Clinical Neuroscience

[Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part I: Concept of resistance]

VADÁSZ Dávid1, SZTRIHA K László1, SAS Katalin1, VÉCSEI László1

NOVEMBER 20, 2012

Clinical Neuroscience - 2012;65(11-12)

[Aspirin and clopidogrel are well established as antiplatelet medication in the treatment of atherothrombotic vascular disease. However, despite treatment, a substantial number of patients experience recurrent ischemic episodes, referred to as aspirin or clopidogrel treatment failure. Various laboratory techniques are available with which to evaluate the effectiveness of antiplatelet drugs. Interestingly, the agreement between the results of the different tests may be poor. The term aspirin or clopidogrel resistance denotes those conditions in which an inadequate inhibitory efficacy of the given antiplatelet agent is detected by an in vitro assay of platelet function. It has been estimated that on average some 30% of patients treated with aspirin, and 20% on clopidogrel, do not achieve an appropriate level of efficacy as concerns platelet activity.]

AFFILIATIONS

  1. University of Szeged, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, Neurology Department, Szeged, Hungary

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Clinical Neuroscience

[Vinpocetin in neurological diseases]

SZAPÁRY László, KÉSMÁRKY Gábor, TÓTH Kálmán, MISNYOVSZKY Melinda, TÓTH Tímea, BALOGH Ágnes, NAGY Krisztián, NÉMETH György, FEHÉR Gergely

[Introduction - Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused territories may be associated with benefitial clinical states. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. Aims - The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. Results - Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheological variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. Summary - Based on the above mentioned results vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.]

Clinical Neuroscience

[New, effective immunomodulatory drug in treatment of multiple sclerosis: the fingolimode]

KOMOLY Sámuel

Clinical Neuroscience

[Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]

SZÉPLAKI Gábor, MERKELY Béla

[Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsingremitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine- 1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.]

Clinical Neuroscience

[Meeting of Hungarian Epilepsy League]

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Clinical Neuroscience

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and β-actin genes in rat brain]

KÁLMÁN János, PÁKÁSKI Magdolna, SZŰCS Szabina, KÁLMÁN Sára, FAZEKAS Örsike, SÁNTHA Petra, SZABÓ Gyula, JANKA Zoltán

[Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer’s disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations - also affecting the metabolism of β-actin - can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], β-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n=16), CIS (n=10), 10 mg/kg sertindole (n=5) and 10 mg/kg sertindole + CIS (n=4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal β-actin (p<0.01), MAPK-1 and APP (p<0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p<0.05). Ours is the first report about CIS induced β-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.]

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[Examination of the efficacy of clopidogrel-hydrogen-sulphate in patients with cerebrovascular disease]

SZAPÁRY László, FEHÉR Gergely

[INTRODUCTION - On the basis of current guidelines, acetylsalicylic acid plus dipyridamole or clopidogrel monotherapy should be used for the long-term treatment of patients with cerebrovascular disease, whereas acetylsalicylic acid monotherapy is not recommended. The efficiency of recently introduced generic clopidogrels has not been assessed in patients with a history of acute stroke. PATIENTS AND METHODS - 100 patients with a history of acute stroke or transient ischaemic attack were involved in our study. The patients received acetylsalicylic acid monotherapy in the first 48 hours, followed by clopidogrel-hydrogen sulphate (Egitromb®) monotherapy. The efficiency of the therapy was assessed on day 7 and 28 of medical therapy. RESULTS - At the first measurement (day 7) after clopidrogel-hydrogen sulphate treatment, the therapy seemed to be inefficient in 11 patients (11%). A strong, clinically significant correlation was found between blood pressure values, blood glucose and lipid parameters, hsCRP levels and platelet aggregation values. At the second measurement (day 28), an aggressive secondary preventive threapy resulted in the normalisation of the above mentioned parameters, and the efficiency of platelet aggregation inhibtion therapy was also improed, whereas no patients proved to be resistant. No unwanted events or haemorrhagic complications were registered. CONCLUSIONS - On the basis of the result of our study, treatment with clopidogrel- hydrogen sulphate is safe and efficient both clinically and on the basis of optical aggregometry. The significance of an aggressive secondary preventive therapy should be considered as a factor that might influence the efficiency of thrombocyte aggregation inhibitory therapy.]

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

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[About the care of patients with hyperuricaemia and gout]

[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]