Dejana R. Jovanovic

Intravenous thrombolytic therapy in patients with stroke mimics: baseline characteristics and safety profile

Background:  The decision to treat with intravenous (i.v.) rt‐PA a patient with acute cerebral ischaemia is based on clinical and imaging criteria recorded in emergency. In such an emergency situation stroke mimics may sometimes be misdiagnosed, and lead to an erroneous prescription of rtPA. The objective of this study was to determine the baseline profile and the outcome in patients with stroke mimics who received i.v. rtPA.

The Frequency of Poststroke Infections and Their Impact on Early Stroke Outcome

INTRODUCTION Poststroke infections are the most common medical complications of stroke and can occur in up to 65% of patients. The aim of this study was to assess the rate of infectious complications during hospitalization of stroke patients and to evaluate the impact of infection in general, including each of the urinary tract infection (UTI), pneumonia, and sepsis, on fatal and poor functional outcome at discharge. METHODS This retrospective study enrolled patients who have been diagnosed with acute ischemic stroke treated in a 1-year period. Poor functional outcome at discharge was defined as severe invalidity and included patients with modified Rankin Scale score of 3-5. Univariate and multivariate analyses were performed. RESULTS We analyzed 133 patients with acute ischemic stroke. Poststroke infection occurred in 63 (47.4%) patients. The most common infection was UTI that was present in 27 (20.3%) patients. Multivariate logistic regression analysis after adjustment for confounders demonstrated that poststroke infection was an independent predictor of poor functional outcome (odds ratio [OR] 12.82, 95% confidence interval [CI] 4.09-40.0, P < .001) and death at discharge (OR 14.92, 95% CI 2.97-76.92, P = .001). When analyzing the impact of each infectious complication, multivariate logistic regression showed that UTIs were an independent predictor of poor functional outcome (OR 14.08, 95% CI 3.06-64.84, P = .001) and death (OR 9.81, 95% CI 1.46-65.68, P = .019) at discharge. CONCLUSION Infection is a frequent poststroke complication and represents an independent predictor of poor functional and fatal early stroke outcome.

Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study

OBJECTIVE The female sex is associated with increased stroke severity and relatively poor functional recovery. Several studies have demonstrated that women with stroke benefit more from intravenous thrombolysis compared with men, while others found the nullification of gender effect among women treated with recombinant tissue plasminogen activator (rtPA). The purpose of our study was to determine any gender differences in the efficacy and safety of systemic thrombolysis among patients with acute ischemic stroke in Serbia. METHODS Data were from the Serbian experience with intravenous thrombolysis in ischemic stroke (SETIS) study, a prospective, ongoing, multicenter, open, and observational study in Serbia of all patients who have received rtPA for acute ischemic stroke. We analyzed sex differences in the baseline characteristics, functional outcome and treatment complications. RESULTS Among 60 women and 96 men with stroke and treated with intravenous thrombolysis, we found that at day 90, no significant sex differences in excellent functional outcome (50.9% of women vs. 57.0% of men, p=0.5), favorable functional outcome (61.4% of women vs. 68.8% of men, p=0.38) or death (8.8% of women vs. 12.9% of men, p=0.60). These results were constant even after adjustments for age, severity of basal neurological deficit and onset to treatment time. CONCLUSION There were no sex differences in functional outcome at 90 days after the stroke among patients treated with IV rtPA. This finding might confirm that thrombolytic therapy nullifies usual sex differences in stroke outcome and suggests that women with stroke may benefit more from rtPA treatment.

Influence of Differences in Case Mix on the Better Outcome of Smokers after Intravenous Thrombolysis for Acute Cerebral Ischemia

Background/Aims: Thrombolysis for myocardial infarction is more effective in smokers. Our aim wasto determine whether smokers treated by intravenous (i.v.) rt-PA for acute cerebral ischemia have better outcomes. Method: Comparison of smokers and non-smokers for baseline characteristics and month-3 outcome in patients treated by i.v. rt-PA for cerebral ischemia in Lille, France, and Belgrade, Serbia. The primary outcome was a modified Rankin scale (mRS) 0–1 or similar to the pre-stroke mRS. Secondary outcomes were an mRS 0–2 and death. Results: We included 459 patients (255 men; median age 65 years, interquartile range 52–76; 135 smokers). Smokers were younger (median 53 vs. 70 years, p < 0.0001) and had less severe strokes (median NIHSS 10 vs. 14, p < 0.0001). At month 3, they were more likely to have an mRS 0–1 [odds ratio (OR) 1.75; 95% confidence interval (CI) 1.17–2.62], or an mRS 0–2 (OR 2.90; 95% CI 1.86–4.52) and less likely to be dead (OR 0.28; 95% CI 0.13–0.61). Smoking was not independently associated with outcome after adjustment for case mix [adjusted OR (adjOR) 0.86; 95% CI 0.52–1.43]. Conclusion: Smoking does not independently influence the outcome in patients treated by rt-PA for cerebral ischemia. The better outcome in smokers is the consequence of differences in case mix.

Recurrent ischemic stroke associated with sildenafil and tadalafil use in a young adult.

Sildenafil and tadalafil are the most frequently prescribed drugs or male impotence function. Frequent adverse effects, such are eadache, flushing, dyspepsia, nasal congestion, or visual disturances, are the main symptoms of vasodilatation [1]. Clinical trials ave not shown an increased risk of cardiovascular diseases among ildenafil users [2]. However, sildenafil should be prescribed with aution to patients with history of hypotension, arrhythmia, preious myocardial infarction, or stroke [1]. Also, several reports of ransient ischemic attacks (TIA), ischemic and hemorrhagic strokes ave been reported after sildenafil/tadalafil ingestion, followed or ot by sexual exertion [3,4]. We describe a 47-year-old male who experienced recurrent schemic strokes in a 2-year period, both in close temporal assoiation with sildenafil and tadalafil ingestion.

Clinical characteristics and outcome in the acute phase of ischemic locked-in syndrome: case series of twenty patients with ischemic LIS.

Background: Locked-in syndrome (LIS) is a condition characterized by quadriplegia and anarthria. The most common cause is a ventral pontine lesion due to atherosclerotic basilar artery disease. Methods: Cases with LIS were prospectively identified among the patients with acute ischemic stroke over 3 years, between 2009 and 2011. Clinical characteristics, topographic localization of lesions, and outcome were determined during the first 6 months from onset of LIS. Results: Our case series consists of 20 patients (mean age 62 ± 10 years; range 46–82). Initially 16 patients had a reduced level of consciousness (mean 3 days; range 1–15). Respiratory disturbance, mainly as impairment of the breathing pattern, was noted in all cases. Five patients died within the first 10 days due to stroke progression or cardiac arrest. In the remaining cases the most frequent causes of death were pulmonary infections and sepsis. Overall mortality in the acute phase of LIS is 75%, and the median survival time is 42 days. There was a statistically significant association between the more extensive parenchymal brain stem lesions and observed mortality. Conclusions: Ischemic LIS is commonly caused by an acute complete occlusion of the basilar artery due to atherosclerotic lesions in intracranial vertebrobasilar vessels. Mortality remains high in the acute phase of the disease.

Intravenous thrombolysis in the treatment of ischemic stroke due to spontaneous artery dissection.

Objectives:Data based on randomized clinical trials regarding intravenous thrombolysis (IVT) versus placebo or any other antithrombotic treatment in ischemic stroke (IS) due to artery dissection (AD) are not available. Methods:We used data from our observational study to examine the efficacy and safety of IVT in patients with IS due to spontaneous AD, as compared with stroke patients of the same cause who were not treated with IVT. Outcome measures were modified Rankin score (mRS) for functional outcome, death from all causes, occurrence of any intracranial hemorrhage, local signs of an intramural hematoma extension, recurrent IS, and recurrent AD. Results:In a 4-year period, 19 of 46 patients with IS due to spontaneous AD were treated with IVT. Favorable outcome (mRS 0-2) after the follow-up period reached 81.5% of non-IVT patients compared with 94.7% of IVT-treated patients (odds ratio, 4.09; 95% confidence interval, 0.44-38.26; P=0.377). However, the patients who received IVT had a significantly higher chance of being without any neurological deficit (mRS 0) after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, and site of dissection compared with non-IVT patients after the follow-up period (P=0.012). No symptomatic intracerebral hemorrhage, worsening of local signs, cases of subarachnoid hemorrhage, or death occurred in both groups of patients. Conclusions:The efficacy of IVT in patients with IS due to the spontaneous AD seemed to be similar or even better to those of patients of the same cause who were not treated with IVT. The complication rate of IVT in spontaneous AD is low.

Long-Term Prognosis in Ischemic Stroke Patients Treated with Intravenous Thrombolytic Therapy

BACKGROUND AND PURPOSE It remains unclear if intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator has an impact on the survival and maintenance of a favorable effect on functional recovery over a long follow-up period. The aim of this study was to assess whether or not IVT treatment has a favorable effect on functional recovery and survival less than 1 year after a stroke. METHODS This matched cohort study included 259 patients with acute ischemic stroke (IS) who were treated with IVT and standard care and 259 patients treated with standard care alone in the stroke unit between February 2006 and January 2013. RESULTS After a median follow-up period of 3 years (range, 1-7 years), survival did not differ significantly between the groups; specifically, 56 patients (21.6%) in the thrombolysed group died versus 62 patients (23.94%) in the nonthrombolysed group (log-rank, .240, P = .624). Based on a multivariate Cox proportional hazards regression model, older age (>70 years), stroke severity (National Institutes of Health Stroke Scale score ≥ 15), diabetes mellitus, and a history of atrial fibrillation were independent predictors of long-term mortality after stroke. After the follow-up period, 144 patients (55.6%) in the IVT-treated group versus 112 patients (43.2%) in the control group had an excellent outcome, with a modified Rankin Scale score of 0-1 (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.16-2.32). Based on a multivariate Cox proportional hazards regression model, an excellent 3-month functional recovery was a strong predictor of favorable outcome (HR = 11.27, 95% CI = 6.45-19.63). CONCLUSION The results suggest that IVT for acute IS has a favorable effect on functional recovery more than 1 year after stroke.

Intravenous Thrombolysis for Acute Cerebral Ischemia in Belgrade, Serbia: Comparison with Lille, France

Background: Worse socioeconomic situation is associated with worse outcomes in stroke cases. Whether it also influences outcomes in patients treated with intravenous thrombolysis remains unknown. The aim of this study was to test the hypothesis that outcomes are less favorable in patients treated with intravenous thrombolysis in Belgrade, Serbia, than in Lille, France. Methods: We compared outcomes at day 7 and month 3, between 123 consecutive stroke patients treated with intravenous thrombolysis in Belgrade and 273 in Lille. Results: At month 3, there was no significant difference between Belgrade and Lille in patients’ excellent outcomes [modified Rankin Scale 0–1; 49.6 vs. 45.4%, odds ratio (OR): 1.21, 95% confidence interval (CI): 0.79–1.86] or in death (11.4 vs. 16.1%, OR 0.67, 95% CI: 0.35–1.27). However, compared with a subgroup of age-matched patients from Lille, Belgrade patients tended to have worse outcomes. Patients from Belgrade were 16 years younger (p < 0.0001), more likely to be men (OR 2.40, 95% CI: 1.52–3.78), and more likely to be smokers (OR 2.24, 95% CI: 1.43–3.51). Also, a trend for a slightly higher rate of symptomatic hemorrhagic transformation was registered in this group (7.3 vs. 3.3%, OR 2.32, 95% CI: 0.90–5.99). In Belgrade, patients arrived 27 min earlier to the hospital (p < 0.0001), but their door-to-needle time was 37 min longer (p < 0.0001). Compared with a subgroup of age-matched patients from Lille, they tended to have worse outcomes. Conclusion: Intravenous thrombolysis-treated stroke patients in Belgrade have similar outcomes and rates of complications as those from Lille.

Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal carotid artery – A Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS)

OBJECTIVE The benefit of intravenous thrombolysis in patients with internal carotid artery (ICA) occlusion is still unclear. The aim of this study was to assess the influence on outcome of intravenous thrombolysis in patients with ICA occlusion comparing to those without it. METHODS Data were from the national register of all acute ischemic stroke patients treated with intravenous thrombolysis in Serbia. Patients with nonlacunar anterior circulation infarction were included and were divided into two groups, those with and those without ICA occlusion. We compared the differences in demographic characteristics, risk factors, baseline NIHSS score, early neurological improvement, 3-month functional outcome, complications and death between these two groups. RESULTS Among 521 included patients there were 13.4% with ICA occlusion. Group with ICA occlusion had more males (82.9% vs. 60.5%; p=0.0008), and more severe stroke (baseline NIHSS score 15.3 vs. 13.6; p=0.004). Excellent functional outcome (mRS 0-1) at 3 months was recorded in 32.9% patients with ICA occlusion and in 50.6% patients without (p=0.009), while favorable functional outcome (mRS 0-2) was recorded in 50.0% of patients with ICA occlusion vs. 60.1% without (p=0.14). Death occurred in 12.9% patients with ICA occlusion and in 17.3% patients without it (p=0.40). There was no significant difference in rate of symptomatic ICH between the two groups (1.4% vs. 4.2%; p=0.5). Multivariate logistic regression analysis showed that ICA occlusion was associated with the absence of early neurological improvement (p=0.03; OR 1.78, 95% CI 1.05-3.04). However, the presence of ICA occlusion was not significantly associated with an unfavorable outcome at 3-month (p=0.44; OR 1.24, 95% CI 0.72-2.16) or with death (p=0.18; OR 0.57, 95% CI 0.25-1.29). CONCLUSION The patients with ICA occlusion treated with intravenous thrombolysis have a worse outcome than patients without it.