The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage.
We analyzed data referring to our prospective population-based registry, including patients with a ...first-ever stroke followed up to 10 years.
In a 5-year period, we included 549 patients (247 men and 302 women; mean age+/-SD, 73.6+/-12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100000 (95% CI, 33.8 to 40.0), 32.9 per 100000 when standardized to the 2006 European population, and 15.9 per 100000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7- and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan-Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1).
Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.
Diabetic retinopathy (DR), diabetic macular edema (DME), and cardiovascular disease (CVD) resulting from vascular damage from persistently elevated blood glucose levels are among the serious ...secondary pathologies associated with long-standing diabetes mellitus. The established link between DR and CVD suggests the need for appropriate and early management of patients with diabetes to minimize CV risk. This is of particular importance in patients with recent, or a history of, major CV events. Early management of DR is a complex task that requires comprehensive evaluation and a multidisciplinary approach to manage complications, risk factors, and interactions between different aspects of the disease. Anti-vascular endothelial growth factor (VEGF) agents have become an important therapeutic modality in ophthalmology. However, their use is contraindicated in patients with DR and/or DME with a CV event in the previous 3 months. In patients with DME, corticosteroids target the multifaceted inflammatory pathways involved in the pathogenesis of DR, with a broader spectrum of action than anti-VEGF agents. In this context, recent guidelines suggest the use of corticosteroids, and in particular dexamethasone intravitreal implant, as a well-tolerated and efficacious first-line treatment in patients with high CV risk, such as a history of or recent major CV events. This review focuses on the subset of diabetic patients with a prior CV event, DR, and DME and discusses the need for a holistic approach in evaluating the optimal therapeutic choice for the care of the individual patient, supported by real-world clinical experience on long-term dexamethasone intravitreal implant therapy.
Symptomatic intracerebral hemorrhage (sICH) is a rare but the most feared complication of intravenous thrombolysis for ischemic stroke. We aimed to develop and validate a nomogram for individualized ...prediction of sICH in intravenous thrombolysis-treated stroke patients included in the multicenter SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register).
All patients registered in the SITS-ISTR by 179 Italian centers between May 2001 and March 2016 were originally included. The main outcome measure was sICH per the European Cooperative Acute Stroke Study II definition (any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline or death <7 days). On the basis of multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver-operating characteristic curve and calibration of risk prediction model by using the Hosmer-Lemeshow test.
A total of 15 949 patients with complete data for generating the nomogram was randomly dichotomized into training (3/4; n=12 030) and test (1/4; n=3919) sets. After multivariate logistic regression, 10 variables remained independent predictors of sICH to compose the STARTING-SICH (systolic blood pressure, age, onset-to-treatment time for thrombolysis, National Institutes of Health Stroke Scale score, glucose, aspirin alone, aspirin plus clopidogrel, anticoagulant with INR ≤1.7, current infarction sign, hyperdense artery sign) nomogram. The area under the receiver-operating characteristic curve of STARTING-SICH was 0.739. Calibration was good (
=0.327 for the Hosmer-Lemeshow test).
The STARTING-SICH is the first nomogram developed and validated in a large SITS-ISTR cohort for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients.
This review provides an updated analysis of the main aspects involving the diagnosis and the management of children with acute ischemic stroke. Acute ischemic stroke is an emergency of rare ...occurrence in children (rate of incidence of 1/3500 live birth in newborns and 1–2/100,000 per year during childhood with peaks of incidence during the perinatal period, under the age of 5 and in adolescence). The management of ischemic stroke in the paediatric age is often challenging because of pleomorphic age-dependent risk factors and aetiologies, high frequency of subtle or atypical clinical presentation, and lacking evidence-based data about acute recanalization therapies. Each pediatric tertiary centre should activate adequate institutional protocols for the optimization of diagnostic work-up and treatments.
Conclusion
: The implementation of institutional standard operating procedures, summarizing the steps for the selection of candidate for neuroimaging among the ones presenting with acute neurological symptoms, may contribute to shorten the times for thrombolysis and/or endovascular treatments and to improve the long-term outcome.
What is Known:
•Acute ischemic stroke has a higher incidence in newborns than in older children (1/3500 live birth versus 1–2/100,000 per year).
•Randomized clinical trial assessing safety and efficacy of thrombolysis and/or endovascular treatment were never performed in children
What is New:
•Recent studies evidenced a low risk (2.1% of the cases) of intracranial haemorrhages in children treated with thrombolysis.
•A faster access to neuroimaging and hyper-acute therapies was associated with the implementation of institutional protocols for the emergency management of pediatric stroke.
Summary Background Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual ...patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. Methods We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0–1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Findings Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0·0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2·55 (95% CI 1·44–4·52) for 0–90 min, 1·64 (1·12–2·40) for 91–180 min, 1·34 (1·06–1·68) for 181–270 min, and 1·22 (0·92–1·61) for 271–360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5·2%) of 1850 patients assigned to alteplase and 18 (1·0%) of 1820 controls, with no clear relation to OTT (p=0·4140). Adjusted odds of mortality increased with OTT (p=0·0444) and were 0·78 (0·41–1·48) for 0–90 min, 1·13 (0·70–1·82) for 91–180 min, 1·22 (0·87–1·71) for 181–270 min, and 1·49 (1·00–2·21) for 271–360 min. Interpretation Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4·5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4·5 h, risk might outweigh benefit. Funding None.
Summary Background Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of ...intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. Methods We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24–36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale NIHSS); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90–180 days. Findings Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 6·8% of 3391 patients allocated alteplase vs 44 1·3% of 3365 patients allocated control; odds ratio OR 5·55 95% CI 4·01–7·70; absolute excess 5·5% 4·6–6·4); of SITS-MOST haemorrhage (124 3·7% of 3391 vs 19 0·6% of 3365; OR 6·67 4·11–10·84; absolute excess 3·1% 2·4–3·8); and of fatal intracerebral haemorrhage (91 2·7% of 3391 vs 13 0·4% of 3365; OR 7·14 3·98–12·79; absolute excess 2·3% 1·7–2·9). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8–2·6%) for strokes with NIHSS 0–4 to 3·7% (2·1–6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% 4·0% to 9·5%) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% 1·5% to 3·0%) and the increased risk of any death within 90 days (0·9% –1·4% to 3·2%). Interpretation Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke. Funding UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.
Objectives
Aim of this study was to evaluate the association between cerebral microbleeds (CMBs) and white matter disease (WMD) with intracerebral hemorrhage (ICH) after intravenous thrombolysis ...(IVT) with rt-PA. We also evaluated whether CMBs characteristics and WMD burden correlate with symptomatic ICH and outcome.
Methods
We included acute ischemic stroke (AIS) patients treated with IVT. The number and location of CMBs as well as severity of WMD were rated analyzing pre- or post-treatment MRI. Multivariable regression analysis was used to determine the impact of CMB and WMD on ICH subgroups and outcome measures.
Results
434 patients were included. CMBs were detected in 23.3% of them. ICH occurred in 34.7% of patients with CMBs. Independent predictors of parenchymal hemorrhage were the presence of CMBs (OR 2.724, 95% CI 1.360–5.464,
p
= 0.005) as well as cortical-subcortical stroke (OR 3.629, 95% CI 1.841–7.151,
p
< 0.001) and atherothrombotic stroke subtype (OR 3.381, 95% CI 1.335–8.566,
p
= 0.010). Either the presence, or number, and location of CMBs, as well as WMD, was not independently associated with the development of SICH. No independent association between the presence, number, or location of CMBs or WMD and outcome measures was observed.
Conclusions
The results of our study suggest that the exclusion of eligible candidates to administration of IV rt-PA only on the basis of CMBs presence is not justified. The clinical decision should be weighed with a case-by-case approach. Additional data are needed to evaluate the benefit-risk profile of rt-PA in patients carrying numerous microbleeds.
Summary Background In September, 2008, the European Acute Stroke Study III (ECASS III) randomised trial and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry ...(SITS-ISTR) observational study reported the efficacy and safety of the extension of the time window for intravenous alteplase treatment from within 3 h to within 4·5 h after stroke onset. We aimed to assess the implementation of the wider time window, its effect on the admission-to-treatment time, and safety and functional outcome in patients recorded in SITS-ISTR. Methods Patients treated according to the criteria of the European Summary of Product Characteristics, except for the time window, were included. Patients were grouped according to whether they were registered into SITS-ISTR before or after October, 2008. We measured admission-to-treatment time and rates of symptomatic intracerebral haemorrhage, mortality, and functional independence at 3 months. Findings 23 942 patients were included in SITS-ISTR between December, 2002, and February, 2010, of whom 2376 were treated 3–4·5 h after symptom onset. The proportion of patients treated within 3–4·5 h by the end of 2009 was three times higher than in the first three quarters of 2008 (282 of 1293 22% vs 67 of 1023 7%). The median admission-to-treatment time was 65 min both for patients registered before and after October, 2008 (p=0·94). 352 (2%) of 21 204 patients treated within 3 h and 52 (2%) of 2317 treated within 3–4·5 h of stroke had symptomatic intracerebral haemorrhage at 3 months (adjusted odds ratio OR 1·44, 95% CI 1·05–1·97; p=0·02). 2287 (12%) of 18 583 patients who were treated within 3 h and 218 (12%) of 1817 who were treated within 3–4·5 h had died by the 3-month follow-up (adjusted OR 1·26, 95% CI 1·07–1·49; p=0·005); 10 531 (57%) of 18 317 patients treated within 3 h of stroke and 1075 (60%) of 1784 who were treated within 3–4·5 h were functionally independent at 3 months (adjusted OR 0·84, 95% CI 0·75–0·95; p=0·005). Interpretation Since October, 2008, thrombolysis within 3–4·5 h after stroke has been implemented rapidly, with a simultaneous increase in the number of patients treated within 3 h; admission-to-treatment time has not increased. Safety and functional outcomes are less favourable after 3 h, but the wider time window now offers an opportunity for treatment of those patients who cannot be treated earlier. Thrombolysis should be initiated within 4·5 h after onset of ischaemic stroke, although every effort should be made to treat patients as early as possible after symptom onset. Funding Boehringer Ingelheim, Ferrer, the European Union Public Health Executive Authority, and Medical Training and Research (ALF) from Stockholm County Council and Karolinska Institutet.
Background
Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke ...patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo.
Methods
Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events.
Results
The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53).
Conclusions
Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
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