Clinical Neuroscience

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

NAGY Zoltán, SIMON László, BORI Zoltán

APRIL 20, 2002

Clinical Neuroscience - 2002;55(03-04)

[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.]

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Clinical Neuroscience

[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 Considering drug therapy, in the past decade tricyclic drugs have been replaced by newly developed antidepressants with milder side-effects profile.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

[Introduction]

NAGY Zoltán

Clinical Neuroscience

[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

[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.]

Clinical Neuroscience

[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.]

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