Klára Fekete

Factors Influencing In-Hospital Delay in Treatment With Intravenous Thrombolysis

Background and Purpose— Shortening door-to-needle time (DNT) for the thrombolytic treatment of stroke can improve treatment efficacy by reducing onset-to-treatment time. The goal of our study was to explore the association between DNT and outcome and to identify factors influencing DNT to better understand why some patients are treated late. Methods— Prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST: 9 central and eastern European countries) on all patients treated with thrombolysis between February 2003 and February 2010 were analyzed. Multiple logistic regression analysis was used to identify predictors of DNT ⩽60 minutes. Results— Altogether, 5563 patients were treated with thrombolysis within 4.5 hours of symptom onset. Of these, 2097 (38%) had DNT ⩽60 minutes. In different centers, the proportion of patients treated with DNT ⩽60 minutes ranged from 18% to 84% (P<0.0001). Patients with longer DNT (in 60-minute increments) had less chance of achieving a modified Rankin Scale score of 0 to 1 at 3 months (adjusted OR, 0.86; 95% CI, 0.77–0.97). DNT ⩽60 minutes was independently predicted by younger age (in 10-year increments; OR, 0.92; 95% CI, 0.87–0.97), National Institutes of Health Stroke Scale score 7 to 24 (OR, 1.44; 95% CI, 1.2–1.7), onset-to-door time (in 10-minute increments; OR, 1.19; 95% CI, 1.17–1.22), treatment center (P<0.001), and country (P<0.001). Conclusions— Thrombolysis of patients with older age and mild or severe neurological deficit is delayed. The perception that there is sufficient time before the end of the thrombolytic window also delays treatment. It is necessary to improve adherence to guidelines and to treat patients sooner after arrival to hospital.

Mannitol Use in Acute Stroke Case Fatality at 30 Days and 1 Year

Background and Purpose— Mannitol is used worldwide to treat acute stroke, although its efficacy and safety have not been proven by randomized trials. Methods— In a tricenter, prospective study, we analyzed the 30-day and 1-year case fatality with respect to mannitol treatment status in 805 patients consecutively admitted within 72 hours of stroke onset. Confounding factors were compared between treated and nontreated patients. Results— Two thirds of the patients received intravenous mannitol as part of their routine treatment (mean dose, 47±22 g/d; mean duration, 6±3 days). The case fatality was 25% versus 16% (P =0.006) at 30 days and 38% versus 25% (P <0.001) at 1 year in the-mannitol treated and nontreated groups, respectively. Mannitol treatment effect was adjusted for age, stroke severity, fever in the first 3 days, and aspirin treatment (for ischemic strokes) in logistic regression models. Depending on the factors entered into the model, either no effect or harm could be attributed to mannitol. When the analysis was restricted to those admitted within 24 hours (n=568), case fatality differed significantly only at 1 year (35% in treated and 26% in nontreated patients, P =0.044). Although the prognostic scores of the Scandinavian Neurological Stroke Scale were similar in treated and nontreated patients, both in ischemic and hemorrhagic strokes, the patient groups differed in several factors that might also have influenced survival. Conclusions— Based on the results of this study, no recommendations can be made on the use of mannitol in acute stroke, and properly randomized, controlled trials should be performed to come to a final conclusion.

Threshold for NIH stroke scale in predicting vessel occlusion and functional outcome after stroke thrombolysis

Background Data are limited on optimal threshold for baseline National Institutes of Health Stroke Scale in predicting outcome after stroke thrombolysis (intravenous thrombolysis). Aims Finding thresholds for baseline National Institutes of Health Stroke Scale scores that predict functional outcome and baseline vessel occlusion. Methods We analyzed 44 331 patients with available modified Rankin Scale score at three-months and 11 632 patients with computed tomography/magnetic resonance angiography documented vessel occlusion at baseline in the SITS-International Stroke Thrombolysis Register. Main outcomes were functional independency (modified Rankin Scale 0–2) at three-months and baseline vessel occlusion. We obtained area under the curves by receiver operating characteristic analysis and calculated multivariately adjusted odds ratio for the outcomes of interest based on baseline National Institutes of Health Stroke Scale scores. Results For functional independency, National Institutes of Health Stroke Scale scores of 12 (area under the curve 0·775) and for baseline vessel occlusion, scores of 11 (area under the curve 0·678) were optimal threshold values. For functional independency, adjusted odds ratio decreased to 0·07 (95% CI 0·05–0·11), and for presence of baseline occlusion, aOR increased to 3·28 (95% CI 3·04–3·58) for National Institutes of Health Stroke Scale scores 12 and 11, respectively, compared with National Institutes of Health Stroke Scale score 0. National Institutes of Health Stroke Scale thresholds decreased with time from stroke onset to imaging, with 2–3 points, respectively, if time to imaging exceeded three-hours. Conclusions Ideally, all acute stroke patients should have immediate access to multimodal imaging. In reality these services are limited. Baseline National Institutes of Health Stroke Scale scores of 11 and 12 were identified as markers of baseline vessel occlusion and functional independency after intravenous thrombolysis, respectively. These values are time dependent; therefore, a threshold of National Institutes of Health Stroke Scale 9 or 10 points may be considered in the prehospital selection of patients for immediate transfer to centers with multimodal imaging and availability of highly specialized treatments.

Autosomal-dominant striatal degeneration is caused by a mutation in the phosphodiesterase 8B gene.

Autosomal-dominant striatal degeneration (ADSD) is an autosomal-dominant movement disorder affecting the striatal part of the basal ganglia. ADSD is characterized by bradykinesia, dysarthria, and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. Using genetic linkage analysis, we have mapped the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1. A maximum LOD score of 4.1 (Theta = 0) was obtained at marker D5S1962. Here we show that ADSD is caused by a complex frameshift mutation (c.94G>C+c.95delT) in the phosphodiesterase 8B (PDE8B) gene, which results in a loss of enzymatic phosphodiesterase activity. We found that PDE8B is highly expressed in the brain, especially in the putamen, which is affected by ADSD. PDE8B degrades cyclic AMP, a second messenger implied in dopamine signaling. Dopamine is one of the main neurotransmitters involved in movement control and is deficient in Parkinson disease. We believe that the functional analysis of PDE8B will help to further elucidate the pathomechanism of ADSD as well as contribute to a better understanding of movement disorders.

Role of Preexisting Disability in Patients Treated With Intravenous Thrombolysis for Ischemic Stroke

Background and Purpose— Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients’ profile and outcome after intravenous thrombolysis. Methods— We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke–Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression. Results— Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS ≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0–2 or returning to the prestroke mRS; 0.80, 0.41, 0.59, respectively). Patients with mRS ≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%). Conclusions— Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.

The Debrecen Stroke Database: demographic characteristics, risk factors, stroke severity and outcome in 8088 consecutive hospitalised patients with acute cerebrovascular disease

Background High stroke mortality in central-eastern European countries might be due to higher stroke incidence, more severe strokes or less effective acute care than in countries with lower mortality rate. Hospital databases usually yield more detailed information on risk factors, stroke severity and short-term outcome than population-based registries. Patients and methods The Debrecen Stroke Database, data of 8088 consecutively hospitalised patients with acute cerebrovascular disease in a single stroke centre in East Hungary between October 1994 and December 2006, is analysed. Risk factors were recorded and stroke severity on admission was scored by the Mathew stroke scale. The modified Glasgow outcome scale was used to describe patient condition at discharge. Results Mean age was 68 ± 13 years, 11·4% had haemorrhagic stroke. The rate of hypertension on admission was 79% in men, and 84% in women, 40·3% of men and 19·8% of women were smokers, and 34% of all patients had a previous cerebrovascular disease in their history. Case fatality was 14·9%, and 43% had some disability at discharge. Outcome at discharge was worse with higher age, higher glucose, higher blood pressure, higher white cell count and erythrocyte sedimentation rate and more severe clinical signs on admission. In multivariate analysis admission blood pressure lost its significance in predicting outcome. Conclusions In this large Hungarian stroke unit database hypertension on admission, smoking and previous cerebrovascular disease were more frequent than in most western databases. These findings indicate major opportunities for more efficient stroke prevention in this and probably other eastern European countries.

Benefit of thrombolysis for stroke is maintained around the clock: Results from the SITS-EAST Registry

The outcome of thrombolysis for early morning and sleep time strokes may be worse because of uncertainty of stroke onset time or differences in logistics. The aim of the study was to analyze if stroke outcome after intravenous thrombolysis differs depending on time of day when the stroke occurs.

Different effect of hyperglycemia on stroke outcome in non-diabetic and diabetic patients - a cohort study

Abstract Objectives: Relationship between hyperglycemia and stroke outcome is unclear, partly due to the small sample size in most studies, and partly due to lack of consensus concerning the cutoff level for hyperglycemia. Methods: In a cohort study, we investigated whether on-admission hyperglycemia is an independent predictor for 30-day case fatality by analyzing data of 2496 consecutive computed tomography (CT) verified acute ischemic stroke patients (2077 non-diabetic and 419 diabetic) included in the prospective, hospital-based Debrecen Stroke Database. Instead of using an arbitrary cutoff level for hyperglycemia, quartiles of on-admission glucose level were used for Kaplan–Meier survival curves and Cox proportional hazard modeling. Results: The four quartiles of serum glucose level were in the range as follows: <5·2 mmol/l, 5·201–6·1 mmol/l, 6·101–7·5 mmol/l, and >7·501 mmol/l (n = 664, 618, 597, and 617, respectively). Among all 2496 participants, the adjusted hazard ratios for death increased with each quartile of admission glucose 1·96 [95% confidence interval (CI): 1·07–3·60; P = 0·03], 1·56 (95% CI: 0·83–2·94; P = 0·17), and 3·04 (95% CI: 1·70–5·44; P<0·0001) for the second, third, and fourth quartiles, respectively). Upon stratification with respect to diabetes, we found similarly high risk for poor outcome among non-diabetic patients, while the risk was considerably lower among diabetic patients. Discussion: These data suggest that even mild elevation of on-admission glucose levels is an independent predictor of 30-day case fatality. So, we propose that the ideal target blood glucose level is lower for non-diabetic than diabetic patients.

Intravenous Thrombolysis for Stroke Recurring Within 3 Months From the Previous Event

Background and Purpose— According to the European license, alteplase can be given no sooner than 3 months after previous stroke. However, it is not known whether past history of stroke influences the effect of treatment. Our aim was to evaluate safety and functional outcome after intravenous thrombolysis administered in everyday practice to patients with previous stroke ⩽3 months compared with those with first-ever stroke. Methods— We analyzed consecutive cases treated with alteplase between October 2003 and July 2014 contributed to the Safe Implementation of Thrombolysis for Stroke–Eastern Europe registry from 12 countries. Odds ratios were calculated using unadjusted and adjusted logistic regression. Results— Of 13 007 patients, 11 221 (86%) had no history of stroke and 249 (2%) experienced previous stroke ⩽3 months before admission. Patients with previous stroke ⩽3 months had a higher proportion of hypertension and hyperlipidemia. There were no significant differences in outcome, including symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study (unadjusted odds ratio 1.27, 95% confidence interval: 0.74–2.15), and being alive and independent at 3 months (odds ratio 0.81, 95% confidence interval: 0.61–1.09). Conclusions— Patients currently treated with alteplase, despite a history of previous stroke ⩽3 months, do not seem to achieve worse outcome than those with first-ever stroke. Although careful patient selection was probably of major importance, our findings provide reassurance that this group of patients may safely benefit from thrombolysis and should not be arbitrarily excluded as a whole. Further studies are needed to identify the shortest safe time lapse from the previous event to treatment with alteplase.

Intravenous thrombolysis for patients with in-hospital stroke onset: propensity-matched analysis from the Safe Implementation of Treatments in Stroke-East registry.

Recent cross‐sectional study data suggest that intravenous thrombolysis (IVT) in patients with in‐hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in‐hospital mortality compared to patients with out‐of‐hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT‐treated patients with IHS and OHS by analysing propensity‐score‐matched data from the Safe Implementation of Treatments in Stroke‐East registry.