Clinical Neuroscience

[Teriflunomide: new oral immunmodulant drug in therapy of multiple sclerosis]

BENCSIK Krisztina, RÓZSA Csilla, VÉCSEI László

MARCH 25, 2015

Clinical Neuroscience - 2015;68(03-04)

[Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative disorder of the central nervous system (CNS). There are nine drugs available in Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to reduce the activity of the disease, from which seven can be used as first line therapies. We have approximately 20 years of experience with the interferon b-1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the patients using one of the first line drugs, the disease remains active, that we call break-through disease. The reasons for break-through disease could be the insufficient adherence and compliance, the appearance of neutralizing antibodies or the high activity of the disease. One of the oral immunomodulating drugs for MS, teriflunomide, was registered in Europe in 2013. Because of the anti-proliferative and anti-inflammatory effect of teriflunomide, it can be used for the reduction of the disease activity in the relapsing-remitting course of MS. The effect of teriflunomide was proved in one Phase II. and four Phase III. (TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to demonstrate in two consecutive placebo-controlled phase 3 clinical trials that significantly reduces the relapse rate (31.5% and 36.3%) and in both studies significantly reduces the sustained disability progression (29.8% and 31.5%) moreover delays the appearance of the clinically definitive MS in patients with clinically isolated syndrome (CIS). According to the TENERE study there were no significant differences observed between teriflunomide 14 mg and IFNb-1a s.c. in time to failure and annualized relapse rate but the treatment satisfaction domains of global satisfaction, side-effects and convenience were significantly improved with teriflunomide compared with s.c. IFNb-1a. ]



Further articles in this publication

Clinical Neuroscience

[Effects of maternal epilepsy and antiepileptic therapy in women during pregnancy]

VANYA Melinda, ÁRVA-NAGY Nóra, SZILI Károly, SZOK Délia, BÁRTFAI György

[Objective - The aim of this study was to analyse the effects of epilepsy and antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome, retrospectively. Methods - We examined the obstetric and fetal outcomes among women with epilepsy (WWE), who were followed-up at the Department of Neurology, and who delivered at the Department of Obstetrics and Gynaecology (n=91) between 31th December 2000 and 31th March 2014. Statistical comparisons of different obstetric and fetal parameters on a sample of 91 WWE and 182 non-WWE were assessed by the chi-square-test, the independent sample t-test. Results - The rate of major congenital malformations (MCMS) among the newborns of all AEDs exposed mothers was 7.69%. There were three peaks of seizures: during the third trimester, during delivery and in the puerperium. The prevalence of miscarriages, post-term birth and the rate of caesarean section were significantly higher among the WWE than among the non-WWE (p=0.001; p<0.001; p=0.02). Parameters of neonates (birth weight, birth length, head-, and chest circumference) were significantly different between the WWE group and the non-WWE group (p=0.003, p<0.001, p<0.001, p<0.001) Conclusions - In contrast with recent publications, there were significant differences in the parameters of neonates between the two groups. Our results are in accordance with those of previous studies from the aspect of AED-related MCM, the elevated risk of miscarriages and pre-existing hypertension. ]

Clinical Neuroscience

[Shifting function of working memory in psychotic disorders]


[Background and aims - Mental disorders with psychotic features are overlapping in many ways and there are a growing number of comparative studies in the last decades regarding this. Cognitive deficit is well underpinned in schizophrenia, but fewer studies are conducted in this area including patients with bipolar affective disorder. Therefore the aim of the present study was to investigate the cognitive performance of these two patient groups and healthy controls. The Wisconsin Card Sorting Task is a very sensitive measure of the shifting function. Schizophrenic patients perform consistently poorer on this task than healthy controls, while there are not much data about individuals with bipolar affective disorder. Methods - The Wisconsin Card Sorting Task and clinical symptom rating scales were administered to 26 patients with schizophrenia, 24 with bipolar affective disorder and 21 healthy controls. Results - Significant differences were found among the performance of the three groups using four different dimensions of the Wisconsin Card Sorting Task. The schizophrenic group made more perseverative errors and achieved less conceptual level responses and completed fewer categories compared to healthy controls. Patients with schizophrenia were able to complete fewer categories and had fewer conceptual level responses than the bipolar group. No significant differences were observed between patients with bipolar disorder and healthy controls. Conclusions - According to these results, patients with schizophrenia and bipolar affective disorder showed no similarities on the Wisconsin Card Sorting Task. Bipolar patients performed the task on the same level as healthy individuals did. The two mental disorders influence cognitive performance differently.]

Clinical Neuroscience

[Measuring of functional impairment of lumbal spine]


[Background and purpose - The purpose of our study was to outline the Hungarian validation process of the Oswestry Disability Index, the Quebec Back Pain Disability Scale, the Roland-Morris Disability Questionnaire and the Core Outcome Measurement Index, as well as to draw up recommendations regarding their future applications. Methods - The Hungarian versions were brought to life after a cultural and linguistic adaptation. Next to the above-mentioned questionnaires, the questionnaire booklet used for validation also contained the WHOQoL-BREF general quality of life questionnaire and a pain measuring Visual Analog Scale. The data of low-back pain patients were registered twice in two weeks. We determined the internal homogeneity (Cronbach alpha), reproducibility, standard error of measurement and the minimal detectable change of the questionnaires. Patients were assigned into different two subgroups (surgical / non-surgical, with / without affection of nerve roots) and differences between the subgroups were examined with the help of the questionnaires. We determined the physical subscale of the WHOQoL-BREF and the correlation between the pain and the studied questionnaires. Results - The value of Cronbach alpha was between 0.85 and 0.95. All four questionnaires showed significant differences (p<0.001) between the subgroups. The correlation studies brought strong and significant results (p<0.001, r>0.5) in every case. The values of reproducibility were between 0.93-0.92. The results of standard measurement error: 4.8 (Oswestry), 5.2 (Quebec), 1.6 (Roland-Morris), 0.59 (Core Index). The minimal detectable change was 13; 14; 4, and 2 points, respectively. Conclusion - The Hungarian versions of all four questionnaires are valid. They can be applied with scientific certainty to measure low back pain patients. From the studied questionnaires, we especially recommend the wide-raging application of the Oswestry Disability Index and the Core Outcome Measurement Index based on their psychometric and application features. ]

Clinical Neuroscience

[Proconvulsive effect of antiepileptic drugs]


[Antiepileptic drugs can provoke and worsen seizures, what is called paradoxical effect. Paradoxical seizure worsening can occur as a nonspecific manifestation of drug intoxication in number of antiepileptic drugs. The other type is a specific type, when antiepileptic drugs with pure GABAergic and sodium channel blocker mechanism of action provoke myoclonic, absence and atonic seizures in specific epilepsy syndromes, mainly in idiopathic generalized epilepsies. Antiepileptic drug-induced exacerbation of seizures is a common, often unrecognized clinical problem, which can be avoided by a careful syndromic diagnosis and by using broad spectrum antiepileptic drugs.]

Clinical Neuroscience

[Do previous offences predict violent acts in psychiatric patients? A retrospective study in Hungary]

BARAN Brigitta, SZABÓ Ádám Ferenc, KARA Borbála, KOVÁCS Magdolna, UZONYI Adél, ANTAL Albert, UNGVARI S Gabor, GAZDAG Gábor

[Aim - To investigate the presence of offences in the previous past history of perpetrators of violent acts who have undergone forced medical treatment. Methods - The documentation of all patients released over a 10-year period from the National Institute of Forensic Psychiatry (IMEI) was reviewed. A comparison was drawn between patients who were convicted of any type of offense before the violent act (patients with previous offences-PPO) and those who were not (patients with no previous offences-PNO). Results - Eighty-six (29%) and 208 (71%) patients formed the PPO and PNO groups, respectively. Prior contact with psychiatric services was significantly higher in the PPO group (p=0.038) and this group was also more likely to offend under the influence of a psychoactive substance (p<0.001). Exceptional brutality and other qualifying factors were more frequent in the PNO group (p=0.019). Conclusion - As IMEI is the only forensic institution in Hungary, the picture presented here reflects the situation in the entire country. A recidivism rate of 29% is within the internationally published range. ]

All articles in the issue

Related contents

Clinical Neuroscience

[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



[Chlamydia pneumoniae has recently been implicated in the pathogenesis of several neurological diseases. As an intracellular parasite with its unusual life cycle it is able to circumvent the immune system and to persist in the organism. It has the ability to modify the function of the infected cell and supposedly induce autoimmune reactions. These properties can make it pathogenic in several chronic neurological diseases including multiple sclerosis, atherosclerosis, stroke, Alzheimer dementia and giant cell arteriitis. The evaluation of the available, often contradictory, data that are based on various different methods is not easy. The importance of the issue is enhanced by the potential need for antibiotic treatment.]

Clinical Neuroscience

[The Expanded Disability Status Scale scoring in patients with multiple sclerosis]


[Gait disturbance is a major symptom in patients with multiple sclerosis. The Expanded Disability Status Scale (EDSS) was first used in clinical trials of multiple sclerosis for the assessment of disability, however it has become more and more widely used in clinical practice as well. Nowadays its use is essential in application of the new diagnostic criteria, the new clinical form classification and in monitoring the efficacy of therapies. EDSS is based on a standardised neurological examination, but focuses on those symptoms that are frequent in multiple sclerosis. Based on the examination it assesses seven functional systems: visual, brainstem, pyramidal, cerebellar, sensory, bowel-bladder and cerebral functions. EDSS scores can be determined based on the scores given in the functional systems and on testing the walking distance. In newer versions the “Ambulation score” has been added. This chapter clarifies the scores based on the maximal walking distance and the need for a walking aid to walk this distance. The Neurostatus/EDSS training method improves the reproducibility of the standardised neurological examination that forms the basis of the EDSS scoring. Of the tests assessing walking, the Timed-25 Foot Walk Test and the self-administered 12-Item Multiple Sclerosis Walking Scale are suitable for routine evaluation of walking performance. An increase of more than 20% in the Timed-25 Foot Walk may be considered a significant change in gait. ]

Clinical Neuroscience

[Alemtuzumab: benefits and challenges of new therapy in multiple sclerosis]

ILLÉS Zsolt, TOBIAS Sejbaek, CSÉPÁNY Tünde

[The widening spectrum of MS treatment is partially due to increasing knowledge about the pathogenesis of MS. The humanized monoclonal antibody against CD52, alemtuzumab has been approved in Europe for the treatment of MS, which results in long-term depletion of B and T cells due to complement- and antibody-mediated cytotoxicity. Based on phase 2 and 3 clinical trials, alemtuzumab decreases the risk of sustained neurological deficit and progression compared to high-dose subcutaneous interferon- β1a in patients with active relapsing-remitting MS, either treatment-naïve or with breakthrough disease. We review advantages and benefits of the treatment, discuss safety concerns, and present a case to describe practical issues.]

Clinical Neuroscience

[Diagnosis of multiple sclerosis: A review of the 2017 revisions of the McDonald criteria]


[The revolutionary progress of research in neuroimmu­nology has led to the introduction of disease modifying therapies in multiple sclerosis at the end of the last century. The International Panel on Diagnosis of Multiple Sclerosis originally proposed the 2001 McDonald criteria to facilitate the diagnosis of MS in patients with the first objective neurological symptom(s) suggesting demyelinating event, when magnetic resonance imaging is integrated with clinical and other paraclinical diagnostic methods. New terms have been introduced to substitute clinical information by MRI: dissemination in space - indicating a multifocal central demyelinating process and dissemination in time - indicating the development of new CNS lesions over time. The criteria for diagnosis of Multiple Sclerosis have continuously evolved, they were modified in 2005 and 2010 allowing for an earlier and more accurate diagnosis of MS over time, and they provided the most up-to-date guidance for clinicians and researchers. The last recommended revisions relied entirely on available evidence, and not on expert opinion thereby reducing the risk of the misdiagnosis. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical, clinically isolated syndrome. In this review, we provide an overview of the recent 2017 revisions to the criteria of dissemination in space and time with the importance of the presence of CSF-specific oligoclonal bands; keeping fully in mind that there is no better explanation for symptoms than diagnosis of MS. In the future, validation of the 2017 McDonald criteria will be needed in diverse populations. Further investigations are required on the value of new MRI approaches, on optic nerve involvement, on evoked potential and optical coherence tomography, in order to assess their possible contribution to diagnostic criteria.]