History Of Intracerebral Hemorrhage Research Articles

Anticoagulation therapy in non-valvular atrial fibrillation after intracerebral hemorrhage: A propensity score–matched study

BackgroundThe effect of antithrombotic therapy on patients with atrial fibrillation who sustained previous intracerebral hemorrhage (ICH) remains uncertain. Data regarding antithrombotic therapy use in these patients are limited. This study aims to compare the clinical and overall outcomes of antithrombotic therapy and usual care in patients with atrial fibrillation who sustained ICH. MethodsWe assembled consecutive patients with atrial fibrillation sustaining an ICH from our institution. Multivariable regression analysis and propensity-matched analysis were applied to assess associations of different antithrombotic therapies and outcomes. The primary outcome was mortality within the longest follow-up. Kaplan-Meier curves and log-rank tests of the time-to-event data were used to assess differences in survival. ResultsIn total, 296 consecutive patients with atrial fibrillation who survived an ICH were included in this study. Our analysis demonstrated that antithrombotic therapy was associated with reduced mortality up to a 4-year duration of follow-up (OR, 0.49, 95 % CI 0.30–0.81). Similar results were obtained from the propensity-matched analysis (OR, 0.58, 95 % CI 0.34–0.98). Subgroup analysis showed that compared with usual care, direct oral anticoagulant (DOAC) with or without antiplatelet was associated with a lower risk of long-term mortality (OR, 0.34, 95 % CI 0.17–0.69). In addition, our analysis observed a significant interaction between cardiac insufficiency and treatment effect (P = 0.04). ConclusionsIn patients with atrial fibrillation who have a history of ICH, administration of antithrombotic therapy, especially DOAC, was associated with lower mortality. Future randomized trials are warranted to test the positive net clinical benefit of DOAC therapy.

Hyperglycemia, Ischemic Lesions, and Functional Outcomes After Intracerebral Hemorrhage.

Background Ischemic lesions observed on diffusion-weighted imaging (DWI) magnetic resonance imaging are associated with poor outcomes after intracerebral hemorrhage (ICH). We evaluated the association between hyperglycemia, ischemic lesions, and functional outcomes after ICH. Methods and Results This was a retrospective observational analysis of 1167 patients who received magnetic resonance imaging in the ERICH (Ethnic and Racial Variations in Intracerebral Hemorrhage) study. A machine learning strategy using the elastic net regularization and selection procedure was used to perform automated variable selection to identify final multivariable logistic regression models. Sensitivity analyses with alternative model development strategies were performed, and predictive performance was compared. After covariate adjustment, white matter hyperintensity score, leukocyte count on admission, and non-Hispanic Black race (compared with non-Hispanic White race) were associated with the presence of DWI lesions. History of ICH and ischemic stroke, presence of DWI lesions, deep ICH location (versus lobar), ICH volume, age, lower Glasgow Coma Score on admission, and medical history of diabetes were associated with poor 6-month modified Rankin Scale outcome (4-6) after covariate adjustment. Inclusion of interactions between race and ethnicity and variables included in the final multivariable model for functional outcome improved model performance; a significant interaction between race and ethnicity and medical history of diabetes and serum blood glucose on admission was observed. Conclusions No measure of hyperglycemia or diabetes was associated with presence of DWI lesions. However, both medical history of diabetes and presence of DWI lesions were independently associated with poor functional outcomes after ICH.

Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage

The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs∗33) variant, identified in six individuals from four independent families of Southeastern Anatolia, severely impaired the invitro tubulogenic process of endothelial colony-forming cells, recapitulating previous evidence in null mice, and caused lack of ESAM expression in the capillary endothelial cells of damaged brain. Affected individuals with bi-allelic ESAM variants showed profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. Phenotypic traits observed in individuals with bi-allelic ESAM variants overlap very closely with other known conditions characterized by endothelial dysfunction due to mutation of genes encoding tight junction molecules. Our findings emphasize the role of brain endothelial dysfunction in NDDs and contribute to the expansion of an emerging group of diseases that we propose to rename as "tightjunctionopathies."

Prevalence and clinical predictors of spasticity after intracerebral hemorrhage.

Spasticity is a common complication of intracerebral hemorrhage (ICH). However, no consensus exists on the relation between spasticity and initial clinical findings after ICH. This retrospective study enrolled adult patients with a history of ICH between January 2012 and October 2020. The modified Ashworth scale was used to assess spasticity. A trained image analyst traced all ICH lesions. Multivariable logistic regression was used to examine the association between ICH lesion sites and spasticity. We finally analyzed 304 patients (mean age 54.86±12.93 years; 72.04% men). The incidence of spasticity in patients with ICH was 30.92%. Higher National Institutes of Health stroke scale (NIHSS) scores were associated with an increased predicted probability for spasticity (odds ratio, OR=1.153 [95% confidence interval, CI 1.093-1.216], p < .001). Logistic regression analysis revealed that lower age, higher NIHSS scores, and drinking were associated with an increased risk of moderate-to-severe spasticity (OR=0.965 [95% CI 0.939-0.992], p = .013; OR=1.068 [95% CI 1.008-1.130], p = .025; OR=4.809 [95% CI 1.671-13.840], p = .004, respectively). However, smoking and ICH in the thalamus were associated with a reduced risk of moderate-to-severe spasticity (OR=0.200 [95% CI 0.071-0.563], p = .002; OR=0.405 [95% CI 0.140-1.174], p = .046, respectively) compared with ICH in the basal ganglia. Our results suggest that ICH lesion locations are at least partly associated with post-stroke spasticity rather than the latter simply being a physiological reaction to ICH itself. The predictors for spasticity after ICH were age, NIHSS scores, past medical history, and ICH lesion sites.

High incidence of intracranial haemorrhage in Egyptian children with congenital afibrinogenaemia.

Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality in patients with congenital afibrinogenaemia. Details on location of cerebral haemorrhage, management and neurological outcomes are lacking. We performed a retrospective study on Egyptian children with congenital afibrinogenaemia who experienced ICH, in order to estimate frequency, symptoms and neurological outcomes. Among 58 children with congenital afibrinogenaemia treated on demand, 18 (31%) had an history of ICH (28 episodes). The first ICH occurred at a median age of 1year (Q1-Q3 1-7 years). Impaired consciousness level, vomiting and seizures were the most common presenting symptoms. Spontaneous bleeding was associated with a more severe clinical presentation and worse neurological outcomes, including hydrocephaly and impaired cognitive development. Only half of ICH events (n=14) were treated in less than 24h from the onset of symptoms. Fibrinogen replacement by Fresh Frozen Plasma (FFP), cryoprecipitate or fibrinogen concentrates was administered in seven (25%), 19 (68%) and three (10%) ICH events, respectively. Overall, seven (25%) ICH occurring in four patients required a surgical intervention. After the ICH, six patients started secondary prophylaxis. The cumulative incidence of ICH at 10 years was 35% (95% CI 23-51) and at 20 years was 40% (95 CI% 26.7-58.8). In our cohort of children with congenital afibrinogenaemia, ICH was very frequent and associated with adverse neurological outcomes and death. Further studies are required to determine whether primary prophylaxis starting early in childhood is indicated after diagnosis.

Underlying microangiopathy and functional outcome of simultaneous multiple intracerebral hemorrhage.

To identify the predominant type of cerebral small vessel disease (SVD) and outcomes in patients with simultaneous multiple intracerebral hemorrhages (SMICH). Consecutive patients with intracerebral hemorrhage (ICH) from a single-center prospective cohort were retrospectively reviewed. Presumed etiology was classified according to the SMASH-U criteria. Demographics, clinical and laboratory variables, and neuroimaging data were compared between patients with primary SMICH and those with single ICH. Functional outcomes were assessed using the modified Rankin scale 90 days after ICH. Of the 598 enrolled patients, 37 (6.2%) met the criteria for SMICH. Risk factors for SMICH included a high burden of deep cerebral microbleeds (CMBs) (odds ratio [OR] 1.06, 95% confidence interval [CI], 1.00-1.12; p = 0.040), white matter hyperintensity scores (OR 1.27, 95% CI 1.04-1.57; p = 0.021), history of ICH (OR 3.38, 95% CI 1.31-8.05; p = 0.008), and low serum magnesium levels (OR 0.01, 95% CI 0.00-0.25; p = 0.007). Based on the SMASH-U classification, 15(40.5%) SMICH were classified as hypertension, whereas 17 (45.9%) as undetermined-etiology. To further explore the potential microangiopathy underlying undetermined-SMICH, these patients with undetermined-etiology were compared to those with cerebral amyloid angiopathy-ICH, and were associated with a higher burden of deep CMBs but less severe centrum semiovale enlarged perivascular spaces. Likewise, compared with hypertension-ICH patients, those with undetermined SMICH were consistently associated with a higher deep CMB counts. Moreover, multivariate analysis revealed that SMICH was independently associated with poor outcomes (OR 2.23, 95%CI 1.03-4.76; p = 0.038). Our results suggest that most patients with primary SMICH harbor hypertensive-SVD as principal angiopathy. Patients with SMICH are at a high risk of poor outcomes. (ClinicalTrials.gov Identifier: NCT04803292).

Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations.

The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM). The authors' institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex. Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03-1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%-29.38%) for the entire cohort, 31.41% (95% CI 23.26%-40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%-49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%-32.29%) for patients on statin medication, and 0% (95% CI 0%-30.13%) for patients on antithrombotic medication. ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

The Use of the ICF Classification Sheet to Assess Cognitive-Behavioral Disorders and Verbal Communication in Patients after Ischemic and Hemorrhagic Stroke during Rehabilitation.

Background: In patients after experiencing stroke, the cognitive-behavioral deficits and disorders of verbal communication limit the effectiveness of rehabilitation. The key is to diagnose them at an early stage of rehabilitation and to implement appropriate psychological and speech therapy. Objective: Identify differences in the frequency and effectiveness of cognitive-behavioral disorder therapy depending on the clinical type of stroke, assessed before and after rehabilitation treatment, and their presentation using the ICF (International Classification of Functioning, Disability, and Health) classification. Materials and Methods: The study was prospective and included the analysis of cognitive-behavioral and verbal communication disorders. The study consisted of 47 patients after intracerebral hemorrhage (ICH) and 47 patients after an ischemic stroke (IS) before the implementation of rehabilitation and after completing a 4-week rehabilitation. Results: In the group after ICH, psychological therapy significantly reduced the disturbances of consciousness and orientation (p < 0.001) and improved the speed of performing tasks in tests (p < 0.001). In patients after IS and ICH, memory and attention function improved significantly (p < 0.001). Moreover, in patients after ICH, language function deficits decreased significantly (p = 0.018). Mood disturbances were maintained in 17% of patients after ICH and 40% of patients after IS (p = 0.007). Speech therapy reduced speech articulation disorders and aphasia in 85% of patients after ICH (p = 0.001) and in 68% of patients after IS (p = 0.033). Conclusions: The frequency and type of cognitive-behavioral and verbal communication disorders vary depending on the history of ICH or IS. The ICF classification may be useful in assessing and analyzing cognitive-behavioral and verbal communication disorders, which may lead to the implementation of appropriate psychological and speech therapy at an early stage of rehabilitation and increase the effectiveness of the therapy.

Factors affecting physician decision-making regarding antiplatelet therapy in minor ischemic stroke.

PurposeTo identify the most important factors affecting physician decision-making regarding antiplatelet therapy.MethodsWe retrospectively gathered data from minor ischemic stroke patients with NIHSS scores ≤ 5 within 72 h of onset from 2010 to 2018. The population was divided into four groups by initial antiplatelet therapy: aspirin monotherapy (AM), dual antiplatelet therapy with aspirin and a loading dose of clopidogrel (clopidogrel loading dose of 300 mg on the first day; DAPT-ALC), dual antiplatelet therapy with aspirin and no loading dose of clopidogrel (clopidogrel 75 mg daily, no loading dose; DAPT-AUC), and clopidogrel monotherapy (CM).ResultsIn total, 1,377 patients were included in the analysis (excluding patients who accepted thrombolytic drugs, participated in other clinical trials, or had not used antiplatelet drugs). The mean ± S.D. age was 62.0 ± 12.7 years; 973 (70.7%) patients were male. The four groups were AM (n = 541, 39.3%), DAPT-ALC (n = 474, 34.4%), DAPT- AUC (n = 301, 21.9%), and CM (n = 61, 4.4%). Patients receiving antiplatelet monotherapy were older than those receiving dual antiplatelet therapy (63.7–65.7 vs. 59.6–61.4 years), and the median initial systolic blood pressure level was higher in the DAPT-ALC group than in the other groups (all P < 0.05). Patients under 75 years old with an admission SBP lower than 180 mmHg, a history of AM, coronary heart disease, no history of intracerebral hemorrhage, stroke onset occurring after guideline recommendations were updated (the year of 2015), onset-to-arrival time within 24 h, and initial NIHSS score ≤ 3 were more likely to take DAPT-ALC than AM. Compared with DAPT-ALC, DAPT-AUC was associated with an initial SBP level lower than 180 mmHg, a history of smoking, hypertension, no history of ICH, previous treatment with antihypertensives, and onset year after the recommendations were updated.ConclusionsMany factors affect doctors' decisions regarding antiplatelet therapy, especially guidelines, age, admission SBP level, and hypertensive disease.

Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED2 score.

Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12-66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.

Comparison of clinical and neuroimaging features between NOTCH3 mutations and nongenetic spontaneous intracerebral haemorrhage.

The NOTCH3 mutation is a common cause of hereditary cerebral small vessel disease (CSVD) and may be a cause of spontaneous intracerebral haemorrhage (ICH). The aim was to investigate the clinical/imaging features for identifying the NOTCH3-mutation-related ICH. The study was based on a cohort of 749 CSVD patients in Taiwan who received next-generation sequencing of CSVD genes including NOTCH3. Patients with a history of ICH (n=206) were included for analysis. The CSVD neuroimaging markers were compared between the patients with NOTCH3 and those without known genetic mutations. After excluding patients with other causes of ICH (structural lesions, systemic/medication related or amyloid angiopathy) and those without neuroimaging, 45 NOTCH3 mutation patients and 109 nongenetic ICH patients were included. The NOTCH3 mutation patients were more likely to have thalamic haemorrhage, a family history of stroke and more severe CSVD neuroimaging markers. A five-point NOTCH3-ICH score was constructed and consisted of a history of stroke in siblings, thalamic haemorrhage, any deep nuclei lacunae, any hippocampal cerebral microbleed (CMB) and a thalamic CMB &gt;5 (one point for each). A score ≥2 had a sensitivity of 88.9% and a specificity of 64.2% in identifying the NOTCH3 mutation. The NOTCH3 mutation patients had a higher risk of recurrent stroke (9.1 vs. 4.5 per 100 person-years, log-rank p=0.03) during follow-up. The patients with NOTCH3-mutation-related ICH had a higher burden of CMBs in the hippocampus/thalamus and a higher recurrent stroke risk. The NOTCH3-ICH score may assist in identifying genetic causes of ICH.

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation.

Optimal antithrombotic management after intracerebral hemorrhage remains one of the central unresolved issues for patients who survive, especially for those patients with atrial fibrillation. Given the observational nature of the studies regarding anticoagulation resumption after intracerebral hemorrhage, there is uncertainty regarding resumption of oral anticoagulation therapy and its timing. There is limited high-quality evidence to guide clinical practice, leading to significant practice variation and uncertainty for patients and providers. Here, we aim to provide the key elements to guide clinicians in their individual decision: whether or not to start or resume anticoagulation in patients with a history of intracerebral hemorrhage.

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage.

Hyperlipidemia is common in patients with intracerebral hemorrhage (ICH). Accumulating evidence indicates that patients with ICH are at risk for future hemorrhage recurrence, cardiovascular disease, and ischemic stroke and highlights the importance of secondary prevention of vascular events after ICH. Although the benefits of intensive treatment of hyperlipidemia for reducing ischemic cardiac and vascular events in patients with ischemic stroke are well established, the benefit versus harm in patients with ICH are less clear. Epidemiological studies suggest that hyperlipidemia is protective against ICH and that intensive lowering of lipids is associated with increased risk for ICH. Similarly, although currently available lipid-lowering treatments have been thoroughly studied in patients with ischemic cardiac and vascular disease, only few randomized trials of these therapies included a very small number of patients with history of ICH. Thus, limiting any definitive conclusions regarding the safety and net benefit of these treatments in ICH populations. Currently, there is no consensus regarding the optimal strategy for management of hyperlipidemia after ICH. In this article, we review relevant literature to outline the competing risks and benefits of lipid-lowering treatments in this vulnerable patient population. We suggest a treatment paradigm based on available data but note that data from dedicated randomized trials are needed to build the necessary evidence to guide optimal lipid-lowering strategy in patients with a history of ICH.

406 The BLED2 Neurologic Event Prediction Score for Patients with Symptomatic Cerebral Cavernous Malformation

INTRODUCTION: Studies using retrospective patient cohorts have identified risk factors associated with recurrent focal neurologic events in patients with symptomatic cerebral cavernous malformations (CCMs). METHODS: Adult patients presenting with symptomatic CCMs causing focal neurologic deficits or seizures were included. Baseline variables included age, gender, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurologic events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurologic events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of the risk factors was devised, and Kaplan-Meier curve analysis compared event-free survival between different score values. Subsequently, 1-, 2-, and 5-year neurologic event rates were calculated for every score value based on the final model. RESULTS: 126 (47%) of 270 patients met inclusion criteria. During a mean follow-up of 4.5 years (54.4 months, range 12-66 months), 55 patients (44%) experienced recurrent neurologic events. Multivariable analysis yielded four risk factors: Bleeding at presentation (HR=1.92, p=0.048), Large size =12mm (HR=2.06, p=0.016), Eloquent location (HR=3.01, p=0.013), and Duration of =1 year since last event (HR=9.28, p=0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point except duration from last event, which was assigned 2 points. The acronym, BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risk of a recurrent neurologic event ranged from 0.6%, 1.2%, and 2.3%, respectively for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively for patients with a BLED2 score of 5. CONCLUSION: The BLED2 risk score predicts prospective neurologic events in symptomatic CCM patients.

Adjusted Morbidity Groups and Intracerebral Haemorrhage: A Retrospective Primary Care Cohort Study.

Background: Intracerebral haemorrhage rates are increasing among highly complex, elderly patients. The main objective of this study was to identify modifiable risk factors of intracerebral haemorrhage. Methods: Multicentre, retrospective, community-based cohort study was conducted, including patients in the Adjusted Morbidity Group 4 with no history of intracerebral haemorrhage. Cases were obtained from electronic clinical records of the Catalan Institute of Health and were followed up for five years. The primary outcome was the occurrence of intracerebral haemorrhage during the study period. Demographic, clinical and pharmacological variables were included. Logistic regression analyses were carried out to detect prognostic variables for intracerebral haemorrhage. Results: 4686 subjects were included; 170 (3.6%) suffered an intracerebral haemorrhage (85.8/10,000 person–year [95% CI 85.4 to 86.2]). The HAS-BLED score for intracerebral haemorrhage risk detection obtained the best AUC (0.7) when used in the highest complexity level (cut-off point ≥3). Associated independent risk factors were age ≥80 years, high complexity and use of antiplatelet agents. Conclusions: The Adjusted Morbidity Group 4 is associated with a high risk of intracerebral haemorrhage, particularly for highly complex patients and the use of antiplatelet agents. The risk of bleeding in these patients must be closely monitored.

Difficult issues in the management of patients with atrial fibrillation: a neurologist's point of view

The article evaluates recent perspectives about the role of oral anticoagulants in the secondary prevention of cardioembolic stroke. The timing of prescribing drugs for ischemic stroke and transient ischemic attack is discussed in accordance with current clinical guidelines and the results of clinical trials. The issues of prescribing oral anticoagulants in some problematic situations, such as the elderly and senile age, reperfusion therapy, presence of hemorrhagic transformation, combined atherosclerosis of major head and neck arteries, cerebral microangiopathy, history of intracerebral hemorrhage, cryptogenic stroke, and low patient compliance are considered. Finally, an anticoagulant therapy algorithm in the acute period of cardioembolic stroke is presented.

Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants.

Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-ε4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age. In this multicenter observational cohort study, very low birth weight (<1500 g, <32 weeks gestational age) children were studied for cerebral palsy (CP) after ultrasound diagnosed ICH stratified by APOE genotype. Follow-up examination was done at the age of 5 to 6 years. Study personnel were blinded for perinatal information and complications. Participants were born between January 1, 2009 and December 31, 2013 and enrolled in the German Neonatal Network. Of 8022 infants primarily enrolled, 2467 children were invited for follow-up between January 1, 2014 and December 31, 2019. Univariate analyses and multivariate logistic regression models were used to assess the impact of APOE genotype (APOE-ε2, APOE-ε3, APOE-ε4) on CP after ICH. Two thousand two hundred fifteen children participated at follow-up, including 363 children with ultrasound diagnosed neonatal ICH. In univariate analyses of children with a history of ICH, APOE-ε3 carriers had lower frequencies of CP (n=33/250; 13.2 [95% CI, 9.4%-17.8%]), as compared to APOE-ε2 (n=15/63; 23.8 [14.6%-35.3%], P=0.037) and -ε4 carriers (n=31/107; 29.0 [21.0%-38.0%], P<0.001), respectively. Regression models revealed an association of APOE-ε4 genotype and CP development (odds ratio, 2.77 [1.44-5.32], P=0.002) after ICH. Notably, at low-grade ICH (grade I) APOE-ε4 expression resulted in an increased rate of CP (n=6/39; 15.4 [6.7-29.0]) in comparison to APOE-ε3 (n=2/105; 1.9 [0.4%-6.0%], P=0.002). APOE-ε4 carriers have an increased risk for long-term motor deficits after ICH. We assume an effect even after low-grade neonatal ICH, but more data are needed to clarify this issue.

Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.

Background and ObjectivesThe goal of this work was to investigate the natural history and outcomes after treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy–related inflammation (CAA-ri).MethodsThis was a multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria recruited through the Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease βiomarkers International Network from January 2013 to March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, gradient recalled echo–T2*, fluid-suppressed T2-weighted (fluid-attenuated inversion recovery), and T1 postgadolinium contrast-enhanced images acquired on 1.5T MRI, was used at the 3-, 6-, 12-, and 24-month follow-up. Centralized reads of MRIs were performed by investigators blinded to clinical, therapeutic, and time-point information. Main outcomes were survival, clinical and radiologic recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri.ResultsThe study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri). Their mean age was 72.9 years; 43.4% were female; 37.1% were APOEε4 carriers; 36.3% had a history of Alzheimer disease; and 33.6% had a history of ICH. A history of ICH and the occurrence of new ICH at follow-up were more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%, p < 0.0001 and 19.3% vs 3.6%, p < 0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% confidence interval [CI] 61.6%–78.5%) and 84.1% (95% CI 76.2%–90.6%) clinically recovered within 3 and 12 months, followed by radiologic recovery in 45.1% (95% CI 36.4%–54.8%) and 77.4% (95% CI 67.7%–85.9%), respectively. After clinicoradiologic resolution of the first-ever episode, 38.3% (95% CI 22.9%–59.2%) had at least 1 recurrence within the following 24 months. Recurrence was more likely if IV high-dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering off (hazard ratio 4.68, 95% CI 1.57–13.93; p = 0.006).DiscussionThese results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in β-amyloid–driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Evaluating the safety and efficacy of intravenous thrombolysis for acute ischemic stroke patients with a history of intracerebral hemorrhage: a systematic review and meta-analysis.

Previous intracerebral hemorrhage (ICH) is labelled as a contraindication for the use of intravenous tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) based on expert opinion. However, there is a paucity of data available regarding the benefits and risks of IV-tPA in this population. Recent small retrospective cohort studies reporting its off-label use suggest it may be beneficial. This study aims to investigate the safety and efficacy of IV-tPA in AIS patients with previous ICH. We performed a systematic review and meta-analysis of studies reporting on IV-tPA use in AIS patients with and without previous ICH. We searched Embase, PubMed and Cochrane Library from inception to 20 April 2021. Outcomes measured included symptomatic ICH (sICH), 3-month modified Rankin Scale (mRS) score, and 3-month mortality. We included seven retrospective cohort studies comprising 5760 AIS patients who had received IV-tPA, of which 134 had previous ICH. There was no significant difference in the odds of sICH (OR 1.57, 95% CI 0.78-3.15, p = 0.21) and 3-month mRS (mRS 0-1: OR 0.78, 95% CI 0.37-1.65, p = 0.52; mRS 0-2: OR 1.07, 95% CI 0.36-3.15, p = 0.90) between patients with and without previous ICH. There was a trend towards higher 3-month mortality in patients with previous ICH (OR 1.69, 95% CI 0.98-2.91, p = 0.06), although this did not reach statistical significance. The use of IV-tPA in AIS patients with previous ICH was not associated with an increased risk of sICH or disability at 3months. Further larger studies are needed to establish the safety and efficacy of IV-tPA use in this population.