Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis

Background

Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT).

Aims

To verify, in an “expert-opinion setting”, the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis.

Patients and method

One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert’s opinion.

Results

After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01).

Conclusions

In a “real world” setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.

     

Cerebral blood flow response to neural activation after acute ischemic stroke: a failure of myogenic regulation?

We tested two hypotheses: (1) neurovascular coupling is impaired after acute ischemic stroke, (2) subcomponent analysis of cerebral blood flow velocity can reveal significant differences between acute ischemic stroke and healthy controls. This was explored through the comparison of nineteen acute ischemic stroke patients with healthy controls. Recordings of cerebral blood flow velocity, blood pressure and end-tidal CO₂ were obtained during 60s of passive elbow flexion. Cerebral blood flow velocity changes were decomposed into standardized subcomponents describing the contributions of blood pressure (V _BP), resistance area product (V _RAP) and critical closing pressure (V _CrCP). The passive paradigm led to a bilateral cerebral blood flow velocity increase in both groups, but in acute ischemic stroke the magnitude of change was significantly lower. Blood pressure increases were shown to be an important contributor to cerebral blood flow velocity response throughout the paradigm in both groups, with no significant difference between groups. The V _CrCP contribution was not different between groups or hemispheres; its continuous rise during activation indicating a vasodilatory effect. On the other hand, the V _RAP contribution showed significant differences (p = 0.03), thus suggesting myogenic impairment in acute ischemic stroke. Cerebral blood flow velocity responses to passive elbow flexion suggest an impairment of neurovascular coupling in acute ischemic stroke. Subcomponent analysis suggests an impairment of the myogenic pathways, giving a greater insight into the different mechanisms contributing to neurovascular coupling. Further research is needed to assess the clinical value of subcomponent analysis of neurovascular coupling and the natural history of such changes following acute ischemic stroke.     

What is the significance of leukoaraiosis in patients with acute ischemic stroke?

BACKGROUND: Leukoaraiosis (LA) may have specific clinical correlates in patients with stroke, but this is not well investigated, so that the significance of LA in patients with stroke remains unclear. METHODS: In a study of 2289 patients with a first-ever acute ischemic stroke, LA was noted in 149 by the use of baseline computed tomography of the brain. These patients were compared with the non-LA group. Statistical tests, including Fisher exact test or a chi(2) test, were used to compare variables, and a multivariate approach using stepwise logistic regression was performed. RESULTS: Patients with LA were significantly older (73.7 vs 62.7 years; P<. 001), and had a higher incidence of hypertension (72.5% vs 47.1%; P<. 001) and subcortical or lacunar infarction (40.3% vs 25.4% and 21.5% vs 8.0%, respectively; P<.001) on neuroimaging studies, compared with the non-LA group. The most common cause of stroke in the LA group was presumed to be small-artery disease associated with hypertension (46% vs 13.5% in the non-LA group). Age and hypertension were very strongly associated with LA (respective odds ratios [95% confidence intervals], 1.06 [1.04-1.08] and 2.33 [1.60-3. 39]). In addition to these risk factors, a close relationship was found between LA and nonsevere stenosis (<50%) of the internal carotid artery (odds ratio, 2.23 [95% confidence interval, 1.32-3. 76]), although the significance of this association remains speculative. The outcome at 1 month after stroke was similar in both groups. CONCLUSION: Our results provide further evidence that LA is related primarily to small-vessel disease.     

Placebo treatment in acute stroke trials : benefit or harm to patients?

BACKGROUND AND PURPOSE: Some stroke patients and their families express reservations about participating in trials of experimental therapies for acute stroke. Among many reasons given for this is the concern that by participating, patients may be deprived of some component of routine care. We sought to determine the effect on outcome of participating in a clinical stroke trial while being treated with placebo. METHODS: Prospective clinical information was collected for all patients admitted with acute ischemic stroke between July 1995 and July 1996. A subgroup of these patients was enrolled in a clinical trial of acute stroke therapy and had been randomly assigned to the placebo group. The control group was selected from concurrent stroke patients who were not enrolled in any clinical trial. The National Institutes of Health Stroke Scale (NIHSS) was performed on admission and on day 7 after admission. The Glasgow Outcome Scale (GOS) was also performed at discharge. Stroke severity was classified as "severe" if NIHSS was >/=9 or GOS >/=3. Group comparisons were performed with chi(2) tests. RESULTS: One hundred twenty-six patients were evaluated. Forty-seven were placebo patients, and 79 were selected as control subjects. There were no significant differences between the groups with respect to age, sex, hematocrit, blood glucose level, history of hypertension, diabetes, smoking, or initial NIHSS. In addition, there was no difference between groups in terms of the frequency of baseline stroke subtype. Among our controls, 55 patients (70%) were on antithrombotic treatment during hospitalization, whereas none of our placebo patients were on any antithrombotic treatment. For the GOS at follow-up, a good outcome was attained by 76% of the control subjects and 72% of placebo patients (not significant). A severe NIHSS (>9) at follow-up, however, was documented in 15% of controls and 59% of placebo patients (P<0.001). There was a trend toward a higher ("worse") mean follow-up NIHSS among placebo patients (mean NIHSS, 11) versus controls (mean NIHSS, 6) (P=0.09). CONCLUSIONS: Patients enrolled in the placebo arms of some acute clinical stroke trials have similar functional outcomes but more severe neurological deficits at 1 week than did a control group. These findings might be partially explained by the withholding of antithrombotic medication and the exclusion criteria inherent in most trials. Vigilance is required to ensure that all patients participating in stroke studies be guaranteed optimal known medical therapy.     

Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing?

Ischaemic stroke is a leading cause of death and long-lasting disability. Several neuroprotective drugs have been developed that have the potential to limit ischaemic brain damage and improve outcome for patients. While promising results with these drugs have been achieved in animal stroke models, all Phase III trials conducted so far indicate that these drugs have failed to live up to their promise. Despite the limits of animal models, which cannot mimic the clinical situation, the disappointing results of neuroprotective trials might largely be due to methodological problems. Future trials with neuroprotective drugs should be performed in stroke (care) units, after sufficient information regarding therapeutic time window, dosage, duration of therapy and safety has been gathered from pilot studies, and a better selection of target patients has been made. Much of this information can now be obtained by techniques that visualize the penumbra, such as combined diffusion-weighted and perfusion MRI. Consideration should also be given to clinical trials with well-designed combinations of treatments.     

What do we (not) know about the management of blood pressure in acute stroke?

Although it is indisputable that high blood pressure should be treated to prevent a first or a recurrent stroke, the management of high blood pressure in the first hours and days after stroke remains controversial. There is no high-quality evidence from randomized controlled trials to guide treatment in the 80% of patients who have elevated blood pressure during the first days after stroke. Theoretically, there are pros and cons for manipulating blood pressure after onset of stroke. Most treatment guidelines suggest leaving blood pressure untouched based on pathophysiologic principles. Post-hoc analyses from randomized trials, however, suggest that elevated blood pressure is associated with recurrent stroke and higher mortality, even after adjustment for potential confounders. On the other hand, preliminary studies have suggested that voluntarily increasing blood pressure might be beneficial in a selected subgroup of patients. In this overview, we present a summary of recent studies on this topic.     

Cerebral ischemic stroke: is gender important?

Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke.