H. B. van der Worp

Early cognitive impairment predicts long-term depressive symptoms and quality of life after stroke

OBJECTIVE The aim of the present study was to examine the predictive value of cognitive impairment in the acute phase after stroke as a risk factor for long-term (six to ten months after stroke) depressive symptoms (DS) and a reduced quality of life (QOL), independent of demographic and neurological predictors. METHODS We evaluated 143 patients within the first 3 weeks post-stroke. Predictor variables included domain-specific cognitive function, demographic data, vascular risk factors, lesion characteristics, and clinical factors. Predictor variables associated with long-term DS (Montgomery Asberg Depression Rating Scale >or=7) and QOL (Stroke-Specific Quality of Life Scale) were identified with multiple logistic and linear regression. RESULTS Long-term DS were independently predicted by cognitive impairment at baseline, DS at baseline, female sex, diabetes mellitus, and previous TIA(s). Cognitive impairment, increasing age, and functional dependence predicted a reduced QOL, whereas hypercholesterolaemia predicted a better QOL. Among all cognitive disorders, unilateral neglect was the greatest risk factor for DS after 6 months, whereas a disorder in visual perception and construction affected QOL the most. CONCLUSIONS Cognitive impairment and vascular risk factors are important predictors of long-term DS and QOL after stroke. The prognostic value of cognition suggests a reactive component in the development or continuation of long-term DS.

Effect of Paracetamol (Acetaminophen) on Body Temperature in Acute Ischemic Stroke A Double-Blind, Randomized Phase II Clinical Trial

Background and Purpose— Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially when they have no fever. The main purpose of this trial was to study whether early treatment of acute ischemic stroke patients with acetaminophen (paracetamol) reduces body temperature. Methods— Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose) acetaminophen or with placebo, administered as suppositories 6 times daily during 5 days. Body temperatures were measured with a rectal electronic thermometer at the start of treatment and after 24 hours and with an infrared tympanic thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals thereafter. The primary outcome measure was rectal temperature at 24 hours after the start of treatment. Results— Treatment with high-dose acetaminophen resulted in 0.4°C lower body temperatures than placebo treatment at 24 hours (95% CI 0.1°C to 0.7°C). The mean reduction from baseline temperature with high-dose acetaminophen was 0.3°C (95% CI 0°C to 0.6°C) higher than that in placebo-treated patients. Treatment with low-dose acetaminophen did not result in lower body temperatures. After 5 days of treatment, no differences in temperature were found between the placebo and the high- or low-dose acetaminophen groups. Conclusions— Treatment with a daily dose of 6000 mg acetaminophen may result in a small, but potentially beneficial, decrease in body temperature shortly after ischemic stroke, even in normothermic and subfebrile patients. Further studies should determine whether this effect is reproducible and whether early reduction of body temperature leads to improved outcome.

Reproducibility of Measurements of Cerebral Infarct Volume on CT Scans

Background and Purpose — Infarct volume is increasingly used as an outcome measure in clinical trials of therapies for acute ischemic stroke. We tested which of 5 different methods to measure infarct size or volume on CT scans has the highest reproducibility. Methods — Infarct volume and total intracranial volume were measured with Leica Q500 MCP image analysis software, or with a caliper, on 38 CT scans of patients who participated in the Tirilazad Efficacy Stroke Study II (TESS II). The scans were performed 8 days (±2 days) after the onset of symptoms. The 5 methods tested were based on (1) semiautomated pixel thresholding, (2) manual tracing of the perimeter, (3) a stereological counting grid, (4) measurement of the 3 largest diameters, and (5) the single largest diameter. The measurements were performed independently by 2 observers; the first observer performed all measurements twice. Results — The single largest diameter did not correlate well with infarct volume. Of the other methods, manual tracing of the perimeter of the infarct had the lowest intraobserver and interobserver variability: coefficients of variation were 8.6% and 14.1%, respectively. For total intracranial volume, manual tracing also provided the highest reproducibility: intraobserver and interobserver coefficients of variation were 3.3% and 4.9%, respectively. Conclusions — Manual tracing of the perimeter is the most reproducible method for measuring the volumes of the infarct and the total intracranial space in multicenter trials of therapies for acute ischemic stroke.

Dietary Vitamin E Levels Affect Outcome of Permanent Focal Cerebral Ischemia in Rats

BACKGROUND AND PURPOSE A supraphysiological amount of vitamin E in the standard diet of laboratory animals may provide partial protection against cerebral ischemic damage in stroke models. The aim of the present study was to test the effect of dietary vitamin E on infarct volume in rats subjected to permanent focal cerebral ischemia. METHODS Male Wistar rats were raised on a vitamin E-deficient diet (n=10) or a control diet containing 62.7 mg vitamin E/kg (n=11) for 13 to 16 weeks, from the age of 3 weeks. The left middle cerebral artery (MCA) was permanently occluded by means of an intraluminal silicone-coated 3-0 suture. Blood flow in the left MCA territory was measured before and after occlusion with laser Doppler flowmetry. The area of infarction was measured in hematoxylin-eosin-stained brain sections by means of an image analysis system. The investigator was not aware of the vitamin E status of the rats. RESULTS Blood flow in the left MCA territory in the second half hour after occlusion was 43+/-17% and 42+/-17% (mean+/-SD) of the baseline value in control and vitamin E-deficient rats, respectively. The mean infarct volume, measured after 48 hours of survival, was 61+/-19 mm3 in control rats and 137+/-76 mm3 in vitamin E-deficient rats (P=0.037). CONCLUSIONS After permanent focal cerebral ischemia, the infarct is larger in vitamin E-deficient rats than in rats raised on a diet with the usual, supraphysiological amount of vitamin E. This may have consequences for cerebral ischemia studies with experimental animals.

Cognition after carotid endarterectomy or stenting A randomized comparison

Objective: To compare the effect on cognition of carotid artery stenting (CAS) and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. Methods: Patients randomized to CAS or CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed neuropsychological examinations (NPE) before and 6 months after revascularization. Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization. Cognitive test results were standardized into z scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. Results: Of the 1,713 patients included in ICSS, 177 were enrolled in the 2 centers during the substudy period, of whom 140 had an NPE at baseline and 120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS was associated with a larger decrease in cognition than CEA, but the between-group difference was not statistically significant: −0.17 (95% CI −0.38 to 0.03; p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization. New ischemic lesions were found twice as often after CAS than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041). Conclusions: Differences between CAS and CEA in effect on cognition were not statistically significant, despite a substantially higher rate of new ischemic lesions after CAS than after CEA. Classification of Evidence: This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small.

Complications of Acute Ischaemic Stroke

Neurological, cardiac, and systemic complications during the first days to weeks after ischaemic stroke can cause substantial morbidity and mortality. The reported 30-day case fatality rate for cerebral infarction varies between 10 and 17%. The incidence and effects of the various complications vary with time after stroke: transtentorial herniation and other cerebral complications prevail during the 1st week, whereas medical complications are more prominent in the weeks thereafter. Many complications are treatable, and some are preventable. The goal of this report is to provide information on their incidence, consequences, and management.

Noninvasive MR imaging of cerebral perfusion in patients with a carotid artery stenosis

Background: Arterial spin labeling (ASL) perfusion MRI with image acquisition at multiple delay times can be used to measure delays in the arrival of arterial blood to the brain. We assessed the effect of a symptomatic internal carotid artery (ICA) stenosis on ASL timing parameters, and evaluated the effect of collateral flow through the circle of Willis. Methods: Forty-four functionally independent patients (30 men, 69 ± 9 years) with a recently symptomatic ICA stenosis ≥50% and 34 sex-matched and age-matched healthy volunteers were investigated. Magnetic resonance angiography and 2-dimensional phase-contrast imaging were used to assess collateral flow in the circle of Willis. Results: In the hemisphere ipsilateral to the ICA stenosis, cerebral blood flow (CBF) was lower (p < 0.01) in the anterior frontal, posterior frontal, parieto-occipital, and occipital regions than in control subjects. The transit times were prolonged (p < 0.01) in the ipsilateral anterior frontal, posterior frontal, and frontoparietal regions when compared with the control subjects. The trailing edge time was prolonged (p < 0.01) in the ipsilateral frontoparietal region when compared to the control subjects. In the 27 patients without a contralateral stenosis, the trailing edge was longer (p < 0.01) in the ipsilateral posterior frontal, frontoparietal, and parieto-occipital regions than in the contralateral regions. Collateral flow via the circle of Willis did not affect CBF and transit or trailing edge times. Conclusion: Arterial spin labeling MRI is a noninvasive tool for imaging cerebral blood flow and delays in the arrival of arterial blood to the brain, and can potentially provide valuable information on the quality of perfusion to the brain in patients with cerebrovascular disease.

Familial occurrence of brain arteriovenous malformations: a systematic review

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke

The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. Overall, tirilazad had no significant effect on infarct volume. In the subgroups of male patients and of those with a cortical infarct, tirilazad significantly reduced infarct volume. These effects were reduced to nonsignificant trends after adjustment for imbalances in baseline characteristics. In conclusion, early treatment of patients with tirilazad has no effect on infarct volume.

VAST: Vertebral Artery Stenting Trial. Protocol for a randomised safety and feasibility trial

BackgroundTwenty to 30 percent of all transient ischaemic attacks and ischaemic strokes involve tissue supplied by the vertebrobasilar circulation. Atherosclerotic stenosis ≥ 50% in the vertebral artery accounts for vertebrobasilar stroke in at least one third of the patients. The risk of recurrent vascular events in patients with vertebral stenosis is uncertain and revascularisation of vertebral stenosis is rarely performed. Observational studies have suggested that the risk of subsequent stroke or death in patients with vertebrobasilar ischaemic events is comparable with that in patients with carotid territory events. Treatment of vertebral stenosis by percutaneous transluminal angioplasty has been introduced as an attractive treatment option. The safety and benefit of stenting of symptomatic vertebral stenosis as compared with best medical therapy alone remains to be elucidated in a randomised clinical trial.Study objectivesThe primary aim of the Vertebral Artery Stenting Trial (VAST) is to assess whether stenting for symptomatic vertebral artery stenosis ≥ 50% is feasible and safe. A secondary aim is to assess the rate of new vascular events in the territory of the vertebrobasilar arteries in patients with symptomatic vertebral stenosis ≥ 50% on best medical therapy with or without stenting.DesignThis is a randomised, open clinical trial, comparing best medical treatment with or without vertebral artery stenting in patients with recently symptomatic vertebral artery stenosis ≥ 50%. The trial will include a total of 180 patients with transient ischaemic attack or non-disabling ischaemic stroke attributed to vertebral artery stenosis ≥ 50%. The primary outcome is any stroke, vascular death, or non-fatal myocardial infarction within 30 days after start of treatment. Secondary outcome measures include any stroke or vascular death during follow-up and the degree of (re)stenosis after one year.DiscussionImprovements both in imaging of the vertebral artery and in endovascular techniques have created new opportunities for the treatment of symptomatic vertebral artery stenosis. This trial will assess the feasibility and safety of stenting for symptomatic vertebral artery stenosis and will provide sufficient data to inform a conclusive randomised trial testing the benefit of this treatment strategy. The VAST is supported by the Netherlands Heart Foundation (2007B045; ISRCTN29597900).