Recurrent Intracerebral Hemorrhage Research Articles

Genetic Variants ε2 and ε4 of APOE Predict Mortality and Poor Outcome Independently in Spontaneous Intracerebral Hemorrhage Within the Chinese Han Population.

The heightened mortality and disability rates, coupled with restricted neurological recovery post intracerebral hemorrhage (ICH), have sparked considerable attention toward its treatment and results. Simultaneously, the influence of the APOE gene on ICH prognosis has been well-documented. This research aimed to explore the relationship between specific APOE alleles in the present cohort and the incidences of mortality, recurrence, and adverse prognosis, as determined by neurological function assessments in ICH patients. Data on patients diagnosed with ICH and hospitalized in the Department of Neurology at our institution from October 2021 to March 2022 were collected, including determining their APOE genotypes. A 1-year follow-up was conducted to evaluate mortality, ICH recurrence, and modified Rankin Scale (mRS) scores at 3 and 12 months. Poor prognosis was defined as an mRS score of ≥ 3. Initially, we analyzed the relationships between different APOE alleles and mortality, recurrence, and poor prognosis. Subsequently, we explored additional factors influencing each prognostic outcome and conducted multivariate analysis to identify independent risk factors. An analysis was conducted on 289 patients diagnosed with ICH. The presence of the ε2 allele was found to be a significant independent predictor for unfavorable outcomes at both 3 months (p = 0.022, OR = 2.138, 95% CI [2.041, 3.470]) and 1 year (p = 0.020, OR = 5.116, 95% CI [5.044, 5.307]). Moreover, the ε4 allele was established as an independent risk factor for ICH recurrence within 1 year (p = 0.025, OR = 2.326, 95% CI [1.163, 2.652]), as well as for mortality at 3 months (p = 0.037, OR = 4.250, 95% CI [4.068, 4.920]) and 1 year (p = 0.023, OR = 4.109, 95% CI [4.016, 4.739]). In conclusions, Both APOE ε2 and ε4 variants independently heighten mortality risk, recurrence, and poor prognosis after ICH. The substantial influence underscores the need for additional investigation into the impact of APOE genotype on ICH prognosis.

Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH. We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI. In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%). Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Combined effect of cortical superficial siderosis and cerebral microbleed on short-term and long-term outcomes after intracerebral haemorrhage

Background and purposeCortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes...

Stroke-heart syndrome: Incidence and clinical outcomes of cardiac complications following intracerebral haemorrhage.

Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database. A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ⩾ 18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4-weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine 5-year incidence of MACE. Before propensity score matching, 171,489 patients with non-traumatic ICH, 15% (n = 26,449) experienced ⩾1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32-1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73-1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications. Newly diagnosed cardiovascular complications following ICH (i.e. stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis.

Cerebral microbleeds is a predictor of recurrent small vessel cerebrovascular disease: Evaluation based on the recurrent stroke pattern

ObjectivesAn increased number of cerebral microbleeds (CMBs) is considered a predictive factor for recurrent small vessel cerebrovascular diseases, including lacunar infarction and non-lobar intracerebral hemorrhage (ICH). However, it is unclear which recurrent stroke pattern is mainly reflected in the number of CMBs. Materials and MethodsThis study enrolled 217 patients with their first stroke (148 deep lacunar infarctions and 69 non-lobar ICHs), between January 2009 and March 2015. The numbers of baseline and newly appearing CMBs in patients with recurrent stroke were compared with those in patients with non-recurrent stroke, and the dynamics of the number of CMBs was evaluated according to recurrent stroke patterns. ResultsFifty-nine patients with recurrent stroke were included in this study. A larger number of baseline and newly appearing CMBs was significantly associated with recurrent stroke (p = 0.04, p < 0.001, respectively). Recurrent stroke patterns were divided into four types: deep lacunar infarction/deep lacunar infarction (37 patients), deep lacunar infarction/non-lobar ICH (eight patients), non-lobar ICH/deep lacunar infarction (eight patients), and non-lobar ICH/non-lobar ICH (six patients). The number of newly appearing CMBs was significantly higher in patients with deep lacunar infarction/non-lobar ICH than in those with other recurrent stroke patterns (p = 0.04). ConclusionsThe number of CMBs is associated with recurrent stroke, including deep lacunar infarction and non-lobar ICH, and differs depending on the recurrent stroke patterns. The increase in the number of CMBs was strongly correlated with the deep lacunar infarction/non-lobar ICH recurrence pattern.

Predicting the recurrence of spontaneous intracerebral hemorrhage using a machine learning model.

Recurrence can worsen conditions and increase mortality in ICH patients. Predicting the recurrence risk and preventing or treating these patients is a rational strategy to improve outcomes potentially. A machine learning model with improved performance is necessary to predict recurrence. We collected data from ICH patients in two hospitals for our retrospective training cohort and prospective testing cohort. The outcome was the recurrence within one year. We constructed logistic regression, support vector machine (SVM), decision trees, Voting Classifier, random forest, and XGBoost models for prediction. The model included age, NIHSS score at discharge, hematoma volume at admission and discharge, PLT, AST, and CRP levels at admission, use of hypotensive drugs and history of stroke. In internal validation, logistic regression demonstrated an AUC of 0.89 and precision of 0.81, SVM showed an AUC of 0.93 and precision of 0.90, the random forest achieved an AUC of 0.95 and precision of 0.93, and XGBoost scored an AUC of 0.95 and precision of 0.92. In external validation, logistic regression achieved an AUC of 0.81 and precision of 0.79, SVM obtained an AUC of 0.87 and precision of 0.76, the random forest reached an AUC of 0.92 and precision of 0.86, and XGBoost recorded an AUC of 0.93 and precision of 0.91. The machine learning models performed better in predicting ICH recurrence than traditional statistical models. The XGBoost model demonstrated the best comprehensive performance for predicting ICH recurrence in the external testing cohort.

Unveiling the mystery: Infective endocarditis as an etiological cause of recurrent intracranial hemorrhage

Intracerebral hemorrhage (ICH) in the context of infective endocarditis (IE) is an uncommon and complex phenomenon involving diverse underlying mechanisms. We present a compelling case of a 48-year-old patient with recurrent ICH, ultimately leading to the diagnosis of IE with vegetation on the anterior leaflet of the mitral valve. The patient underwent a successful mitral valve replacement followed by a gradual improvement in neurological symptoms. This case report delves into the intricate diagnostic journey, highlighting the significance of suspecting IE in patients presenting with ICH. A multidisciplinary and comprehensive management approach played a pivotal role in achieving positive outcomes.

Serum YKL-40 as a Predictive Biomarker of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage Recurrence.

Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, p = 0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5 ng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829-12.189, p = 0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, p = 0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence.

Risk and benefit of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.

This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding. A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software. The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15). Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of all-cause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials.

Association of LDL-cholesterol

Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

Rationale and Design of the Statin Use in Intracerebral Hemorrhage Patients (SATURN) Trial

Introduction: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCEs) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes, and quality of life. Methods: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, phase III clinical trial with blinded end-point assessment. A planned total of 1,456 patients with lobar ICH will be recruited from 140 sites in the USA, Canada, and Spain. Patients presenting within 7 days of a spontaneous lobar ICH that occurred while taking a statin will be randomized (1:1) to continuation (control) versus discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a 2-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. Conclusion: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from or be harmed by statins.

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Minocycline in Severe Cerebral Amyloid Angiopathy: A Single-Center Cohort Study.

Evidence from animal studies suggests that minocycline may reduce lobar intracerebral hemorrhage (ICH) recurrence in cerebral amyloid angiopathy, possibly by inhibiting perivascular extracellular matrix degradation in cerebral small vessels. There is currently no evidence of its safety or efficacy in humans with cerebral amyloid angiopathy. To provide preliminary data to support future studies of minocycline's efficacy, the authors performed a retrospective single-center cohort study to assess the incidence of recurrent ICH in patients with an aggressive clinical course of probable cerebral amyloid angiopathy who had been prescribed minocycline off-label via shared decision-making. Crude incidence rate ratios were calculated to compare incidence rates before versus after treatment. Sixteen patients (mean age at minocycline initiation, 66.3±3.5 years; women 62.5%; median of 3 lobar ICHs [range, 1-6]) were initiated on minocycline and followed for a median of 12.4 months (range, 1.8-61.4 months). Adverse events were reported in 4 of 16 patients (gastroenteric, n=3; dizziness, n=1) and were considered mild. ICH incidence sharply increased the year before minocycline initiation compared with the preceding years (2.18 [95% CI, 1.50-3.07] versus 0.40 [95% CI, 0.25-0.60] events per patient-year) and fell to 0.46 (95% CI, 0.23-0.83) events per patient-year afterwards. Incidence rate ratios of recurrent ICH after minocycline was lower (0.21 [95% CI, 0.11-0.42], P<0.0001) compared with the year before initiation. Minocycline appeared safe and generally tolerated in a small group of patients with clinically aggressive cerebral amyloid angiopathy and was associated with reduced ICH recurrence. Determining whether this reduction represents a biological response to minocycline rather than a regression to the mean, however, will require a future controlled treatment trial.

Abstract TMP78: Disparities in Experiencing Major Adverse Cardiovascular Events Among Survivors of Spontaneous Intracerebral Hemorrhage by Hematoma Location

Background: Large studies evaluating the association of hematoma location with the risk of developing major adverse cardiovascular events (MACE) among survivors of intracerebral hemorrhage (ICH) in the United States are lacking. Methods: We identified adult (&gt;=18 years) ICH survivors from the state inpatient and the state emergency department databases of Florida, New York, Maryland, Washington, and Georgia (2016 - 2019). We fit a series of multivariable Fine-Gray sub-distribution hazard models, with the competing risk of death, and report the sub-distribution hazard ratio (SHR) and 95% confidence interval (CI) of the independent associations of hematoma location (lobar vs. non-lobar) with recurrent ICH (r-ICH), acute ischemic stroke (AIS), acute myocardial infarction (AMI), and MACE (any stroke, AMI, systemic embolism, or vascular death). Results: Among 10,652 ICH patients (median age [IQR]: 70 [58 - 80] years; 47.7% female; 43.2% lobar ICH), 3.3%, 3.1%, 0.5%, and 8.1%, respectively, experienced r-ICH, AIS, AMI, and MACE. Patients with lobar ICH (vs. non-lobar ICH) had a higher risk of r-ICH (SHR, CI: 1.67, 1.35 - 2.07) and MACE (1.28, 1.14 - 1.44). Blacks (vs. Whites) have a higher risk of AIS (1.64, 1.32 - 2.03) and MACE (1.42, 1.22 - 1.65). Also, privately insured patients (vs. Medicare) have a lower risk of r-ICH (0.45, 0.31 - 0.67), AIS (0.71, 0.53 - 0.95), and MACE (0.58, 0.47 - 0.71). Patients from low-income zip codes have a higher risk of AMI (1.83, 1.23 - 2.15) and MACE (1.16, 1.02 - 1.32). Patients with atrial fibrillation had a higher risk of AIS (1.47, 1.18 - 1.84) and MACE (1.26, 1.07 - 1.49). Patients with a high risk of metabolic syndrome (&gt;= 2 of the following: hypertension, diabetes, hyperlipidemia, or obesity) have a higher risk of AIS (1.37, 1.13 - 1.65), AMI (1.81, 1.19 - 2.75), and MACE (1.28, 1.13 - 1.44). Conclusions: Developing targeted secondary prevention strategies tailored to the specific sociodemographic and clinical profiles of ICH survivors is warranted.

Abstract WP158: Cortical Superficial Siderosis is Associated With Ischemia After Intracerebral Hemorrhage

Background: Ischemia on diffusion weighted imaging (DWI) after intracerebral hemorrhage (ICH) increases the risk of future ischemic stroke. Radiographic markers of small vessel disease, including cerebral microbleeds (CMB), are associated with DWI lesions. Though cortical superficial siderosis (cSS) is also a hemorrhagic small vessel disease subtype, it is unclear if cSS similarly relates to DWI lesions. We hypothesized that cSS would represent a more severe phenotype of small vessel disease and would associate with DWI lesions after ICH independent to other small vessel disease markers. Methods: Using the Intracerebral Hemorrhage Outcomes Project (ICHOP), we included all cases of spontaneous ICH who underwent DWI and susceptibility imaging/gradient echo. DWI hyperintensities were identified if &gt;10mm from the hematoma with decreased ADC signal. cSS were identified as subarachnoid hemosiderin deposition without acute subarachnoid hemorrhage. The relationship of cSS with DWI lesion presence as the outcome was assessed with logistic regression adjusted for ICH score, blood pressure change within 24 hours, and small vessel disease markers (CMB and white matter hyperintensity). Sensitivity analyses were performed to adjust for demographics and ICH location. A secondary analysis using linear regression assessed the association with the number of DWI lesions adjusted for similar covariates. Results: Of 198 patients analyzed, DWI lesions were observed in 31.3% and cSS in 10.6%. The presence of cSS was associated with DWI lesions (adjusted OR 3.72, CI: 1.29-10.72), independent of other small vessel disease markers. Separate sensitivity analyses adjusting for sex, race, and ICH location did not change the association of cSS with DWI lesions. In secondary analyses, cSS was not associated with greater number of DWI lesions counts (b 0.213, CI -0.53-0.63). Discussion: cSS is associated with the presence of DWI lesions, independent to other small vessel disease markers. cSS may represent a severe phenotype of small vessel disease with a risk of ICH recurrence and ischemia. Further work is required to investigate underlying mechanisms and optimal strategies to mitigate competing risks of future hemorrhage and ischemic events in these patients.

Prevalence, clinical characteristics, and risk factors of intracerebral haemorrhage in CADASIL: a case series and systematic review

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.MethodsA retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.ResultsTen cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).ConclusionsICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.

An Online Dynamic Radiomics–Clinical Nomogram to Predict Recurrence in Patients with Spontaneous Intracerebral Hemorrhage

ObjectiveRadiomics can reflect the heterogeneity within the focus. We aim to explore whether radiomics can predict recurrent intracerebral hemorrhage (RICH) and develop an online dynamic nomogram to predict it. MethodsThis retrospective study collected the clinical and radiomics features of spontaneous intracerebral hemorrhage (ICH) patients seen in our hospital from October 2013 to October 2016. We used the minimum redundancy maximum relevancy and the least absolute shrinkage and selection operator methods to screen radiomics features and calculate Rad-score. We use the univariate and multivariate analyses to screen clinical predictors. Optimal clinical features and Rad-score were used to construct different logistics regression models called the clinical model, radiomics model, and combined-LR model. The Delong testing was performed to compare performance between different models. The model with the best predictive performance was used to construct an online dynamic nomogram. ResultsOverall, 304 ICH patients were enrolled in this study. 14 radiomics features was selected to calculate the Rad-score. The patients with RICH had a significantly higher Rad-score than without (0.5 VS. -0.8, p < 0.001). The predictive performance of the combined-LR model with Rad-score was better than that of the clinical model for both the training (AUC, 0.81 vs. 0.71, p = 0.02) and testing (AUC, 0.65 vs. 0.58, p = 0.04) cohorts in statistically. ConclusionsRadiomics features were determined related to RICH. Adding Rad-score into conventional clinical models significantly improves the prediction efficiency. We developed a online dynamic nomogram to accurately and conveniently evaluate RICH.

Left atrial appendage occlusion in patients with spontaneous intracerebral hemorrhage: An observational study

BackgroundPatients with atrial fibrillation (AF) and intracerebral hemorrhage (ICH) are at high risk of ischemic and recurrent bleeding events. Therefore, the decision of restarting or avoiding anticoagulation is challenging. Left atrial appendage occlusion (LAAO) is an alternative for these patients. However, few data are available about safety of early LAAO and factors associated with ischemic stroke and ICH recurrence. MethodsA unicentric, observational, retrospective study including all patients with AF and a previous ICH who underwent LAAO. We analyzed baseline clinical and neuroimaging characteristics, procedural outcomes, post-procedural therapies and long-term follow-up. ResultsForty patients were included, whose mean age was 76.6 ±7.6 years and 73 % were men. In patients in whom a Magnetic Resonance (MR) was performed (n=22, 55 %), cortical microbleeds were detected in 15 (68 %) and cortical superficial siderosis in one patient. The procedure was successful and safe in 100 % of the patients and it was performed within 30 days of the ICH in 37 % of them. After a median follow up of 46.2 months [26-69], intracranial hemorrhage (ICrH) recurrence occurred in 6 patients (5 ICH and 1 subdural hematoma –SDH-) and the index ICH was lobar in all of them. Ischemic events were significantly lower than expected according to the CHA2DS2-VASc score (7.5 % vs. 16.6 %, p=0.048) and bleeding events were similar to expected by the HAS-BLED score (20 % vs 23.4 %, p=0.63). ConclusionsIn patients with ICH and AF, early LAAO was found to be safe and associated with a reduction in ischemic stroke. However, recurrent ICH risk remains high, and it appears to be mainly driven by cerebral amyloid angiopathy.

Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage.

This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral hemorrhage (ICH) complements earlier updates about blood pressure-lowering, lipid-lowering, and oral anticoagulation or left atrial appendage occlusion for atrial fibrillation after ICH. When used for secondary prevention in people without ICH, antiplatelet agents reduce the risk of major adverse cardiovascular event (rate ratio, 0.81 [95% CI, 0.75-0.87]) and might increase the risk of ICH (rate ratio, 1.67 [95% CI, 0.97-2.90]). Before 2019, guidance for clinical decisions about antiplatelet agent use after ICH has focused on estimating patients' predicted absolute risks and severities of ischemic and hemorrhagic major adverse cardiovascular event and applying the known effects of these drugs in people without ICH to estimate whether individual ICH survivors in clinical practice might be helped or harmed by antiplatelet agents. In 2019, the main results of the RESTART (Restart or Stop Antithrombotics Randomized Trial) randomized controlled trial including 537 survivors of ICH associated with antithrombotic drug use showed, counterintuitively, that antiplatelet agents might not increase the risk of recurrent ICH compared to antiplatelet agent avoidance over 2 years of follow-up (12/268 [4%] versus 23/268 [9%]; adjusted hazard ratio, 0.51 [95% CI, 0.25-1.03]; P=0.060). Guidelines in the United States, Canada, China, and the United Kingdom and Ireland have classified the level of evidence as B and indicated that antiplatelet agents may be considered/reasonable after ICH associated with antithrombotic agent use. Three subsequent clinical trials have recruited another 174 participants with ICH, but they will not be sufficient to determine the effects of antiplatelet therapy on all major adverse cardiovascular events reliably when pooled with RESTART. Therefore, ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) aims to recruit 4148 ICH survivors to determine the effects of antiplatelet agents after ICH definitively overall and in subgroups.

The impact of antiplatelet drugs on recurrent stroke in patients with intracerebral hemorrhage

BackgroundThe influence of antiplatelet drugs on the risk of hemorrhagic stroke and the reduction of ischemic stroke in patients with intracerebral hemorrhage (ICH) remains unclear. This study aimed to elucidate the impact of antiplatelet therapy on the risk of recurrent stroke in ICH patients. MethodsThe study encompassed ICH survivors discharged from a central Taiwanese teaching hospital between January 1, 2013, and December 31, 2019. Patient hospitalization and treatment data were retrieved from electronic medical records. The primary endpoint was re-hospitalization due to ischemic or hemorrhagic stroke. Patients who continued antiplatelet drug use for over a month prior to stroke recurrence constituted the antiplatelet drug use group. Risk factors for recurrent hemorrhagic and ischemic strokes were evaluated using binary logistic regression. ResultsThe study incorporated 407 ICH patients, each monitored for 4 years post-stroke. Recurrent stroke incidence showed no significant disparity between hemorrhagic and ischemic strokes. Hemorrhagic stroke recurrence stood at 5.16 % (21/407), and ischemic stroke recurrence was 4.42 % (18/407). In the non-antiplatelet group, hemorrhagic and ischemic stroke rates were 5.48 % (20/365) and 3.56 % (13/365) respectively. In the antiplatelet group, the rates were 2.38 % (1/42) for hemorrhagic and 11.9 % (5/42) for ischemic stroke, with a significantly higher ischemic stroke rate (p = 0.03). Hypertension emerged as a risk factor for recurrent hemorrhagic stroke, while diabetes mellitus was identified as a risk factor for ischemic stroke. Antiplatelet drug use did not escalate the risk of recurrent ICH. ConclusionDiabetes mellitus and hypertension are risk factors for recurrent ischemic and hemorrhagic strokes respectively in ICH patients. Antiplatelet therapy does not appear to elevate the risk of recurrent hemorrhagic stroke in these patients.