Clinical Neuroscience - 2002;55(03-04)

Clinical Neuroscience

APRIL 20, 2002

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

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

[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.]

Clinical Neuroscience

APRIL 20, 2002

[Genetics and hemostasis in young stroke patients]

PONGRÁCZ Endre, TORDAI Attila, CSORNAI Márta, NAGY Zoltán

[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

APRIL 20, 2002

[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

APRIL 20, 2002

[Mental disorders after stroke]

VARGA Dániel

[Stroke represents a major public health problem in Hungary, but relatively little attention is directed toward poststroke neuropsychiatric disturbances. Stroke patients frequently represent mood disturbances, cognitive decline, anxiety disorders, and sometimes serious schizophorm or paranoid states. Poststroke depression is the most common and possibly amenable form to therapeutic intervention. Depressiv symptoms have negativ effect on the rehabilitation process, quality of life and even on long-term survival. Considering drug therapy, in the past decade tricyclic drugs have been replaced by newly developed antidepressants with milder side-effects profile. Our knowledge on the relationship among vascular and other types of dementia has been extended in the recent years. This development also has some therapeutic implications. It seems likely that other psychiatric disorders, psychoses, pathological affect and personality disorders also inhibit recovery and limit long-term quality of life, but abvailable data on this topic is limited.]

Clinical Neuroscience

APRIL 20, 2002

[The problems of the post-stroke care]

CSORNAI Márta

[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

APRIL 20, 2002

Clinical Neuroscience

APRIL 20, 2002

[Regulatory mechanisms in focal cerebral ischemia. Perspectives in neuroprotective treatment]

NAGY Zoltán, SIMON László, BORI Zoltán

[Permanent or temporary disruption of cerebral blood flow rapidly depletes brain regions of their limited energy reserves (glycogen, glucose, oxygen, ATP) leading to an energy crisis. Tissue damage occurs due to the energy crisis. The central part of the damage, the ischaemic “core” region is surrounded by zones of the shell-like penumbra. Necrotic, as well as apoptotic cell death could be identified in the penumbra. Going away from the ischaemic core different neurochemical processes are occuring by space and time.“Immediate early response” genes (c-fos, fos-B, c-Jun, krox 20, 24) are activated, heatshock proteins (hsp 70, 72, HSF, HSE, HIF), cytokines (TNF-α, IL-1β), inflammatory factors (COX), adhesion and glial factors (ICAM-1, ELAM-1, P-selectin), vasoactive factors (IL -6, -10, PAF), reactive oxigen radicals and connected factors (O2, OH, NO, NOS, SOD) are produced within minutes and hours. Cell deaths, necrosis and apoptosis due to the activation of calpains, caspases and nucleases occur in days. In parallel, growth factors and plasticity proteins (BDNF, NGF, TGF-β, VEGF, PDGF, GAP-43) are activated as a basis of functional rehabilitation.]

Clinical Neuroscience

APRIL 20, 2002

[MR investigations in stroke]

KENÉZ József, BARSI Péter

[In the article digital imaging methods are presented with special emphasis on the use on diagnostics of cerebral circulation studies. Recently, fundamental changes have happened in this field, concerning especially the MR investigations. These changes have influenced the therapeutic strategies of ischaemic stroke. Authors give the theoretical background on the diffusion and perfusion MR imaging, emphasising the importance of their “mismatch” and its impact in the estimation of the outcome of ischaemic events. More recently, new, controversial facts arose, regarding the reasons of the introduction of the theory of so called “negative” and “positive” mismatches. As a consequence, a level of uncertainty took place in the judgement of prognostics. The leading institutions are searching the way to solve the problem which seems to be the quantitative evaluation of the diffusion, perfusion and mismatch data. The advent of the multislice spiral CT with very fast imaging and the importance of CT investigations increased. With this new kind of equipment, even perfusion studies can be performed using iodinated contrast medium.]

Clinical Neuroscience

APRIL 20, 2002

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

PÁNCZÉL Gyula, BÖNÖCZK Péter, NAGY Zoltán

[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.]