Clinical Neuroscience

[Marker molecules of endothelial cell dysfunction in acute ischemic stroke]

SZEGEDI Norbert, MAY Zsolt, ÓVÁRY Csaba, SKOPÁL Judit, NAGY Zoltán

APRIL 20, 2002

Clinical Neuroscience - 2002;55(03-04)

[Introduction - 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 patomechanism 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 specifities 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. Patients and methods - 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, β-thromboglobulin. Results - The mean of von Willabrend 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 β-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, β-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. Conclusions - While early determination of β-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.]



Further articles in this publication

Clinical Neuroscience

[Genetics and hemostasis in young stroke patients]


[Background and purpose - The classical risk factors did not explain all the possible ethiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this geneticoepidemiological study the author’s aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. Methods - 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and β fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. Results - An increased frequency of GP IIIa heterozygousity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age <50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). Conclusion - Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.]

Clinical Neuroscience

[The problems of the post-stroke care]


[All patients having had stroke or TIA require special post-hospital care, being mainly the task of general pracititioners. The number of patients surviving stroke in Hungary is approximately 30 000/year. An important focus of care is secondary prevention: antithrombotic treatment and risk factors reduction. In case of residual signs of stroke, rehabilitation must also be organized and supported by the general practitioner. Medical conditions of cerebrovascular patients requiring special care demand are reviewed by the author. In this respect, some post-stroke conditions like dementia and depression require extra attention.]

Clinical Neuroscience

[New methods in stroke intensive therapy: hemicraniectomy in patients with complete middle cerebral artery infarction and treatment of intracerebral and intraventricular hemorrhage with urokinase]

KAKUK Ilona, MAJOR Ottó, GUBUCZ István, NYÁRY István, NAGY Zoltán

[Life-threatening, complete middle cerebral artery infarction occurs in up to 10% of all stroke patients. The “malignant media occlusion” is an infarction occupying more than 50% of middle cerebral artery territory. The malignant, space-occupying supratentorial ischemic stroke is characterised by a mortality rate of up to 80%. Several reports indicate, that hemicraniectomy in this situation can be life-saving. Hemicraniectomy increases cerebral perfusion pressure and optimises retrograde perfusion via the leptomeningeal collateral vessels. A case of a patient is presented, having progressive neurological deterioration due to massive cerebral infarctions. The patient rehabilitation was successful. Decompressive surgery is life saving and can also give acceptable functional recovery. Hemorrhagic stroke is due to stroke in 15% of cases and in 10%, it is “spontaneous” intracerebral hematoma. The intracerebral and intraventricular hemorrhage represents one of the most devastating types of stroke associated with high morbidity and mortality. The 30-day mortality rate is 35% to 50% and most survivors are left with a neurological disability. The value of surgical therapy is debatable. The aspiration and urokinase therapy of the hematoma of intracerebral hemorrhage could improve final neurological outcome. Spontaneous, nontraumatic intraventricular hemorrhage frequently carries a grave prognosis. A large part of morbidity after intraventricular hemorrhage is related to intracranial hypertension from hydrocephalus. One patient presented had intracerebral hemorrhage and another had intraventricular hemorrhage treated with urokinase. Rapid and extensive reduction in the amount of intracerebral and intraventricular blood occurred. Urokinase lysis is safe and can be a potentially beneficial intervention in intracerebral and intraventricular hemorrhage. By performing decompressive craniectomy, the neurologists of stroke departments and intensive care units with the neurosurgeons will have to play major role in the management of stroke patients.]

Clinical Neuroscience


Clinical Neuroscience

[Vasoreactivity impairment in brainstem and hemispherial small vessel disease, a comparative study]


[Aims - Cerebrovascular small vessel disease may lead to an impairment of vasoreactivity (VR). Vasoregulatory impairment in internal carotid artery distribution area has been established. In this study the authors sought the answer to the question if VR of vertebrobasilar (VB) territory was impaired in brainstem small vessel diseases and if vasoregulatory impairment differed between the two distribution territories. Methods - VR of carotid and VB territory was compared applying different functional tests (ventilation, tilting, acetazolamide) in 25 patients with brainstem lacunar infarcts, 20 patients with periventricular leukoaraiosis and in 35 control subjects. Cerebral blood flow velocity (CBFV) of basilar artery (BA) and middle cerebral artery (MCA) was monitored with transcranial Doppler (TCD), systemic blood pressure and CO2 partial pressure of expired air were also registered. Results - In the BA territory the VR was significantly smaller in the patient than in the control group (3.1± 4.6 cm/sec/kPa vs. 8.2 ± 6.2 cm/sec/ kPa, p=0.01) during hypercapnia. In a subgroup of patients with mean baseline CBFV<25 cm/sec, the VR was significantly smaller and PI nonsignificantly higher than in patients with baseline CBFV >25cm/s (VRCO2 1.5±2.0 cm/sec/kPa vs. 6.5±6.5 cm/sec/kPa, p=0.007; PI 1.11±0.30 vs. 1.0±0.26, p=0.4) indicating higher vascular resistance in the former group. Results of tilting tests showed similar but nonsignificant changes while acetazolamide tests revealed no differences between the two groups. In the MCA territory the VR was significantly lower in patients than in the controls during hypercapnia (4.7±3.7 cm/sec/kPa vs. 18.4±6.8 cm/sec/kPa, p< 0.001) and showed a nonsignificant tendency to be lower in patients than in controls during hypocapnia (14.6±13.8 cm/sec/kPa vs. 24.7±21.2 cm/sec/kPa, p=0.1). Although CBFV measurements during acetazolamide test tended to support these findings, they showed no significant differences between patients and controls. During head-up tilt the CBFV did not differ significantly between the two groups. The VRCO2 is significantly higher in the MCA than in the BA territory (18.4 CI95 2.98 vs. 10.1 CI95 3.01; p<0.001). The impairment of VRCO2 was more severe in the MCA territory (VR decreased to 26% of baseline in the MCA and to 34% in the BA territory). Conclusion - The capacity of carotid territory VR exceeds that of VB territory. The impairment of VR is present in both the carotid and VB territories and is more severe in the former region. The most feasible test to reveal this impairment is the hypercapnic test. There is a strong correlation between the extent of vasoregulatory impairment and baseline CBFV in brainstem small vessel diseases.]

All articles in the issue

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Clinical Neuroscience

Risk factors for ischemic stroke and stroke subtypes in patients with chronic kidney disease

GÜLER Siber, NAKUS Engin, UTKU Ufuk

Background - The aim of this study was to compare ischemic stroke subtypes with the effects of risk factors, the relationship between grades of kidney disease and the severity of stroke subtypes. Methods - The current study was designed retrospectively and performed with data of patients who were hospitalised due to ischemic stroke. We included 198 subjects who were diagnosed with ischemic stroke of Grade 3 and above with chronic kidney disease. Results - In our study were reported advanced age, coronary artery disease, moderate kidney disease as the most frequent risk factors for cardioembolic etiology. Hypertension, hyperlipidemia, smoking and alcohol consumption were the most frequent risk factors for large-artery disease. Female sex and anaemia were the most frequent risk factors for small-vessel disease. Dialysis and severe kidney disease were the most frequent risk factors in unknown etiologies, while male sex, diabetes mellitus, prior stroke and mild kidney disease were the most frequent risk factors for other etiologies. National Institute of Health Stroke Scale (NIHSS) scores were lower for small-vessel disease compared with other etiologies. This relation was statistically significant (p=0.002). Conclusion - In order to improve the prognosis in ischemic stroke with chronic kidney disease, the risk factors have to be recognised and the treatment options must be modified according to those risk factors.

Clinical Neuroscience

L-arginine pathway metabolites can discriminate paroxysmal from permanent atrial fibrillation in acute ischemic stroke

CSÉCSEI Péter, VÁRNAI Réka, NAGY Lajos, KÉKI Sándor, MOLNÁR Tihamér, ILLÉS Zsolt, FARKAS Nelli, SZAPÁRY László

Background - Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS). Methods - A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded. Results - Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p<0.001). Both ADMA (p<0.001) and symmetric dimethylarginine (SDMA) (p<0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p<0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 μmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029). Conclusions - Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.

Clinical Neuroscience

[Effective, safe stroke prevention with novel oral anticoagulants in patients with atrial fibrillation. Focus on dabigatran]

SZAPÁRY László, FEHÉR Gergely, BOSNYÁK Edit, DELI Gabriella, CSÉCSEI Péter

[Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2×150 mg or apixaban in 2×5mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF. Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.]

Clinical Neuroscience

[Neurointerventional treatment of acute ischemic stroke: the Kaposvár experience]

RADNAI Péter, SZŐTS Mónika, RÁDAI Ferenc, HORVÁTH Gyula, VARGA Csaba, FOGAS János, SZÖRÉNYI Péter, HORVÁTH Zoltán, BAJZIK Gábor, MOIZS Mariann, REPA Imre, NAGY Ferenc, VAJDA Zsolt

[Aim of the study - In the present study, we report procedural and mid-term functional outcome data on the first 50 neurointerventional treatments of acute ischemic stroke in the Kaposi Mór County Hospital, Kaposvár, Hungary. Materials and methods - Endovascular recanalization of occluded large cervical and intracranial arteries was performed following an unsuccessful intravenous lysis or when intravenous lysis was contraindicated. A control cohort was retrospectively formed by analyzing data of 16 patients who has been unsuccesfully treated with iv. lysis before neurointervention was available in our hospital. Results and conclusion - Recanalization rate was 84% and major complication rate was 2% in the neurointerventional group. Mid-term good functional outcome, defined as mRS 0-2, was achieved in 44% in the neurointerventional and in 13% in the intravenous lysis group, after 11.5 and 39.7 months follow-up period, respectively. Subgroup analysis revealed patient age as the strongest predictive factor of good functional outcome. Our data shows that neurointerventional treatment of acute ischemic stroke gives substantially improved functional outcome, in accordance with the results of the recently published international randomized trials.]

Clinical Neuroscience

[Systemic thrombolysis after the administration of idarucizumab in acute ischemic stroke]


[Introduction - Expanding indications have resulted in an increasing number of patients taking novel oral anticoagulants, posing a major treatment dilemma in acute ischemic stroke. Case presentation - We present a successful intravenous thrombolysis in a dabigatran-treated patient with acute ischemic stroke after the administration of idarucizumab. Discussion - According to current guidelines, systemic thrombolysis is contraindicated under treatment with novel oral anticoagulants (taken within 48 hours). In this scenario, idarucizumab offers a solution by reversing the anticoagulant effect of dabigatran. Conclusion - Although there have only been case reports published so far, the dabigatran-antidote idarucizumab seems to give new therapeutic opportunities in the treatment of acute ischemic stroke.]