The 7-year follow-up of the Hungarian BICAMS validation cohort implies that cognitive performance may improve in multiple sclerosis patients.

BACKGROUND: Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS) and has a great impact on the patients' quality of life, so screening is essential. The brief international cognitive assessment for multiple sclerosis (BICAMS) was developed for this purpose. However, longitudinal data is lacking with the use of the battery. OBJECTIVE: This study is to assess the performance of patients after 5 and 7 years of the original BICAMS validation study and to identify any influencing factors. METHODS: BICAMS was used to measure cognitive function of 52 relapsing-remitting MS patients (RRMS) from the original validation study after 5 years (n = 43) and again, after 7 years (n = 42). Patients filled out the fatigue impact scale (FIS) and multiple sclerosis quality of life-54 (MSQoL-54) questionnaire, and we evaluated expanded disability status scale (EDSS). RESULTS: There was an improvement in the BVMT-R and the CVLT-II assessments at both the 5-year (p<0.001 and p=0.025) and the 7-year retest (p<0.001 and p=0.002). The prevalence of CI significantly decreased at the 5-year mark (p=0.021) but remained stable after that. There was no deterioration in MSQoL scores during the study. The basic cognitive performance is the most important influencing factor, but the duration of the disease, the EDSS score, and the escalation of the therapy also affect the cognitive scores. CONCLUSION: This is the longest longitudinal study utilizing the BICAMS battery, reinforcing its feasibility as a clinical screening tool. It seems that cognitive performance may improve in the long term and early initiation of effective therapy may influence this outcome.

Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants.

BACKGROUND: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries. METHODS: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference. RESULTS: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic. CONCLUSION: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.

[Follow up examination of multiple sclerosis patients treated with alemtuzumab in Multiple Sclerosis Centre, Szeged]. / Alemtuzumabterápiával kezelt sclerosis multiplexes betegek követéses vizsgálata a szegedi Sclerosis Multiplex Centrumban.

Background and purpose: Therapeutic strategy of relapse-remitting multiple sclerosis has changed significantly during the past decade. While earlier escalating therapy was widely applied, recently, in case of high disease activity, induction therapy has become available. Methods: In our study, we processed the data of our alemtuzumab treated patients from our register. Alte-ra-tions in relapse rate and MRI activity due to the treatment were determined. These data were compared in patients treated with alemtuzumab as an escalating and as an induction therapy. We noted the observed side effects. Results: The 49 patients observed in the study had undergone two cycles of alemtuzumab therapy. The drug was applied as an induction therapy in 9 cases. Average relapse rate during the two years was 1.4±1.0, which decreased to 0.1±0.3 in the two years following the therapy. The average EDSS before therapy was 2.7±2.2 in the induction therapy group and 2.7±1.7 in the escalating therapy group. After the treatment, this score decreased to 1.6±0.6 and 2.5±1.8 in the induction and the escalating therapy group, respectively. We found clinical and MRI progression in case of 4 patients. As regards to side effects, cytokine release was detected in 51.0% of the patients following the first cycle, and 24.5% of the patients following the second cycle of the therapy. Infection related to the therapy was observed in 28.6%, while autoimmune thyreoiditis was diagnosed in 18.3% of the patients. Conclusion: The tight follow-up of the treated patients and the precise documentation of the register enable the comparison of results yielded by placebo controlled clinical studies with daily practice, as well as to gain information on the benefits of induction therapy as a paradigm shift in treating MS patients.

The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary.

BACKGROUND: Fingolimod was approved and reimbursed by the healthcare provider in Hungary for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS) in 2012. The present study aimed to assess the effectiveness, safety profile, and persistence to fingolimod in a real-life setting in Hungary in RRMS patients who were either therapy naïve before enrollment or have changed to fingolimod from another disease-modifying therapy (DMT) for any reason. METHODS: This cross-sectional, observational study with prospective data collection was performed nationwide at 21 sites across Hungary. To avoid selection bias, sites were asked to document eligible patients in consecutive chronological order. Demographic, clinical, safety and efficacy data were analysed for up to 5 years from 570 consenting adult patients with RRMS who had received treatment with fingolimod for at least one year. RESULTS: 69.6% of patients remained free from relapses for the whole study duration; in the first year, 85.1% of patients did not experience a relapse, which rose to 94.6% seen in the 5th year. Compared to baseline at study end, 28.2% had higher, and 9.1% had lower, meanwhile, 62.7% of the patients had stable EDSS scores. Overall, the annualized relapse rate decreased from 0.804 observed at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (77.0%, 82.1%, 85.2%, 89.7%, and 89.0% relative reduction, respectively) after 1, 2, 3, 4, and 5 years of treatment. The greatest reduction rate was seen in the group of therapy naïve patients. Treatment persistence on fingolimod after 60 months was 73.4%. CONCLUSION: In this nationwide Hungarian cohort, most patients under fingolimod treatment were free from relapses and disability progression. In addition, fingolimod has proven to be a well-tolerated DMT that has sustained its manageable safety profile, high efficacy, and positive benefit/risk ratio for up to 5 years in a real-life setting.

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations.

INTRODUCTION: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient's health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. AREAS COVERED: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. DISCUSSION: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

Do Hungarian multiple sclerosis care units fulfil international criteria?

A PATIENTS: Because of the past 3 decades' extensive research, several disease modifying therapies became available, thus a paradigm change is multiple sclerosis care was necessary. In 2018 a therapeutic guideline was created recommending that treatment of persons with multiple sclerosis should take place in specified care units where the entire spectrum of disease modifying therapies is available, patient monitoring is ensured, and therapy side effects are detected and treated promptly. In 2019 multiple sclerosis care unit criteria were developed, emphasizing personnel and instrumental requirements to provide most professional care. However, no survey was conducted assessing the real-world adaptation of these criteria. OBJECTIVE: To assess whether Hungarian care units fulfil international criteria. METHODS: A self-report questionnaire was assembled based on international guidelines and sent to Hungarian care units focusing on 3 main aspects: personnel and instrumental background, disease-modifying therapy use, number of people living with multiple sclerosis receiving care in care units. Data on number of persons with multiple sclerosis were compared to Hungarian prevalence estimates. Descriptive statistics were used to analyse data. RESULTS: Out of 27 respondent care units, 3 fulfilled minimum requirements and 7 fulfilled minimum and recommended requirements. The least prevalent neighbouring specialties were spasticity and pain specialist, and neuro-ophthalmologist and oto-neurologist. Only 15 centres used all available disease modifying therapies. A total number of 7213 people with multiple sclerosis received care in 27 respondent centres. Compared to prevalence estimates, 2500 persons with multiple sclerosis did not receive multiple sclerosis specific care in Hungary. CONCLUSION: Less than half of Hungarian care units provided sufficient care for people living with multiple sclerosis. Care units employing fewer neighbouring specialties, might have difficulties diagnosing and providing appropriate care for persons with multiple sclerosis, especially for people with progressive disease course, contributing to the reported low number of persons living with multiple sclerosis.

Functional Connectivity Lateralisation Shift of Resting State Networks is Linked to Visuospatial Memory and White Matter Microstructure in Relapsing-Remitting Multiple Sclerosis.

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing-remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman's correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = - 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing-remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms.

Rare complication of West Nile viral encephalitis.

In our case report, we are presenting a 72 years old male patient. The patient's symptoms were fever, dizziness, general weakness at the time of admission. The laboratory and CSF tests revealed central nervous system inflammation. West Nile virus was identified from the cerebrospinal fluid. After the symptoms of infection and during supporting treatment, severe, progressing hyponatremia evolved with unknown pathology. According to previous investigations and our diagnostic and therapeutic algorithm cerebral salt wasting syndrome identified as occasion.

Neurodegeneration in Multiple Sclerosis: Symptoms of Silent Progression, Biomarkers and Neuroprotective Therapy-Kynurenines Are Important Players.

Neurodegeneration is one of the driving forces behind the pathogenesis of multiple sclerosis (MS). Progression without activity, pathopsychological disturbances (cognitive impairment, depression, fatigue) and even optic neuropathy seems to be mainly routed in this mechanism. In this article, we aim to give a comprehensive review of the clinical aspects and symptomology, radiological and molecular markers and potential therapeutic targets of neurodegeneration in connection with MS. As the kynurenine pathway (KP) was evidenced to play an important role in the pathogenesis of other neurodegenerative conditions (even implied to have a causative role in some of these diseases) and more and more recent evidence suggest the same central role in the neurodegenerative processes of MS as well, we pay special attention to the KP. Metabolites of the pathway are researched as biomarkers of the disease and new, promising data arising from clinical evaluations show the possible therapeutic capability of KP metabolites as neuroprotective drugs in MS. Our conclusion is that the kynurenine pathway is a highly important route of research both for diagnostic and for therapeutic values and is expected to yield concrete results for everyday medicine in the future.

Epidemiology of multiple sclerosis in Central Europe, update from Hungary.

OBJECTIVES: Not so long ago, a novel phenotypic classification of multiple sclerosis (MS) and revisions to the McDonald diagnostic criteria were published. Good quality, standardized, and therefore comparable epidemiological data from the Central European region altogether are scarce, and data based on the aforementioned criteria are nonexistent; thus, an update is needed. MATERIALS AND METHODS: Patients residing in Csongrád county with a definitive diagnosis of MS according to the 2017 McDonald criteria were included and evaluated by the 2014 revised phenotypic classification. RESULTS: A total of 420 patients were included, of whom 313 were females (female/male ratio 2.925:1). Standardized prevalence was 101.8/100,000, and incidence was 4.44/100,000. Relapsing-remitting disease type was identified in 288 (68.57%) cases, of which 230 patients (79.86%) were treated and of which 202 patients (87.8%) showed no disease activity with their current treatment. Progressive disease type was seen in 132 (31.43%) cases, with 72 patients (54.54%) receiving treatment. More than half of the treated patients (178, 57%) were administered platform therapies, while 134 (43%) received highly active disease modifying therapies. CONCLUSION: The prevalence of MS in Hungary similarly to other countries shows a constant increase in the past decades. The majority of our patients received treatment and had a stable disease while being treated. The distribution of disease courses, phenotypes, and treatment status fell in line with data in the literature based on MS registries with a large number of participants. Ours is the first study to give epidemiological data based on the most recent McDonald criteria and phenotypic classification from the Central European region.

[The role of MRI in measuring the effectivity of disease modifying treatments I]. / Az MRI helye a sclerosis multiplex kezelés hatékonyságának megítélésében I.: mérési markerek.

MRI has a significant role in the diagnosis of multiple sclerosis. The newer and newer treatment options of the disease make it necessary to monitor the effectiveness of the therapy. Besides the clinical signs (clinical relapses and progression), the different MRI parameters can also reflect the disease activity. In our current article we summarize those MRI markers, which best predict the long-term disability, based on the international standards.

[The role of MRI in measuring the effectivity of disease modifying treatments II]. / Az MRI helye a sclerosis multiplex kezelés hatékonyságának megítélésében II.: mérési protokollok.

The paraclinical examinations, principally the MRI have an increasing significance in the diagnosis of multiple sclerosis. However, MRI markers also have a prominent role in monitoring of the disease-course and activity, and also in the planning of possible therapeutic changes. In accordance with previously published international guidelines, in this article we propose a protocol for the monitoring the treatment efficacy in multiple sclerosis. This could be the basis of a consensus based guideline to be implemented in Hungary.

[The Multiple Sclerosis Registry of Szeged]. / A Szegedi Sclerosis Multiplex Regiszter.

Multiple sclerosis (MS) is a rare disease of the central nervous system considering the total population, the prevalence in Hungary is 83.9/100.000. The first MS registry was established in Denmark in the middle of the 1950's. This was followed by the establishment of several national, then international databases with the number of enrolled patients in the hundred-thousands. At the beginning, the primary goal of the registries were the epidemiological surveys, focusing on the number of patients, the prevalence, the incidence, the mortality and the co-morbidity. As of today, however, with the rapid advancement and development of new disease modifying therapies (DMT) with different effectiveness and adverse reactions, the therapeutic use of the registries became even more essential: the modern, up-to-date, well established registries become integral part of the DMTs' monitorization. The Multiple Sclerosis Registry of Szeged was first established as a "paper-based" database, then, in 2012, it was upgraded to an electronic, easily contactable and useable internet-based registry. As of today, it contains the socio-demographic and clinical data of more than 600 patients; we constantly add new patients as well as keep the registry up-to-date with the refreshment of old patients' data. Aside from the "classical" clinical data, it can be used for the recording and assessment of the MRI scans and the data on psychopathological and quality of life assessments, which are becoming more and more important in everyday MS management. The establishment of the internet-based registry incredibly helped both the monitorization of the effectiveness of DMTs, and the success of the new epidemiological and psychopathological surveys.

[Change of therapeutic algorithm in sclerosis multiplex based on two case reports]. / Terápiás algoritmus változása sclerosis multiplexben két esettanulmány alapján.

The aim of our case reports is to demonstrate the therapeutic use and possibilities one has with alemtuzumab, should it be used either as a first or second line therapy. Our first patient's disease in the beginning seemed to be benign. It was not the case however, over several years the diesase showed high activity both radiologically and clinically, she was treated with alemtuzumab as part of an esclationbased therapeutic strategy. The second patient's disease on the other hand showed formidable activity since the very beginning both radiologically and clinically. Therefore we were facing a very disastrous prognosis on the long run, accordingly he received alemtuzumab treatment very early into his illness.

Mortality in Hungarian patients with multiple sclerosis between 1993 and 2013.

OBJECTIVE: We aimed to assess the causes of death, the mortality and survival time of MS patients in Hungary. PATIENTS AND METHODS: Between 1993 and 2013, 740 patients (10,303person-years) were treated at our Outpatients' Clinic, of which 121 died. The causes of death were established from the pathological records or the medical certificates of the cause of death. The standardized mortality ratios (SMR) were calculated. Survival time was assessed with Gehan-Breslow test. RESULTS: Sixty-four percent of our patients died of MS-related causes. The SMR was 2.52. Primary progressive (PPMS) patients' SMR was higher (4.10) than initially relapsing patients' (RR/SPMS) was. There was no difference between the genders (2.46 for men vs 2.57 for women). The median survival time of woman was 3years longer (p<0.001). RR/SPMS patients' median survival (35years) was more than twice as long as PPMS patients' (14years). DISCUSSION: The frequency of the MS-related cause of death, SMR and the median survival times were mostly similar to previous results from Scandinavia and North-America, despite the very different socio-economic backgrounds of these areas which shows that the survival risk can solely be attributed to MS itself. These are the first data on the topic from Central-Eastern-Europe.

The effects of fatigue, depression and the level of disability on the health-related quality of life of glatiramer acetate-treated relapsing-remitting patients with multiple sclerosis in Hungary.

BACKGROUND: The common symptoms of multiple sclerosis are fatigue, depression, cognitive dysfunction, pain and sexual dysfunction, which influence the health-related quality of life of the patients. OBJECTIVE: We aimed to determine the correlations between the health-related quality of life, the level of disability, fatigue and depression in glatiramer acetate-treated patients with multiple sclerosis in Hungary. METHODS: The Hungarian versions of the Multiple Sclerosis Quality of Life-54, Fatigue Impact Scale and Beck Depression Inventory questionnaires were completed by 428 relapsing-remitting multiple sclerosis patients treated with glatiramer acetate from 19 Hungarian centers. RESULTS: The prevalence of fatigue was found to be 62.4%. The prevalence of depression was lower (13.4%) than that described in previous studies (36-54%) among patients with multiple sclerosis. Significant differences in the health-related quality of life were found between fatigued and non-fatigued patients. The level of disability, fatigue, depression and the duration of the disease correlated significantly with the quality of life. However, linear regression analysis indicated that the quality of life was predicted by the level of disability, depression, social and cognitive fatigue, but not by physical fatigue. CONCLUSIONS: Decreasing the disease activity in multiple sclerosis with immunomodulatory therapy, together with improvements of the diagnostics and treatment of the accompanying depression and fatigue are of high priority to improve the health-related quality of life of patients with multiple sclerosis.

The Hungarian validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery and the correlation of cognitive impairment with fatigue and quality of life.

BACKGROUND: Multiple Sclerosis (MS) causes not only somatic, but also cognitive impairment regardless of the patients׳ age or the course of the disease. The Brief International Cognitive Assessment for MS (BICAMS) test, published in 2011, is a short cognitive questionnaire: a fast, reliable, sensitive and specific tool for the evaluation of the patients׳ cognitive state. OBJECTIVES: Our primary objective was to assess the validity of the Hungarian version of the BICAMS test. Our secondary objective was to evaluate the impact of the cognitive impairment on the patient׳s quality of life and fatigue׳s impact on the patients׳ cognitive state. METHODS: 65 RR-MS patients and 65 age, sex and education matched healthy control (HC) subjects completed the test and were retested after 3 weeks. The patients also completed the MS Quality of Life 54 (MSQoL54) and the Fatigue Impact Scale (FIS) assessments. Group differences were calculated by paired sample T-tests. The test-retest reliability was measured by intraclass correlation coefficients. To analyze the difference between the test-retest performances of the two groups we used two-way repeated measures ANOVA where the BICAMS battery was the single composite outcome and one-way repeated measures ANOVA. To assess the impact of the cognitive decline on the patients׳ quality of life and fatigue׳s impact on the cognitive state, we examined the correlations between results in the BICAMS and the MSQoL54 and FIS. RESULTS: We found significant difference (p ≤ 0.001, p = 0.017 in the first CVLT-II assessment) between MS patients and members of the HC group in all four evaluated parameters of BICAMS test in both sessions. The correlation coefficients were very strong between the tests and retests (r > 0.8; p < 0.001; r = 0.678, p < 0.001 between the CVLT-II assessments). We found that the HC group performed significantly (p = 0.020) better in the retest sessions as compared to their original performance than the patients did and this difference is solely due to the difference between the CVLT-II performances. We have found significant negative correlation between the patients׳ cognitive function and the fatigue score (r < -0.3, p < 0.05). Seven of the MSQoL-54 subscales correlated with the BICAMS performance (r > 0.3; < 0 .05). CONCLUSIONS: The Hungarian version of the BICAMS test is a valid and reliable method for the evaluation of MS patients׳ cognitive function. It seems that because of the short retest period, the members of the HC group remembered the CVLT-II words thus performed better than the patients did. Also apparently fatigue can have a negative impact on the patients׳ cognitive state, and cognitive impairment could worsen the patients׳ quality of life.

APOE epsilon status in Hungarian patients with primary progressive multiple sclerosis.

PRINCIPLES: Apolipoprotein E (ApoE), an important glycoprotein in the transport, uptake and redistribution of cholesterol, is necessary in nerve tissue repair. The APOE gene (APOE) is involved in neurodegenerative diseases, the best-known association being that between the APOE ε4 allele and Alzheimer's disease. Multiple sclerosis (MS) is a chronic inflammatory neurological disease. The aim of this study was to assess (multicentre assessment) the possible influence of the APOE gene on the susceptibility of primary progressive MS (PPMS) in Hungary. METHODS: Polymerase chain reaction and restriction fragment length polymorphism were carried out on DNA isolated from 135 volunteers. RESULTS: The number of PPMS patients without the ε2 allele was found to be remarkably high, whilst the ε2 allele was overrepresented in the RRMS group. A markedly high frequency of the ε4 allele was found in the PPMS group and a very low frequency in the HC group. With regards to the clinical parameters, significant differences were observed between the RRMS and PPMS groups. Differences were also detected regarding the EDSS and MSSS scores when the patients were grouped by the presence or absence of the ε2 allele. All of the observed differences in the clinical parameters disappeared when the patients were further stratified by the type of MS. CONCLUSIONS: Our findings suggest that the presence of the ε2 and ε4 alleles may play a role in the development of the disease. However, if any type of the disease has already developed the alleles show no association with the clinical parameters.

Short communication: treatment of relapsing-remitting multiple sclerosis 96 patients with IFN-beta 1b: results of a 6-year follow-up.

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.