Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population-Based Stroke Registry.

BACKGROUND: We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population-based stroke registry and provided data to inform on the figures of the disease in women and in men. METHODS AND RESULTS: Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30-day and 1-year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first-ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years; P<0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 [interquartile range, 6-20] versus 9 [interquartile range, 4-15], respectively; P=0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0-22.6) per 100 000 person-years in women and 30.2 (95% CI, 27.4-33.2) per 100 000 person-years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 [95% CI, 0.58-0.78]; P<0.001) and did not change over time in both sexes (P for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1-year case-fatality rates in women versus men (48.5% versus 40.1%; P=0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality. CONCLUSIONS: We found lower ICH incidence in women than in men. However, women showed a higher 1-year case-fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.

Epidemiology and outcomes of intracerebral hemorrhage associated with oral anticoagulation over 10 years in a population-based stroke registry.

BACKGROUND: Recent years have seen a change in the use of anticoagulants in the general population due to the availability of direct oral anticoagulants (DOACs) as an alternative to vitamin K antagonists (VKAs) and increased detection of atrial fibrillation. It is important to have updated epidemiological data to understand how this change is impacting on the occurrence and outcome of intracerebral hemorrhage (ICH). PATIENTS AND METHODS: Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Oral anticoagulants (OAC)-related ICH was defined as an ICH occurring within 48 h from the intake of DOAC or VKAs, regardless of the measured international normalized ratio on hospital admission. RESULTS: We included 748 first-ever ICH, of whom 108 (14.4%) were OAC-related. Specifically, 75 (69.4%) ICHs occurred on VKA and 33 (30.6%) on DOAC. The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) was stable over time (p = 0.226). Among OAC-ICHs, we observed an increase in the overall incidence of DOAC-ICH (p for trend < 0.001) which overcome that of VKA-ICH in 2020 (incidence rate ratio (IRR) 4.71, 95% confidence interval (CI): 1.22-33.54; p = 0.022). Patients with OAC-ICH showed higher 30-day case fatality rates than those with non-OAC-ICH (48.1% vs 34.1%; p = 0.007). CONCLUSION: No changes over time were detected in the incidence of OAC-ICH, but throughout the study period, there was a change in OAC-ICH from mostly VKA-related to mostly DOAC-related. Mortality in patients with OAC-ICH was higher than in patients with non-OAC-ICH.

Predictors for hemorrhagic transformation and cerebral edema in stroke patients with first-pass complete recanalization.

BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.

Mechanical thrombectomy in patients with heart failure: the Italian registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: Heart failure (HF) is the second most important cardiac risk factor for stroke after atrial fibrillation (AF). Few data are available on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with HF. METHODS: The source of data is the multicentre Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). All AIS patients ≥ 18 years receiving MT were categorised in two groups: HF and no-HF. Baseline clinical and neuroradiological findings on admission were analysed. RESULTS: Of 8924 patients, 642 (7.2%) had HF. Compared to the no-HF group, HF patients had higher prevalence of cardiovascular risk factors. Rate of complete recanalisation (TICI 2b-3) was 76.9% in HF vs 78.1% in no-HF group (p = 0.481). Rate of symptomatic intracerebral haemorrhage at 24-h non-contrast computed tomography (NCCT) was 7.6% in HF vs 8.3% in no-HF patients (p = 0.520). At 3 months, 36.4% of HF patients and 48.2% of no-HF patients (p < 0.001) had mRS 0-2, and mortality was, respectively, 30.7% and 18.5% (p < 0.001). In multivariate logistic regression, HF was independently associated with mortality at 3 months (OR 1.53, 1.24-1.88 95% CI, p < 0.001). In multivariate ordinal regression, HF patients had a probability of transitioning to a higher mRS level of 1.23 (1.05-1.44 95% CI, p = 0.012). The propensity score analysis of two groups matched for age, sex, and NIHSS at admission yielded the same results. CONCLUSION: MT is safe and effective in HF patients with AIS. Patients with HF and AIS suffered from higher 3-month mortality and unfavourable outcome regardless of acute treatments.

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

BACKGROUND AND OBJECTIVES: The 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). METHODS: This 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 ßiomarkers 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. RESULTS: The 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). DISCUSSION: These 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 ß-amyloid-driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.

Cerebral Amyloid Angiopathy-Related Inflammation: Report of a Case with Very Difficult Therapeutic Management.

Background. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature. Case Report. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of elevated anti-amyloid autoantibodies in the cerebrospinal fluid (CSF). Steroid therapy produced significant improvements in clinical and investigational assessments, but after two months, it caused Acute Respiratory Distress Syndrome. After steroid therapy discontinuation the patient presented a rapidly progressive dementia, Guillain-Barré syndrome, new cerebral ischemic lesions, and thrombosis of the right cephalic and subclavian veins that were treated with subcutaneous heparin. After a week the patient died because of brain hemorrhage. Conclusion. This case suggests caution in steroid therapy discontinuation and antithrombotic therapy administration in patients with CAA-ri. The CSF search of anti-amyloid autoantibodies could be helpful to support the diagnosis.