Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to assess the feasibility and safety of fast-track hospitalizations in a selected cohort of patients with stroke. METHODS: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion-weighted imaging were included. Neurological deficits of the included patients were non-disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared - fast-track hospitalizations (≤72 h) and long-term hospitalizations (>72 h). The primary end-point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3-6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). RESULTS: Amongst the 521 patients who met the inclusion criteria, fast-track hospitalizations were performed in 79 patients (15%). In the fast-track group, seven patients (8.9%) met the primary end-point, compared to 37 (8.4%) in the long-term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42-2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end-point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51-3.16, P = 0.61). The costs of fast-track hospitalizations were lower, on average, by $4994. CONCLUSIONS: Fast-track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long-term hospitalizations.

Management of patients with stroke treated with direct oral anticoagulants.

Since their market approval, direct oral anticoagulants (DOACs) are being increasingly used for stroke prevention in patients with atrial fibrillation. However, the management of DOAC-treated patients with stroke poses several challenges for physicians in everyday clinical practice, both in the acute setting and in long-term care. This has spurred extensive research activity in the field over the past few years, which we review here.

Serum neurofilament light chain in patients with acute cerebrovascular events.

BACKGROUND AND PURPOSE: Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion-weighted imaging (MR-DWI) and (iv) functional outcome at 3 months. RESULTS: We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score < 7, 13.1 pg/mL [interquartile range (IQR), 5.3-27.8]; NIHSS score 7-15, 16.7 pg/mL (IQR, 7.4-34.9); and NIHSS score > 15, 21.0 pg/mL (IQR, 9.3-40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels [9.0 pg/mL (95% confidence interval, 4.0-19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3-34.4), P < 0.001], also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR-DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors. CONCLUSIONS: In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR-DWI acquired on admission or functional outcome at 3 months.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Prognostic significance of pulsatile tinnitus in cervical artery dissection.

BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants.

BACKGROUND AND PURPOSE: To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS: This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS: Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION: New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

Anemia in young patients with ischaemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). METHODS: The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. RESULTS: Amongst 1206 study patients (691 CeAD and 515 non-CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke (P = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, P = 0.023; non-CeAD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome (P = 0.004). CONCLUSION: Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.

Stroke in first-degree relatives of patients with cervical artery dissection.

BACKGROUND AND PURPOSE: Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non-CeAD) causes were compared. METHODS: The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age- and sex-matched non-CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non-CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI). RESULTS: In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non-CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22-0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23-0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. CONCLUSION: Relatives of CeAD patients had fewer strokes at a young age than relatives of non-CeAD IS stroke patients.

Simple variables predict miserable outcome after intravenous thrombolysis.

BACKGROUND AND PURPOSE: To test the predictability of miserable outcome amongst ischaemic stroke patients receiving intravenous thrombolysis (IVT) based on a simple variables model (SVM) and to compare the model's predictive performance with that of an existing score which includes imaging and laboratory parameters (DRAGON). METHODS: The SVM consists of the parameters age, independence before stroke, normal Glasgow coma verbal score, able to lift arms and able to walk. In a derivation cohort (n = 1346) and a validation cohort (n = 638) of consecutive IVT-treated stroke patients, the probability estimated by SVM and the observed occurrence of miserable 3-month outcome (modified Rankin score 5-6) were compared. The performances of SVM and the DRAGON score were compared. The area under the receiver operating curve (AUC) (95% confidence interval, CI) and the bootstrapping approach were used to compare the predictive performance. RESULTS: The AUCs to predict miserable outcome in the derivation cohort were 0.807 (95% CI 0.774-0.838) using the SVM and 0.822 (0.790-0.850) using the DRAGON score (P = 0.3). For the validation cohort, AUCs were 0.786 (0.742-0.829) for the SVM and 0.809 (0.774-0.845) for the DRAGON score (P = 0.23). Only one patient with an SVM probability of >70% for miserable outcome in either cohort had a good outcome whilst 83% had a miserable outcome. An online SVM calculator to estimate the probability of miserable outcome for individual patients is available under http://www.unispital-basel.ch/SVM-Tool. CONCLUSION: The SVM was similar in accuracy to the DRAGON score for predicting miserable outcome after IVT. As these simple variables are available already at the pre-hospital stage, the SVM may facilitate and accelerate pre-hospital triage of patients at high risk for miserable outcome after IVT towards endovascular treatment.

Echographic risk index and cerebral ischemic brain lesions in patients randomized to stenting versus endarterectomy for symptomatic carotid artery stenosis.

PURPOSE: It remains to be determined whether the impact of plaque characteristics on procedural risks differs between carotid artery stenting (CAS) and endarterectomy (CEA). We studied whether quantitative assessment of carotid plaque echolucency on ultrasound predicts the risk of embolism during CAS or CEA. MATERIALS AND METHODS: In 50 consecutive patients with symptomatic carotid stenosis randomized to CAS (n = 26) or CEA (n = 24) in the International Carotid Stenting Study (ICSS), semi-automated grayscale measurement of carotid plaques on baseline ultrasound was performed. We determined the grayscale median (GSM), percentage of echolucent plaque area, and a previously defined echographic risk index (ERI) calculated with the echolucent area and degree of stenosis. Brain MRI including diffusion-weighted imaging (DWI) was performed within 7 days before and 3 days after treatment. The primary outcome was the presence of at least 1 new hyperintense DWI lesion (DWI+) after treatment. RESULTS: In the CAS group, DWI+ patients (n = 18) had a significantly higher ERI at baseline (mean 0.11 ±â€Š0.12) than patients without new lesions (n = 8; mean 0.03 ±â€Š0.01; p = 0.012). GSM (mean 26.7 ±â€Š18.7 versus 34.3 ±â€Š8.0, p = 0.16) and echolucent plaque area (mean 42.8 ±â€Š21.1 versus 31.2 ±â€Š8.2, p = 0.054) did not differ significantly. In the CEA group, there were no differences in plaque echogenity measurements between patients with (n = 2) and without DWI lesions (n = 22). CONCLUSION: Patients with echolucent plaques causing severe narrowing are at increased risk for cerebral embolism during CAS. Quantitative ultrasound plaque analysis, with ERI in particular, may add to clinical variables in identifying patients at risk for procedural stroke with CAS, but larger studies with clinical endpoints are needed.

Elevated peripheral leukocyte counts in acute cervical artery dissection.

BACKGROUND AND PURPOSE: It has been suggested that inflammation may play a role in the development of cervical artery dissection (CeAD), but evidence remains scarce. METHODS: A total of 172 patients were included with acute (< 24 h) CeAD and 348 patients with acute ischaemic stroke (IS) of other (non-CeAD) causes from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study, and 223 age- and sex-matched healthy control subjects. White blood cell (WBC) counts collected at admission were compared across the three groups. RESULTS: Compared with healthy control subjects, CeAD patients and non-CeAD stroke patients had higher WBC counts (P < 0.001). Patients with CeAD had higher WBC counts and were more likely to have WBC > 10 000/µl than non-CeAD stroke patients (38.4% vs. 23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts were higher in CeAD (9.4 ± 3.3) than in IS of other causes (large artery atherosclerosis, 8.7 ± 2.3; cardioembolism, 8.2 ± 2.8; small vessel disease, 8.4 ± 2.4; undetermined cause, 8.8 ± 3.1; P = 0.022). After adjustment for age, sex, stroke severity and vascular risk factors in a multiple regression model, elevated WBC count remained associated with CeAD, as compared with non-CeAD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60-4.11; P < 0.001) and healthy controls (OR = 6.27; 95% CI 3.39-11.61; P < 0.001). CONCLUSIONS: Acute CeAD was associated with particularly high WBC counts. Leukocytosis may reflect a pre-existing inflammatory state, supporting the link between inflammation and CeAD.

Migraine in cervical artery dissection and ischemic stroke patients.

OBJECTIVE: Several small to medium-sized studies indicated a link between cervical artery dissection (CeAD) and migraine. Migrainous CeAD patients were suggested to have different clinical characteristics compared to nonmigraine CeAD patients. We tested these hypotheses in the large Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) population. METHODS: A total of 968 CeAD patients and 653 patients with an ischemic stroke of a cause other than CeAD (non-CeAD IS) were recruited. CeAD patients with stroke (CeAD(stroke), n = 635) were compared with non-CeAD IS patients regarding migraine, clinical characteristics, and outcome. CeAD patients with and without migraine were compared in terms of clinical characteristics and outcome. RESULTS: Migraine was more common among CeAD(stroke) patients compared to non-CeAD IS patients (35.7 vs 27.4%, p = 0.003). The difference was mainly due to migraine without aura (20.2 vs 11.2%, p < 0.001). There were no differences in prevalence of strokes, arterial distribution, or other clinical or prognostic features between migrainous and nonmigrainous CeAD patients. CONCLUSION: Migraine without aura is more common among CeAD(stroke) patients compared to non-CeAD IS patients. The mechanisms and possible causative link remain to be proved. Although CeAD is often complicated by stroke, our data do not support increased risk of stroke in migrainous CeAD patients.

Thrombolysis in cervical artery dissection--data from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) database.

OBJECTIVE: To examine whether thrombolysis for stroke attributable to cervical artery dissection (CeAD(Stroke) ) affects outcome and major haemorrhage rates. METHODS: We used a multicentre CeAD(Stroke) database to compare CeAD(Stroke) patients treated with and without thrombolysis. Main outcome measures were favourable 3-month outcome (modified Rankin Scale 0-2) and 'major haemorrhage' [any intracranial haemorrhage (ICH) and major extracranial haemorrhage]. Adjusted odds ratios [OR (95% confidence intervals)] were calculated on the whole database and on propensity-matched groups. RESULTS: Among 616 CeAD(Stroke) patients, 68 (11.0%) received thrombolysis; which was used in 55 (81%) intravenously. Thrombolyzed patients had more severe strokes (median NIHSS score 16 vs. 3; P < 0.001) and more often occlusion of the dissected artery (66.2% vs. 39.4%; P < 0.001). After adjustment for stroke severity and vessel occlusion, the likelihood for favourable outcome did not differ between the treatment groups [OR(adjusted) 0.95 (95% CI 0.45-2.00)]. The propensity matching score model showed that the odds to recover favourably were virtually identical for 64 thrombolyzed and 64 non-thrombolyzed-matched CeAD(Stroke) patients [OR 1.00 (0.49-2.00)]. Haemorrhages occurred in 4 (5.9%) thrombolyzed patients, all being asymptomatic ICHs. In the non-thrombolysis group, 3 (0.6%) patients had major haemorrhages [asymptomatic ICH (n = 2) and major extracranial haemorrhage (n = 1)]. CONCLUSION: As thrombolysis was neither independently associated with unfavourable outcome nor with an excess of symptomatic bleedings, our findings suggest thrombolysis should not be withheld in CeAD(Stroke) patients. However, the lack of any trend towards a benefit of thrombolysis may indicate the legitimacy to search for more efficient treatment options including mechanical revascularization strategies.

Gender and cervical artery dissection.

BACKGROUND AND PURPOSE: To analyze previously established gender differences in cervical artery dissection (CeAD). METHODS: This case-control study is based on the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) population comprising 983 consecutive CeAD patients (mean age: 44.1 ± 9.9 years) and 658 control patients with a non-CeAD ischemic stroke (IS) (44.5 ± 10.5 years). RESULTS: Cervical artery dissection was more common in men (56.7% vs. 43.3%, P < 0.001) and men were older (46.4 vs. 41.0 years, P < 0.001). We assessed putative risk factors for CeAD including vascular risk factors, recent cervical trauma, pregnancies, and infections. All gender differences in the putative risk factors and outcome were similar in the CeAD and the non-CeAD IS groups. CONCLUSION: Our analysis of the largest collection of CeAD patients to date confirms male predominance and differences in age at dissection between men and women. Gender differences in putative risk factors may explain the higher frequency of CeAD in men and their older age, but the putative risk factors are probably not specific for CeAD.

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.

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.

Outcome of intravenous thrombolysis in stroke patients weighing over 100 kg.

BACKGROUND: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. METHODS: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0-2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. RESULTS: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). CONCLUSION: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.

IV thrombolysis and statins.

OBJECTIVE: To examine whether prior statin use affects outcome and intracranial hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT). METHODS: In a pooled observational study of 11 IVT databases, we compared outcomes between statin users and nonusers. Outcome measures were excellent 3-month outcome (modified Rankin scale 0-1) and ICH in 3 categories. We distinguished all ICHs (ICH(all)), symptomatic ICH based on the criteria of the ECASS-II trial (SICH(ECASS-II)), and symptomatic ICH based on the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) trial (SICH(NINDS)). Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals were calculated. RESULTS: Among 4,012 IVT-treated patients, 918 (22.9%) were statin users. They were older, more often male, and more frequently had hypertension, hypercholesterolemia, diabetes, coronary heart disease, and concomitant antithrombotic use compared with nonusers. Fewer statin users (35.5%) than nonusers (39.7%) reached an excellent 3-month outcome (OR(unadjusted) 0.84 [0.72-0.98], p = 0.02). After adjustment for age, gender, blood pressure, time to thrombolysis, and stroke severity, the association was no longer significant (0.89 [0.74-1.06], p = 0.20). ICH occurred by trend more often in statin users (ICH(all) 20.1% vs 17.4%; SICH(NINDS) 9.2% vs 7.5%; SICH(ECASS-II) 6.9% vs 5.1%). This difference was statistically significant only for SICH(ECASS-II) (OR = 1.38 [1.02-1.87]). After adjustment for age, gender, blood pressure, use of antithrombotics, and stroke severity, the OR(adjusted) for each category of ICH (ICH(all) 1.15 [0.93-1.41]; SICH(ECASS-II) 1.32 [0.94-1.85]; SICH(NINDS) 1.16 [0.87-1.56]) showed no difference between statin users and nonusers. CONCLUSION: In stroke patients receiving IVT, prior statin use was neither an independent predictor of functional outcome nor ICH. It may be considered as an indicator of baseline characteristics that are associated with a less favorable course.

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.