Blood pressure management in acute stroke

Blood pressure (BP) is elevated in 75% or more of patients with acute stroke and is associated with poor outcomes. Whether to modulate BP in acute stroke has long been debated. With the loss of normal cerebral autoregulation, theoretical concerns are twofold: high BP can lead to cerebral oedema, haematoma expansion or haemorrhagic transformation; and low BP can lead to increased cerebral infarction or perihaematomal ischaemia. Published evidence from multiple large, high-quality, randomised trials is increasing our understanding of this challenging area, such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke. Here we review the evidence for BP modulation in acute stroke, discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit

The role of glyceryl trinitrate, a nitric oxide donor, in acute stroke

Nitric oxide donors (e.g. glyceryl trinitrate (GTN)) are candidate treatments for acute stroke with haemodynamic, reperfusion, and neuroprotective properties. In order to establish the safety and efficacy of NO donors in acute stroke a Cochrane systematic review and meta-analysis was performed. Transdermal GTN was assessed in 5 trials (n=4197) in acute stroke. Overall, GTN was safe and lowered blood pressure but did not influence clinical outcome. However, early treatment with GTN within 6 hours (n=312) improved clinical outcomes across a variety of domains (death and dependency, death, disability, cognition, mood, and quality of life). Using data from the large Efficacy of Nitric Oxide in Stroke (ENOS) trial, the haemodynamic properties of GTN were explored. GTN lowered BP and its derivatives including BP variability. Further, increased BP variability was associated with poor functional and cognitive outcomes and increased death at day 90. The safety and efficacy of transdermal GTN in important subgroups in acute stroke was assessed. GTN was safe in the context of blood markers of dehydration with no precipitous drops in BP seen in such patients. GTN in the context of ipsilateral or bilateral carotid stenosis was safe and may improve outcome in severe ipsilateral carotid stenosis. Although GTN was safe, it did not improve outcome in patients with lacunar syndromes either overall or within 6 hours of onset. Baseline imaging markers of small vessel disease and ‘brain frailty’ were associated with functional and cognitive outcomes 90 days after stroke. In summary, this thesis has confirmed the safety of transdermal GTN in acute stroke both overall and in important subgroups. Mechanistic data suggest that GTN may reduce BP variability, which seems to be more strongly associated with outcome than absolute BP or trend in BP. Transdermal GTN is safe to be administered in acute stroke patients with elevated BP prior to blood markers of dehydration or carotid stenosis status being known. Baseline imaging markers of SVD and ‘brain frailty’ predict clinical outcome and should be used as minimisation criteria in future acute stroke trials and may help guide future clinical decision-making

Acute treatment of stroke (except thrombectomy)

Purpose of Review: The management of patients with acute stroke has been revolutionized in recent years with the advent of new effective treatments. In this rapidly evolving field, we provide an update on the management of acute stroke excluding thrombectomy, looking to recent, ongoing, and future trials.Recent Findings: Large definitive trials have provided insight into acute stroke care including broadening the therapeutic window for thrombolysis, alternatives to standard dose alteplase, the use of dual antiplatelet therapy early after minor ischemic stroke, and treating elevated blood pressure in intracerebral hemorrhage. Further ongoing and future trials are eagerly awaited in this ever-expanding area.Summary: Although definitive trials have led to improvements in acute stroke care, there remains a need for further research to improve our understanding of pathophysiological mechanisms underlying different stroke types with the potential for treatments to be tailored to the individual

The Spatial Extent of (U)LIRGs in the Mid-Infrared. II. Feature Emission

We present results from the second part of our analysis of the extended mid-infrared (MIR) emission of the Great Observatories All-Sky LIRG Survey (GOALS) sample based on 5-14 micron low-resolution spectra obtained with the IRS on Spitzer. We calculate the fraction of extended emission as a function of wavelength for all galaxies in the sample, FEE_lambda, and spatially separate the MIR spectrum of galaxies into their nuclear and extended components. We find that the [NeII] emission line is as compact as the hot dust MIR continuum, while the polycyclic aromatic hydrocarbon (PAH) emission is more extended. The 6.2 and 7.7 micron PAH emission is more compact than that of the 11.3 micron PAH, which is consistent with the formers being enhanced in a more ionized medium. The presence of an AGN or a powerful nuclear starburst increases the compactness of the hot dust MIR continuum, but has a negligible effect on the spatial extent of the PAH emission on kpc-scales. Globally, the spectra of the extended emission component are homogeneous for all galaxies in GOALS. This suggests that the physical properties of star formation taking place at distances farther than 1.5 kpc from the nuclei of (U)LIRGs are very similar, resembling local star-forming galaxies with L_IR < 10^11 Lsun, as well as star formation-dominated ULIRGs at z~2. In contrast, the MIR spectra of the nuclear component of local (U)LIRGs are very diverse. This implies that the observed variety of their integrated MIR properties arise, on average, only from the processes that are taking place in their cores.Comment: 16 pages, 7 figures, accepted for publication in Ap

Results from the tranexamic acid for primary intracerebral haemorrhage-2 (TICH-2) trial

Background: Haematoma expansion leads to worse outcome in intracerebral haemorrhage (ICH). Tranexamic acid (TXA) is a promising haemostatic agent to prevent haematoma expansion and improve outcome after ICH. Methods: TICH-2 is a multicentre prospective double blind randomised controlled trial, which recruited patients presenting within 8 hours of primary ICH to receive intravenous TXA or placebo. Primary outcome is modified Rankin Scale at day 90 and will be analysed using ordinal logistic regression, adjusted for minimisation criteria. Secondary outcomes will be analysed using adjusted binary logistic regression and multiple linear regression; these include haematoma expansion at 24 hours, day 7 National Institute of Health Stroke Scale (NIHSS), day 90 Barthel Index, quality of life, cognition and mood. Results: A total of 2325 patients were recruited between 14th March 2013 and 30th September 2017, from 12 countries: United Kingdom (n= 1910), Italy, Georgia, Switzerland, Malaysia, Hungary, Poland, Ireland, Turkey, Sweden, Denmark and Spain. Randomisation characteristics included: age 68.9 (13.8) years; male 1301 (56.0%); time from onset to randomisation 3.6 hours [2.6, 5.0]; NIHSS 13 (7.5); Glasgow coma scale 13.4 (2.1); systolic blood pressure 172.6 (27.2) mmHg; intraventricular haemorrhage 745 (32.0%) and prior antiplatelet use 610 (26.2%). Conclusion: TICH-2 is the largest trial of TXA in spontaneous ICH and recruited over its original target of 2000 patients. The results will be available in May 2018 and will inform whether TXA should be recommended for the treatment of acute spontaneous ICH

Blood pressure management in acute stroke

Blood pressure (BP) is elevated in 75% or more of patients with acute stroke and is associated with poor outcomes. Whether to modulate BP in acute stroke has long been debated. With the loss of normal cerebral autoregulation, theoretical concerns are twofold: high BP can lead to cerebral oedema, haematoma expansion or haemorrhagic transformation; and low BP can lead to increased cerebral infarction or perihaematomal ischaemia. Published evidence from multiple large, high-quality, randomised trials is increasing our understanding of this challenging area, such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke. Here we review the evidence for BP modulation in acute stroke, discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit