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 effect of transdermal glyceryl trinitrate in acute stroke patients with carotid stenosis: data from the Efficacy of Nitric Oxide in Stroke trial

Background: There is concern that blood pressure lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the context of carotid stenosis. The effect of glyceryl trinitrate (GTN) on outcome in acute stroke patients with carotid stenosis is unclear. We sought to assess GTN’s effect in this context using data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS randomised 4011 patients with acute stroke and raised systolic blood pressure to transdermal GTN or no GTN within 48 hours of onset. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split: 70%. Bilateral carotid stenosis was split: 50%. Data are odds ratios (OR) with 95% confidence intervals (CI) adjusted for baseline prognostic factors. Results: 2023 (60.5%) ischaemic stroke participants had carotid imaging. Compared with participants with 70% ipsilateral stenosis was associated with an unfavourable shift in mRS at 90 days (OR 1.88, 95% CI 1.44-2.44, p70% stenosis who received GTN had a favourable shift in mRS (OR 0.56, 95% CI 0.34-0.93, p=0.024) compared to those who received no GTN. Tendencies towards less dependency, albeit non-significant, were seen in 30-50% and 50-70% groups. No differences in mRS were seen across groups of bilateral stenosis or between those who received GTN or not. Conclusions:Severe ipsilateral carotid stenosis is associated with poorer functional outcome at 90 days following ischaemic stroke. GTN appears safe in acute stroke patients with ipsilateral or bilateral carotid stenosis

Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions

Ischaemic strokes evoke blood–brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions. Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection

Who should have a pre–discharge home assessment visit after a stroke? A qualitative study of occupational therapists' views

Introduction: The number of patients who have a pre-discharge home assessment visit following a stroke has been reported to vary nationally. The purpose of this research was to explore the factors influencing occupational therapists' decisions to complete such visits. Method: Semi-structured interviews were completed with 20 senior occupational therapists working with stroke in-patients, from a range of urban and rural locations in the United Kingdom. The interviews explored their views about those patients for whom a pre-discharge home assessment visit would and would not be required. The interviews were analysed using thematic analysis. Findings: Three themes were identified: the patient's level of physical, cognitive, or perceptual impairment and its impact on performance in activities of daily living; factors relating to the patient's home environment, including the availability of support within the home environment; and other influences on occupational therapists. The presence of a cognitive impairment was a particularly important factor. Conclusions: Occupational therapists balanced aspects from each of these themes in order to determine whether a visit was needed or not. Although the level of impairment was important, the most dependent patients were not necessarily those believed to be the most likely to need a visit

Elevated plasminogen activators are associated with hematoma progression in spontaneous intracerebral hemorrhage

Endogenous fibrinolysis might lead to hematoma progression in spontaneous intracerebral hemorrhage (ICH). We studied plasma biomarkers of fibrinolysis and hemostasis in twenty-two patients with ICH and nine healthy controls (HC) in a single-center study. Patients with ICH had significantly higher D-dimer and plasmin-alpha-2-antiplasmin complexes compared to HC. At baseline, patients with hematoma progression had higher urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) and lower plasminogen levels, compared to those with no progression. 24-hour and day-7 matrix metalloproteinase-9 (MMP-9) was significantly increased in patients with hematoma progression

Occupational therapy predischarge home visits for patients with a stroke (HOVIS): results of a feasibility randomized controlled trial

Objective: To assess the feasibility of conducting a randomized controlled trial of occupational therapy predischarge home visits for people after stroke. Design: Randomized controlled trial and cohort study. We randomized eligible patients for whom there was clinical uncertainty about the need to conduct a home visit to a randomized controlled trial; patients for whom a visit was judged ‘essential’ were enrolled into a cohort study. Setting: Stroke rehabilitation unit of teaching hospital. Participants: One hundred and twenty-six participants hospitalized following recent stroke. Interventions: Predischarge home visit or structured, hospital-based interview. Main outcome measures: The primary objective was to collect information on the feasibility of a randomized controlled trial, including eligibility, control intervention and outcome assessments. The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale at one month after discharge from hospital. Secondary outcomes included mood, quality of life and costs at one week and one month following discharge. Results: Ninety-three people were allocated to the randomized controlled trial; 47 were randomized to intervention and 46 to control. Thirty-three were enrolled into the cohort study. More people were allocated to the randomized controlled trial as the study progressed. One hundred and thirteen people (90%) received the proposed intervention, although there was a need for stricter protocol adherence. Follow-up was good: at one month 114 (90%) were assessed. There were no significant differences between the groups in the randomized controlled trial for the primary outcome measure at one month. The average cost of a home visit was £208. Conclusion: A trial is feasible and warranted given the resource implications of predischarge occupational therapy home visits

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

Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333)

Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3-30 days post ischaemic stroke into a phase II randomised (1:1), double blind, placebo-controlled trial. Subjects received dexamphetamine (5mg initially, then 10mg for 10 subsequent doses with 3 or 4 day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl-Meyer, FM), and functional scales (Barthel index, BI and modified Rankin score, mRS). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 minutes after, the first 2 doses. 33 subjects were recruited, age 33-88 (mean 71) years, males 52%, 4-30 (median 15) days post stroke to inclusion. 16 patients were randomised to placebo and 17 amphetamine. Amphetamine did not improve motor function at 90 days; mean (standard deviation) FM 37.6 (27.6) vs. control 35.2 (27.8) (p=0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate, were 11.2 mmHg (p=0.03), 9.5 mmHg (p=0.04) and 7 beats/minute (p=0.02) higher respectively with amphetamine, compared with control. A non-significant reduction in myocardial perfusion (Buckberg Index) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and heart rate without altering cerebral haemodynamics