Antiseizure medication is typically used as primary prevention for patients with intracerebral haemorrhage of high severity, and these drugs have not generally shown any association with improved ...functional outcome.4–6 Findings of a small randomised controlled trial (n=72) comparing valproate with placebo did not show any difference between groups in occurrence of seizures at 1 year, the primary endpoint, although a significant improvement in the National Institutes of Health Stroke Scale (NIHSS) at 12 months, a secondary endpoint, was noted with valproate.7 These unresolved issues are important for improving the management of patients with acute intracerebral haemorrhage. A larger admission intracerebral haemorrhage volume and younger age are components of the CAVE score, which estimates development of late seizures after intracerebral haemorrhage.9 Moreover, more deaths were reported in the placebo group (n=6) than in the levetiracetam group (n=3), and adverse events were more common, suggesting a higher severity of intracerebral haemorrhage—a well established risk factor for seizures—in the placebo group.1,2 However, in patients in the levetiracetam group, the location of their intracerebral haemorrhage was frequently lobar, more patients in this group had a previous ischaemic stroke, and the duration of interpretable continuous EEG was longer (by about 20%) compared with the placebo group. ...logistic, financial, and technical factors with implementation of continuous EEG (leading to missing data and poor recruitment in this study) remain challenges for achieving the sample size required in clinical trials to test effectiveness of seizure prophylaxis to improve clinical outcomes.
Observational data indicate that haemorrhagic transformation occurs in up to 46% of patients, with variable contributions to functional outcome.1 The association of high blood pressure with increased ...risk of intraparenchymal haemorrhage after reperfusion favours the use of lower blood pressures targets (systolic blood pressure goal of <140 mm Hg),2 although evidence comes from studies with differing inclusion criteria and definitions of haemorrhagic complications, modest differences in mean and maximum systolic blood pressure between good and poor outcome groups, and underpowered hypothesis-generating designs. Importantly, BP-TARGET showed that intensive blood pressure management did not reduce the risk of reperfusion injury, as measured by the presence of radiographic intraparenchymal haemorrhage. The average systolic blood pressure, however, suggests a U-shaped association with the primary outcome, with the lowest haemorrhage rates at 110–140 mm Hg compared with the extremes, similar to reported observational data.5 A second limitation is that BP-TARGET did not evaluate other (potentially more impactful) dynamic blood pressure parameters, such as blood pressure change (from baseline to study end) and blood pressure variability (standard deviation and successive variation).
A care bundle is a small but crucial set of treatments that, when implemented together, can improve outcomes.1 Acute spontaneous intracerebral haemorrhage has few effective treatments and ...intracerebral haemorrhage-specific recommendations for care bundles.2,3 In clinical practice, intracerebral haemorrhage is often approached with negativity.4 Moreover, the synergistic benefits of specialised nursing care, neurointensive and neurosurgical care, blood pressure control, reversal of coagulopathy, and other interventions have not been ascertained.5 In The Lancet, Lu Ma and colleagues6 report the results of INTERACT3, a cluster randomised, pragmatic, multicentre, blinded endpoint, stepped wedge controlled trial performed in 144 hospitals in ten predominantly low-income and middle-income countries to investigate the efficacy and safety of a care bundle incorporating early intensive blood pressure lowering and management protocols for hyperglycaemia, pyrexia, and abnormal anticoagulation in patients with intracerebral haemorrhage presenting within 6 h of symptom onset. The percentage of patients with the early withdrawal of active life support was minimal (<1%), but patient location after hospital admission might have been a bias since intensive care unit admission was 5% higher in the care bundle group than the usual care group, as was the use of intravenous blood pressure lowering treatments on days 2–7, typically an intensive care unit intervention. ...the absence of level 1 evidence for all bundle components might affect acceptance, especially for blood pressure control, where guidelines have differed.6–8 INTERACT 3 is promising, demonstrating that an intracerebral haemorrhage care bundle focused on physiological control interventions, whether synergistic or not, might promote better outcomes in hospitals where care has not previously optimised sustained interventions.
Antithrombotic therapy is a cornerstone of primary and secondary prevention of ischaemic coronary artery disease and stroke; up to 44% of patients who present with spontaneous intracerebral ...haemorrhage are taking antithrombotics.1,2 Clinicians commonly face the challenging decision of whether to restart antithrombotic therapy and, if so, when because of a perceived increased risk of recurrent intracerebral haemorrhage.2,3 Nevertheless, we know that survivors face a major ongoing risk of death in the decade after an event.4 Observational studies report decreased incidence of ischaemic cardiovascular events in patients with intracerebral haemorrhage who started antiplatelet therapy after the event, with no increased risk of recurrent intracerebral haemorrhage and no worse functional outcomes.5–8 These data are compromised from event misclassification, ascertainment bias, and, most substantially, confounding by indication. The study, however, did not achieve the required sample size of 720 subjects with at least 2 years of follow-up. ...exposure to the planned sample of different individuals with intracerebral haemorrhage did not occur. ...the primary outcome is in part driven by a low proportion of non-lobar haemorrhage in patients on antiplatelet therapy (3·9% vs 11·8% in those avoiding antiplatelet therapy).
BACKGROUND AND PURPOSE—The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to ...summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism.
METHODS—We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes.
RESULTS—Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25–0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58–1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses.
CONCLUSIONS—In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk–benefit profile of anticoagulation resumption after ICH.
Although intracerebral hemorrhage (ICH) is a devastating disease worldwide, the pathologic changes in ultrastructure during the acute and chronic phases of ICH are poorly described. In this study, ...transmission electron microscopy was used to examine the ultrastructure of ICH-induced pathology. ICH was induced in mice by an intrastriatal injection of collagenase. Pathologic changes were observed in the acute (3 days), subacute (6 days), and chronic (28 days) phases. Compared with sham animals, we observed various types of cell death in the injured striatum during the acute phase of ICH, including necrosis, ferroptosis, and autophagy. Different degrees of axon degeneration in the striatum were seen in the acute phase, and axonal demyelination was observed in the ipsilateral striatum and corpus callosum at late time points. In addition, phagocytes, resident microglia, and infiltrating monocyte-macrophages were present around red blood cells and degenerating neurons and were observed to engulf red blood cells and other debris. Many synapses appeared abnormal or were lost. This systematic analysis of the pathologic changes in ultrastructure after ICH in mice provides information that will be valuable for future ICH pathology studies.
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