Clinical Neuroscience

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

TAR Lilla, VÉCSEI László

MARCH 30, 2012

Clinical Neuroscience - 2012;65(03-04)

[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.]

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[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

[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.]

Clinical Neuroscience

[EDITORIAL COMMENT]

RAJNA Péter

[Editorial comment 2012;65(03-04)]

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Clinical Neuroscience

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[Family planning is an exceptionally important question in multiple sclerosis, as women of childbearing age are the ones most often affected. Although it is proven that pregnancy does not worsen the long-term prognosis of relapsing-remitting multiple sclerosis, many patients are still doubtful about having children. This question is further complicated by the fact that patients – and often even doctors – are not sufficiently informed about how the ever-increasing number of available disease-modifying treatments affect pregnancies. Breastfeeding is an even less clear topic. Patients usually look to their neurologists first for answers concerning these matters. It falls to the neurologist to rationally evaluate the risks and benefits of contraception, pregnancy, assisted reproduction, childbirth, breastfeeding and disease modifying treatments, to inform patients about these, and then together come to a decision about the best possible therapeutic approach, taking the patients’ individual family plans into consideration. Here we present a review of relevant literature adhering to international guidelines on the topics of conception, pregnancy and breastfeeding, with a special focus on the applicability of approved disease modifying treatments during pregnancy and breastfeeding. The goal of this article is to provide clinicians involved in the care of MS patients with up-to-date information that they can utilize in their day-to-day clinical practice. ]

Clinical Neuroscience

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Clinical Neuroscience

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Clinical Neuroscience

[Is second-line immunomodulatory treatment effective in multiple sclerosis?]

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