Significance of microbleeds in patients with transient ischaemic attack.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prognostic significance of microbleeds in TIA-patients. In patients with a transient ischaemic attack (TIA), the prognostic value of microbleeds is unknown. METHODS: In 176 consecutive TIA patients, the number, size, and location of microbleeds with or without acute ischaemic lesions were assessed. We compared microbleed-positive and microbleed-negative patients with regard to the end-point stroke within 3 months. RESULTS: Four of the seven patients with subsequent stroke had microbleeds. Microbleed-positive patients had a higher risk for stroke [odds ratios (OR) 8.91, 95% CI 1.87-42.51, P<0.01] than those without microbleeds. Microbleed-positive patients with accompanying acute ischaemic lesions had a higher stroke risk than those with neither an acute ischaemia nor a microbleed (OR 6.20, 95% CI 1.10-35.12; P=0.04). CONCLUSION: Microbleeds alone or in combination with acute ischaemic lesions may increase the risk for subsequent ischaemic stroke after TIA within 3 months.

Optimizing the risk estimation after a transient ischaemic attack - the ABCDE⊕ score.

BACKGROUND AND PURPOSE: The risk of stroke after a transient ischaemic attack (TIA) can be predicted by scores incorporating age, blood pressure, clinical features, duration (ABCD-score), and diabetes (ABCD2-score). However, some patients have strokes despite a low predicted risk according to these scores. We designed the ABCDE+ score by adding the variables 'etiology' and ischaemic lesion visible on diffusion-weighted imaging (DWI) -'DWI-positivity'- to the ABCD-score. We hypothesized that this refinement increases the predictability of recurrent ischaemic events. METHODS: We performed a prospective cohort study amongst all consecutive TIA patients in a university hospital emergency department. Area under the computed receiver-operating curves (AUCs) were used to compare the predictive values of the scores with regard to the outcome stroke or recurrent TIA within 90 days. RESULTS: Amongst 248 patients, 33 (13.3%, 95%-CI 9.3-18.2%) had a stroke (n = 13) or a recurrent TIA (n = 20). Patients with recurrent ischaemic events more often had large-artery atherosclerosis as the cause for TIA (46% vs. 14%, P < 0.001) and positive DWI (61% vs. 35%; P = 0.01) compared with patients without recurrent events. Patients with and those without events did not differ with regard to age, clinical symptoms, duration, blood pressure, risk factors, and stroke preventive treatment. The comparison of AUCs [95%CI] showed superiority of the ABCDE+ score (0.67[0.55-0.75]) compared to the ABCD(2) -score (0.48[0.37-0.58]; P = 0.04) and a trend toward superiority compared to the ABCD-score (0.50[0.40-0.61]; P = 0.07). CONCLUSION: In TIA patients, the addition of the variables 'etiology' and 'DWI-positivity' to the ABCD-score seems to enhance the predictability of subsequent cerebral ischaemic events.

Anterior pituitary axis hormones and outcome in acute ischaemic stroke.

BACKGROUND: Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. METHODS: In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. RESULTS: In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. CONCLUSION: Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.

Etiology of late cerebrovascular events after carotid endarterectomy.

BACKGROUND: Progressive carotid artery disease has been shown to cause cerebrovascular events years after a patient's carotid thromboendarterectomy (CEA). Yet, some late cerebrovascular events in CEA patients are attributable to other etiologies. OBJECTIVE: We sought to determine frequency and characteristics of late cerebrovascular events in post-CEA patients attributable to etiologies other than progressive carotid disease. METHODS: In a post hoc analysis of data from a CEA-registry with long-term follow-up, all patients with transient ischaemic attack (TIA) or stroke occurring >1 month post-CEA were identified. The etiologies of these events were dichotomized into the groups large-artery atherosclerosis (LAA) and that non-large-artery atherosclerosis (non-LAA), i.e. all other etiologies (Trial of Org 10172 in Acute Stroke Trial-criteria). Frequency and characteristics of both groups were compared. RESULTS: Sixty of 361 post-CEA patients (16.6%; 95%CI 12.9-20.9%) had late cerebrovascular events after 7 years (median). Thirty patients had ischaemic strokes and 30 had TIAs. These events were attributable to LAA in 48% (29/60) and to non-LAA in 52% (31/60). In the LAA group, contralateral carotid stenosis (62%; 18/29) was more frequent than recurrent ipsilateral stenosis (38%; 11/29). Amongst non-LAA patients, cardioembolism (29%; 9/31) and small-artery-occlusion (23%; 7/31) were the most frequent causes. LAA and non-LAA patients did not differ in age, time since CEA, risk factor profile, type of event, and baseline medication. CONCLUSION: In post-CEA-patients, half of the late cerebrovascular events were attributable to etiologies other than LAA. Clinical features did not distinguish LAA-events from non-LAA events. Thus, stroke prevention in post-CEA patients should not be confined to screening for progressive carotid disease but includes efforts to optimize the management of risk factor and cardiac diseases.

The role of routine echocardiography in unselected patients with cerebrovascular ischaemic events.

BACKGROUND: Cardiac embolism is an important etiology of cerebrovascular ischaemic events (CIE). Echocardiography is routinely performed in patients with CIE despite guidelines recommending restriction of echocardiography to patients with clinically suspected cardioembolism. OBJECTIVE: The aim of this study was to examine the therapeutic impact and prognostic role of echocardiographic findings in an unselected population suffering from CIE. METHODS: Between November 2006 and November 2007, 319 patients with CIE underwent evaluation by transthoracic echocardiography (TTE) and in addition by transesophageal echocardiography (TEE) if deemed mandatory (n = 49). The combined clinical end-point included death or recurrent CIE, occurring during a follow-up period of 3 and 12 months, respectively. RESULTS: After 3 months of follow-up, the combined end-point was noted in 30 (9%) and after 12 months in 43 (13%) patients. In multivariate analysis, atrial fibrillation (AF) (HR 2.12, 95% CI 1.38-3.25; P < 0.001) and coronary artery disease (CAD: HR 1.85, 95% CI 1.21-2.81; P = 0.004) were predictors of events occurring during short-term follow-up. After 1 year of follow-up, AF (HR 1.67, 95% CI 1.19-2.32; P = 0.003) and CAD (HR 1.5, 95% CI 1.09-2.06; P = 0.01) were associated with the combined end-point. Echocardiographic parameters assessed at study entry were not independently related to an adverse outcome. CONCLUSION: Whereas AF and CAD appear to increase the risk of events after suffering from CIE, echocardiographic findings were not independently associated with the combined end-point of recurrent CIE or death.

Restenosis after carotid endarterectomy: significance of newly acquired risk factors.

BACKGROUND: In patients who had carotid endarterectomy (CEA), the significance of newly acquired cerebrovascular risk factors (CRFs) is unknown. Newly acquired CRFs are defined as CRFs not present prior to CEA (baseline CRFs) but acquired during long-term follow-up. OBJECTIVE: We sought to determine the significance of newly acquired CRFs in CEA patients with regard to progressive ICA disease (> or =50% restenosis; occurrence or progression of contralateral stenosis). METHODS: In a single-center CEA-registry, 361 CEA patients with annual follow-up visits for 7 years were identified. Hazard ratios (HR) were calculated for (i) any baseline CRF (hypertension, diabetes, hypercholesterolemia, coronary heart disease (CHD), peripheral artery disease (PAD), smoking), (ii) any newly acquired CRF, and (iii) for the use of statins and antihypertensives. RESULTS: No baseline CRF was associated with progressive ICA disease (unadjusted analysis). After adjustment for age and gender, smoking (HR 1.52, 95%CI 1.02-2.26), diabetes (HR 1.64, 95%CI 1.00-2.68), and hypercholesterolemia (HR 1.61, 95%CI 1.03-2.52) were weakly related to progressive ICA disease. Newly acquired hypertension (HR 2.44, 95%CI 1.57-3.79), CHD (HR 2.73, 95%CI 1.81-4.11), diabetes (HR 2.30, 95%CI 1.39-3.80), and PAD (HR 3.94, 95%CI 2.69-5.76) were associated with progressive ICA disease; also, after adjustment for baseline CRFs. Acquisition of at least one new CRF was related to progressive ICA disease (HR(adjusted) 8.07, 95%CI 4.97-13.12). Neither statins nor antihypertensive drugs did alter the odds for progressive ICA disease. CONCLUSION: CRFs acquired during long-term follow-up after CEA may independently contribute to progressive ICA stenosis after endarterectomy. Newly acquired CRFs might be more hazardous than CRFs present prior to CEA.

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Stroke severity, its correlates and impact on thrombolysis in a population-based study.

OBJECTIVE: Data about the distribution of stroke severity and its correlates are sparse. In a population-based approach, we determined the NIH Stroke Scale Score (NIHSSS) and studied associations with demographic variables, stroke unit care, etiology, the onset assessment interval (OAI), and the rate of thrombolysis. METHODS: We performed a databank-based post-hoc analysis of data ascertained during the prospective, population-based stroke study among the 188,015 permanent residents of Basel City, Switzerland. RESULTS: In 246/269 (91.4%) patients, NIHSSS was available. The median NIHSSS was 5.0 +/- 6.0. NIHSSS 0-6, 7-15, and >15 were present in 156 (63%), 56 (23%), and 34 (14%) patients. Higher NIHSSS were associated with advancing age (p = 0.038), female gender (p = 0.04), stroke unit treatment (p = 0.003), cardioembolism (p < 0.001), shorter OAI (p = 0.009), and thrombolytic therapy (p < 0.001). In multivariate regression analyses, age, OAI, and thrombolysis correlated independently with higher NIHSSS. Stroke unit patients differed from non-stroke unit patients in shorter OAI, younger age, and higher NIHSSS. CONCLUSION: In a geographically defined stroke population, 1/3 patients had moderate-to-severe stroke. Patients with less severe strokes were younger, sought medical attention later and were less likely to receive thrombolysis. Thus, public stroke awareness programs might consider targeting also younger individuals and stress that also mild-to-moderate strokes benefit from emergency medical care.

The probability of restenosis, contralateral disease progression, and late neurologic events following carotid endarterectomy: a long-term follow-up study.

BACKGROUND: Most studies that have reported on the progression of ipsilateral and/or contralateral internal carotid artery (ICA) stenosis are restricted to a few years. METHODS: Based on a single-center carotid endarterectomy (CEA) registry, we sought all patients with CEA for symptomatic high-grade ICA stenosis between 1970 and 2002. 361 CEA patients (mean age 66 years, 73% male) with annual carotid ultrasound and clinical follow-up were identified. Kaplan-Meier analysis was used to estimate the occurrence of (i) progressive ICA stenosis or restenosis of either the operated or contralateral side, and (ii) cerebrovascular events over time of either the operated or contralateral side. RESULTS: Progressive ICA disease was more likely on the contralateral than on the ipsilateral ICA (hazard ratio 2.71; CI 1.8-4.1, p < 0.001). After 5 years, the probability for progressive ICA disease was 5.2% for the ipsilateral versus 15.8% for the contralateral ICA. After 15 years, the likelihood was 37% for both sides. In the presence of progressive restenosis of the ipsilateral ICA, the 20-year probability of further ischemic cerebrovascular events was 50% compared to 18% in patients without ICA disease progression. For the contralateral ICA, the probability of further ischemic events was 24.5% in patients with ICA disease progression compared to 9.6% without ICA disease progression (15 years). CONCLUSION: 15 years after CEA, one third of the patients can be expected to develop progressive ICA disease. While ICA disease progression seems to be more prominent on the contralateral ICA within the first years, this difference fades out after 15 years. One out of 2 patients with ipsilateral ICA disease progression can be expected to have a recurrent cerebral ischemic event within 15 years. It remains to be determined whether consequent application of high-dose statins, optimal blood pressure management and antithrombotic therapy can reduce this rate.

Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke.

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.

Stress hormones predict cerebrovascular re-events after transient ischemic attacks.

BACKGROUND: TIA is a strong predictor of subsequent stroke. The hypothalamic stress hormone copeptin is an accurate prognostic marker in acute ischemic stroke. This study assessed prognostic reliability of 2 distinct stress hormones, copeptin and cortisol, for the risk stratification of re-events in patients with TIA. METHODS: We conducted a prospective study in patients admitted to the emergency department with a TIA. Clinical risk scoring using the ABCD2 score was determined and both hormones were measured in plasma on admission. The primary endpoint was a cerebrovascular re-event within 90 days. RESULTS: We included 107 consecutive patients with TIA. Re-events occurred in 10 patients (9%). Copeptin levels were higher in patients with a re-event compared with patients without re-event (p = 0.02), in contrast to cortisol (p = 0.53). Copeptin revealed a higher area under the receiver operating characteristics curve (AUC) to predict re-events compared to the ABCD2 score (AUC of 0.73 vs 0.43; p < 0.01) and improved its prognostic accuracy (AUC of combined model of 0.77; p = 0.002). CONCLUSION: Measurement of plasma copeptin but not cortisol levels in patients with TIA provides additional prognostic information beyond the ABCD2 clinical risk score alone. If confirmed in future studies, routine copeptin measurement may be an additional tool for risk stratification and targeted resource allocation after TIA.

[Really drunk?]. / Wirklich betrunken?

We report about a 42-year-old patient who was admitted to the emergency department because of suspected alcohol abuse. He declared himself to be drunk. He stated in his case history that he had suffered from right sided neck and facial pain for several days. The clinical examination revealed a left sided hemiparesis. Together with the demonstrated right hemispherical brain ischemia by computed tomography, a presumptive diagnosis of a dissection of the right internal carotid artery was made. This diagnosis was finally confirmed by ultrasound and magnetic resonance imaging. A therapy with full dose heparin was begun and oral anticoagulation was subsequently initiated. After two weeks of follow-up, the neurological deficiencies were partially regredient.