Yakup Krespi

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.

Underfunding of Stroke Research A Europe-Wide Problem

Background and Purpose— Previous studies in the United States and the United Kingdom have shown that stroke research is underfunded compared with coronary heart disease (CHD) and cancer research despite the high clinical and financial burden of stroke. We aimed to determine whether underfunding of stroke research is a Europe-wide problem. Methods— Data for the financial year 2000 to 2001 were collected from 9 different European countries. Information on stroke, CHD, and cancer research funding awarded by disease-specific charities and nondisease-specific charity or government-funded organizations was obtained from annual reports, web sites, and by direct communication with organizations. Results— There was marked and consistent underfunding of stroke research in all the countries studied. Stroke funding as a percentage of the total funding for stroke, CHD, and cancer was uniformly low, ranging from 2% to 11%. Funding for stroke was less than funding for cancer, usually by a factor of ≥10. In every country except Turkey, funding for stroke research was less than that for CHD. Conclusions— This study confirms that stroke research is grossly underfunded, compared with CHD and cancer, throughout Europe. Similar data have been obtained from the United States suggesting that relative underfunding of stroke research is likely to be a worldwide phenomenon.

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.

Safety of Statin Pretreatment in Intravenous Thrombolysis for Acute Ischemic Stroke

Background and Purpose— A recent meta-analysis investigating the association between statins and early outcomes in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) indicated that prestroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage. We investigated the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Methods— We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) registry on consecutive AIS patients treated with IVT during an 8-year period. Early clinical recovery within 24 hours was defined as reduction in baseline National Institutes of Health Stroke Scale score of ≥10 points. Favorable functional outcome at 3 months was defined as modified Rankin Scale scores of 0 to 1. Symptomatic intracranial hemorrhage was diagnosed using National Institute of Neurological Disorders and Stroke, European-Australasian Acute Stroke Study-II and SITS definitions. Results— A total of 1660 AIS patients treated with IVT fulfilled our inclusion criteria. Patients with statin pretreatment (23%) had higher baseline stroke severity compared with cases who had not received any statin at symptom onset. After adjusting for potential confounders, statin pretreatment was not associated with a higher likelihood of symptomatic intracranial hemorrhage defined by any of the 3 definitions. Statin pretreatment was not related to 3-month all-cause mortality (odds ratio, 0.92; 95% confidence interval, 0.57–1.49; P=0.741) or 3-month favorable functional outcome (odds ratio, 0.81; 95% confidence interval, 0.52–1.27; P=0.364). Statin pretreatment was independently associated with a higher odds of early clinical recovery (odds ratio, 1.91; 95% confidence interval, 1.25–2.92; P=0.003). Conclusions— Statin pretreatment seems not to be associated with adverse outcomes in AIS patients treated with IVT. The effect of statin pretreatment on early functional outcomes in thrombolysed AIS patients deserves further investigation.

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.

Factors influencing door-to-imaging time: analysis of the safe implementation of treatments in Stroke-EAST registry.

BACKGROUND Brain imaging is logistically the most difficult step before thrombolysis. To improve door-to-needle time (DNT), it is important to understand if (1) longer door-to-imaging time (DIT) results in longer DNT, (2) hospitals have different DIT performances, and (3) patient and hospital characteristics predict DIT. METHODS Prospectively collected data in the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) registry from Central/Eastern European countries between 2008 and 2011 were analyzed. Hospital characteristics were obtained by questionnaire from each center. Patient- and hospital-level predictors of DIT of 25 minutes or less were identified by the method of generalized estimating equations. RESULTS Altogether 6 of 9 SITS-EAST countries participated with 4212 patients entered into the database of which 3631 (86%) had all required variables. DIT of 25 minutes or less was achieved in 2464 (68%) patients (range, 3%-93%; median, 65%; and interquartile range, 50%-80% between centers). Patients with DIT of 25 minutes or less had shorter DNT (median, 60 minutes) than patients with DIT of more than 25 minutes (median, 86 minutes; P < .001). Four variables independently predicted DIT of 25 minutes or less: longer time from stroke onset to admission (91-180 versus 0-90 minutes; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.8), transport time of 5 minutes or less (OR, 2.9; 95% CI, 1.7-4.7) between the place of admission and a computed tomography (CT) scanner, no or minimal neurologic deficit before stroke (OR, 1.3; 95% CI, 1.02-1.5), and diabetes mellitus (OR, .8; 95% CI, .7-.97). CONCLUSIONS DIT should be improved in patients arriving early and late. Place of admission should allow transport time to a CT scanner under 5 minutes.

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.

Clinical and Radiological Features in CADASIL and NOTCH3-Negative Patients: A Multicenter Study from Turkey

Background: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. Methods: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. Results: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). Conclusion: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Electroencephalographic Patterns Recorded by Continuous EEG Monitoring in Patients with Change of Consciousness in the Neurological Intensive Care Unit

INTRODUCTION Our aim was to examine the frequency of various electrographic patterns including periodic discharges (PD), repetitive spike waves (RSW), rhythmic delta activities (RDA), nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) in continuous EEG monitoring (cEEG) of the critically ill patients with change of consciousness and the presence of specific clinical and laboratory findings associated with these important patterns in this study. METHODS Patients with changes of consciousness in the neurological intensive care unit (NICU) were consecutively monitored with cEEG during 2 years. Their clinical, electrophysiological, radiological and laboratory findings were evaluated retrospectively. RESULTS This sample consisted of 57 (25 men) patients with a mean age of 68.2 years. Mean duration of cEEG monitoring was 2532.6 minutes. The most common electrographic patterns were PD (33%) and NCS-NCSE (26.3%). The presence of NCS-NCSE was significantly associated with PD (57.9%, p<0.001). PD and NCS-NCSE were the mostly seen in patients with acute stroke and hypoxic encephalopathy. Duration of monitoring was significantly longer in the group with PD and NCS-NCSE (p:0.004, p:0.014). Detection of any electrographic pattern in EEG before monitoring was associated with the presence of any pattern in cEEG (59.3%, p<0.0001). Convulsive or nonconvulsive seizure during monitoring was common in patients with electrographic patterns (p<0.0001). 66.7% of NCS-NCSE was seen within the first 12 hours and 26.7% was seen within the 12-24 hours of the monitoring. CONCLUSION Detection of any electrographic pattern in EEG before monitoring was associated with the presence of any important pattern in cEEG monitoring. This association suggest that at least 24 hours-monitoring of these patients could be useful for the diagnosis of clinical and/or electrographic seizures.

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.