Recurrent Intracerebral Hemorrhage Research Articles

Abstract 127: Untreated Hypertension After Intracerebral Hemorrhage

Objective: We previously reported that 46.9% of acute intracerebral hemorrhage (ICH) patients had untreated hypertension (HTN) on admission. We sought to investigate the prevalence of untreated HTN among patients at follow-up after ICH. Methods: ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) is a prospective multi-center study of ICH among whites, blacks, and Hispanics. Cases were enrolled at 42 recruitment sites. Subjects’ ethnicity, history of HTN, type of insurance, HTN medications, and level of education were collected. Patients were considered to have HTN if they received this diagnosis prior to or during initial ICH admission. Stroke events at follow-up included ischemic stroke, transient ischemic attack, subarachnoid hemorrhage, and recurrent ICH. Medication use was also recorded at follow-up. Results: Of 3,000 cases of ICH, there were 1,822 with HTN who had at least one follow-up, of which 9.4% had untreated HTN. Compared with treated patients at 3 months, those untreated at 3 months more frequently were white or Hispanic (p=0.0064), female (p=0.0236), over 65 years old (p<0.0001), or on Medicare (p<0.0001). Among those treated at 3 months, 60.5% were prescribed beta blockers, 54.9% calcium channel blockers, 52.9% ACE inhibitors, 31.5% diuretics, 16.6% vasodilators, 12.6% angiotensin receptor blockers, 10.3% alpha agonists, 2.8% nitrates, 2.5% alpha blockers, and 3.7% others. Stroke events occurred by 12 months in 5.5% of treated compared with 5.6% of untreated patients. Conclusions: Despite a high rate of untreated HTN at admission, the rate at follow-up was substantially lower. Overall, Hispanics were more likely and blacks less likely to be untreated than whites. Despite the lack of difference in stroke events identified among treated versus untreated patients, there was limited power to identify differences in a short-term follow-up due to a low rate of stroke recurrence and a low proportion of untreated HTN.

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study

SummaryBackgroundIdentification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.MethodsWe identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.FindingsAmong 110 adults (median age 83 years [IQR 76–87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86–0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88–100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78–100).InterpretationThe CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.FundingUK Medical Research Council, The Stroke Association, and The Wellcome Trust.

CT scanning to diagnose CAA: back to the future?

CT scanning to diagnose CAA: back to the future?

Mixed-location cerebral hemorrhage/microbleeds: Underlying microangiopathy and recurrence risk.

To assess the predominant type of cerebral small vessel disease (SVD) and recurrence risk in patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed locations (mixed ICH). Of 391 consecutive patients with primary ICH enrolled in a prospective registry, 75 (19%) had mixed ICH. Their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to those of 191 patients with probable cerebral amyloid angiopathy (CAA-ICH) and 125 with hypertensive strictly deep microbleeds and ICH (HTN-ICH). ICH recurrence and case fatality were also analyzed. Patients with mixed ICH showed a higher burden of vascular risk factors reflected by a higher rate of left ventricular hypertrophy, higher creatinine values, and more lacunes and severe basal ganglia (BG) enlarged perivascular spaces (EPVS) than patients with CAA-ICH (all p < 0.05). In multivariable models mixed ICH diagnosis was associated with higher creatinine levels (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-5.0, p = 0.010), more lacunes (OR 3.4, 95% CI 1.7-6.8), and more severe BG EPVS (OR 5.8, 95% CI 1.7-19.7) than patients with CAA-ICH. Conversely, when patients with mixed ICH were compared to patients with HTN-ICH, they were independently associated with older age (OR 1.03, 95% CI 1.02-1.1), more lacunes (OR 2.4, 95% CI 1.1-5.3), and higher microbleed count (OR 1.6, 95% CI 1.3-2.0). Among 90-day survivors, adjusted case fatality rates were similar for all 3 categories. Annual risk of ICH recurrence was 5.1% for mixed ICH, higher than for HTN-ICH but lower than for CAA-ICH (1.6% and 10.4%, respectively). Mixed ICH, commonly seen on MRI obtained during etiologic workup, appears to be driven mostly by vascular risk factors similar to HTN-ICH but demonstrates more severe parenchymal damage and higher ICH recurrence risk.

Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke.

BackgroundThis study was performed to determine the clinical correlates and long‐term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke.Methods and ResultsWe recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long‐term risks (3126 patient‐years of follow‐up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2–4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all P<0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07–5.05]; 2–4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50–9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25–27.81]; P trend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (P trend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: P trend<0.0001; ischemic stroke P trend=0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11–33.21]; P=0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk.ConclusionsIn Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.

Cerebral Amyloid Angiopathy: An elderly patient with a past history of lobar brain hemorrhage and recent history of recurrent lobar brain hemorrhages

Background: Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage. Brain amyloid-related imaging abnormalities (ARIA) can be classified into two groups; those with edema or sulcal effacement (ARIA-E) and those with cerebral microbleeds or small hemorrhages (ARIA-H). There is an aggressive form of CAA, called CAA-related inflammation (CAA-ri) which is characterized by vascular or perivascular inflammation. Current treatment guidelines do not recommend routine use of steroids for intraparenchymal hemorrhage. Methods: We describe the clinical course, radiologic and pathologic findings of a 78-year-old man with recurrent intracerebral hemorrhage. Diagnostic studies included CT and MRI-scans of the brain, histopathology studies and autopsy. Results: The patient was diagnosed with a vasculitic form of amyloid angiopathy. Treatment with steroids resulted in clinical and radiological improvement. Conclusions: There might be a benefit of steroid or other immunosuppressive therapy in some patients with recurrent lobar hemorrhage related to CAA. Patients demonstrating edema out of proportion to the size of hematoma and extension of edema to the sub-cortical U fibers on imaging studies due to underlying vasculitis or CAA-ri may be candidates for such therapeutic interventions.

Spotlight on the November 21 issue

#### Notable in Neurology This issue features an article that describes the pathophysiologic nature of small diffusion-weighted imaging lesions in cerebral amyloid angiopathy and another that shows small vessel disease burden is associated with increased blood–brain barrier leakage in both the acutely ischemic and nonischemic area. A featured Views & Reviews article describes the recurrent traumatic brain injury risk in the general population. ### Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study Patients with multifocal cortical superficial siderosis (cSS) have a higher risk of recurrent intracerebral hemorrhage. The authors explored the mechanisms of cSS and validated …

Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study.

In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0-4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH. The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77-5.75; p < 0.0001). The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

Assessing clinical outcome using brain score as a predictor of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) patients in a tertiary hospital in Manila

Background: Spontaneous intracerebral hemorrhage (ICH), the second most common cause of stroke, has a high rate of morbidity and mortality. One of the independent predictors of poor outcome in ICH patients is hematoma expansion. Wang et al developed a simple algorithm, BRAIN, which is a 24-point score based on Baseline ICH volume, Recurrent ICH, Anticoagulation with warfarin at symptom onset, Intraventricular extension, and Number of hours to baseline computed tomography from symptom onset, which predicts in percentage the probability of hematoma expansion in ICH patients within the next 24 hours (Table 1).

Computed Tomography Angiography Spot Sign as an Indicator for Ultra-Early Stereotactic Aspiration of Intracerebral Hemorrhage.

Ultra-early surgical clot removal relieves mechanical compression on adjacent normal brain tissue and limits the toxic effects of a hematoma, which might improve the outcomes in patients with intracerebral hemorrhage (ICH); however, hematoma expansion frequently occurs within 20 hours after the ictus, and this limits the use of ultra-early surgery. Computed tomography angiography spot sign was recently validated as an important predictor of hematoma expansion in patients with ICH. Fifty-nine patients with ICH and negative spot sign who received ultra-early stereotactic aspiration (<6 hours after ictus; n= 32 [Ultra-early group]) or routine stereotactic aspiration (≥6 hours after ictus; n= 27 [Routine group]) were included in retrospective analysis. The percentage of rebleeding was not significantly different between the 2 groups. Perihematoma edema 7 days after surgery in the Ultra-early group was significantly less frequent than that in the Routine group. For long-term outcomes, the proportion of patient fatalities and Glasgow Outcome Scale score were not significantly different between the 2 groups; however, for patients with severe symptoms, the rate of good neurological outcome in the Ultra-early group was higher than that in the Routine group. Ultra-early stereotactic aspiration might decrease the volume of perihematoma edema and improve the functional outcomes to some extent, without increasing the recurrence of ICH and patient fatalities. Our findings suggest that using negative spot sign as an indicator for performing ultra-early stereotactic aspiration could be a safe and effective protocol for ICH patients.

Anticoagulation in Patients With Atrial Fibrillation in the Setting of Prior Hemorrhage: An Ongoing Dilemma.

See releated articles, pp 2653, 2660, 2665, 2671 A clinician needs to counsel a patient with atrial fibrillation on the advisability of resuming anticoagulation after a parenchymal brain hemorrhage resulting in a persistent, albeit nondisabling functional impairment. The issue to be addressed is straightforward; the advice to be offered, however, is far from clear. Relevant prospective, randomized controlled trials are lacking,1,2 and the vagaries of providing recommendations based on observational studies and experience (eminence-based medicine) often lead to choices that are later refuted when adequately tested. This is, in part, because historic event rates in populations can change over time,3,4 and conclusions from observational studies can be affected by several biases.5 Causing further uncertainty, the results of case–control and other nonrandomized studies may be contradictory because of differences in cohort characteristics and unmeasured confounding.6 Yet, the patient cannot await the collection of the high-quality data required to support more definitive guidance. Healthcare providers turn to authoritative clinical guidelines to review current evidence-based opinions for patient evaluation and management. The American College of Chest Physicians guidelines indicate that, “In patients with a history of a symptomatic primary intracerebral hemorrhage, we suggest against the long-term use of antithrombotic therapy for the prevention of ischemic stroke.”1 The writers, however, remark that patients might benefit from antithrombotic therapy if they are at relatively low risk of recurrent intracerebral hemorrhage (ICH) and relatively high risk (>7% per year) of thromboembolic events. Similarly, the American Heart Association/American Stroke Association secondary stroke prevention guidelines suggest that, “The decision to restart antithrombotic therapy after intracerebral hemorrhage related to antithrombotic therapy depends on the risk of subsequent arterial or venous thromboembolism, the risk of recurrent ICH, and the overall status of the patient and must, therefore, be …

Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke.

Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive. We hypothesized that genetic determinants of myeloperoxidase levels influence the development of vascular instability, leading to increased primary intracerebral haemorrhage and lacunar stroke risk. We used a discovery cohort of 1409 primary intracerebral haemorrhage cases and 1624 controls from three studies, an extension cohort of 12 577 ischaemic stroke cases and 25 643 controls from NINDS-SiGN, and a validation cohort of 10 307 ischaemic stroke cases and 29 326 controls from METASTROKE Consortium with genome-wide genotyping to test this hypothesis. A genetic risk score reflecting elevated myeloperoxidase levels was constructed from 15 common single nucleotide polymorphisms identified from prior genome-wide studies of circulating myeloperoxidase levels (P < 5 × 10-6). This genetic risk score was used as the independent variable in multivariable regression models for association with primary intracerebral haemorrhage and ischaemic stroke subtypes. We used fixed effects meta-analyses to pool estimates across studies. We also used Cox regression models in a prospective cohort of 174 primary intracerebral haemorrhage survivors for association with intracerebral haemorrhage recurrence. We present effects of myeloperoxidase elevating single nucleotide polymorphisms on stroke risk per risk allele, corresponding to a one allele increase in the myeloperoxidase increasing genetic risk score. Genetic determinants of elevated circulating myeloperoxidase levels were associated with both primary intracerebral haemorrhage risk (odds ratio, 1.07, P = 0.04) and recurrent intracerebral haemorrhage risk (hazards ratio, 1.45, P = 0.006). In analysis of ischaemic stroke subtypes, the myeloperoxidase increasing genetic risk score was strongly associated with lacunar subtype only (odds ratio, 1.05, P = 0.0012). These results, demonstrating that common genetic variants that increase myeloperoxidase levels increase risk of primary intracerebral haemorrhage and lacunar stroke, directly implicate the myeloperoxidase pathway in the pathogenesis of cerebral small vessel disease. Because genetic variants are not influenced by environmental exposures, these results provide new support for a causal rather than bystander role for myeloperoxidase in the progression of cerebrovascular disease. Furthermore, these results support a rationale for chronic inflammation as a potential modifiable stroke risk mechanism, and suggest that immune-targeted therapies could be useful for treatment and prevention of cerebrovascular disease.

Predictors for recurrent spontaneous intracerebral hemorrhage: A retrospective study

Predictors for recurrent spontaneous intracerebral hemorrhage: A retrospective study

Cerebral Arterial Stenosis in Patients with Spontaneous Intracerebral Hemorrhage.

ObjectiveSpontaneous intracerebral hemorrhage (ICH) and ischemic stroke share common vascular risk factors such as aging and hypertension. Previous studies suggested that the rate of recurrent ICH and ischemic stroke might be similar after ICH. Presence of cerebral arterial stenosis is a potential risk factor for future ischemic stroke. This study investigated the prevalence and factors associated with cerebral arterial stenosis in Korean patients with spontaneous ICH.MethodsA total of 167 patients with spontaneous ICH were enrolled. Intracranial arterial stenosis (ICAS) and extracranial arterial stenosis (ECAS) were assessed by computed tomography angiography. Presence of ICAS was defined if patients had arterial stenosis in at least one intracranial artery. ECAS was assessed in the extracranial carotid artery. More than 50% luminal stenosis was defined as presence of stenosis. Prevalence and factors associated with presence of ICAS and cerebral arterial stenosis (presence of ICAS and/or ECAS) were investigated by multivariable logistic regression analysis.ResultsThirty-two (19.2%) patients had ICAS, 7.2% had ECAS, and 39 (23.4%) patients had any cerebral arterial stenosis. Frequency of ICAS and ECAS did not differ among ganglionic ICH, lobar ICH, and brainstem ICH. Age was higher in patients with ICAS (67.6±11.8 vs. 58.9±13.6 years p=0.004) and cerebral arterial stenosis (67.9±11.6 vs. 59.3±13.5 years, p<0.001) compared to those without stenosis. Patients with ICAS were older, more frequently had diabetes, had a higher serum glucose level, and had a lower hemoglobin level than those without ICAS. Patients with cerebral arterial stenosis were older, had diabetes and lower hemoglobin level, which was consistent with findings in patients with ICAS. However, patients with cerebral arterial stenosis showed higher prevalence of hypertension and decreased kidney function compared to those without cerebral arterial stenosis. Multivariable logistic regression analyses showed that aging and presence of diabetes independently predicted the presence of ICAS, and aging, diabetes, and hypertension were independently associated with presence of cerebral arterial stenosis.Conclusion19.2% of patients with spontaneous ICH had ICAS, but the prevalence of ECAS was relatively lower (7.2%) compared with ICAS. Aging and diabetes were independent factors for the presence of ICAS, whereas aging, hypertension, and diabetes were factors for the cerebral arterial stenosis.

Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis.

Objective:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity).Methods:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models.Results:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years): OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.Conclusions:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.

Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers

IntroductionAn MRI-based score of total small vessel disease burden (CAA-SVD-Score) in cerebral amyloid angiopathy (CAA) has been demonstrated to correlate with severity of pathologic changes. Evidence suggests that CAA-related intracerebral hemorrhage (ICH) recurrence risk is associated with specific disease imaging manifestations rather than overall severity. We compared the correlation between the CAA-SVD-Score with the risk of recurrent CAA-related lobar ICH versus the predictive role of each of its components. MethodsConsecutive patients with CAA-related ICH from a single-center prospective cohort were analyzed. Radiological markers of CAA related SVD damage were quantified and categorized according to the CAA-SVD-Score (0–6 points).Subjects were followed prospectively for recurrent symptomatic ICH. Adjusted Cox proportional hazards models were used to investigate associations between the CAA-SVD-Score as well as each of the individual MRI signatures of CAA and the risk of recurrent ICH. ResultsIn 229 CAA patients with ICH, a total of 56 recurrent ICH events occurred during a median follow-up of 2.8years [IQR 0.9–5.4years, 781 person-years). Higher CAA-SVD-Score (HR=1.26 per additional point, 95%CI [1.04–1.52], p=0.015) and older age were independently associated with higher ICH recurrence risk. Analysis of individual markers of CAA showed that CAA-SVD-Score findings were due to the independent effect of disseminated superficial siderosis (HR for disseminated cSS vs none: 2.89, 95%CI [1.47–5.5], p=0.002) and high degree of perivascular spaces enlargement (RR=3.50–95%CI [1.04–21], p=0.042). ConclusionIn lobar CAA-ICH patients, higher CAA-SVD-Score does predict recurrent ICH. Amongst individual elements of the score, superficial siderosis and dilated perivascular spaces are the only markers independently associated with ICH recurrence, contributing to the evidence for distinct CAA phenotypes singled out by neuro-imaging manifestations.

Antiplatelet Resumption after Antiplatelet-Related Intracerebral Hemorrhage: ARetrospective Hospital-Based Study.

Antiplatelet resumption in patients who developed intracerebral hemorrhage (ICH) while on antiplatelet therapy (antiplatelet-related ICH) represents an important medical dilemma. We aimed to study the long-term cardiovascular outcomes of antiplatelet-related ICH survivors, and the risk of recurrent ICH with antiplatelet resumption. This was an observational study of 109 antiplatelet-related ICH survivors. The clinical end points were recurrent ICH, ischemic vascular events, and vascular death (fatal ICH or ischemic vascular events). Predictors of recurrent ICH and vascular death were derived using a multivariable Cox regression model. The median duration of follow-up was 3.5 years (interquartile range, 1.6-5.8 years). Ischemic vascular events were more common than recurrent ICHs (6.8 per 100 patient-years vs. 2.6 per 100 patient-years; P= 0.028). Antiplatelet use was not associated with an elevated risk of recurrent ICH (hazard ratio [HR], 1.11,95% confidence interval [CI], 0.27-4.62). A mean follow-up systolic blood pressure of >140 mmHg increased the risk of both recurrent ICH (HR, 4.28; 95%CI,1.01-18.11) and vascular death (HR, 11.14; 95%CI, 2.72-45.62). Cerebral amyloid angiopathy (CAA) was an independent predictor for recurrent ICH (HR, 24.34; 95% CI, 2.80-211.47). Antiplatelet resumption after antiplatelet-related ICH did not appear to carry a clinically significant risk of recurrent ICH, whereas inadequate blood pressure control and CAA contributed to a more robust risk. Antiplatelet resumption should be considered, especially in survivors with adequate blood pressure control and without CAA.

Total small vessel disease score and risk of recurrent stroke: Validation in 2 large cohorts.

Objective:In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke.Methods:Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered.Results:In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16–1.51, p < 0.0001; c statistic 0.61, 0.56–0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11–2.13, p = 0.009; c statistic 0.65, 0.54–0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59–0.74, p < 0.0001 and 0.60, 0.55–0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60–0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56–0.65, phet = 0.76) on internal validation.Conclusions:The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.

Previous hypertensive hemorrhage increases the risk for bleeding and ischemia for PCI patients on dual antiplatelet therapy

Objectives: The use of antiplatelet therapy after intracerebral hemorrhage remains controversial, while the use of dual antiplatelet therapy (DAPT) is required after cardiac stenting. In this study, we examine the risk of bleeding and ischemic events for PCI patients with a history of hypertensive hemorrhage on DAPT.Methods: A total of 128 cases and 153 controls were selected from Chinese patients with cardiac stenting on dual anti-platelet therapy for a single-center retrospective case-control study. Patients with a history of hypertensive hemorrhage were selected for the case group, while patients with a history of hypertension were chosen as control. All patients were on aspirin 100 mg and clopidogrel 75 mg after cardiac stenting, and were followed for a duration of 12–48 months. The primary outcomes were intracerebral hemorrhage, major bleeding, and major adverse cardiovascular and cerebrovascular events.Results: A history of previous hypertensive hemorrhage was not found to be a risk factor for intracerebral hemorrhage and major bleeding while on dual anti-platelet therapy. However, a history of either hypertensive hemorrhage or coronary artery disease was independently found to be risk factors for major adverse cardiovascular and cerebrovascular events. On sub-group analysis, patients with a history of hypertensive hemorrhage within 12 months were found to be at higher risk for bleeding on dual anti-platelet therapy, while patients with history of hypertensive hemorrhage outside of 12 months on dual anti-platelet therapy did not have the same increased risk.Conclusion: A history of hypertensive hemorrhage and coronary heart disease were two independent risk factors for major adverse cardiovascular and cerebrovascular events in PCI patients taking DAPT. A history of hypertensive hemorrhage less than 12 months had an increased risk for recurrent intracerebral hemorrhage and major bleeding in PCI patients taking DAPT.

Abstract 212: Cortical Superficial Siderosis and Risk of Recurrent Intracerebral Haemorrhage in Cerebral Amyloid Angiopathy: A Meta-analysis

Background: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre. Methods: We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis. Results: Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (&gt;3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I 2 : 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p&lt;0.0001, I 2 : 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p&lt;0.0001, I 2 : 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age. Conclusions: Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.