Explore the vast range of titles available.

Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH. We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART. Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0–5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8–3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6–7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0–3·3; hazard ratio [HR] 3·2, 95% CI 1·6–6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0–3·2, vs 1·6 per 100 patient-years, 0·6–4·4; HR 1·1, 95% CI 0·5–2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0–10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2–4·7; HR 0·9, 95% CI 0·4–2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7–10·9, vs 0·7 per 100 patient-years, 0·1–5·6; HR 8·2, 3·3–20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0–24·1, vs 6·8 per 100 patient-years, 3·6–12·5; HR 1·78, 95% CI 1·16–2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6–7·5, vs 0·9 per 100 patient-years, 0·2–4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9–6·0, vs 4·4 per 100 patient-years, 2·6–6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9–5·9, vs 5·3 per 100 patient-years, 3·3–7·2). The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials. UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre.

We sought to summarize Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) features of intracerebral hemorrhage (ICH) associated with cerebral amyloid angiopathy (CAA) in published observational radio-pathological studies. In November 2016, two authors searched OVID Medline (1946-), Embase (1974-) and relevant bibliographies for studies of imaging features of lobar or cerebellar ICH with pathologically proven CAA (\"CAA-associated ICH\"). Two authors assessed studies' diagnostic test accuracy methodology and independently extracted data. We identified 22 studies (21 cases series and one cross-sectional study with controls) of CT features in 297 adults, two cross-sectional studies of MRI features in 81 adults and one study which reported both CT and MRI features in 22 adults. Methods of CAA assessment varied, and rating of imaging features was not masked to pathology. The most frequently reported CT features of CAA-associated ICH in 21 case series were: subarachnoid extension (pooled proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies) and an irregular ICH border (64%, 95% CI 32-91%, I2 = 85%, five studies). CAA-associated ICH was more likely to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA-associated ICH 7/41 vs. non-CAA ICH 0/42; χ2 = 7.8, p = 0.005). Superficial siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 = 35%, 3 studies). Subarachnoid extension and an irregular ICH border are common imaging features of CAA-associated ICH, but methodologically rigorous diagnostic test accuracy studies are required to determine the sensitivity and specificity of these features.

Brain banks are used to gather, store, and provide human brain tissue for research and have been fundamental to improving our knowledge of the brain in health and disease. To maintain this role, the legal and ethical issues relevant to the operations of brain banks need to be more widely understood. In recent years, researchers have reported that shortages of high-quality brain tissue samples from both healthy and diseased people have impaired their efforts. Closer collaborations between brain banks and improved strategies for brain donation programmes will be essential to overcome these problems as the demand for brain tissue increases and new research techniques become more widespread, with the potential for substantial scientific advances in increasingly common neurological disorders.

Samarasekera N, Rodrigues MA, Toh PS, Al-Shahi Salman R (2017) Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: PLoS ONE12(7): e0180923. https://doi.org/10.1371/journal.pone.0180923 Citation: Samarasekera N, Rodrigues MA, Toh PS, Al-Shahi Salman R (2017) Correction: Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: Samarasekera N, Rodrigues MA, Toh PS, Salman RA-S (2017) Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy:

AimsPharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not been previously studied in humans after ICH. Our study aims to address this gap.MethodsWe selected cases with fatal ICH from a prospective community-based inception cohort study and age-matched and sex-matched controls who died suddenly of non-neurological disease. We used immunohistochemistry to quantify Nrf2 (% total area stained overall and % of nuclei stained) and CD68 expression in controls and perihaematomal, ipsilateral and contralateral brain tissue from cases. We measured downstream haem oxygenase-1 (HMOX1) and NAD(P)H dehydrogenase quinone 1 [NQO1] expression using RNA in situ hybridisation.Results26 ICH cases (median age: 82 (IQR 76–86); 13 (50%) male) and eight controls (median age: 79 (IQR 77–80); 3 (37.5%) male) were included. We found no significant differences in overall % of Nrf2 staining between ICH cases and controls. However, the mean % of nuclei staining for Nrf2 seemed higher in perihaematomal compared with contralateral regions, although this was only statistically significant >60 days after ICH (25% (95% CI 17% to 33%) vs 14% (95% CI 11% to 17%), p=0.029). The percentage of perihaematomal tissue staining for CD68 was higher >60 days after ICH (6.75%, 95% CI 2.78% to 10.73%) compared with contralateral tissue (1.45%, 95% CI 0.93% to 1.96%, p=0.027) and controls (1.08%, 95% CI 0.20% to 1.97%, p=0.0008). RNA in situ hybridisation suggested increased abundance of HMOX1 and NQO1 transcripts in perihaematomal versus distant ipsilateral brain tissue obtained <7 days from onset of ICH.ConclusionsWe found evidence of Nrf2 activation in human brain tissue after ICH. Pharmacological augmentation of Nrf2 activation after ICH might be a promising therapeutic approach.

Identification 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. We 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. Among 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). The 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. UK Medical Research Council, The Stroke Association, and The Wellcome Trust.

  ICH in animal models seems to trigger humoral and cellular inflammatory responses: the consequent migration and recruitment of neutrophils and activation of native microglia results in oxidative stress and neuronal necrosis [38],[39], cytokines such as tumour necrosis factor α and interleukin 1-β lead to apoptosis [40],[41], complement activation causes erythrocyte lysis [42], and matrix metalloproteinases may result in oedema, necrosis, and blood-brain barrier disruption [43].\\n Tramiprosate is a synthetic compound that competes with glycosaminoglycans for binding to β-amyloid peptide, reducing amyloid fibril formation and deposition, and demonstrated a good safety profile in a phase II study [70]. [...]treatments that have proven beneficial in animal models might translate from the bench to the bedside, although there are concerns about the rodent ICH models used and the methodological quality of animal experiments [45],[46],[73].

BackgroundInflammatory responses to intracerebral haemorrhage (ICH) are potential therapeutic targets. We aimed to quantify molecular markers of inflammation in human brain tissue after ICH compared with controls using meta-analysis.MethodsWe searched OVID MEDLINE (1946–) and Embase (1974–) in June 2020 for studies that reported any measure of a molecular marker of inflammation in brain tissue from five or more adults after ICH. We assessed risk of bias using a modified Newcastle-Ottawa Scale (mNOS; mNOS score 0–9; 9 indicates low bias), extracted aggregate data, and used random effects meta-analysis to pool associations of molecules where more than two independent case–control studies reported the same outcome and Gene Ontology enrichment analysis to identify over-represented biological processes in pooled sets of differentially expressed molecules (International Prospective Register of Systematic Reviews ID: CRD42018110204).ResultsOf 7501 studies identified, 44 were included: 6 were case series and 38 were case–control studies (median mNOS score 4, IQR 3–5). We extracted data from 21 491 analyses of 20 951 molecules reported by 38 case–control studies. Only one molecule (interleukin-1β protein) was quantified in three case–control studies (127 ICH cases vs 41 ICH-free controls), which found increased abundance of interleukin-1β protein after ICH (corrected standardised mean difference 1.74, 95% CI 0.28 to 3.21, p=0.036, I2=46%). Processes associated with interleukin-1β signalling were enriched in sets of molecules that were more abundant after ICH.ConclusionInterleukin-1β abundance is increased after ICH, but analyses of other inflammatory molecules after ICH lack replication. Interleukin-1β pathway modulators may optimise inflammatory responses to ICH and merit testing in clinical trials.

BackgroundThe aim of this study was to determine the strength of the association between intracerebral haemorrhage (ICH) and cerebral amyloid angiopathy (CAA) in a systematic review of published neuropathological studies.MethodsIn April 2011, Ovid Medline (from 1950) and Embase (from 1980) were searched for neuropathological studies that quantified the prevalence of CAA in patients with ICH and in a control group without ICH. Two authors extracted data from each study and meta-analysed their results using a random effects model.Results10 neuropathological cross sectional or case control studies were identified, involving 481 cases with ICH and 3219 controls. There was no association between CAA and ICH in any location (OR 1.21, 95% CI 0.87 to 1.68; 10 studies, I2 29%), deep ICH (OR 0.81, 95% CI 0.30 to 2.19; five studies, I2 58%) or cerebellar ICH (OR 2.05, 95% CI 0.55 to 7.63; four studies, I2 0%). CAA was significantly associated with lobar ICH, both overall (OR 2.21, 95% CI 1.09 to 4.45; six studies, I2 40%) and in the three studies where average ages for cases and controls were comparable (OR 3.24, 95% CI 1.02 to 10.26).ConclusionsThere is an association between CAA and lobar ICH, although the association might be stronger if potential confounding factors, distinctive clinical and imaging features of ICH due to CAA and CAA neuropathological severity are taken into account.

Objectives Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ε4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-ε4 and ε2 are associated with lobar ICH. The generally accepted explanation is that APOE-ε4 promotes vascular amyloid deposition, while APOE-ε2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence for these allele-specific effects. Methods We systematically identified published studies with data on APOE genotype and histopathological assessment of postmortem brains for CAA severity. We obtained unpublished data from these for meta-analyses of the effects of ε4-containing (ε4+) and ε2-containing (ε2+) genotypes on progression to severe CAA. Results Of six eligible studies (543 eligible participants), data were available from 5 (497 participants, 353 with CAA). Meta-analyses showed a possible association of ε4+ genotypes with severe CAA (ε4+ vs ε4−: severe vs mild/moderate CAA, OR 2.5, 95% CI 1.4 to 4.5, p=0.002; severe vs moderate CAA, OR 1.7, 95% CI 0.9 to 3.1, p=0.11). For ε2+ versus ε2− genotypes, there was no significant association, but the very small number of participants with ε2+ genotypes (22) precluded reliable estimates. Conclusions We found a possible association of severe CAA with APOE-ε4 but not APOE-ε2. However, our findings do not exclude a biologically meaningful association between APOE-ε2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms.