L.J. Kappelle

Diffusion-Weighted Magnetic Resonance Imaging in Acute Stroke

BACKGROUND AND PURPOSE Diffusion-weighted MRI (DWI) is highly sensitive in detecting early cerebral ischemic changes in acute stroke patients. In this study we compared the sensitivity of DWI with that of conventional MRI techniques. Furthermore, we investigated the prognostic value of the volume of ischemic lesions on DWI scans and of the apparent diffusion coefficient (ADC). METHODS We performed DWI, fluid-attenuated inversion recovery, spin-echo T2-weighted MRI, and spin-echo proton density-weighted MRI in 42 patients with acute stroke and 15 control subjects. The volume of ischemic lesions was measured on early (<60 hours after onset) and follow-up MRI scans. Clinical outcome was measured 4 months after onset of symptoms with the National Institutes of Health Stroke Scale, the Barthel Index, and the Rankin Scale. RESULTS With DWI, 98% of the ischemic lesions were detected, and with fluid-attenuated inversion recovery, 91% were detected, whereas with early T2-weighted or proton density-weighted scans, only 71% (P=0.002, chi2) and 80% (P=0.02, chi2) of lesions, respectively, were found. Lesion volume on early DWI scans correlated significantly with clinical outcome ratings (P<0.01). In patients with a first-ever stroke, a lesion volume of < or =22 mL on DWI predicted good outcome with a 75% sensitivity and a 100% specificity. The mean ADC of ischemic lesions was 29% lower than the ADC of normal-appearing parts of the brain (P<0.001). The ADC ratio correlated significantly with clinical outcome (P<0.05). CONCLUSIONS DWI is a better imaging method than conventional MRI in detecting early ischemic lesions in stroke patients. Lesion size as measured on DWI scans and, to a lesser extent, ADC values are potential parameters for predicting clinical outcome in acute stroke patients.

Long-term survival and vascular event risk after transient ischaemic attack or minor ischaemic stroke: a cohort study

BACKGROUND Determinants of survival and of risk of vascular events after transient ischaemic attack (TIA) or minor ischaemic stroke are not well defined in the long term. We aimed to restudy these risks in a prospective cohort of patients after TIA or minor ischaemic stroke (Rankin grade< or =3), after 10 years or more. METHODS We assessed the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986-89; arterial cause of cerebral ischaemia). We included 24 hospitals in the Netherlands that recruited at least 50 patients. Primary outcomes were all-cause mortality and the composite event of death from all vascular causes, non-fatal stroke, and non-fatal myocardial infarction. We assessed cumulative risks by Kaplan-Meier analysis and prognostic factors with Cox univariate and multivariate analysis. FINDINGS Follow-up was complete in 2447 (99%) patients. After a mean follow-up of 10.1 years, 1489 (60%) patients had died and 1336 (54%) had had at least one vascular event. 10-year risk of death was 42.7% (95% CI 40.8-44.7). Age and sex-adjusted hazard ratios were 3.33 (2.97-3.73) for age over 65 years, 2.10 (1.79-2.48) for diabetes, 1.77 (1.45-2.15) for claudication, 1.94 (1.42-2.65) for previous peripheral vascular surgery, and 1.50 (1.31-1.71) for pathological Q waves on baseline electrocardiogram. 10-year risk of a vascular event was 44.1% (42.0-46.1). After falling in the first 3 years, yearly risk of a vascular event increased over time. Predictive factors for risk of vascular events were similar to those for risk of death. INTERPRETATION Long-term secondary prevention in patients with cerebral ischaemia still has room for further improvement.

Cognitive Disorders in Acute Stroke: Prevalence and Clinical Determinants

Background: Although cognitive impairment early after stroke is a powerful predictor of long-term functional dependence and dementia, little is known about the characteristics and determinants of cognitive dysfunction in acute stroke. Methods: We administered a neuropsychological examination covering 7 cognitive domains to 190 patients within 3 weeks after a first stroke. We also assembled lesion characteristics, clinical factors at admission, demographic characteristics and vascular risk factors. Multivariate logistic regression adjusted for age, gender and education was performed to examine determinants of acute cognitive impairment. Results:Overall, 74% of patients with a cortical stroke, 46% with a subcortical stroke and 43% with an infratentorial stroke demonstrated acute cognitive impairment.Disorders in executive functioning (39%) and visual perception/construction (38%) were the most common. The prevalence and severity of deficits in executive functioning, language, verbal memory and abstract reasoning was more pronounced following left compared to right cortical stroke (all p < 0.05). Intracerebral haemorrhage (OR = 5.6; 95% CI = 1.2–25.4) and cortical involvement of the stroke (OR = 3.6; 95%, CI = 1.3–9.9) were independent determinants of acute cognitive impairment, whereas premorbid moderate alcohol consumption exerted a protective effect (OR = 0.4; 95% CI = 0.1–1.1). Conclusions:Cognitive impairment is common in the first weeks after stroke, with executive and perceptual disorders being the most frequent. Intracerebral haemorrhage, cortical involvement of the lesion and premorbid moderate alcohol consumption are independently associated with acute cognitive impairment.

The prognostic value of domain-specific cognitive abilities in acute first-ever stroke

Objective: To evaluate the prognostic value of domain-specific cognitive abilities in acute stroke with respect to long-term cognitive and functional outcome in addition to neurologic and demographic predictors. Methods: The authors evaluated 168 patients within the first 3 weeks after first-ever stroke. The prevalence of neuropsychological impairment was calculated vs 75 matched healthy controls. The authors also recorded demographic data, vascular risk factors, lesion characteristics, and clinical factors at admission. Independent predictor variables associated with long-term cognitive impairment (assessed with a follow-up neuropsychological examination) and functional impairment (assessed with the modified Barthel Index and the Frenchay Activities Index) were identified with stepwise multiple logistic regression. Areas under receiver operator characteristic curves were used to compare the predictive value of three models, i.e., a standard medical model, a purely cognitive model, and a model consisting of both medical and cognitive predictors. Results: Thirty-one percent of patients showed long-term cognitive impairment. Basic and instrumental ADL disturbances remained present in 19% and 24% of patients. Domain-specific cognitive functioning predicted cognitive and functional outcome better than any other variable. Moreover, the prediction of instrumental ADL functioning improved when cognitive predictors were added to the standard medical model (p < 0.05). Impairments in abstract reasoning and executive functioning were independent predictors of long-term cognitive impairment. Inattention and perceptual disorders were more important in predicting long-term functional impairment. Conclusion: Domain-specific cognitive abilities in the early phase of stroke are excellent independent predictors of long-term cognitive and functional outcome.

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.

Soluble Adhesion Molecules Reflect Endothelial Cell Activation in Ischemic Stroke and in Carotid Atherosclerosis

BACKGROUND AND PURPOSE Activation of endothelial cells and platelets plays an important role in the development of atherosclerosis and thrombotic disorders. Soluble adhesion molecules originating from these cells can be demonstrated in plasma. We hypothesized that elevated plasma concentrations of soluble P-selectin (sP-selectin), soluble intercellular adhesion mole-cule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) can reflect activation of endothelial cells and/or platelets in acute ischemic stroke and in previously symptomatic internal carotid artery stenosis. METHODS Plasma was sampled from patients within 2 days of acute ischemic stroke (n = 28), from patients with a previous (> 1 week) transient or persistent ischemic neurological deficit associated with stenosis of the internal carotid artery (n = 34), and from control patients without a history of vascular disease (n = 34). Concentrations of sP-selectin, sICAM-1, sVCAM-1, and sE-selectin were measured by means of an enzyme-linked immunosorbent assay. RESULTS Compared with control subjects, sP-selectin and sE-selectin were significantly elevated in the acute stage of ischemic stroke (P < .0001 and P = .001, respectively) as well as in previously symptomatic carotid stenosis (P < .0001 and P = .0007). sICAM-1 and sVCAM-1 were not increased. CONCLUSIONS The elevated levels of sE-selectin indicate that endothelial cell activation occurs both in the acute stage of ischemic stroke and in previously symptomatic carotid atherosclerosis. Increased sP-selectin concentrations reflect endothelial cell activation as well but may also be caused by platelet activation.

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.

Cerebral Hemodynamics in Relation to Patterns of Collateral Flow

BACKGROUND AND PURPOSE We sought to investigate the relation between collateral flow via different pathways and hemodynamic parameters measured by dynamic susceptibility contrast-enhanced MRI in patients with severe carotid artery disease. METHODS Dynamic susceptibility contrast-enhanced MRI was performed in 66 patients and 33 control subjects. Patients had severe stenosis (>70%, n=12), unilateral occlusion (n=38), or bilateral occlusion (n=16) of the internal carotid artery (ICA). Cerebripetal flow and collateral flow via the circle of Willis were investigated with MR angiography. Collateral flow via the ophthalmic artery was investigated with transcranial Doppler sonography. RESULTS Patients with ICA stenosis had well-preserved cerebral perfusion and were in general not dependent on collateral supply. Patients with unilateral ICA occlusion had impaired cerebral perfusion. However, appearance time, peak time, and mean transit time in white matter were less increased in patients with than in patients without collateral flow via the circle of Willis (P<0.05). Furthermore, patients with collateral flow via both anterior and posterior communicating arteries had less increased regional cerebral blood volume than patients with collateral flow via the posterior communicating artery only (P<0.05). Patients with bilateral ICA occlusion had severely compromised hemodynamic status despite recruitment of collateral supply. CONCLUSIONS In patients with unilateral ICA occlusion, the pattern of collateral supply has significant influence on hemodynamic status. Collateral flow via the anterior communicating artery is a sign of well-preserved hemodynamic status, whereas no collateral flow via the circle of Willis or flow via only the posterior communicating artery is a sign of deteriorated cerebral perfusion.

Early depressive symptoms after stroke: neuropsychological correlates and lesion characteristics

OBJECTIVE To examine the relation between depressive symptoms and specific cognitive functions in patients with a recent stroke and to examine associations with lesion characteristics. METHODS We studied 126 of 183 consecutive patients within 3 weeks after a first-ever symptomatic stroke (mean interval, 8.3+/-4.3 days). Presence and severity of depressive symptoms was assessed with the Montgomery Asberg Depression Rating Scale. Neuropsychological functioning was examined by means of a detailed neuropsychological examination covering six cognitive domains. We included a healthy control group (N=75) to obtain normative data for the neuropsychological examination. Functional impairment was measured with the modified Barthel Index and the modified Rankin Scale. Symptomatic and preexistent lesion characteristics were determined on CT or MRI. RESULTS Of the included patients, 40% demonstrated mild and 12% moderate to severe depressive symptoms. Severity of depressive symptoms was related to lesion volume (p=0.008), functional impairment (all p<0.004), and degree of overall cognitive impairment (p=0.005). After adjustment for lesion size, a specific neuropsychological profile emerged in patients with moderate to severe depressive symptoms, affecting primarily memory, visual perception, and language (all p<0.05). No association was found between severity of depressive symptoms and lesion location, presence of preexistent lesions (white matter lesions and silent infarcts), and demographic factors (age, education, and gender). CONCLUSIONS Moderate or severe symptoms of depression in the early stage poststroke are associated with a specific pattern of cognitive impairment, lesion size, and functional status. We suggest that depressive symptoms early after stroke are, at least in part, a reactive phenomenon secondary to severe cognitive and functional deficits.

Outcome in patients with basilar artery occlusion treated conventionally

Background: Most data on the outcome of basilar artery occlusion are from recent case series of patients treated with intra-arterial thrombolysis. The limited knowledge on the outcome after a conventional treatment approach comes from a few small case series of highly selected patients. Objective: To provide more data on the outcome of conventional treatment. Methods: Data were analysed on patients from three centres with symptomatic basilar artery occlusion treated conventionally. Conventional therapy was defined as treatment with antiplatelets, anticoagulation, or both. Results: Data were available on 82 patients. The case fatality was 40%. Among survivors, 65% remained dependent (Rankin score 4–5). Patients younger than 60 years (odds ratio = 3.1 (95% confidence interval, 1.0 to 9.5)) and those with a minor stroke (OR = 3.1 (1.0 to 9.6)) were more likely to have a good outcome (Rankin score 0–3). Patients with a progressive stroke were less likely to have a good outcome (OR = 0.3 (0.08 to 1.2)) than patients with a maximum deficit at onset or fluctuating symptoms at presentation. Conclusions: Conventional treatment of symptomatic basilar artery occlusion is associated with a poor outcome in almost 80% of patients, which emphasises the importance of the search for a more effective treatment approach.