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Introduction: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality., Patients and Methods: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014., Results: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26)., Discussion and Conclusion: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Ciccone reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals.Dr Paciaroni reports compensation from SANOFI-AVENTIS U.S. LLC for other services; compensation from PFIZER CANADA INC for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services.The other Authors have nothing to disclose.

Objective: To investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH)., Methods: We performed a case-control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1-Q4)., Results: We analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively)., Conclusions: Our findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding., Methods: We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH., Results: We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32)., Conclusions: In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH., (© 2018 American Academy of Neurology.)

Whether to resume antithrombotic treatment after oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002-2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06-0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06-0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09-0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02-0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk., Competing Interests: None declared., (Schattauer GmbH Stuttgart.)

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated., Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH., Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones., Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: Diffusion-weighted imaging (DWI) studies focusing on apparent diffusion coefficient (ADC) abnormalities have provided conflicting results about the nature and fate of perihematomal edema., Methods: We investigated 35 patients with supratentorial spontaneous intracerebral hemorrhage (SICH) by using DWI scanning obtained at 48 h and 7 days after symptom onset. Regional ADC (rADC) values were measured in three manually outlined regions of interest: (1) the perihematomal hyperintense area, (2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim, and (3) a mirror area, including the clot and the perihematomal region, located in the contralateral hemisphere., Results: rADC mean levels were lower at 7 days than at 48 h in each ROI (p < 0.00001), showing a progressive normalization of initial vasogenic values. Perihematomal vasogenic rADC values were more frequent (p < 0.00001) at 48 h than at 7 days, whereas perihematomal cytotoxic and normal rADC levels were more represented (p < 0.02 and p < 0.001, respectively) at 7 days than at 48 h. A neurological worsening was more frequent (p < 0.02) in patients with than in those without perihematomal cytotoxic rADC values at 7 days., Conclusion: Our findings suggest that the transition from acute to subacute phases after SICH is characterized by a progressive resolution of perihematomal vasogenic edema associated with an increase in cytotoxic ADC values. In the subset of patients with perihematomal cytotoxic rADC levels in subacute stage after bleeding, irreversible damage development seems to be related to poor clinical outcome.

Introduction: We sought to quantify perfusion changes associated to acute spontaneous intracerebral hemorrhage (SICH) by means of computed tomography perfusion (CTP) imaging., Materials and Methods: We studied 89 patients with supratentorial SICH at admission CT by using CTP scanning obtained within 24 h after symptom onset. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV) and mean transit time (rMTT) levels were measured in four different regions of interest manually outlined on CT scan: (1) hemorrhagic core; (2) perihematomal low-density area; (3) 1 cm rim of normal-appearing brain tissue surrounding the perilesional area; and (4) a mirrored area, including the clot and the perihematomal region, located in the non-lesioned contralateral hemisphere., Results: rCBF, rCBV, and rMTT mean levels showed a centrifugal distribution with a gradual increase from the core to the periphery (p < 0.0001). Perfusion absolute values were indicative of ischemia in hemorrhagic core, oligemia in perihematomal area, and hyperemia in normal-appearing and contralateral areas. Perihematomal rCBF and rCBV mean levels were higher in small (< or = 20 ml) than in large (>20 ml) hematomas (p < 0.01 and p < 0.02, respectively)., Conclusion: Multi-parametric CTP mapping of acute SICH indicates that perfusion values show a progressive improvement from the core to the periphery. In the first 24 h, perihemorrhagic region was hypoperfused with CTP values which were not suggestive of ischemic penumbra destined to survive but more likely indicative of edema formation. These findings also argue for a potential influence of early amounts of bleeding on perihematomal hemodynamic abnormalities.

In this study, we investigated 40 patients (18 male, 22 female; mean age = 64.5 +/- 11.0; GCS = 9 to 14) with acute supratentorial spontaneous intracerebral hemorrhage (SICH) at admission by using a 1-tesla magnetic resonance imaging (MRI) unit equipped for single-shot echo-planar spin-echo isotropic diffusion-weighted imaging (DWI) sequences. All DWI studies were obtained within 48 hours after symptom onset. Regional apparent diffusion coefficient (rADC) values were measured in 3 different regions of interest (ROIs) drawn freehand on the T2-weighted images at b 0 s/mm2 on every section in which hematoma was visible: 1) the perihematomal hyperintense area; 2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim; 3) an area mirroring the region including the clot and perihematomal hyperintense area placed in the contralateral hemisphere. rADC mean values were higher in perihematomal hyperintense and in contralateral than in normal appearing areas (p < 0.001), with increased rADC mean levels in all regions examined. Our findings show that rADC values indicative of vasogenic edema were present in the perihematomal area and in normal appearing brain tissue located both ipsilateral and contralateral to the hematoma, with lower levels in non-injured areas located in the T2 hyperintense rim around the clot.

A single-section deconvolution-derived computerized tomographic perfusion imaging was performed in 45 patients (22 male and 23 female; mean age=69.89+/-10.07 years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF and rCBV were lower in the hemorrhagic core than in the perihematomal low density area (p<0.001), and in the perihematomal low density area than in normal appearing brain parenchyma (p<0.001). Mean rMTT values were higher in perihematomal low density area than in normal appearing area (p<0.01) and in both hemorrhagic and perihematomal area than in controlateral ROI (p<0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and controlateral areas. We found a concentric distribution of all CT perfusion parameters characterized by an improvement from the core to the periphery, with low perihematomal rCBF and rCBV values suggesting edema formation.