[Theoretical approach and prognostic significance of high disease activity in multiple sclerosis]. / A magas betegségaktivitás elméleti megközelítése és prognosztikai fontossága sclerosis multiplexben.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination and neurodegeneration. In addition to the inflammatory immune processes that characterise the onset of the disease with relapses, chronic inflammation is also present from the onset of the disease. The catabolic processes induced by chronic inflammation are responsible for the axonal degeneration that causes the progression of the disease. The activity of the disease is well defined, an important prognostic factor, and a determining factor in the indication of disease-modifying therapies. It is important to establish disease activity at the time of diagnosis and to monitor it continuously during patient care, both clinically and radiologically, as it is the basis for deciding on the current treatment. If detected on the basis of the professional guideline, it is necessary to start or switch to a highly effective therapy. 

[Assessment of compliance and patient pathway among multiple sclerosis patients on disease modifying treatment]. / Compliance- és betegútvizsgálat betegségmódosító kezelés alatt álló sclerosis multiplexes betegeknél.

Background and purpose:

Epidemiological data and the number of patients treated suggest that the proportion of Hungarian patients with Multiple Sclerosis (MS) receiving disease-modifying therapy (DMT) is lower than in some neighboring countries. We investigated possible reasons for this.

First we analysed patient compliance based on an anonymised database of the National Health Insurance Fund (NHIF). A total of 5441 patients were included in the analysis from NHIF prescription data from 1 July 2014 to 28 February 2021. In the second part of the study, a quantitative and qualitative assessment of patient journeys of MS patients was conducted. 

The compliance of Hungarian MS patients is good compared to international MS treatment data and outstanding compared to other neurological and other diseases, e.g. cardiovascular. This cannot be said about the results of the patient pathway analysis based on patient interviews. Patients indicated that they often have difficulty accessing public health care. Tracing their pathways revealed that they needed to see 3-5 doctors (general practitioner, various specialists) before a diagnosis was made. However, they gave positive feedback about MS Centres. They trusted their doctors, found them empathetic, but they would have liked more time to discuss lifestyle issues.

Compared to some neighbou­ring countries, Hungary has a lower proportion of patients with treated MS, which, given the good compliance of patients, highlights the problem of patient path in Hungary. Further training of fellow physicians is also a task for neurologists specialising in MS. Just as the most common symptoms of stroke have been successfully introduced into the public consciousness, the same can be the aim for MS.

New insights into the burden and costs of multiple sclerosis in Europe: Results for Hungary.

INTRODUCTION: To estimate the value of interventions in multiple sclerosis (MS) - where lifetime costs and outcomes cannot be observed - outcome data have to be combined with costs. This requires that cost data be regularly updated. OBJECTIVES AND METHODS: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of disability, from the societal perspective, in HUF 2015. RESULTS: A total of 521 patients (mean age 47 years) participated; 85% were below retirement age, and of these, 47% were employed. Employment was related to disability and MS affected productivity at work for 82% of those working. Overall, 94% and 66% of patients experienced fatigue and cognitive difficulties as a problem, respectively. The mean utility and annual costs were 0.691 and 3,432,000HUF at Expanded Disability Status Scale (EDSS) 0-3, 0.491 and 5,262,000HUF at EDSS 4-6.5 and 0.076 and 6,235,000HUF at EDSS 7-9, respectively. The average cost of a relapse was estimated at 240,500HUF. CONCLUSION: This study illustrates the burden of MS on Hungarian patients and provides current data that are important for the development of health policies.

Treatment of relapsing multiple sclerosis in Hungary - consensus recommendation from the Hungarian neuroimmunology society.

Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.

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.

Contributing factors to health-related quality of life in multiple sclerosis.

BACKGROUND: Health-related quality of life (HRQoL) is lower in people with multiple sclerosis (PwMS) compared to the healthy population, psychological symptoms accompanying multiple sclerosis (MS) have a serious impact on the HRQoL of PwMS. Data regarding the subject, however, remain conflicting. OBJECTIVES: To evaluate the patients' sociodemographic attributes, education, fatigue, depression, and cognitive impairment level of impact on the HRQoL for the whole cohort as well as comparing the sexes. MATERIALS AND METHODS: Three hundred and twenty-two relapse-remitting MS patients filled out the Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI), MS Quality of Life-54 (MSQoL-54) questionnaires, cognitive impairment were identified using Brief International Cognitive Assessment for MS (BICAMS) test. The patients' data were acquired from our clinic's MS registry or from patients' files. RESULTS: Depression and fatigue were found to have the most ubiquitous and robust effect on the overall and any given subdivision of the HRQoL composite. Other factors had a slight effect on some of the subscales when the whole cohort was evaluated. When the genders were compared, differences were found on 10 domains. CONCLUSION: Psychopathological symptoms have a more powerful influence on the HRQoL of MS patients than physical impairment, also these symptoms influence men's and women's HRQoL with different power. This invokes the need for complex and personalized care in the treatment of PwMS. Ours is the first study to show a difference between the sexes in this regard.

Prevalence of cognitive impairment among Hungarian patients with relapsing-remitting multiple sclerosis and clinically isolated syndrome.

BACKGROUND: Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS); its prevalence is reported to be 43-70%. It is one of the most important determinants of MS patients' quality of life, as it is one of the main factors for MS patients becoming unemployed. AIM: We aimed to determine the prevalence of CI among the relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS) patients in Hungary, to evaluate the predicting factors of CI and to assess the differences between sexes and patients with different educational levels. PATIENTS AND METHODS: Five-hundred and fifty-three CIS and RRMS patients were enrolled to our study from three Hungarian MS centers. Age at screening, age at disease onset, disease duration, EDSS score, sex and educational levels were analyzed as socio-demographic factors. The BICAMS battery was used to assess their cognitive state, the BDI-II battery to assess depression. For statistical analysis, we utilized logistical regression, and used Fisher exact tests, chi-square tests and one-way ANOVA. RESULTS: The mean age of our patients was 44.93 ± 11.69 years, mean age at disease onset was 31.95 ± 10.01 years, the mean disease duration was 13.05 ± 8.05 years and the median EDSS score 2.0 (Range: 6.5, IQR:2.0) points. Three-hundred and sixteen (57.1%) patients had CI. Sex, educational level and EDSS score proved to be significant predictors of CI (OR: 2.71, p < 0.001; OR: 1.94, p = 0.023; OR: 0.47, p = 0.003 respectively). CI was significantly (p < 0.001) more frequent among men (70.1%) than women (52.0%). We found, that educational level and EDSS score were only a significant predicting factor among women. Thus, the prevalence of CI among women with college or university degree was significantly (p < 0.001) less common (39.4%) than women with 12-15 years of education (57.4%) and women without a high school degree (66.7%). Also, we found that among women with higher EDSS score than 2 points, the prevalence of CI is 69.9% as compared to women with EDSS score between 0 and 2 points, where the prevalence is 42.8% (p < 0.001). No such differences were observed among man. DISCUSSION: Our prevalence data is similar to those reported in the literature (43-70%), and almost identical to the one assessment using the BICAMS battery. We found that men are more vulnerable to CI than women in MS, as was reported recently. We are the first to report however, that higher educational level and lower EDSS scores are only associated with better cognitive performance in women.

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.

Tumour necrosis factor alpha gene (TNF-alpha) -376 polymorphism in Hungarian patients with primary progressive multiple sclerosis.

Tumour necrosis factor alpha (TNF-alpha) is associated with clinical activity in relapsing-remitting multiple sclerosis (RRMS) and the development of progressive disease. Our aim was to investigate the TNF-alpha -376 polymorphism in primary progressive MS (PPMS) patients. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 45 PPMS patients, 45 age and sex-matched RRMS patients and 45 healthy controls (HC). The GG genotype and the guanine allele (G) were detected significantly more often in the PPMS group as compared with the HC group (p=0.027; p=0.032). The G allele may be one of the factors responsible for progression in PPMS.