Csaba Ováry

The aim of our study was to compare subtype-specific incidence rates, case-fatality rates and outcome predictors in different geographical areas, and decide what drives the variations. Analyzing standardized, prospective stroke registers in the Akita Prefecture, Japan, and in Hungary with catchment areas of more than 1.2 and 1.5 million during the same 18 months, we assumed population and ethnic variations in subtype-specific incidence rates, indicating higher risk of ischemic stroke in Hungary and higher risk of hemorrhagic stroke in Japan. The determinants of 28-day case-fatality rates, at least in part, also varied in different populations. However, survival from stroke was mainly influenced by stroke management.

The authors summarised their experiences of systemic intravenous thrombolysis using recombinant tissue-type plasminogen activator with 3 hours therapeutic window in acute ischaemic stroke. The aim of this work was to test the safety and efficacy of systemic thrombolysis in our unselected, community-based patient population. The mean door-to-needle time was 45 minutes, the number of bleeding complications and successful recanalisation was similar to the results of the large international trials. In spite of these facts the functional outcome of our patients turned out to be worse. Compared to the baseline characteristics of the international trials the initial neurological deficit--a well known bad prognostic parameter- and also the comorbidity of our patients was more severe. In Hungary only patients with alarming, initial symptoms arrive quickly enough for thrombolysis to the hospital, while in most of the patients with less severe stroke symptoms the delay for hospital admission is more than 3 hours. The authors assume that with more effective patient education it might be possible to solve this problem and make thrombolysis to exert a greater impact on the effectiveness of the acute stroke therapy.

In an open, observational study, 40 consecutive ischemic stroke patients eligible for thrombolytic therapy using the combined ECASS/NINDS inclusion criteria have been treated intravenously with 1.5 M units of streptokinase. The therapeutic window was 3 hours or shorter. The safety analysis documented a low rate (5%) of intracerebral hemorrhages, and an additional 13% rate of hemorrhagic transformation of the initial infarction. Two patients died due to intracerebral bleeding. The efficacy of the SK thrombolysis was significant in 53% of the patients (the mean of the improvement on the NIH stroke scale was 15 points), while an other 42% of the patients achieved only the mean of 4 points improvement on their NIHSS score. These results are of the same magnitude, as those documented in the NINDS trial with rt-PA. Time window rather than the thrombolytic agent itself seems to be the decisive factor for successful thrombolysis. The good safety profile of SK in acute stroke using the ECASS/NINDS criteria, and the cost-effectiveness of the drug underline the necessity of a new SK trial with the recently accepted inclusion and exclusion criteria.

In spite of all similarities, ischemic stroke cases representing 80% of the acute cerebrovascular accidents, different steps of platelet activation, coagulation and fibrinolytic cascade are involved in the pathomechanism of the different stroke subtypes. The differentiation of the atherothrombotic, cardioembolic and lacunar forms of acute ischemic stroke is based on the comprehensive evaluation of clinical signs, neuroimaging technics, and diagnostic ultrasound, but also a significant effort was made to characterize the specificities of the underlying processes of the coagulation system by signal molecules, in order to clarify their possible role and to support the diagnostic and therapeutic decisions. The von Willebrand factor was studied as the marker of endothelial injury in 34 acute ischemic stroke patients within 24 hours after the onset of their stroke, and repeatedly 2, 4, and 12 weeks thereafter. To determine the probable source of the von Willebrand factor, usually released not only by endothelial cells, but also by platelets, the authors simultaneously measured the levels of an additional endothelial marker, thrombomodulin, and a platelet activation marker, beta-thromboglobulin. The mean of von Willebrand factor levels measured in stroke patients on the first day was 123%, whereas the mean of the control group 72% (p < 0.05). There was no significant difference according to stroke subtype. Von Willebrand values determined two weeks later showed a further 60% increase in stroke patients, and after a gradual fall their level remained above the concentration of the control group. The beta-thromboglobulin level measured in stroke group was significantly higher, than in control individuals (171 IU/ml vs. 32 IU/ml, p < 0.001). This was characteristic for atherothrombotic and cardioembolic stroke, but not for lacunar infarctions. If measured repeatedly, beta-thromboglobulin levels decreased rapidly in the first two weeks, than somewhat slower. Soluble thrombomodulin was slightly elevated in stroke patients (4.24 ng/ml) compared to healthy subjects (3.81 ng/ml), without statistical significance, and without major differences between subgroups. While early determination of beta-thromboglobulin can contribute to the differential diagnoses of the subtypes of ischemic stroke, the long-lasting elevation of von Willebrand factor may reflect endothelial dysfunction caused by several factors in the microvasculature of the penumbra.