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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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


Clinical Neuroscience

[Study of the effects of vinpocetin on cognitive functions]


[Introduction - Chronic cerebral hypoperfusion is a risk factor for the development of certain types of dementia. Mild cognitive impairment is a stage of predementia condition, because the symptoms are similar but not as severe as the symptoms in patients with dementia. Vinpocetine, due to its complex mechanism of action, has an important role in the improvement of chronic cerebral hypoperfusion. Objectives - The aim of our study was to determine the severity of the cognitive decline and to investigate the efficacy and safety of per os 18 months vinpocetine treatment in patients with mild cognitive impairment. Methods - We used psychometrical tests (MMSE, ADASCog) to assess the cognitive functions. CGIC-PGIC was used to evaluate the overall change in the disease status. ADL was used to assess the patient’s daily activity and the Hamilton Depression Scale to evaluate the patient’s mood. The assessments were performed at six visits during the 18 months treatment period. Results - At the beginning of the treatment, the stage of our patients’ mild cognitive impairment was moderately severe. Significant improvement was detected in the psychometrical tests after the 18 months treatment period. The overall status of the disease improved significantly according both to the patient and the investigator. Also significant improvement was detected in daily activity. The complex improvement of the clinical symptoms affected the patients’ mood positively. Moreover, vinpocetine was safe and had a good tolerability during the whole study period. Conclusions - Vinpocetine, due its complex mechanism of action, improved significantly the cognitive functions, overall disease status and quality of life in patients with chronic cerebral hypoperfusion. As a result, vinpocetine treatment can be recommended for patients with mild cognitive impairment.]

Clinical Neuroscience

[Neurological and psychiatrial aspects of urine incontinence]


Clinical Neuroscience

[In memoriam András Fazekas MD 1941-2012]

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[Family planning in multiple sclerosis: conception, pregnancy, breastfeeding]

RÓZSA Csilla

[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

Paraoxonáz-1-aktivitás és fenotípusos megjelenése sclerosis multiplexben

KURTULUS Fatma, YAMAN Aylin, ELLIDAG Yasar Hamit, EREN Esin, GÖMCELI Bicer Yasemin, YILMAZ Necat

Introduction - Human serum paraoxonase (PON1) and arylesterase (ARE) are lipophilic antioxidant enzymes. PON-1 serum activity diverges in individuals and populations, which might be due to polymorphisms in the PON-1 gene. The PON1 activity phenotyping method, based on the ratio of the stimulated PON activity and the ARE activity, could determine the low-activity homozygotes (QQ), intermediate activity heterozygotes (QR), and high-activity homozygotes (RR) regardless of the genotype. The aim of the present study was to determine the PON1 phenotype distribution and enzymatic activity of PON1 and ARE in multiple sclerosis (MS) patients. Materials and methods - Thirty-four relapsing remitting MS (RRMS) patients (22 females and 12 males; median age 42 (range 20-55) years) in the remission phase and thirty-four age-sex matched healthy controls (19 females and 15 males; median age 37 (21-60) years) were included in this study. All patients had clinically definite MS according to McDonald’s criteria. Results - Serum PON1 and ARE enzyme activities, as well as salt-stimulated PON1, were not significantly different between the patient and control groups. Phenotype distributions were as follows: QQ 58.8%, QR 38.2%, and RR 3% in MS patients (n=34); QQ 44.1%, QR 50%, and RR 5.9% in the control group (n=34). QQ (low activity) phenotypic distribution was more common in MS patients than controls, but this difference was not significant (p=0.14). Conclusions - Our results did not reveal meaningful relationships between PON1 activity or PON1 phenotypes and MS. More studies in larger samples and in all phases of the disease are needed in the future.

Clinical Neuroscience



[Even tough the central nervous system (CNS) of gastropods has long been used as a model for studying different neuronal networks underlying behaviors, there is only little information on the molecular components of the extracellular matrix (ECM) of the nervous tissue. Therefore, the aim of the present study was to identify some of the ECM molecules by acid-base histochemistry. Staining with alcian blue at strong acidic pH, and with acridine orange at different pH and salt concentrations was carried out on cryostat sections taken from CNS preparations of adult specimens of the terrestrial snail, Helix pomatia, and the aquatic species, Lymnaea stagnalis, in order to visualize mild (carboxyl) and strong (sulphate) acidic groups, which are characteristic for different glucosaminoglycans. According to our findings, sulphated proteoglycans were abundant in the periganglionic sheath of both species, and they also occurred in the neuropil of Helix, whereas they were absent in Lymnaea. The interperikaryonal space contained mainly carboxyl residues, which might refer to the presence of hyaluronic acid. It is concluded that the ECM of the snail CNS, similarly to that in vertebrates, is partly composed of polymer macromolecules of different chemical properties. It is suggested that adaptation to environmental conditions and/or altered neuronal plasticity are responsible for the differences found in chemical characters of the ECM molecules between the two snail species.]

Clinical Neuroscience

[Current questions of multiple sclerosis: the secunder progressive form of the disease]


[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

Clinical Neuroscience

[Current issues of neuroimaging diagnostics of multiple sclerosis]


[Magnetic resonance imaging techniques have been routinely used in diagnostics and follow-up of multiple sclerosis and magnetic resonance imaging findings are incorporated into the current diagnostic criteria of the disease. International guidelines were created aiming to define the indication, timing, minimum requirements and interpretation of magnetic resonance examination in multiple sclerosis. In Hungary, there is a lack of widely-accepted standardized protocol, therefore presenting the magnetic resonance diagnostic criteria and the international guidelines may prove useful. It may also point towards consideration of a national guideline.]