Thompson G. Robinson

Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage

BACKGROUND Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. METHODS We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physicians choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups. RESULTS Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. CONCLUSIONS In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 ClinicalTrials.gov number, NCT00716079.).

National Clinical Guidelines for Stroke.

National Clinical Guidelines for Stroke. Intercollegiate Working Party for Stroke, Royal College of Physicians. (Pp 150; £15.95.) Lavenham Press, 2000. ISBN 1-86016-120-0.\***| Stroke is a common problem, being the third cause of mortality in the UK and the leading cause of adult disability with a resultant significant cost burden to the NHS and social services. The guidelines highlight the wide national variation in the implementation of evidence based practice as seen in the Stroke Associations National Survey and the Royal College of Physicians …

Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial

BACKGROUND Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke. METHODS Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008. FINDINGS 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05). INTERPRETATION Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.

Cardiac Baroreceptor Sensitivity Predicts Long-Term Outcome After Acute Ischemic Stroke

Background and Purpose— The baroreceptor reflex arc is important in the short-term regulation of the cardiovascular system, and small studies have reported impaired cardiac baroreceptor sensitivity (BRS) after acute stroke. However, the prognostic significance of impaired BRS is uncertain. Methods— One hundred twenty-four patients underwent simultaneous ECG and noninvasive beat-to-beat blood pressure (BP) monitoring within 72 hours of neuroradiologically confirmed acute ischemic stroke. Cardiac BRS was assessed from the combined &agr;-index by means of power spectral analysis techniques. Baseline data for acute stroke patients were compared with those of a control group matched for age, sex, and casual BP. Patients were followed up for a median of 1508 days (range, 9 to 2656 days), and outcome was compared between patients with and without impaired BRS. Results— Median BRS values were significantly lower in stroke patients than in controls (5 [interquartile range, 3.5 to 7.4] versus 6.2 [interquartile range, 4.5 to 8.3] ms/mm Hg;P =0.04). Sixty-one (33 male) patients (mean age, 70.2 [SD 10.5] years) had impaired BRS (≤5.0 ms/mm Hg) compared with 63 (35 male) patients (mean age, 70.6 [SD 11.7] years) without impaired BRS (>5.0 ms/mm Hg). Stroke patients with impaired BRS values had a significantly poorer prognosis (28% versus 8% mortality rate during the follow-up period) although there were no differences in age, stroke severity, stroke type, or casual or 24-hour BP parameters between the 2 groups. Conclusions— Impaired cardiac BRS is associated with increased long-term mortality after acute ischemic stroke, irrespective of age, sex, stroke type, and BP. This may reflect cardiac arrhythmias, but the mechanisms underlying this association are unknown, although therapies that improve cardiac BRS after stroke warrant further investigation.

Ionospheric modification experiments in northern Scandinavia

Abstract The heating facility at Ramfjordmoen near Tromso, Norway, is briefly described, and a survey is given of the experiments performed with this facility until now. These experiments comprise D -region modification, polar electrojet modulation at VLF, ELF and ULF, HF absorption and backscatter due to short-scale field-aligned irregularities, stimulated radio wave emission of the modified ionospheric plasma, short-time scale HF absorption due to the parametric decay instability, airglow modification, excitation of large-scale irregularities, and F -region cross modulation.

Effects of antihypertensive treatment after acute stroke in the Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial

BACKGROUND Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. METHODS The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register, number ISRCTN89712435. FINDINGS 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0.86, 95% CI 0.65-1.14; p=0.3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10-17) and the difference in diastolic blood pressure was 8 mm Hg (6-10; difference between groups p<0.0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. INTERPRETATION Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. FUNDING The Health Foundation and The Stroke Association.

Cardiac Baroreceptor Sensitivity Is Impaired After Acute Stroke

BACKGROUND AND PURPOSE The blood pressure (BP) fall and increased BP variability after acute stroke have been previously described. The underlying pathophysiological mechanisms producing these findings are unclear but may include abnormalities of cardiac baroreceptor reflex arc and/or changes in sympathetic nervous system activity. To date, evidence of impaired cardiac baroreceptor sensitivity (BRS) after stroke is limited to patients with chronic disease as determined by invasive methodology. Therefore, it was proposed to assess cardiac BRS and sympathovagal balance with the use of novel noninvasive techniques after acute stroke. METHODS Thirty-seven acute stroke patients underwent simultaneous surface electrocardiographic and noninvasive beat-to-beat BP recording. Cardiac BRS was assessed by power spectral analysis techniques, and sympathovagal balance was determined from the ratio of the low- to high-frequency powers for pulse interval variability. The responses were compared with a control group matched for age, sex, and BP. RESULTS Median cardiac BRS was significantly lower in stroke patients than in control subjects (high-frequency alpha-index, 4.89 versus 6.50 ms/mm Hg; P = .007; combined alpha-index, 4.65 versus 5.46 ms/mm Hg; P = .02). Median normalized high- but not low-frequency power of systolic BP variability was significantly greater in stroke patients (11.0 versus 6.7 normalized units; P < .001), probably reflecting differences in the mechanical effects of respiration on BP in stroke patients. No significant differences were observed in the power spectrum of pulse interval variability between stroke patients and control subjects. Patients with tight hemisphere strokes, however, had a significant reduction in median high-frequency pulse interval power compared with patients with left hemisphere strokes (8 versus 20 normalized units; P = .03), which may reflect a change in sympathovagal balance in favor of increased sympathetic tone in this group. CONCLUSIONS The impairment of cardiac BRS may be important in explaining the increased BP variability after stroke. There was no significant difference in surrogate measures of sympathovagal activity between acute stroke patients and control subjects, but right hemisphere stroke patients had a significant alteration in the sympathovagal balance of pulse interval variability compared with left hemisphere stroke patients. This sympathetic predominance in right hemisphere strokes may be important in the development of cardiac arrhythmias after stroke. The prognostic implications of these findings need to be further explored.

Which Parameters of Beat-to-Beat Blood Pressure and Variability Best Predict Early Outcome After Acute Ischemic Stroke?

BACKGROUND AND PURPOSE In hypertensive populations, increasing blood pressure (BP) levels and BP variability (BPV) are associated with a greater incidence of target organ damage. After stroke, elevated 24-hour BP levels predict a poor outcome, although it is uncertain whether shorter-length BP recordings assessing mean BP levels and BPV have a similar predictive role. The objectives of this study were to compare the different measures of beat-to-beat BP and BPV on outcome after acute ischemic stroke and assess whether these parameters were affected by stroke subtype. METHODS Ninety-two consecutive admissions with a CT-confirmed diagnosis of acute ischemic stroke were recruited, of whom 54 had cortical infarction, 29 subcortical, and 9 posterior circulation infarction. Casual and two 5-minute recordings of beat-to-beat BP (Finapres, Ohmeda) were made under standardized conditions within 72 hours of ictus, with mean BP levels taken as the average of this 10-minute recording and BPV as the standard deviation. Outcome was assessed at 30 days as dead/dependent or independent (Rankin </=2). The effects of BP, BPV, and stroke subtype on outcome were studied with the use of logistic regression. Stroke subjects were subsequently divided by BP quartiles and within each quartile into low- and high-variability groups; the influence of high BPV on outcome was also assessed. RESULTS The odds ratio for death/dependency was significantly higher in cortical strokes compared with subcortical and posterior circulation strokes even after controlling for differences in BP and BPV (OR 4.19, P=0.002). Beat-to-beat systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP +/- SD) levels were higher in the dead/dependent group compared with the independent group (MAP 106+/-20.4 mm Hg vs 97+/-19.1 mm Hg, P<0.02), as was MAP variability: 6.1 (interquartile range 4.5 to 7.4 mm Hg) versus 4.9 (3.8 to 6.4 mm Hg, P=0.02). The odds ratio for a poor outcome was 1. 38 (P=0.014) for every 10-mm Hg increase in MAP and 1.32 (P=0.02) for every 1-mm Hg increase in MAP variability. Casual BP measurements had no prognostic significance. For the group as a whole when separated into BP quartiles, those with a high MAP and DBP but not SBP variability within each quartile had a worse prognosis compared with those with a low BPV. CONCLUSIONS A poor outcome at 30 days after ischemic stroke was dependent on stroke subtype, beat-to-beat DBP, and MAP levels and variability. Important prognostic information can be readily obtained from a short period of noninvasive BP monitoring in the acute stroke patient. These findings have important implications, particularly regarding the use of hypotensive agents in the acute stroke period.

Carotid and vertebral artery dissection syndromes

Cervicocerebral arterial dissections (CAD) are an important cause of strokes in younger patients accounting for nearly 20% of strokes in patients under the age of 45 years. Extracranial internal carotid artery dissections comprise 70%–80% and extracranial vertebral dissections account for about 15% of all CAD. Aetiopathogenesis of CAD is incompletely understood, though trauma, respiratory infections, and underlying arteriopathy are considered important. A typical picture of local pain, headache, and ipsilateral Horner’s syndrome followed after several hours by cerebral or retinal ischaemia is rare. Doppler ultrasound, MRI/MRA, and CT angiography are useful non-invasive diagnostic tests. The treatment of extracranial CAD is mainly medical using anticoagulants or antiplatelet agents although controlled studies to show their effectiveness are lacking. The prognosis of extracranial CAD is generally much better than that of the intracranial CAD. Recurrences are rare in CAD.

The Predictive Role of 24-Hour Compared to Casual Blood Pressure Levels on Outcome following Acute Stroke

The predictive value of casual blood pressure (BP) levels following acute stroke on outcome is currently unclear. This may in part reflect the observer bias and variability of casual recordings, which are reduced with 24-hour recordings. We therefore proposed to assess the prognostic significance of 24-hour compared to casual BP in predicting 30-day mortality, dependency and neurological outcome. A total of 136 consecutive patients were assessed within 24 h of ictus by one observer, with casual and 24-hour BP recording, and National Institutes of Health Stroke Scale and Modified Rankin Scale scores. Repeat assessments were made at 7 and 30 days. Admission casual and 24-hour systolic BP (SBP) and diastolic BP levels were significantly higher in patients with poor outcome at 1 month following acute stroke, whether expressed in terms of mortality, dependency or neurological deterioration, on single-variable logistic regression analysis. However, of these variables, only admission 24-hour (not casual) SBP remained a significant outcome predictor in a multiple model containing factors with an established association with poor prognosis. The odds ratio for outcome of death or dependency associated with each 10-mm-Hg increase in 24-hour SBP at admission was 1.88 (95% confidence interval: 1.27-2.78). For an outcome of death or high dependency, the model had a specificity of 75% and sensitivity of 76% when tested by the jackknife technique. Therefore, increasing 24-hour BP levels following acute stroke predict poor outcome. Whether BP should be reduced pharmacologically in the acute stroke period now warrants a suitable prospective intervention trial.