INTRODUCTION:Cognitive impairment (CI) is a significant burden for patients with multiple sclerosis (MS). However crucial its assessment is, longitudinal measurement of cognitive performance is susceptible to learning effect, making the results of repeated evaluations difficult to interpret. Reliable change index (RCI) and standardized regression based norms (SRB) are accepted statistical methods to assess the reliability of a difference score between two observations. Thus, our aims were to provide RCIs and SRBs for all three subtests of the Brief International Cognitive Assessment for MS (BICAMS) battery and to measure the prevalence of true cognitive worsening and improvement. METHODS:We retrospectively evaluated the first interim analysis data of the longitudinal follow-up or our BICAMS prevalence study-cohort after 1-year. We analyzed the data of 242 MS patients. RESULTS:We calculated both the RCIs and the SRBs for all three subtests of the BICAMS battery. According to the RCI, 5.4%, 6.9% and 14.6% worsened while 12.3%, 34.3% and 10.6% improved on the SDMT, BVMT-R and CVLT-II respectively. In case of SRB method, 3.8%, 8.3% and 19.7% worsened while 3.8%, 7.6% and 0.0% improved. The κ values revealed a mild-to-moderate agreement (κ=0.391-0.540; p<0.001). In case of the BVMT-R and the CVLT-II assessments the baseline scores influenced this outcome significantly (BVMT-R: OR: 1.068; 90%CI: 1.001-1.138; CVLT-II: OR: 1.096; 90%CI: 1.041-1.153). CONCLUSION:Comparing the methods, RCI seems to be better in cases with already established CI, while SRB, the more complex method, seemingly detects change better in cognitively intact patients.

Background - POEMS syndrome is a potentially well manageable disease with an ascendant therapeutic arsenal nowadays. The early recognition of the syndrome is key to prevent serious multiorgan damage, and that is still a big challenge for physicians. With the following two case reports the authors aimed to highlight the consequences of late recognition of the disease and summarize the potential therapeutic options for POEMS syndrome. Results - We have presented two patients' cases with a long history of examination and treatment because of uncleared polyneuropathy. Through these cases we could see how serious could be the consequences of late diagnosis and despite multiorgan impairment there are still therapeutic options which could improve the patient's condition. Although the diagnosis of POEMS syndrome is not easy, it must raise our mind the thought and be prudent when we start a treatment in polyneuropathy.

There is scarce information in Middle-Eastern Europe regarding the prevalence of anxiety in patients with multiple sclerosis (pwMS) and its association with different clinical-demographic factors. We aimed to determine the prevalence of anxiety in Hungarian MS patients and to analyze associated factors. We evaluated 260 PwMS with the STAI-5 anxiety questionnaire. Fatigue (FIS), depression (BDI-II) and cognition (BICAMS) were also measured. Patients underwent standard neurological evaluations to evaluate Expanded Disability Status Scale (EDSS), and also measured the fine motor skills of the hand with the 9-hole peg test (9HPT), and the walking distance with the 25-foot walking test (T25FW). We identified 23.1

Introduction:Natalizumab (NAT), a highly effective disease modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS), was approved for clinical use in Hungary on February 1, 2010. In this study we aimed to assess its effectiveness in view of the concept of "No Evidence of Disease Activity" (NEDA-3), furthermore evaluate its effect on limb function, pathopsychological symptoms (cognition, fatigue, depression) and quality of life (QoL). Patients and methods:From February 1, 2010, to December 1, 2022, 121 eligible patients were consecutively enrolled from the MS center of the University of Szeged, Hungary. Here, we report data on 6-years of follow-up. First, we evaluated the proportion of patients reaching the NEDA-3 state and any possible influencing factors. Then, we assessed the change of upper and lower limb functions via the 9-hole-peg test (9HPT) and the 25-feet walk test (TW25F). Finally, we assessed the change of pathopsychological symptoms (cognition, fatigue, depression) and QoL via the BICAMS, FIS, BDI-II and MSQoL-54 questionnaires, and the possible influencing factors behind it. Results:Cumulatively, 97 patients (80.2 %) achieved NEDA-3 throughout the follow-up period. On a year-by-year basis, the proportion changed from 95.9 % in the 1st year to 84.3 %, 81.3 %, 76.4 %, 74.5 % and 78.9 % in the 2nd, 3rd, 4th, 5th and 6th year respectively (p<0.001). Baseline EDSS scores and the type of preceding DMT affected this outcome. Both the upper and the lower limb functions remained stable. Cognitive functions improved (p<0.001), fatigue and depression scores remained stable during the follow-up period. QoL remained stable or improved in all subscales of MSQoL-54 questionnaire. Conclusion:Our 6-years long detailed follow-up study demonstrates that NAT not only reduces disease activity and progression. It effectively protects from the worsening of limb function, cognitive and other psychological impairments, and stabilizes the patients' quality of life in basically every measurable aspect.

Célkitűzések – A POEMS szindróma egy potenciálisan jól menedzselhető betegség napjainkban, egyre bővülő terápiás arzenállal. A szindróma korai felismerése, ami a gyakorló orvosok számára továbbra is kihívást jelent, nagy jelentőségű a súlyos többszervi károsodás megelőzése szempontjából. Az alábbi két eset bemutatásával a szerzők a betegség késői szövődményeire hívják fel a figyelmet, illetve az elérhető terápiás lehetőségeket mutatják be POEMS szindrómában. Eredmények – Az alábbiakban két olyan beteg esete kerül bemutatásra, akiknél hosszú kivizsgálás és kezelés történt tisztázatlan polyneuropathia miatt. Az esetek jól mutatják, hogy milyen súlyos többszervi eltérés jön létre a késői diagnózisig, illetve hogy az alkalmazható kezelés súlyos esetben is javíthat a beteg állapotán. Bár a POEMS szindróma diagnózisának felállítása továbbra sem könnyű, eszünkbe kell, hogy jusson és kellően körültekintőnek kell lennünk, amikor polyneuropathia miatt kezelést indítunk.

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.

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.

Multiple sclerosis (MS) is the inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide. In the last decade, a new era was heralded in by a new phenotypic classification, a new diagnostic protocol and the first ever therapeutic guideline, making personalized medicine the aim of MS management. However, despite this great evolution, there are still many aspects of the disease that are unknown and need to be further researched. A hallmark of these research are molecular biomarkers that could help in the diagnosis, differential diagnosis, therapy and prognosis of the disease. Proteomics, a rapidly evolving discipline of molecular biology may fulfill this dire need for the discovery of molecular biomarkers. In this review, we aimed to give a comprehensive summary on the utility of proteomics in the field of MS research. We reviewed the published results of the method in case of the pathogenesis of the disease and for biomarkers of diagnosis, differential diagnosis, conversion of disease courses, disease activity, progression and immunological therapy. We found proteomics to be a highly effective emerging tool that has been providing important findings in the research of MS.

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.

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.

BackgroundFingolimod 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.MethodsThis 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.Results69.6% 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%.ConclusionIn 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.

Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients&rsquo; 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. Author commentary: the current diagnostic criteria of MS rely 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 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.

BACKGROUND:Cognitive decline is a prominent symptom of MS. Clear connection between cognitive status and white matter microstructural changes has not been unequivocally observed to date.OBJECTIVE:To characterise the relationship between white matter microstructure and cognitive performance a partial least squares (PLS) approach was used.METHODS:53 RR MS patients' T1 and DTI images and BICAMS subtests were used in our analysis. Standard FSL pipeline was used to obtain diffusion parameters. A PLS approach was applied to reveal the diffusion parameter patterns responsible for the cognitive dysfunction.RESULTS:The first latent variable (LV) was mainly associated with demyelination, while the second and third explained axonal damage. While the first two LV represented mainly Brief Visuospatial Memory Test (BVMT) and Single Digit Modality Test (SDMT), the third LV depicted diffusion alterations mainly the verbal subtest. The first LVs spatial map showed demyelination in the corpus callosum. The second LVs spatial map showed the diffusion alterations in the thalamus. The third LV depicted diffusion alterations in the putative left superior longitudinal fascicle.CONCLUSION:Visual memory demanding tasks versus language functions depend on distinct patterns of diffusion parameters and the spatial organisation. Axial diffusivity alterations, a putative marker of irreversible axonal loss explained around 20% of variability in the cognitive functions.

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.

Over the past years, an increasing amount of evidence has emerged in support of the kynurenine pathway’s (KP) pivotal role in the pathogenesis of several neurodegenerative, psychiatric, vascular and autoimmune diseases. Different neuroactive metabolites of the KP are known to exert opposite effects on neurons, some being neuroprotective (e.g., picolinic acid, kynurenic acid, and the cofactor nicotinamide adenine dinucleotide), while others are toxic to neurons (e.g., 3-hydroxykynurenine, quinolinic acid). Not only the alterations in the levels of the metabolites but also disturbances in their ratio (quinolinic acid/kynurenic acid) have been reported in several diseases. In addition to the metabolites, the enzymes participating in the KP have been unearthed to be involved in modulation of the immune system, the energetic upkeep of neurons and have been shown to influence redox processes and inflammatory cascades, revealing a sophisticated, intertwined system. This review considers various methods through which enzymes and metabolites of the kynurenine pathway influence the immune system, the roles they play in the pathogenesis of neuroinflammatory diseases based on current evidence with a focus on their involvement in multiple sclerosis, as well as therapeutic approaches.

Background: In the recent years, many novel Disease-Modifying Drugs (DMD) have been introduced to the market in the treatment of multiple sclerosis. Objectives: To provide the reader with an up to date, compact review on the pharmacokinetic properties, mechanism of action, and clinical attributes of one of the most recently approved drugs in the therapy of multiple sclerosis, cladribine. Conclusion: Cladribine tablets proved to be a highly efficient treatment choice for RelapsingRemitting Multiple Sclerosis (RRMS), especially for patients with high disease activity. It is the first DMD for MS with a complex mechanism of action, by inhibiting the adenosine-deaminase enzyme it increases the intracellular levels of deoxyadenosine triphosphate, which with relative selectivity depletes both T- and B-cells lines simultaneously. However long term follow-up safety and effectiveness data are still missing, and clear treatment protocols are lacking beyond the first two treatment years cladribine should prove to be a valuable addition to the therapeutic palette of RRMS, and potentially for Clinically Isolated Syndrome (CIS) as well.

AbstractObjectivesNot 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 MethodsPatients 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.ResultsA 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.ConclusionThe 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.

Next to the disseminated clinical symptoms, cognitive dysfunctions are common features of multiple sclerosis (MS). Over the recent years several different MRI measures became available representing the various features of the pathology, but the contribution to various clinical and cognitive functions is not yet fully understood. In this multiparametric MRI study we set out to identify the set of parameters that best predict the clinical and cognitive disability in MS. High resolution T1 weighted structural and high angular resolution diffusion MRI images were measured in 53 patients with relapsing remitting MS and 53 healthy controls. Clinical disability was inflicted by EDSS and cognitive functions were evaluated with the BICAMS tests. The contribution of lesion load, partial brain, white matter, gray matter and subcortical volumes as well as the diffusion parameters in the area of the lesions and the normal appearing white matter were examined by model free, partial least square (PLS) approach. Significance of the predictors was tested with Variable Importance in the Projection (VIP) score and 1 was used for threshold of significance. The PLS analysis indicated that the axial diffusivity of the NAWM contributed the most to the clinical disability (VIP score: 1.979). For the visuo-spatial working memory the most critical contributor was the size of the bilateral hippocampi (VIP scores: 1.183 and 1.2 left and right respectively). For the verbal memory the best predictors were the size of the right hippocampus (VIP score: 1.972), lesion load (VIP score: 1.274) and the partial brain volume (VIP score: 1.119). In case of the information processing speed the most significant contribution was from the diffusion parameters (fractional anisotropy, mean and radial diffusivity, VIP scores: 1.615, 1.321 respectively) of the normal appearing white matter. Our results indicate that various MRI measurable factors of MS pathology contribute differently to clinical and cognitive disability. These results point out the importance of the volumetry of the subcortical structures and the diffusion measures of the white matter in understanding the disability progression.

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.

Multiple sclerosis (MS) is the autoimmune, neurodegenerative disease of the central nervous system (CNS). Typically, it affects the young adult population, however, up to 10% of the cases, it can develop in childhood. Atypical manifestations, such as the tumefactive variant (tMS) or acute disseminated encephalomyelitis (ADEM), especially coupled with fulminant disease course, are even more rare and pose a considerable differential diagnostic and therapeutic challenge. Recently, the therapeutic strategy on the use of disease modifying therapies (DMTs) in MS has shifted to the direction of a more individualized approach, that takes the personal differences heavily into account, in particular regard to the activity and prognosis of the disease. Despite this change has only been applied to adults yet, it is plausible to predict, that it will soon be applied to pediatric patients as well, particularly, as several randomized studies are under way concerning DMTs in pediatric populations. To our best knowledge, we are the first to report a successful natalizumab treatment of pediatric fulminant tMS, in case of a 13.5 years old girl. We feel that this report demonstrates the need of early and adequate treatment in such an aggressive case, because it can reverse the course of a possibly fatal disease. (C) 2018 Elsevier Ltd. All rights reserved.