Clinical Neuroscience

[Neuroprotection in brain ischemia - doubts and hopes]


MARCH 15, 2004

Clinical Neuroscience - 2004;57(03-04)

[In ischaemic stroke the two major potential therapeutic strategies are aimed at either improving cerebral blood flow or directly interacting with the cytotoxic cascade - a large body of evidence gained from animal studies is in support of them. In clinical trials direct neuroprotection by blocking the neurotoxic cascade remained ineffective, although there are several clinical trials still in progress. We summarize the experimental data and present the results of clinical trials and also discuss why so many drugs, which were effective in animal studies, failed in human trials. It is emphasized, that 1. in most animal studies the reduction of infarct size, i.e. the amount of saved penumbral tissue, was the outcome measure, whereas neurological function remained unassessed; 2. the recovery of intellectual performance and higher cortical functions are of major importance in the future quality of life in stroke victims; however, it is impossible to examine these parameters appropriately in animal studies; 3. in many clinical trials the patient population was rather heterogenous and low in number, the study protocol was not optimal and the critical analysis of the subacute and chronic phase was lacking or insufficient. We present the major experimental stroke models, discuss their similarities, differencies and limitations as compared to the human pathophysiological processes. The pitfalls of extrapolating data from animal studies to clinical practice are also summarized. The complex network of functional and morphological intercellular connections, the long timescale of neurotoxic and reparative events and the lessons learned from clinical trials suggest, that the use of drug combinations (therapeutic cocktails) targeting multiple steps of the neurotoxic cascade would hopefully result in more effective treatment of ischaemic stroke. Strategies to facilitate brain plasticity and regeneration is an additional promising tool to enhance recovery in brain ischaemia.]



Further articles in this publication

Clinical Neuroscience

[12th Annual Meeting of the Hungarian Society of Neuroradiology]

Clinical Neuroscience

[Effect lesions of extrahypothalamic brain structures on testicular functions in rats with special emphasis on asymmetry]


[Introduction - The aim of our studies was to investigate the involvement of extrahypothalamic brain structures in the control of testicular functions with special emphasis on the effect of right- and left-sided structures. Material and method - We performed lesion of the insular cortex, the amygdala, interrupted part of nerve fibers to and from the insular cortex, and cut the major commissural pathway of the brain the corpus callosum in adult male rats and studied the effect of the interventions on testicular steroidogenesis, serum testosterone and gonadotrop hormone concentrations. Results - Following lesion of the insular cortex on the right side serum testosterone level and steroidogenesis of the testes decreased (in the case of the left testis the difference was significant). Similar lesion on the left side did not change the parameters studied. Both right- and left-sided lesion induced a significant increase in serum LH concentration. The effect was more pronounced after right-sided lesion. Interruption of nerve fibers above the amygdala by a paramedian sagittal knife cut on the right or on the left side resulted in opposite effect on testicular steroidogenesis: right-sided intervention increased while left-sided one reduced testosterone secretion. Only left-sided cut influenced (decreased) serum testosterone level. There was no changes in LH concentration. Both right- and left-sided lesion of the amygdala induced a significant decrease in basal testosterone secretion in vitro of both testes and in serum testosterone level. However, serum LH concentration decreased only after left-sided surgery. Interruption of the corpus callosum in animals with leftsided orchidectomy induced a significant rise in steroidogenesis of the remaining (right) testis. Both sham surgery and callosotomy combined with left orchidectomy resulted in a significant increase in serum FSH level. Conclusion - Results of our studies suggest that extrahypothalamic brain structures and interventions influence endocrine functions of the testis through the hypothalamohypophyseal- testicular axis and by a direct neural route.]

Clinical Neuroscience

[Report from the UEMS/European Board of Neurology Meeting]


Clinical Neuroscience

[Neurological aspects of some sleep disorders]


[My aim is to examine the relation between some sleep disorders and neurological diseases; to analyse their mutual interactions in order to achieve new practical data for clinical use. In the theoretical part I summarise some main points of sleep physiology concentrating on the associations of sleep regulation and neurological diseases. In my examinations, besides clinical methods, the most important tools used are sleep analyses performed by polysomnography and MESAM IV as well as brain imaging methods. To assess clinical state of my stroke patients I utilised NIH Stroke Scale. I found pathological sleep apnoea frequency in more than half of the patients in any type (bleeding/infarction) of acute stroke. In a prospective study, sleep apnoea parameters remain permanent during 3 months in the ischaemic group; on the other hand, sleep apnoea improves during follow up after brain haemorrhages. I showed pathological sleep apnoea frequency in myasthenia gravis among male patients without daytime respiration complaint. I looked for the link between the mechanism of the sleep disorder and the underlying organic lesion in two cases. In this analyses I took into account the function of the affected structure in sleep regulation. I found a basal forebrain tumour, affecting sleep regulating centres underlying severe insomnia and I suggest a neurovascular compression of the lateral preoptic area of the hypothalamus being the reason of sleep related painful erection, a parasomnia of unknown origin.]

Clinical Neuroscience

[Newer approaches in self-theories]


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[The connection between the socioeconomic status and stroke in Budapest]


[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]

Clinical Neuroscience

[The Comprehensive Aphasia Test in Hungarian]


[In this paper we present the Comprehensive Aphasia Test-Hungarian (CAT-H; Zakariás and Lukács, in preparation), an assessment tool newly adapted to Hungarian, currently under standardisation. The test is suitable for the assessment of an acquired language disorder, post-stroke aphasia. The aims of this paper are to present 1) the main characteristics of the test, its areas of application, and the process of the Hungarian adaptation and standardisation, 2) the first results from a sample of Hungarian people with aphasia and healthy controls. Ninety-nine people with aphasia, mostly with unilateral, left hemisphere stroke, and 19 neurologically intact control participants were administered the CAT-H. In addition, we developed a questionnaire assessing demographic and clinical information. The CAT-H consists of two parts, a Cognitive Screening Test and a Language Test. People with aphasia performed significantly worse than the control group in all language and almost all cognitive subtests of the CAT-H. Consistent with our expectations, the control group performed close to ceiling in all subtests, whereas people with aphasia exhibited great individual variability both in the language and the cognitive subtests. In addition, we found that age, time post-onset, and type of stroke were associated with cognitive and linguistic abilities measured by the CAT-H. Our results and our experiences clearly show that the CAT-H provides a comprehensive profile of a person’s impaired and intact language abilities and can be used to monitor language recovery as well as to screen for basic cognitive deficits in aphasia. We hope that the CAT-H will be a unique resource for rehabilitation professionals and aphasia researchers in aphasia assessment and diagnostics in Hungary. ]

Clinical Neuroscience

The applications of transcranial Doppler in ischemic stroke


Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

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

Hyperhomocysteinemia in female migraineurs of childbearing ages


Background and purpose - Migraine is a risk factor for ischemic stroke in women of childbearing ages. Previous researches revealed a higher prevalence of hyperhomocysteinemia in migraineurs. Possible differences on the frequencies of hyperhomocysteinemia between migraine with aura and migraine without aura could contribute the established variances in stroke risk between these migraine types. Therefore, we aimed to search if the frequency of hyperhomocysteinemia was different between these subtypes of migraine or not. Methods - We analyzed the findings of serum homocysteine levels in female migraineurs of 16-49 years old who admitted to our outpatient clinic. Results - Homocysteine level was elevated in 13.3% of study population. There were not any significant differences on median serum homocysteine levels between migraine with aura (8.0 mikromol/L) and without aura (8.5 mikromol/L). (p=0.426) The frequencies of hyperhomocysteinemia were also similar (9.1% versus 16.7%, respectively; p=0.373). Correlation analyses did not reveal any linear correlation between ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura (p=0.417 and p=0.647, respectively). Similarly, any linear correlation between disease ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura was not detected (p=0.359 and p=0.849, respectively). Conclusion - The median serum homocysteine levels and the frequencies of hyperhomocysteinemia are similar between migraine with aura and without aura in women of childbearing ages. Therefore, the variances on stroke risk ratios between these types of migraine are probably not originated from the differences of serum homocysteine status.