECT (p = 0.016) were associated with poor outcome.DiscussionConsequences of IVT in CAA patients can be dramatic. Larger studies are needed to compare IVT risks and outcome between CAA and non-CAA patients, also including CAA patients with chronic intracerebral hemorrhage or cortical superficial siderosis. In addition, future studies should try to identify clinical, biological and radiological features at high risk for brain hemorrhage and poor outcome in order to assess the risk-benefit ratio for IVT in CAA.Clinical trial registration-URL:http://www.clinicaltrials.gov. Unique identifier: NCT05565144     

Pharmacotherapy for Patients with Atrial Fibrillation and Cerebral Microbleeds

Background: Patients with cerebral microbleeds have increased risk of intracranial hemorrhage and ischemic stroke. No trial specifically informs antithrombotic therapy for patients with cerebral microbleeds and atrial fibrillation. We investigated the safety of anticoagulation versus no anticoagulation with regard to cerebrovascular outcomes and mortality. Methods: All consecutive atrial fibrillation patients from 2015 to 2018 with MRI evidence of ≥1 cerebral microbleed at time of imaging were reviewed. Patients were treated with warfarin, direct oral anticoagulants, or neither. Primary outcome was all-cause mortality informed by National Death Registry and the composite of ischemic and hemorrhagic stroke. All statistical tests were 2-sided and significant at P < .05. Results: The median interval from patient identification until the end of electronic health record surveillance was 9.93 months (interquartile range, 2.83-19.17 months). We identified 308 atrial fibrillation patients with cerebral microbleeds; 128(41.6%) were on warfarin, 88(28.6%) on direct oral anticoagulants, and 92(29.9%) on neither. Over the surveillance interval, 87 deaths, 51 ischemic strokes, and 14 hemorrhagic strokes occurred. The estimated likelihoods of the composite stroke outcome and ischemic stroke only did not differ significantly among the 3 groups. However, patients taking direct oral anticoagulants had a significantly smaller likelihood of all-cause mortality than patients who were not anticoagulated (adjusted hazard ratio: .44[.23, .83], P=.012). Conclusions: In patients with coprevalent atrial fibrillation and cerebral microbleeds, we did not detect differences in subsequent ischemic stroke, hemorrhagic stroke, or both, comparing warfarin, direct oral anticoagulants, or neither. Patients treated with direct oral anticoagulants had better survival than nonanticoagulated patients.     

Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds

Abstract Background   Retrospective studies suggested that cerebral microbleeds (MB) on magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH). Objective   To compare the benefit of anti-thrombotic agents in stroke prevention (absolute risk reduction 2.49 –6 %) versus risk of ICH in ischaemic stroke patients with MB. Materials and methods   We prospectively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on MRI were documented. Primary end points were subsequent ICH, recurrent cerebral infarct (CI) and mortality. Results   A total of 908 patients were recruited. MB were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 ± 15.4 months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 % (no MB), 1.9 % (1 MB), 4.6 % (2–4 MB) and 7.6 % (≥ 5 MB) (p < 0.001). There was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and 3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and 15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did not increased with quantity of MB. Survival analyses showed that age, presence of MB, mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH. Conclusion   Risk and mortality of ICH increased with quantity of MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are still warranted. However, in patients with ≥ 5 MB, the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra precautions should be taken to minimize risk of ICH. Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings.     

Cerebral Small Vessel Diseases and Sleep Related Strokes

Background and Purpose: Sleep related Stroke (SRS) is common and has been associated with cerebral small vessel diseases (SVD) in ischemic strokes (ISs). We tested the hypothesis that SRS is associated with SVD in both ischemic and hemorrhagic stroke. Methods: Prospectively collected data from patients consecutively enrolled after intracerebral hemorrhage (ICH) related to SVD or after IS were analyzed. Symptom onset was recorded as SRS versus awake. Each ICH was grouped according to lobar and deep locations. The IS cohort was etiologically characterized based on the Causative Classification of Stroke system. Frequencies of SRS within and between ICH and IS cohorts as well as its associations (etiology, risk factors) were analyzed. Results: We analyzed 1812 IS (mean age 67.9 years ± 15.9 years, 46.4% female) and 1038 ICH patients (mean age 72.5 years ± 13.0 years, 45.4% female). SRS was significantly more common among SVD-related ICH patients (n = 276, 26.6%) when compared to all IS (n = 363, 20.0%, P < .001) and in both, small artery occlusion (SAO) related IS and lobar ICH within the respective IS and ICH cohorts (16.3% SRS versus 9.1% awake for SAO within all IS, P < .001; and 57.1% SRS versus 47.7% awake for lobar bleeds within all ICH, P = .008). These associations remained significant after controlling for age, sex and risk factors. Conclusions: SRS was associated with SVD. The SAO etiology and cerebral amyloid angiopathy related lobar ICH suggest that the presence of SVD can interact with sleep or arousal related hemodynamic changes to cause ischemic and hemorrhagic stroke.     

Joint Effects of GWAS SNPs in Coagulation System Confer Risk to Hypertensive Intracerebral Hemorrhage

Recent genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with coagulation system, including hemostatic factors and hematological phenotypes. However, few articles described the relationships between these SNPs and the risk of hemorrhagic stroke. The aim of our study was to evaluate the roles of these SNPs as risk factors and survival predictors for hemorrhagic stroke. Thirteen SNPs from GWAS in coagulation system were genotyped in a Chinese Han population including 1000 patients with hemorrhagic stroke (intracerebral hemorrhage, ICH = 743; subarachnoid hemorrhage, SAH = 257) and 1044 population-based controls. The associations between the genetics risk score (GRS) and risk of hemorrhagic stroke as well as post-stroke adverse outcomes were determined. No individual SNP was associated with the risk of hemorrhagic stroke. The GRS was calculated by summing the number of risk alleles of each SNP, and a total of 13 SNPs were included. Meanwhile, the GRS cutoffs values were defined to be close to quartiles or tertiles in control subjects. For quartiles, individuals with GRS about 8–9, 10–11, ≥12 had 1.28 (OR 1.28, 95% CI 0.98–1.68, p = 0.067)-, 1.36 (OR 1.36, 95% CI 1.04–1.79, p = 0.026)-, 1.53 (OR 1.53, 95% CI 1.13–2.07, p = 0.006)-fold increase in ICH risk compared to those with GRS ≤7, respectively; for tertiles, individuals with GRS about GRS 9–10, ≥11 had 0.98 (OR 0.98, 95% CI 0.78–1.23, p = 0.067)- and 1.26 (OR 1.26, 95% CI 1.00–1.59, p = 0.048)-fold increase in ICH risk compared to those with GRS ≤8, respectively. Further stratification analyses indicated that this association was only found in hypertensive ICH subjects. However, no statistical difference was found in the volume of hematoma, activities of daily living scale as well as hospital death in the ICH patients based on GRS values. Joint effects of SNPs associated with low coagulation factor levels might confer risk to ICH patients with hypertension. However, the clinical value on risk stratification and survival prediction was limited.     

磁敏感加权成像在脑出血中的应用价值

目的 探讨MRI磁敏感加权成像(SWI)在脑出血中的应用价值.方法 对12例经CT确诊的脑出血患者于发病2 d内及2周后分别进行MRI常规序列及SWI扫描,并进行血肿分期及对各序列的病灶显示率、微出血灶的分布和出血量评估.结果 在12例脑出血患者中,共发现33处出血灶.SWI、T,WI、T<,2>WI、Flair序列对...     

Intracranial hemorrhage

The initial and exclusive use of MRI in patients with a stroke syndrome is feasible, probably cost-effective, and even time saving when considering its potential wealth of information. MRI may be the diagnostic tool of choice in patients with all stages of stroke, especially in the hyperacute assessment of ICH, and could be equivalent to CT and CTA in SAH diagnosis. The authors’ aim is to provide a comprehensive review about the potential role of MRI in evaluating ICH and SAH. Emerging applications, such as the assessment of microbleeds as a risk factor for secondary hemorrhage after thrombolysis and perihemorrhagic ischemic changes as a potential marker for patients likely to benefit from hematoma evacuation, are reviewed.     

Prevalence and clinical characteristics of cortical superficial siderosis in patients with acute stroke

Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of hemosiderin deposition in subpial brain layers. However, cSS has not been fully studied in patients with acute stroke. Here, we investigated the prevalence of cSS in patients with acute stroke and analyzed the relationship between cSS and different clinical and neuroimaging characteristics. From September 2014 through June 2016, consecutive patients with acute stroke who were admitted to our department were retrospectively investigated. We analyzed the prevalence of cSS and the associations between cSS and risk factors, the topographic distribution of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs). In total, 739 patients (589 patients with ischemic stroke/transient ischemic stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4 years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P < 0.0001), WMLs (P = 0.0105), and lobar and non-lobar CMBs (both P < 0.0001); no associations between cSS and age, sex, cardiovascular risk factors, IS subtype classification, or antiplatelet and anticoagulant therapy were found. In a multivariable logistic regression analysis, high numbers of lobar CMBs (≥ 2; odds ratio, 11.03; 95% confidence interval, 2.03–205.40; P = 0.0029) were independently associated with cSS. Furthermore, cSS was often located near lobar CMBs. Our results suggest that cSS is prevalent in ICH and is independently associated with lobar CMBs; however, no associations between cSS and other risk factors or comorbidities were observed.     

The impact of cerebral microbleeds on intracerebral hemorrhage and poor functional outcome of acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis

It is still controversial whether pre-existing cerebral microbleeds (CMBs) increase the risks of intracranial hemorrhage (ICH) and poor functional outcome (PFO) in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Therefore, we performed a systematic review and meta-analysis to determine the impact of CMBs on ICH and PFO of AIS patients with IVT. We searched PubMed, EMBASE and Web of Science from inception to August 3, 2016, with language restriction in English. We included studies that reported the relationship between CMBs and ICH or PFO after thrombolysis. Two retrospective and nine prospective studies met inclusion criteria (total 2702 patients). The overall prevalence of CMBs on pre-IVT MRI scans was 24.0%. Pre-existing CMBs on MRI scans were not significantly associated with a higher risk of early sICH (OR 1.74; 95% CI 0.91–3.33; I ² = 44.5%). Subgroup analyses did not substantially influence these associations. The presence of CMBs was associated with the increased risk of 3-month PFO (OR 1.58; 95% CI 1.08–2.31; I ² = 54.2%), PH (OR 2.14; 95% CI 1.34–3.42; I ² = 11.0%) and any ICH (OR 1.42; 95% CI 1.04–1.95; I ² = 0.0%), respectively. This meta-analysis showed that CMBs presence was not significantly associated with the increased risk of early sICH after IVT. However, the results also demonstrated that CMBs presence increased the risks of 3-month PFO, PH and any ICH after IVT. Due to a small number of included studies and methodological limitations, the results of this meta-analysis should be interpreted cautiously. CMBs presence should not be a contraindication to IVT for AIS patients based on the existing evidence.     

Thrombolysis for ischemic stroke in patients with old microbleeds on pretreatment MRI

BACKGROUND: Old asymptomatic microbleeds (MBs) visualized on T2-weighted MRI are indicative of microangiopathy. They may be a marker of increased risk of intracerebral hemorrhage (ICH) following thrombolysis. However, data regarding this potential risk are limited. METHODS: A retrospective analysis of pretreatment T2-weighted MRI was performed in consecutive stroke patients who received intravenous tissue plasminogen activator (tPA). We aimed to assess the impact of MBs on the risk of cerebral bleeding. The frequency and location of MBs were assessed and compared with the location of ICH after thrombolysis. RESULTS: Forty-four patients were studied. MBs were present on pretreatment MRI in 8 cases (18.2%). At day 1, symptomatic ICH occurred in none of 8 patients with MBs versus 1 of 36 patients without (NS). At day 1, ICH occurred in 3 of 8 patients with MBs versus 10 of 36 patients without (NS). At day 7, symptomatic ICH occurred in 1 of 8 patients with MBs versus 2 of 36 patients without (NS). At day 7, ICH occurred in 5 of 8 patients with MBs versus 12 of 36 patients without (NS). No ICH occurred at the site of an MB. ICH occurred within the ischemic area in all patients who bled. CONCLUSIONS: Our study suggests that stroke patients with a small number of MBs on pretreatment MRI could be treated safely with thrombolysis. Larger prospective studies are needed to address the predictive value of detection of MBs with regard to the risk of tPA-induced ICH.     

Effect of antiplatelet therapy on the incidence,prognosis, and rebleeding of intracerebral hemorrhage

Objective

Antiplatelet medications are increasingly being used for primary and secondary prevention of ischemic attacks owing to the increasing prevalence of ischemic stroke occurrences. Currently, many patients receive antiplatelet therapy (APT) to prevent thromboembolic events. However, long-term use of APT might also lead to an increased occurrence of intracerebral hemorrhage (ICH) and affect the prognosis of patients with ICH. Furthermore, some research suggest that restarting APT for patients who have previously experienced ICH may result in rebleeding events. The precise relationship between APT and ICH remains unknown.

Methods

We searched PubMed for the most recent related literature and summarized the findings from various studies. The search terms included “antiplatelet,” “intracerebral hemorrhage,” “cerebral microbleeds,” “hematoma expansion,” “recurrent,” and “reinitiate.” Clinical studies involving human subjects were ultimately included and interpreted in this review, and animal studies were not discussed.

Results

When individuals are administered APT, the risk of thrombotic events should be weighted against the risk of bleeding. In general, for some patients’ concomitant with risk factors of thrombotic events, the advantages of antiplatelet medication may outweigh the inherent risk of rebleeding. However, the use of antiplatelet medications for other patients with a higher risk of bleeding should be carefully evaluated and closely monitored. In the future, a quantifiable system for assessing thrombotic risk and bleeding risk will be necessary. After evaluation, the appropriate time to restart APT for ICH patients should be determined to prevent underlying ischemic stroke events. According to the present study results and expert experience, most patients now restart APT at around 1 week following the onset of ICH. Nevertheless, the precise time to restart APT should be chosen on a case-by-case basis as per the patient's risk of embolic events and recurrent bleeding. More compelling evidence-based medicine evidence is needed in the future.

Conclusion

This review thoroughly discusses the relationship between APT and the development of ICH, the impact of APT on the course and prognosis of ICH patients, and the factors influencing the decision to restart APT after ICH. However, different studies' conclusions are inconsistent due to the differences in quality control. To support future clinical decisions, more large-scale randomized controlled trials are required.     

脑微出血与脑卒中

目的探讨脑微出血与脑卒中发生、发展的联系。方法卒中患者83例，分为脑缺血组（43例）和脑出血组（40例），以同期住院的50岁以上非脑卒中患者设立对照组（32例）。采用T2加权梯度回波MRI观察各病例脑微出血、卒中病灶、腔隙性梗塞以及白质疏松情况，同时记录卒中患者的高血压、糖尿病、高脂血症、卒中病史以及阿司匹林使用史。结果微出血在缺血组和出血组的发生率分别为34．9％、75．0％，对照组9．4％。各组微出血均最常见于基底节区。微出血与高血压、卒中病史相关（P〈0．01），与高脂血症、糖尿病病史及使用阿司匹林无关（P〉0．05）。微出血的严重程度与腔隙性梗塞、白质疏松的严重程度相关（P〈0．01）．．微出血在卒中病灶区域同侧或对侧分布无显著性差异（P〉0．05）。出血组微出血在卒中病灶区域的分布率明显高于缺血组。结论微出血与脑卒中．特别是与出血性脑卒中有密切关系，对卒中患者出血性转化具有预测意义。     

Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.     

Association between cerebral microbleeds and prior primary intracerebral hemorrhage in ischemic stroke patients

OBJECTIVE: To investigate association between cerebral microbleeds (CMB) and prior intracerebral hemorrhage (ICH) on MRI and topographic correlation of the two types of lesions. PATIENTS AND METHODS: Two hundred and sixty consecutive patients (67.0+/-11.1 years) with ischemic stroke were included. CMB and prior ICH were assessed on T2-gradient-echo MRI. The presence and number of CMB as predictors for prior ICH were examined. Topographic correlations between CMB and ICH lesions in patients with prior ICH in the infratentorial, basal ganglionic/thalamic and cortico-subcortical regions were tested. RESULTS: CMB were observed in 113 (43.5%) patients and a total of 50 prior primary ICH lesions were observed in 39 (15.0%) patients. Among the ICH lesions, 39 (78%) were asymptomatic. Presence of CMB (odds ratio 2.53, p=0.015) and number of CMB (odds ratio 1.11, p<0.001) were independent determinants for prior ICH. Topographic correlation between CMB and ICH was significant in the basal ganglionic/thalamic region (p=0.017), but not in the infratentorial (p=0.548) or cortico-subcortical regions (p=0.389). CONCLUSION: CMB were associated with prior ICH on MRI of patients with ischemic stroke. CMB in the basal ganglion or thalamus was associated with prior ICH in the same region.     

Silent microbleeds are associated with volume of primary intracerebral hemorrhage

The authors performed a correlative radiologic study on the micro-bleeds and volume of intracerebral hemorrhage in the supratentorial ICH patients. In the patients with lobar or putaminal hemorrhage, the hemorrhage volumes increased more than twofold or threefold in the patients with micro-bleeds. Moreover, the presence of microbleeds was an independent risk factor for large-sized hemorrhage. These data show that microbleeds may be associated with a larger ICH volume.     

Serum cystatin C and cerebral microbleeds in patients with acute cerebral stroke

Recent studies have shown that kidney dysfunction is associated with cerebral microbleeds (CMB). Cystatin C is a more useful measurement than creatinine-based estimating equations for evaluating kidney function. The purpose of this study was to clarify the relationship between cystatin C levels and CMB in patients with acute cerebral stroke. This cross-sectional study included a total of 485 patients with acute ischemic stroke and 129 patients with cerebral hemorrhage. The serum levels of cystatin C were significantly higher in acute cerebral stroke patients with CMB than in those without (p < 0.001). Multivariate logistic regression analyses showed that for each single standard deviation increase of cystatin C levels, there was a significant increase in the presence of CMB after adjusting for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction, and white matter hyperintensity in patients with acute stroke. The odds ratio (95% confidence interval) in patients with acute cerebral infarction and cerebral hemorrhage were 2.92 (1.81–6.93) and 2.98 (1.76–6.97), respectively. The present study suggests that elevated levels of cystatin C are associated with the presence of CMB in acute stroke patients, independent of conventional risk factors.     

R558C NOTCH3 Mutation in a CADASIL Patient with Intracerebral Hemorrhage: A Case Report with Literature Review

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease, which is characterized by migraine, recurrent ischemic strokes, psychiatric disorder, progressive cognitive decline, and occasionally intracerebral hemorrhage (ICH). ICH events have been reported in a high proportion of East Asian CADASIL patients with R544C mutation in exon 11 of NOTCH3; however, whether any other specific NOTCH3 mutation determines the ICH phenotype has yet to be explored.Case presentationWe report the case of a 60-year-old male CADASIL patient with a novel R558C mutation in exon 11 of the NOTCH3 gene, who presented with ICH in the basal ganglia and cerebellum. Brain imaging revealed multiple confluent white matter hyperintensities and abundant cerebral microbleeds (CMBs) in the bilateral basal ganglia, thalamus, and cerebellum. The patient had been having recurrent ischemic strokes prior to this ICH event, and had taken antiplatelet and antihypertensive agents for six months. We analyzed the possible reasons for ICH onset in the patient to recommend certain guidelines for the clinic.ConclusionsNovel R558C mutation-related CADASIL vasculopathy and numerous CMBs, uncontrolled hypertension, and antiplatelet therapy could collectively contribute to ICH onset in the patient with CADASIL. These findings suggest that a diagnosis of CADASIL should also be considered when patients present with ICH, whenever MRI imaging reveals typical white matter abnormalities. Furthermore, this case report emphasizes the importance of CMB assessment, appropriate blood pressure control, and cautious assessment of the risk-benefits of antiplatelet medication in patients with CADASIL.     

Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population

BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be associated with cerebral amyloid angiopathy (CAA). These studies were performed primarily on the North American population and investigated in partly selected patient cohorts. METHODS: 193 consecutive patients suffering from primary intracerebral hemorrhage (ICH) were included in our study. The localization of the ICH, i.e. cortico-subcortical, deep white matter, basal ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and vascular risk factors. In 101 of these patients, the APOE genotype was also correlated to the presence and distribution of microbleeds and other microangiopathy-related damage, as shown by magnetic resonance imaging (MRI). RESULTS: We found neither an association of a specific APOE genotype with ICH localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our study of an unselected Central European population, the APOE genotype was not confirmed as a candidate for providing additional diagnostic and potentially prognostic information in patients with ICH.     

Silent cerebral microbleeds on susceptibility-weighted imaging of patients with ischemic stroke and leukoaraiosis

Abstract

Objective: Cerebral microbleeds (CMBs) are an increasingly recognized in patients with cerebrovascular disease who undergo the new MRI techniques. Susceptibility-weighted MRI is sensitive to detect silent microbleeds which are associated with microangiopathy from atherosclerosis, amyloid angiopathy or asymptomatic elderly individuals. CMBs are intracerebral old hemosiderin deposits in the perivascular space, and the clinical significance of such 'microbleeds' remains controversy. We investigated the incidence of microbleeds among different ischemic stroke subtypes and the severity of leukoaraiosis.

Methods: In this study, we collected 137 patients (73.5 ± 9.1 years old, 84 men and 53 women) who were divided into five groups: atherothrombotic infarction (34 patients), cardioembolic infarction (24 patients), lacunar infarction (35 patients), other determined or undetermined infarction (21 patients) and control (23 patients), in which 52 had primary stroke and 62 had recurrent stroke. Microbleeds were counted and leukoaraiosis was graded using susceptibility-weighted, T1-, T2- and FLAIR MRI with a 3.0 T system.

Results: Microbleeds were high in lacunar infarction (25.7%) and atherothrombotic infarction patients (20.6%). Microbleeds were low in patients with cardioembolic infarction (4.2%). Both microbleeds (≥grade 2) and leukoaraiosis in severity (≥grade 2) were higher in the recurrent stroke group (14.5 and 48.4%) than those in the primary stroke group (3.8 and 7.7%). Leukoaraiosis (r=0.803, p<0.05) and recurrent stroke (r=0.708, p<0.05) were significantly associated with microbleeds.

Conclusions: Asymptomatic CMBs are observed with a markedly higher frequency in recurrent stroke, and are closely associated with the severity of leukoaraiosis.