Tamara Sauer

Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials

Objective To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice. Design A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany. Setting All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants. Participants Data from 84 439 patients with acute ischaemic stroke were analysed, 10 263 (12%) were treated with thrombolytic therapy and 74 176 (88%) were not treated. Main outcome measures Primary endpoint was the dichotomised score on a modified Rankin scale at discharge (“favourable outcome” score 0 or 1 or “unfavourable outcome” score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis). Results After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92). Conclusion The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.

Predictors and early outcome of hemorrhagic transformation after acute ischemic stroke.

Background: Hemorrhagic transformation (HT) after acute ischemic stroke is frequently detected using magnetic resonance imaging (MRI), in particular in patients treated with tissue plasminogen activator (tPA). Knowledge about causes and early clinical consequences of HT mostly arises from computed tomography-based studies. We analyzed potential predictors and early outcome of HT after stroke detected by MRI with T2*-weighted gradient echo sequences (T2*-MRI). Methods: 122 consecutive stroke patients (mean age 65.5 years, 41% women) who underwent T2*-MRI within 6–60 h after stroke onset were included. 25.4% of patients were treated with tPA; the overall detection rate of HT on T2*-MRI was 20.5%. Potential predictors of HT, such as age, sex, blood pressure, stroke etiology, prior antithrombotic medication, neurological deficit on admission, tPA treatment, and specific MRI findings, were analyzed. In addition, we evaluated the effect of HT on early outcome: a decrease of >4 points on the National Institute of Health Stroke Scale (NIHSS) on day 5 was considered early improvement, and an increase of >4 points was considered early deterioration. Results: The main predictor for occurrence of HT was tPA treatment (48.4 vs. 11.1%; odds ratio 7.50; 95% confidence interval 2.9–19.7; p < 0.001). Furthermore, the development of HT was associated with a severer neurological deficit on admission (mean NIHSS score 9.9 vs. 5.9; p = 0.003), and territorial infarction (88 vs. 58.8%; p = 0.007). 19 patients (15.6%) showed early improvement which was associated with the occurrence of HT (p = 0.011) and tPA treatment (p < 0.001). Conclusions: HT is a frequent finding on T2*-MRI in patients with acute ischemic stroke associated with tPA treatment, territorial infarction and severer neurological deficits on admission. However, HT does not cause clinical deterioration; it is rather related to a favorable early outcome likely reflecting early recanalization and better reperfusion in these patients.

Comparison of the new ASCO classification with the TOAST classification in a population with acute ischemic stroke

Precise analysis of stroke subtypes is important for clinical treatment decisions, the prognostic evaluation of patients, as well as defining stroke populations in clinical studies. The TOAST classification is the most widely used and approved form for etiologic subtyping. Increasing knowledge about stroke mechanisms and the introduction of new diagnostic techniques have supported the promotion of the new ASCO phenotypic classification, which aims to characterize patients using different grades of evidence for stroke subtypes. We prospectively assigned 103 consecutive patients from our stroke center for subtype classification using ASCO and TOAST. Clinical features and complementary investigations were recorded according to our standardized acute stroke care protocol. Evidence grade 1 with ASCO was assessed in 12.62% for large artery disease (A), 23.30% small-vessel disease (S), 36.89% cardiac source (C) and 1.94% another cause (O). Evidence grades 1–3 were identified in 60.19% A, 75.73% S, 49.51% C, and 3.88% O. A total of 68.93% of the patients were classified in more than one category, and only 3.88% remained completely undetermined. The κ value for inter-rater agreement was 0.92–1. Using TOAST, the distribution was 9.71% A, 23.30% S, 34.95% C, 1.94% O, and 30.10% undetermined. The ASCO classification showed a good concordance with TOAST. The inter-rater agreement was high. The comprehensive character of ASCO allows the recording of important additional information. This may be helpful for a specific treatment adaptation in each individual patient and creation of different etiological profiles in view of adapted clinical trials.

Intravenous thrombolysis for acute ischaemic stroke in the elderly: data from the Baden-Wuerttemberg stroke registry

In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed.

Restriction of therapy mainly explains lower thrombolysis rates in reduced stroke service levels

Objective: To assess the influence of preexisting disabilities, age, and stroke service level on standardized IV thrombolysis (IVT) rates in acute ischemic stroke (AIS). Methods: We investigated standardized IVT rates in a retrospective registry-based study in 36,901 patients with AIS from the federal German state Baden-Wuerttemberg over a 5-year period. Patients admitted within 4.5 hours after stroke onset were selected. Factors associated with IVT rates (patient-level factors and stroke service level) were assessed using robust Poisson regression modeling. Interactions between factors were considered to estimate risk-adjusted mortality rates and potential IVT rates by service level (with stroke centers as benchmark). Results: Overall, 10,499 patients (28.5%) received IVT. The IVT rate declined with service level from 44.0% (stroke center) to 13.1% (hospitals without stroke unit [SU]). Especially patients >80 years of age and with preexisting disabilities had a lower chance of being treated with IVT at lower stroke service levels. Interactions between stroke service level and age group, preexisting disabilities, and stroke severity (all p < 0.0001) were observed. High IVT rates seemed not to increase mortality. Estimated potential IVT rates ranged between 41.9% and 44.6% depending on stroke service level. Conclusions: Differences in IVT rates among stroke service levels were mainly explained by differences administering IVT to older patients and patients with preexisting disabilities. This indicates considerable further potential to increase IVT rates. Our findings support guideline recommendations to admit acute stroke patients to SUs.

Characterization of patients with recurrent ischaemic stroke using the ASCO classification

The ASCO score has the advantage of allowing a more comprehensive characterization of ischaemic stroke patients and their risk factors, as reflected in different grades of evidence of atherosclerotic changes (A), small vessel disease (S), potential cardiac (C) or other (O) sources. It might also help to characterize patients with recurrent ischaemic stroke and document the etiology of stroke recurrence as well as the further development of risk factor constellations.

Intravenous Thrombolysis is Effective in Young Adults: Results from the Baden-Wuerttemberg Stroke Registry

Background The efficacy of intravenous thrombolysis (IVT) is sufficiently proven in ischemic stroke patients of middle and older age by means of randomized controlled trials and large observational studies. However, data in young stroke patients ≤50 years are still scarce. In this study, we aimed to evaluate the effectiveness and safety of IVT in young adults aged 18–50 years. Data from a consecutive and prospective stroke registry was analyzed that covers a federal state with 10.8 million inhabitants in southwest Germany. Methods Our analysis comprises 51,735 ischemic stroke patients aged 18–80 years and hospitalized from January 2008 to December 2012. Of these, 4,140 (8%) were aged 18–50 years and 7,529 (15%) underwent IVT. Data on 8,439 patients (16% of the study population) were missing for National Institutes of Health stroke severity score at admission and/or modified Rankin Scale (mRS) at discharge and were excluded from outcome analysis. In sensitivity analysis, patients with incomplete data were also examined. Binary logistic regression models were used adjusted for patient, hospital, and procedural parameters and stratified by age group (18–50 and 51–80 years, subgroup analyses 18–30, 31–40, and 41–50 years) to assess the relationship between IVT and mRS at discharge. Results IVT appears equally effective in young adults 18–50 years (adjusted odds ratio 1.40, 95% confidence interval 1.12–1.75; p = 0.003), compared to patients 51–80 years of age (1.33, 1.23–1.43; p < 0.001). Age-stratified analyses suggest an inverse relation of age and effectiveness, which appears to be highest in very young patients 18–30 years of age (2.78, 1.10–7.05; p = 0.03). Discussion Ischemic stroke etiology, vascular dynamics, and recovery in young patients differ from those of middle and older age. The evidence from routine hospital care in Germany indicates that IVT in young stroke patients appears to be at least equally effective as in the elderly.

Vertebral Artery Hypoplasia Does Not Influence Lesion Size and Clinical Severity in Acute Ischemic Stroke.

BACKGROUND Vertebral artery hypoplasia (VAH) is common, but its role in acute ischemic stroke (AIS) is uncertain. We aimed to evaluate the frequency, characteristics, and role of VAH in a large typical cohort of patients with AIS. METHODS Up to 815 AIS patients (52.8% men, mean age 70 ± 14 years) were included in the study. All patients received a stroke work-up including brain imaging and duplex ultrasound. VAH was defined by a vessel diameter of less than or equal to 2.5 mm or a difference to the contralateral side of greater than 1:1.7. Vascular risk factors and stroke features were recorded. The subgroup of patients with posterior circulation AIS and magnetic resonance imaging was analyzed additionally, including the parameter of stroke extent. RESULTS Up to 111 patients (13.6%) had VAH, with a mean diameter of 2.4 ± .4 mm. Patients with VAH were significantly younger (P = .037) and more often male (P = .033). There was no difference considering the National Institutes of Health Stroke Scale and modified Rankin Scale scores on admission or history of stroke. The distribution of patients without VAH was significantly different among the groups with anterior, posterior, and both circulations ischemia (P = .009). In the group with posterior circulation stroke, 36 patients (20.9%) had VAH. There were no differences in age, sex, history of stroke, risk factors, vascular territory, stroke size, or etiology. VAH patients had less often embolic stroke patterns (P = .009). CONCLUSIONS VAH is more common in patients with posterior circulation stroke and in younger patients. Apart from that, we found no clear evidence that VAH would be a predisposing factor for stroke or that it increased the risk for larger ischemic lesions in the posterior circulation.

Neuroleptic‐like Malignant Syndrome After Battery Depletion in a Patient with Deep Brain Stimulation for Secondary Parkinsonism

Neuroleptic malignant syndrome (NMS) is characterised by impairment of consciousness, high fever, rhabdomyolysis, rigidity, and autonomic dysfunction 1. Although this syndrome was originally described in patients taking neuroleptic drugs, it may also occur in patients with Parkinsons disease (PD) during withdrawal of dopaminergic drugs called neuroleptic-like malignant syndrome or parkinsonism-hyperpyrexia syndrome (PHS) 1. This article is protected by copyright. All rights reserved.

Diurnal Variation of Intravenous Thrombolysis Rates for Acute Ischemic Stroke and Associated Quality Performance Parameters

Introduction Based on data from the Baden-Wuerttemberg stroke registry, we aimed to explore the diurnal variation of acute ischemic stroke (IS) care delivery. Materials and methods 92,530 IS patients were included, of whom 37,471 (40%) presented within an onset-to-door time ≤4.5 h. Daytime was stratified in 3-h time intervals and working vs. non-working hours. Stroke onset and hospital admission time, rate of door-to-neurological examination time ≤30 min, onset-/door-to-imaging time IV thrombolysis (IVT) rates, and onset-/door-to-needle time were determined. Multivariable regression models were used stratified by stroke onset and hospital admission time to assess the relationship between IVT rates, quality performance parameters, and daytime. The time interval 0:00 h to 3:00 h and working hours, respectively, were taken as reference. Results The IVT rate of the whole study population was strongly associated with the sleep–wake cycle. In patients presenting within the 4.5-h time window and potentially eligible for IVT stratification by hospital admission time identified two time intervals with lower IVT rates. First, between 3:01 h and 6:00 h (IVT rate 18%) and likely attributed to in-hospital delays with the lowest diurnal rate of door-to-neurological examination time ≤30 min and the longest door-to-needle time Second, between 6:01 h and 15:00 h (IVT rate 23–25%) compared to the late afternoon and evening hours (IVT rate 27–29%) due to a longer onset-to-imaging time and door-to-imaging time. No evidence for a compromised stroke service during non-working hours was observed. Conclusion The analysis provides evidence that acute IS care is subject to diurnal variation which may affect stroke outcome. An optimization of IS care aiming at constantly high IVT rates over the course of the day therefore appears desirable.