Clinical Neuroscience

[PhD thesis New non-invasive transcranial stimulation techniques in neuroplasticity research]

DANIELLA Terney

MARCH 30, 2012

Clinical Neuroscience - 2012;65(03-04)

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Clinical Neuroscience

[In memoriam András Fazekas MD 1941-2012]

VOLT munkatársai

Clinical Neuroscience

[Botulinum neurotoxin-A therapy in migraine]

TAJTI János, SZOK Délia, TUKA Bernadett, CSÁTI Anett, KURIS Anikó, MAJLÁTH Zsófia, LUKÁCS Melinda, VÉCSEI László

[Although migraine is a common, paroxysmal, highly disabling disorder, the primary cause and the pathomechanism of migraine attacks are enigmatic. Experimental results suggest that activation of the trigeminovascular system is crucial in its pathogenesis. This activation leads to the release of vasoactive neuropeptides (calcitonin gene-related peptide - CGRP, and substance P - SP) and to neurogenic inflammation, and peripheral and central sensitisation are expressed. Botulinum neurotoxin-A (BoNT-A), a potent toxin produced by Clostridium botulinum, affects the nervous system through specific cleavage of the soluble NSF-attachment protein receptor complex (SNARE), like synaptosomal-associated protein of 25 kDa (SNAP-25). The result of this multistage process is blockade of the presynaptic release of pain neurotransmitters such as CGRP, SP and glutamate. A pooled analysis of the data from two programmes of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT 1 and 2) with BoNT-A in chronic migraine demonstrated significant benefit of BoNT-A over placebo with regard to the numbers of headache days and migraine episodes. BoNT-A diminished the frequency of acute headache pain medication intake, and resulted in reductions in headache impact and improvements in scores on the Migraine-Specific Quality of Life Questionnaire. The treatments with BoNT-A proved safe and were well tolerated.]

Clinical Neuroscience

[Fingolimod therapy in multiple sclerosis - the issue of the pathomechanism]

TAR Lilla, VÉCSEI László

[Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system with neurodegenerative chararacteristics. The newly discovered per os administrable drug fingolimod (FTY720) has a different mechanism of action than the current disease-modifying therapies. In vivo the drug binds to four out of the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod-phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1-phosphate receptors in the membrane of lymphocytes thus in contrast to sphingosine-1-phosphate it acts like a functional antagonist. In experimental autoimmune encephalomyelitis - an animal model of multiple sclerosis - fingolimod blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the lymph nodes and therefore reduces the peripheral lymphocyte count especially the encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood-brainbarrier constructing endothelial cells also contributes to the complex mechanism of action. Additionally due to its liphohilic nature fingolimod is able to penetrate the blood brain barrier thus, beside its peripheral effects the drug can probably modulate the cells of the central nervous system directly. Presumably it can reduce neurodegeneration caused by astrogliosis through modification of astrocyte and oligodendrocyte activity. The results of current clinical studies are holding out with bright prospective in the aspect of either the favourable effects or the well tolerated side effects.]

Clinical Neuroscience

[Stroke prevention - A population screening day in district XII of Budapest]

FOLYOVICH András, BAKOS Mária, KÁNTOR Zita, HERTELENDY Anna, HORVÁTH Eszter, ZSIGA Katalin, LAKATOS Henriette, VADASDI Károly

[Along with advances in the treatment of acute stroke, new efforts have been made to enhance efficiency of the prevention of cerebrovascular diseases. Population screening is a way to contact high-risk patients, and there is an increasing international and national experience with the procedure. However, efforts are associated with high costs, so an efficient method, complying with local features, should be selected from the various methods. A stroke prevention day was organized in Szent János Hospital, localized in district XII, and data were analyzed. Taking advantage of the potentials of a large hospital, a comprehensive risk assessment - within the capacity of health care workers - was performed. Program and contact information of the screening day was published in the local newspaper of the district. Data of 48 residents of the district were analyzed. In addition to neurologists, a radiologist, a cardiologist and an ophtalmologist, as well as health care workers were involved in the project. A data sheet was filled in for all participants, including known risk factors, BMI, blood pressure and serum cholesterol levels. All participants had duplex sonography of the cervical vessels, cardiac evaluation and ophtalmic examination. Data were analyzed anonymously, and - if participants approved - postcode and educational level were also recorded. Among the 48 individuals screened, 35 were female and 13 were male. Average age was 62.86 (±8.57) years, and participants were typically of higher educational level. 5 individuals had no known risk factors, most of them had 2-3 risk factors, and multiple risk factors were not uncommon. Individuals with six and seven risk factors were also found. 20 of 27 patients with known hypertension had target blood pressure levels. By duplex sonography, 36 individuals had mild, 4 had significant atherosclerosis. There was no significant carotid stenosis or occlusion. Based on ophtalmic evaluation, 26 patients had signs of vascular disease (mainly hypertensive fundus changes). Cardiac evaluation detected 14 patients with cardiovascular risk. The high standard of primary care in the district was reflected by the fact that all the 6 highrisk individuals were already taken care of by general practitioners (GP-s). One of the leading conclusions from the evaluation of the data is that local press, family ties and local communities play a major role in recruiting people for a screening day. In order to increase efficiency and cost-efficacy of the program, GP-s should also be involved in the planning process, because efficiency may be increased by pre-selecting high-risk individuals.]

Clinical Neuroscience

[One year follow-up after stroke. A preliminary feasibility study in Josephtown of Budapest]

SZŐCS Ildikó, SZATMÁRI Szabolcs, FEKETE Klára, ORBÁN-KIS Károly, VASTAGH Ildikó, FOLYOVICH András, AJTAY András, BERECZKI Dániel

[Stroke is a major public health issue in Hungary with considerable regional differences in mortality. We have limited information to explain such regional differences. To assess these differences, we would need comparative followup studies optimally carried out by personal contact with the patient or the carer. According to several epidemiological studies, follow-up can be carried out with significantly lower cost and similar efficiency by telephone contact or regular mail. In this pilot study we intend to assess: 1. the efficacy of telephone follow-up one year after stroke in this geographical region 2. whether the efficacy of follow-up can be further increased with questionnaires sent out by regular mail 3. whether telephone and mail-based assessment is sufficient to perform a larger population based study. We included 135 patients hospitalized consecutively for acute cerebrovascular disease (stroke or TIA) by the Department of Neurology, Semmelweis University in January and February of 2008. Based on residence, patients were divided into three groups: those living in the least wealthy district of Budapest (i.e. District-8); those living in other districts of the city; and those living in suburban areas. One year after the hospital treatment follow-up was possible by telephone in 76%. Further 12 patients could be contacted by questionnaire sent out by regular mail. Efficacy of follow-up was altogether 84%. Even in this small group of patients, we have found a tendency for more severe strokes (p=0.06) and higher acute case fatality (32% vs. 5%, p=0.029) in residents of District-8 of Budapest compared to those residing in more wealthy districts of the city and in suburban areas. Survival rate one year after stroke or TIA was only 39% in those living in District-8, 66% in those living in other districts and 75% in suburban dwellers (p=0.006). Telephone and mail-based questionnaires are insufficient for follow-up in these regions even when applied in combination. These preliminary data raise the possibility that the socio-economical conditions might influence stroke severity and outcome in the population. A larger study to address this issue would require more accurate definition of patient-groups and more efficient follow-up methods.]

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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.

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Lege Artis Medicinae

[Vaccines against COVID-19 pandemic]

FALUS András, SZEKANECZ Zoltán

[The rapidly spreading SARS-CoV2 respiratory virus has evoked an epidemic with serious aftermath around the world. In addition to the health effects, the global economic damage is actually unpredictable. At the same time, the pandemic has launched a series of unprecedented collaborative scientific research, including the development of vaccines. This study summarizes up-to-date information on vaccines, immune memory, and some emerging clinical effects.]

Lege Artis Medicinae

[A short chronicle of three decades ]

KAPRONCZAY Katalin

[Hungarian professional periodicals started quite late in European context. Their publish­ing, editing and editorial philosophy were equally influenced by specific historical and political situations. Certain breaking points of history resulted in termina­tion of professional journals (War of In­de­pendence 1848-1849, First and Se­cond World Wars), however there were pe­riods, which instigated the progress of sciences and founding of new scientific journals. Both trends were apparent in years after the fall of former Hungarian regime in 1990. The structure of book and journal publishing has changed substantially, some publishers fell “victim” others started successfully as well. The latters include the then-established publishing house Literatura Medica and its own scientific journal, Lege Artis Me­di­cinae (according to its subtitle: New Hun­garian Medical Herald) issued first in 1990. Its appearance enhanced significantly the medical press market. Its scientific publications compete with articles of the well-established domestic medical journals however its philosophy set brand-new trends on the market. Concerning the medical community, it takes on its problems and provides a forum for them. These problems are emerging questions in health care, economy and prevention, in close interrelation with system of public health institutions, infrastructure and situation of those providing individual health services. In all of them, Lege Artis Medicinae follows consequently the ideas of traditional social medicine.]

Hypertension and nephrology

[Association between cyclothymic affective temperament and hypertension]

NEMCSIK János, BATTA Dóra, KŐRÖSI Beáta, RIHMER Zoltán

[Affective temperaments (cyclothymic, hypertymic, depressive, anxious, irritable) are stable parts of personality and after adolescent only their minor changes are detectable. Their connections with psychopathology is well-described; depressive temperament plays role in major depression, cyclothymic temperament in bipolar II disorder, while hyperthymic temperament in bipolar I disorder. Moreover, scientific data of the last decade suggest, that affective temperaments are also associated with somatic diseases. Cyclothymic temperament is supposed to have the closest connection with hypertension. The prevalence of hypertension is higher parallel with the presence of dominant cyclothymic affective temperament and in this condition the frequency of cardiovascular complications in hypertensive patients was also described to be higher. In chronic hypertensive patients cyclothymic temperament score is positively associated with systolic blood pressure and in women with the earlier development of hypertension. The background of these associations is probably based on the more prevalent presence of common risk factors (smoking, obesity, alcoholism) with more pronounced cyclothymic temperament. The scientific importance of the research of the associations of personality traits including affective temperaments with somatic disorders can help in the identification of higher risk patient subgroups.]