Search

Objective: To assess the differences of treatment outcomes regarding disease activity in patients with highly active relapsing multiple sclerosis (RMS), treated with autologous hematopoietic stem cell transplantation (HSCT) or alemtuzumab (ATZ)., Methods: Open-label prospective single-center observational cohort study, enrolling patients with highly active RMS for treatment with ATZ or HSCT between 2014 and 2021., Results: A total of 50 patients (31/50 (62 %) in HSCT vs 19/50 (38 %) in ATZ group) were included. There were no significant differences in relapse rate, MRI activity or disability worsening between the two study groups during the first two years after treatment onset. However, at 3 to 5 years follow-up, HSCT was superior to ATZ in all the aforementioned aspects. Kaplan-Meier analysis at 5 years post treatment revealed superiority of HSCT in relapse rate (69.6 % vs 95.7 %, p = 0.027), MRI activity (54.5 % vs 75.1 %, p = 0.038) and disability worsening (57.1 % vs 90.9 %, p =  0.031)., Conclusions: ATZ may halt disability progression early in the course of highly active RMS, but the disability starts accumulating later, while in HSCT patients disability improvement is consistent both 3 and 5 years after treatment onset., Competing Interests: Declaration of Competing Interest M.V. Conception and design of the study, primary data analysis, drafting of the manuscript; G.F.K. Overall revision for accuracy of the data, tables and Figures, scientific accuracy of the manuscript; R.K. Concept of the study, revision of the manuscript for scientific accuracy; V.T. Data analysis, drafting of the manuscript, revision for scientific accuracy; N.G. conception and design of the study, acquisition of the data, analysis and interpretation of the data, and drafting of the manuscript, revision for scientific accuracy. All of the authors discussed the results and contributed to and approved the final manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study, we aimed to assess the quality of life, fatigue, anxiety, and depression after Autologous haematopoietic stem cell transplantation (AHSCT) and to investigate its impact of on separate domains of health status and fatigue in patients with multiple sclerosis (MS). Overall, 18 patients with highly active relapsing MS (mean age 36.3 years, 83.3% female) underwent the AHSCT in Vilnius Multiple Sclerosis center, and we prospectively collected Short Form 36, Health Survey Questionnaire, Fatigue Descriptive Scale, and Hospital Anxiety and Depression Scale beforeand Month3, 12, and 24 after AHSCT. The median score of Expanded Disability Status Scale at Month3 after transplant improved in 14 patients (77.8%). A significant improvement in physical functioning, vitality, and pain was found at Month3 after AHSCT (p < 0.05), which was sustained until Month12 and 24. The improvement in fatigue score was found at Month12 after AHSCT, which was sustained until Month24. Decrease in EDSS score had a positive impact on the better HRQoL outcomes, especially physical and social outcomes. Thus, AHSCT improved quality of life and reduced symptoms of fatigue in patients with highly active relapsing MS. The improvement was determined earlier in the domains of QoL than in the fatigue., (© 2022. The Author(s).)

Less than half of patients with chronic diseases, including multiple sclerosis (MS), adhere to their prescribed medications. Treatment selection is essential for patient adherence. The aim of this study was to explore the potential factors influencing nonadherence to disease-modifying therapies (DMTs) in MS. This prospective, cross-sectional study was performed at the Multiple Sclerosis Center between 2018 and 2021. In total, 85 patients were eligible for final analysis. Forty-one patient (48.2%) with MS were non-adherent to DMT. Male sex, oral administration of drugs, and longer treatment duration were associated with nonadherence. The mean Expanded Disability Status Scale score did not differ between the adherent and non-adherent patients (p > 0.05). Patients with a higher score on the Symbol Digit Modalities Test, who were receiving self-injection therapy, had shorter treatment duration, and higher disability, were more likely to be adherent to DMT than those without. To minimize nonadherence in patients with MS, the patient's information processing speed should be considered before DMT initiation, and appropriate treatment options should be discussed., (© 2022. The Author(s).)

There is some evidence that cognition may be impaired during multiple sclerosis (MS) relapse. The aims of this study were to assess the cognitive status with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in MS patients during relapse, in stable patients, and in healthy controls; to evaluate cognitive changes up to 3 months after relapse; and to estimate the impact of different factors on cognition after relapse. BICAMS was performed in 60 relapsing, 30 stable patients and 30 controls. Relapsing MS patients were assessed during relapse and one and three months after relapse. SDMT score was lower in relapsing than in stable patients. The mean scores of all BICAMS tests were higher one month after relapse than during relapse (p < 0.001). SDMT score after relapse improved in younger patients, who had more severe relapse (p < 0.05). BVMT-R score improved more in men, in patients with biologically active interferon-beta, in patients treated with methylprednisolone and in patients who were rehabilitated (p < 0.05). CVLT-II score improved in women and in patients with shorter relapse (p < 0.05). A neuropsychological assessment, like the evaluation of physical disability, is important during relapse. BICAMS may be suitable for a quick and effective assessment of cognition during relapse.

Background: Upper extremity (UE) motor function deficits are commonly noted in multiple sclerosis (MS) patients and assessing it is challenging because of the lack of consensus regarding its definition. Instrumented biomechanical analysis of upper extremity movements can quantify coordination with different spatiotemporal measures and facilitate disability rating in MS patients., Objective: To identify objective quantitative parameters for more accurate evaluation of UE disability and relate it to existing clinical scores., Methods: Thirty-four MS patients and 24 healthy controls (CG) performed a finger-to-nose test as fast as possible and, in addition, clinical evaluation kinematic parameters of UE were measured by using inertial sensors., Results: Generally, a higher disability score was associated with an increase of several temporal parameters, like slower task performance. The time taken to touch their nose was longer when the task was fulfilled with eyes closed. Time to peak angular velocity significantly changed in MS patients (EDSS > 5.0). The inter-joint coordination significantly decreases in MS patients (EDSS 3.0-5.5). Spatial parameters indicated that maximal ROM changes were in elbow flexion., Conclusions: Our findings have revealed that spatiotemporal parameters are related to the UE motor function and MS disability level. Moreover, they facilitate clinical rating by supporting clinical decisions with quantitative data.

BACKGROUND With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. MATERIAL AND METHODS We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. RESULTS Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. CONCLUSIONS The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS., Competing Interests: Conflicts of interests The authors have no conflicts of interest to declare.

BACKGROUND Assessment of cognitive impairment (CI) in multiple sclerosis (MS) patients is very useful, but it requires time-consuming expert evaluation with specialized materials. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was created as a brief and specific instrument for the evaluation of CI. The aims of this study were to assess the cognitive status of MS patients by using the Lithuanian version of BICAMS, to evaluate the test-retest reliability of the Lithuanian version of BICAMS, and to measure the impact of CI on disability and duration of MS. MATERIAL AND METHODS We enrolled 50 MS patients and 20 cognitively normal control subjects, matched for age, gender, and level of education. Cognitive functions were assessed by the BICAMS tests, which include the Symbol Digit Modalities Test, the Brief Visuospatial Memory Test Revised, and the California Verbal Learning Test, 2nd edition. RESULTS MS patients performed significantly worse than controls on the 3 neuropsychological tests of BICAMS (p<0.001). Younger and intellectually employed persons performed significantly better on these tests than older persons, manual workers, or unemployed persons (p<0.05). MS patients with higher disability scores tended to perform worse on the tests (p<0.05), but we found no relationship between BICAMS test scores and the duration of the disease or relapse rate (p>0.05). Test-retest reliability was excellent for all 3 subtests (r>0.8, p<0.05). CONCLUSIONS Our study shows that BICAMS is a valid and acceptable cognitive assessment tool that can be recommended for routine use in Lithuania for assessing patients with MS.

Background: Neutralizing antibodies (NAb) to interferon-beta (IFN-β) are associated with reduced bioactivity and efficacy of IFN-β in multiple sclerosis (MS). The myxovirus resistance protein A (MxA) gene expression is one of the most appropriate markers of biological activity of exogenous IFN-β. We hypothesized that therapeutic plasma exchange (TPE) can restore the ability of IFN-β to induce the MxA mRNA expression and that maintenance plasmapheresis can sustain the bioavailability of IFN-β., Material and Methods: Eligible patients underwent 4 primary separate plasma exchange sessions. After the induction TPE sessions, they were transferred to maintenance plasmapheresis. Bioactivity of IFN-β was expressed as in vivo MxA mRNA induction in whole blood using RT-qPCR., Results: Six patients with low IFN-β bioavailability detected by the MxA mRNA response were included. Four patients became biological responders after induction plasmapheresis. In 2 patients an increase of MxA mRNA expression was found, but the values persisted below the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was transient: MxA mRNA expression values reverted to the baseline levels after 1-2 months., Conclusions: Therapeutic plasma exchange is able to restore the bioavailability of IFN-β in the majority of studied patients, but the effect of TPE on the IFN-β bioavailability was transient.

The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is the most common chronic demyelinating neurodegenerative central nervous system disease among young adults. Considering its extent in a relatively young population, multiple sclerosis determines a significant socioeconomic burden to the society due to the cost of disease modifying treatment and a lower working capacity of patients and their caregivers. It is important to control neuroinflammation in the central nervous system caused by the pathologic activity of immune cells by considering a high efficacy treatment early in the disease course in order to prevent accumulation of neurological damage and to improve long term outcomes. According to the newest clinical studies, anti-CD20 therapies have proven their effectiveness and safety in active relapsing multiple sclerosis treatment: since 2018, ocrelizumab, and, since 2023, ofatumumab have both been available as treatment options in Lithuania. Because of its high potency and safety, as well as the specific mechanism of action, ofatumumab is effective in lower doses, and, after initial training at a health care facility, it can be self-administered through subcutaneous injection. This article reviews the efficacy, safety data and treatment indications of the latest available anti-CD20 monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is most common in neurodegenerative diseases which start at advanced age. Epilepsy and multiple sclerosis are diseases that can cause cognitive dysfunction for young persons, which is un common for healthy individuals and isn't associated with neither physiological changes of advanced age nor with neuronal death. The aim of this study was to investigate cognitive features of persons with multiple sclerosis, and epilepsy and healthy controls, locate cognitive impairments and assess their relationships with disease, health and demographic variables. 90 persons participated in this study: 30 with epilepsy, 30 with multiple sclerosis and 30 healthy controls. Individuals with multiple sclerosis or epilepsy were taken from VUL SK Neurology Department and VULS SK Consultation Clinic. Cognitive functions were assessed with CANTABeclipse 3.0.0 neuropsychologic test battery. The selected tests assess 1. choice reaction time; 2. working memory capacity; 3. spatial planning and spatial working memory; 4. episodic learning and memory. The results showed impaired cognitive functioning in epilepsy and multiple sclerosis groups compared to control group. Persons with multiple sclerosis performed significantly worse on tests of choice reaction time, spatial span and spatial planning; persons with epilepsy -- on tests of spatial span, spatial planning and episodic learning and memory. Cognitive dysfunction in persons with epilepsy correlates with disease duration and seizure frequency. In persons with multiple sclerosis, physical disability and disease duration were not associated with cognitive abilities. In all three groups age, but not education, had significant influence on performance on tests of episodic learning and memory. Correlations between sex and cognitive abilities were found: control group men showed shorter reaction times, epilepsy group men per formed better on spatial working memory tasks, multiple sclerosis group women made less mistakes in choice re action time test. [ABSTRACT FROM AUTHOR]

Dimethyl fumarate is a third oral therapy approved for the treatment of relapsing-remitting multiple sclerosis. Dimethyl fumarate and fumaric acid esters have been well known for many years as they are effective for the treatment of psoriasis. However, only a few years ago, two Phase III clinical trials have shown that dimethyl fumarate is also effective and safe in the treatment of relapsing-remitting multiple sclerosis. Since 2016, treatment with dimethyl fumarate is also available and compensated for patients in Lithuania. The drug is used to treat patients with first line treatment ineffective enough, contraindicated, or when side effects appear to first line treatment. The article presents the mechanism of action of dimethyl fumarate, its efficacy and safety in clinical trials and its place in a multiple sclerosis treatment algorithm. Patients treated with dimethyl fumarate at Vilnius university hospital Santaros klinikos and treatment appointment indications are reviewed; the efficacy and safety, as well as side effects of the drug that led to its discontinuation are evaluated. [ABSTRACT FROM AUTHOR]

Introduction. Fingolimod is orally administered therapy for relapsing forms of multiple sclerosis. Phase 2 and 3 trials of fingolimod treatment led to a significant reduction in clinical and magnetic resonance imaging measures of disease activity compared to placebo or interferon beta-1a. Aim of the study. To assess relapse rate and disability progression in patients with highly active multiple sclerosis treated with fingolimod in Vilnius Multiple Sclerosis center. Materials and methods. 92 patients with highly active multiple sclerosis were included in the study. All patients were treated with fingolimod in Vilnius Multiple Sclerosis center in March 2017. Relapse rate was assessed two years before and during treatment with fingolimod. The EDSS was assessed two years before starting fingolimod, during the first dose of fingolimod and during the last visit in MS center. Results. 98.9% of patients were pre-treated with other disease modifying drugs. Mean duration of fingolimod treatment for all patients was 16.7±12.2 mths; for those who were treated more than 12 mths, mean duration was 23.7±11.0 mths. Relapse rate during two years was significantly higher in patients receiving first-line treatment than in fingolimod treatment - 2.2±0.9 and O. 6±0.8 retapses respectively (p<0.001). Mean EDSS deteriot rated by 0.99±0.81 points in patients receivmg first-line treatment and by 0.13±0.41 points in fingolimod treatment (p<0.05). Disability progression was significantly higher in patients with higher retapse rate receivmg first-line treatment for two years (r=-0.29, p=0.033), while in patients on fingolimod treatment this relation was not significant (p>0.05). Conclusions. Retapse rate and disabiltty progression were significantly lower in patients on fingolimod treatment than in patients receiving first line therapy, as assessed in two-year period. [ABSTRACT FROM AUTHOR]

Tumor-like multiple sclerosis is one of the rare variants of multiple sclerosis. It presents with a large intracranial lesion, more than 2.0 cm in diameter, with mass effect, perilesional edema, and/or ring enhancement. Diagnostics is challenging and invasive methods are often used. A case of tumor-like multiple sclerosis is presented in this paper. The diagnosis was established without a biopsy. Relapsing-remitting course developed in less than six months. Also most recent studies regarding tumor-like multiple sclerosis are discussed, with special focus on diagnostics and treatment options. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. It is usually progressive and causes irreversible damage to the central nervous system leading to life long neurological disability. Are lapsing remitting form of the disease occurs initially in 85-90% patients. However, secondary progressive course of multiple sclerosis develops within 10-15 years in most cases. This article reviews the treatment of multiple sclerosis with monoclonal antibody natalizumab. Clinical trials provided a level evidence of natalizumab efficacy for treatment of relapsing remitting and secondary progressive multiple sclerosis. Natalizumab significantly reduces annual relapse rate and progression of disability as well as development of new demyelinating and contrast enhancing lesions of the central nervous system. Natalizumab, is well tolerated, serious side effects are rare. Patients on natalizumab treatment fall into higher risk category for progressive multifocal leuconcephalopathy, which is an opportunistic infectious disease of the central nervous system. The article provides recommendations and algorithms for stratifying the individual risk of progressive multifocal leucoencephalopathy and further patients' monitoring aiming to reduce the frequency and consequences of this complication. There is also a re view of patients treated with natalizumab in Lithuania, Vilnius University Hospitals Santariskiu klinikos Centre of Neurology. [ABSTRACT FROM AUTHOR]

Background. Subjective fatigue as well as subjective cognitive impairment are very frequent complaints reported by patients with multiple sclerosis (MS). The question how these subjective complaints are related to objective cognitive functions (CF) is not finally clear therefore investigations in this field are relevant. There is no enough data in Lithuanian MS population compared with healthy controls also. Objectives. We aimed to characterize relation ships between subjective self reported fatigue/cognitive im pairment and objective fatigue/depression/anxiety/cognitive impairment in the presence of MS. Inorder to high light specific features of these relation ships the same analysis was carried out for control group of healthy subjects. Study group and meth ods. The study included 88 patients with MS (mean age 40.90±11.05). 43 patients had relapsing remitting MS (mean age 33.65±9.24). The rest 45 had secondary progressive MS (mean age 47.82±7.72). All patients were investigated in Vilnius University Hospital Santariskiu klinikos. Inclusion criteria were as follows: MS diagnosis established using McDonalds 2005 revisited criteria compatible with reviewed McDonalds 2010 criteria, concomitant diseases were excluded, patients did not use antidepressants and anxiolythics during one month period. Control group consisted of 40 healthy subjects (mean age 36.68±11.38). Depression and anxiety was measured by means of Hospital Anxiety and Depression Scale (HAD). Fatigue was measured by means of Fatigue descriptive scale (FDS). Finally general disability was estimated using Expanded disability status scale (EDSS). Results. To find how CF relates to objective depression/fatigue/anxiety we have built several linear regression models with for ward selection. Models were built for MS and control groups separately. In each of the models one of cognitive function tests acted as dependent variable mean while list of in dependents included objective depression, fatigue, anxiety and additional factors to account for their possible influence 5.In consequence of this analysis we have obtained that in MS group none of the cognitive function tests was related to objective fatigue or anxiety how ever there was a series of tests related to objective depression (FPT, RAVLT&lowbar;A6, RAVLT&lowbar;A3, RAVLT&lowbar;A4, RAVLT&lowbar;A6; in all cases regression coefficients were negative and ranged from-0.596 to -0.147; p<0.05). In case of control group RAVLT&lowbar;6, RAVLT&lowbar;A7 and RAVLT&lowbar;recogn depended on objective fatigue and only one test (TMB) depended on depression (regression coefficient 3.466; p<0.05). In the same way exploring relationship of cognitive function with subjective cognitive impairment and subjective fatigue we obtained that in MS group there was no relationship between objective cognitive function and subjective complaints at all. However in control group RAVLT&lowbar;A6 results depended on subjective fatigue (regression coefficient -0.371; p<0.05). Finally we have calculated partial correlation coefficients 6 between subjective fatigue/cognitive impairment and objective depression/anxiety/fatigue. In MS group subjective fatigue significantly correlated with objective fatigue (r=0.447; p<0.001). In control group we did not observe significant correlations at all. Conclusions. Our findings suggest that in presence of MS objective cognitive functions are related to depression how ever it does not seem that they are related to fatigue (neither objective nor subjective). In the absence of MS, results are, conversely, more influenced by fatigue (objective and subjective) than depression. Since in MS group objective fatigue significantly correlated with objective one, we can state that in the light of disease subjective complaints are in formative. This is not the case in the absence of MS as in healthy controls. [ABSTRACT FROM AUTHOR]

Introduction. Recent studies demonstrate relationship between type of multiple sclerosis (MS) and cognitive dysfunction (CD). It is also known that cognitive dysfunction depends on the other factors such as number of demyelinated lesions and local atrophy detected in brain magnetic resonance imaging (MRI). At the very beginning of the disease cognitive alterations might be the only markers indicating impairment in MS. Progression in cognitive dysfunction despite stable values calculated according Expanded disability status scale, EDSS, shows MS progression itself, therefore studies in this field are very relevant. Different patterns of cognitive alterations and their expression in relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) are revealed. Determination in cognitive and MRI markers differences between RRMS and SPMS could be helpful in distinguishing forms of MS additionally in clinical examination. Despite stability in physical examination, progression in CD shows that MS treatment potentially is not enough effective and requires revision in selection of disease modifying therapy more effective as possible. Goals. In this study we sought to compare patients having relapsing-remitting (RR) MS to those having secondary-progressive (SP) MS with respect to congnitive impairments and investigate the relationship of cognitive dysfunction with linear MRT markers, number of lesions and as well as type of MS. Methods. The study involved 43 patients with established RR (mean age 33.65±9.24) and 45 patients with established SP (47.82±7.72) MS. All patients were investigated in Vilnius University hospital "Santariškių klinikos". Inclusion criteria were as follows: MS diagnosis established according McDonalds revisited 2005 criteria, compatible with reviewed McDonalds 2010 criteria, concomitant diseases were excluded, patients did not used antidepressants and anxiolythics during one month period. In order to assess cognitive functions the cognitive tests battery was applied. Working memory was tested by performing Digit Span Forwards Test (DSf), speed of psychomotor reactions was detected by using Digital Symbol Substitution Test (DSST), Trail Making Test A (TMT A), frontal functions were tested by Trail Making Test B (TMT B), Five Point Test (FPT), Letter Fluency Test (DAS), Category fluency Test, verbal memory - Rey Auditory Verbal Learning Test (RAVLT), visual memory - Rey-Osterrieth Complex Figure Test (ROCFT). Brain MRI T2W and T1W lesion load was calculated. Linear MRI parameters to measure local atrophy were applied: width of third ventricle, bicaudatus index, bifrontal index, Hucmann index, index of frontal atrophy, Evans index and index of corpus callosum. Results. Comparison of RR and SP groups with respect to congnitive function has shown that there were differences with respect to all tests but* DSF test (4.88±0.98 (RR) vs 5.20±3.47 (SP); p=0.478). Comparison with respect to linear MRT markers did not produce difference only in case of bifrontal index (1.86±0.23 (RR) vs 1.86±0.22 (SP); p = 0.978). Looking for the best predictor of type of MS results were as follows. In case of cognitive tests the best predictive ability was demonstrated by RAVLT4 (area under receiver operator curve = 0.884; p<0.001) and DSST (area under receiver operator curve = 0.873; p<0.001) whereas in case of linear MRT markers bicaudalus index was the most informative one (area under receiver operator curve = 0.864; p<0.001). Cognitive function tests correlated with MRT markers (maximal correlation was observed between DSST and bicaudalus index: r=-0.570 (p<0.001)) as well as number of MRI lesions (maximal correlation was observed with TMTA: r=0.339 (p<0.001) however binary variable indicating MS type was most frequently retained in stepwise linear regression models for prediction of cognitive dysfunction by MRT markers, number of lesions and MS type. Conclusions. Our results confirm that cognitive dysfunction in MS are related to linear MRT markers, number of lesions and type of MS, however in SPMS the alterations are expresssed more. Slowing in verbar learning, speed of psychomotor reactions and decreased attention are the mostly affected domains of CD in MS. Rey Auditor Verbal Learning Test, RAVLT(4), and Digital Symbol Substitution Test, DSST, are the most prominent tests when distinguishing between RRMS and SPMS forms. Linear MRT marker bicaudalus index was the most informative in discrimination between RR and SP MS forms. [ABSTRACT FROM AUTHOR]

Background. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of central nervous system that is the major course of the disability of young adults. Cognitive dysfunction has negative impact on patients' daily activities, their ability to work, drive, maintain normal social relationships and therefore significantly worsen the patient's quality of life. Patients and methods. A prospective research was performed in Vilnius University Hospital Santariskiu Klinikos Centre of Neurology in 2010 - the first study assessing cognitive function in patients with multiple sclerosis, using an automated computerized neuropsychological test battery CANTAB (Cambridge Neuropsychological Test Automated Battery). There were 20 subjects with clinical definite MS and 20 healthy control subjects participating (>18 years old). Every subject was given CANTAB (Cambridge Neuropsychological Test Automated Battery) tests, evaluating choice response speed, spatial planning, spatial working memory, episodic memory, remembering and working memory capacity. Four cognitive tests were performed: choice reaction time (CRT), spatial span (SSP), Stockings of Cambridge (SOC) and Paired Associates Learning. Results. Choice reaction time: patients 0.431±0.106426 seconds, healthy controls 0.303±0.046620 seconds (p-value 0,000). Healthy persons have made an average of 0.45±0.686 errors per 100, patients have made 1.6± 1.818 errors per 100 (p-value = 0.012). Attention capacity: for patients 5.2±0.696 objects and 6.6± 1.095 objects for healthy controls (p = 0.000). Problems, solved with minimum number of turns: patients 6.74±2.207 problems, healthy controls - 8.15±2.159 problems (p = 0.051). Movements of the figures used to solve problems at all levels: for patients - 18.9868±2.50205 movements, for healthy controls with average 17.2875±2.05560 movements (p = 0.026). Number of errors made in PAL test: patients have made 35.45±38.627 errors, healthy persons 12.55±25.938 errors (p = 0.034). How many of the tasks solved correctly the first time in the PAL test: patients the first time solved 4.95±1.317 tasks, healthy persons 6.35±1.089 tasks (p = 0.001). The total number of times the test was repeated before PAL test was solved correctly: patients 17.1±6.561 times, healthy persons - 11.5±4.059 (p = 0.002). Number of boxes correctly showed immediately after the first presentation in the PAL test: patients - 15.70±5.069, healthy controls - 20.80±3.679 (p = 0.001). The strongest negative statistically significant correlation between EDSS value and attention capacity (correlation coefficient -0.522, p-value = 0.001). Statistically significant negative correlation seen between physical disability and this criterion - the number of tasks correctly solved the first time in the PAL test (correlation coefficient -0.477, p-value = 0.002). The strongest statistically significant correlation seen between duration of disease and reaction rate (r = 0.414, p = 0.008), attention capacity (r = - 0.395, P = 0.012) and the number of tasks correctly solved the first time in the PAL test (r = -0.400, P = 0.011). Conclusions: 1) Cognitive functions in MS patients are significantly worse than in the control group. 2) Cognitive functions rates significantly correlated with physical disability (EDSS scores). The strongest correlation was with attention capacity and speed of reaction. 3) Duration of the disease correlates with these cognitive functions: reaction speed, attention capacity and some rates of episodic memory (there is no strong correlation); duration of disease has no correlation with frontal functions. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of central nervous system that is the major course of the disability of young adults. Cogiivim pairment can occur even in early stages of MS and also in clinically isolated syndrome (CIS). As disease modifying drugs (DMD) can at ten u ate inflammatory processes and prevent brain atrophy, they may also have positive benefits oncognitivedys function in MS patients. Clinical trials demonstrate that interferon beta and natalizumab positively affect cognitive functions in MS patients. Most patients with relapsing multiple sclerosis had stable cognitive performance during 10 years of pro spective evaluation, some of which may be related to the therapeutic effect of glatirameracetate. There is clear evidence that early DMD treatment has positive effect on cognitive functions, until clinically isolated syndrome has not converted to definite MS. Immunosupressants (mitoxantrone and cyclophosphamide) can also positively affect cognitive functions in MS. Further studies are needed for de tailed evaluation of DMD effect on cognitive dysfunction in MS. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is a major course of disability inpatients with multiple sclerosis (MS). The prevalence of cognitivedys-function (CD) is estimated up to 65% MS patients. Natural history studies suggest that CD develops early in MS even in a clinically isolated syndrome and it is not likely to remit. Patients with MS who have cognitive impairment most commonly display deficits in the cognitive domains of memory, learning, attention, and information processing. In diagnosing CD in a patient with MS, it is important first to recognize and to treat the common comorbidities of fatigue, anxiety and, depression. The article describes physical and CD correlations with magneticresonance imaging (MTI) parameters: T2 burdenlesion, T1 "black holes", and brain atrophy. The value of whole brain atrophy and regional brain atrophy is reviewed. Newer imaging techniques to evaluate potential relation ships between cognitive dysfunction and brain pathology are described. Magnetization transfer imaging (MTI), diffusion tensor MRI (DT-MRI), positronemission tomography (PET), single-photonemission tomography (SPET), functional MRI (fMRI), and MR spectroscopy are the methods providing additional valuable information about brain pathology and its correlations with cognitive tests. MRI techniques provide specific information and ideally should be used for monitoring MS evolution, physical and cognitive disability as well. Data from longitudinal studies concerning MS progression is presented. The article provides results from two pilot crossectional studies performed in Vilnius University hospital Santariškiūklinikos Department of Neurology concerning CD in MS and relationship between brain MRI focal changes, parameters of brain atrophy and disability. Routine cognitive testing would be helpful to evaluate CD. As worsening cognitive impairment may indicate progressive disease course in the absent of increasing physical disability, individual MS patient monitoring and the treatment to delay disease progression and cognitive decline progression is obligatory also. [ABSTRACT FROM AUTHOR]

Manifestations of cognitive, affective and psychotic disorders and actuality of their differentiation in multiple sclerosis patients are described in the article. The cognitive disorders influence on the quality of live of MS patients is tremendous. Moreover, cognitive disorders negatively affect the ability of patients to adhere therapeutic protocols and to benefit from the most recent disease management advances. Depression, bipolar affective disorder, pseudobulbar affect and psychosis are pointed as not uncommon in MS. Prevalence, diagnos tics and clinical correlates of such disorders are revealed. Cognitive impairment and main cognitive domains — attention and processing speed, executive functions, short term working and long term memories — affected in MS patients are discussed. Relation of cognition to other aspects of MS — physical disability, duration of illness, disease course, genetics and medications — are summarised. Natural history of cognitive changes — the onset and manifestation in clinically isolated syndromes — is mentioned. Significance of cognitive impairment in MS, its detection and management are important. The perception of cognitive assessment as costly, time-consuming, complicated and difficult to interpret leads to the situation that fails to incorporate cognitive testing into standard clinical evaluation of patients with MS. Summary of recommended therapy methods, pharmaceutical and nonpharmaceutical, are summarised suggesting that disease modifying drugs may help to preserve cognitive functions in MS patients. Continual professional education is needed to raise awareness of the importance of cognitive impairment in patients with MS. [ABSTRACT FROM AUTHOR]

Clear definitions of multiple sclerosis course are essential because clinicians need them before they can assign treatment to patients, and from a research perspective they help to frame and interpret all clinical data. Rapidly progressive disease course is needed to be recognized as earlier as possible in term to shift immunomodifying therapy with interferon to more aggressive treatment with immunosuppressant mitoxantrone. Reasons of possible suboptimal responders to early disease modifying treatment are analyzed, describing potential influence of patient precise regiment of treatment, appearance of neutralizing antibodies against interferons beta and their influence to clinical course of the disease progression. This article discusses the methods of monitoring disease progression using disability scales, relapses and MRI and reviews the clinical efficacy and tolerability of multiple sclerosis modifying therapies. It describes immunosuppressant mitoxantrone, gives us information about its chemical structure, pharmacokinetics and mechanism of action. Preclinical and clinical data are widely described reviewing its use to patients with a suboptimal response to high-dose interferon therapy or those with rapidly progressive disease. Recommendations of mitoxantrone for multiple sclerosis in clinical practice are provided. Because mitoxantrone was introduced for the treatment of malignant multiple sclerosis into clinical practice since 2005 in Lithuania, we presented main demographical characteristics of multiple sclerosis patients treated with mitoxantrone during the period 2005-2007, some experienced adverse reactions, and potential benefit of this immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Background. Various clinical trials have shown that interferon beta (IFN - beta) therapy is effective in patients with relapsing - remitting multiple sclerosis (RRMS). It has been proved that IFN beta significantly reduces relapse rate, slows the progression of the disease, and suppresses the formation of new foci of demielinisation in central nervous system. However the impact of disease modifying treatment on emotional state, fatigue and quality of life (QoL) has not been widely investigated yet and results of various studies are contradictory. Therefore the aim of this research was to assess the influence of IFN - beta therapy on emotional state, fatigue and quality of life in patients with multiple sclerosis. Materials and methods. Only patients with RRMS were included in this study. Two groups of patients - 31 patient who had not been treated with IFN beta (IFN- group) and 29 patients that had been treated with IFN beta (IFN+ group) were investigated. The group of 30 healthy controls (control group) was also questionnaired. The groups did not differ in age and sex. Participants were interviewed and then they answered Hospital Anxiety and Depression scale (HAD), Fatique Descriptive Scale (FDS), 36-item Short-Form Health Survey (SF-36) in order to assess their emotional state, fatigue, and quality of life. Disability status in multiple sclerosis patients was evaluated using Expanded Disability Status Scale (EDSS). Patients with EDSS score = 6.0 were excluded from the futher research. Results. Physical health measure (PCS, SF-36) signifi- cantly differed between the groups with the highest score (that is with the best Q0L) in control group and the lowest score in RRMS patients without IFN - beta therapy. There was also a significant diference comparing Mental health measure (MCS, SF-36) between controls and INF- group, and between IFN+ and IFN- groups showing the poorest mental health in IFN- group. The level of anxiety (the mean score of HAD Anxiety subscale) was significantly higher in patients without IFN - beta therapy (8.3) in comparison to controls (5.6; p = 0.005). The level of anxiety was significantly higher in patients without IFN - beta (8.3) than in those receiving IFN- beta (6.1; p = 0.02). The level of depression (the mean score of HAD Depression subscale) was significantly higher in patients without IFN- beta therapy (5.1) than in controls (3.1; p = 0.04). However there was no significant difference between the groups of patients with RRMS. Assessing fatigue related with multiple sclerosis we found that the level of fatigue (the mean score of FDS) in IFN - group (6.7) was substantially higher than in IFN+ group (3.7; p = 0.008). Multiple linear regression analysis revealed major determinants of composite physical and mental health summary scores in groups of RRMS patients. Our research demonstrated that fatigue, anxiety, depression and disability were independently associated with impaired QoL in RRMS. The most important determinants of physical health in IFN+ group were disability status (beta -0.443, p < 0.05) and anxiety (beta = -0.378, p < 0.05) whereas in IFN - group multiple sclerosis related fatigue had the main role (beta = -0.526, p < 0.01). Depression in IFN+ group (beta = -0.508, p < 0.05) and both depression (beta -0.363, p <0.05) and anxiety (beta = -0.476, p < 0.01) in IFN- group were significant determinants of mental health mea- sure. Conclusions. Treatment with IFN - beta improves general physical and mental health measures in patients with RRMS. There was no significant influence of IFN - beta therapy on the level of depression. INF - beta therapy may reduce the level of anxiety in RRMS. Treatment with IFN - beta was also associated with significantly lower rates of multiple sclerosis related fatigue which has a substantial influence on QoL in multiple sclerosis patients. [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NFL) is a structural neuronal protein highly expressed in large myelinated axons. Axonal damage leads to increased NFL levels in cerebrospinal fluid and blood. Therefore, it could be a potential diagnostic biomarker for various neurological disorders, especially caused by neurodegeneration and inflammation. New sensitive immunoassays for NFL measurement in the blood offer possibilities of monitoring disease progression and assessing treatment response. An increasing amount of data suggests that NFL could also be a prognostic marker for many disorders. The purpose of this article is to review the literature on the role of NFL in the context of dementia, amyotrophic lateral sclerosis, HIV-associated neurocognitive disorders, multiple sclerosis, and other neurological diseases. [ABSTRACT FROM AUTHOR]

The novel coronavirus 2019 (COV1D-19) and the subsequent pandemic present a challenge to neurologists treating patients with multiple sclerosis (MS) worldwide. Many national professional bodies have responded rapidly by issuing guidelines for the COVID-19 pandemic, primarily focused on MS disease-modifying therapies (DMTs). In this article, we review implications of COVID-19 for people with MS, including general health advice, the risk of respiratory infections, basic recommendations for relapse management, MS treatment, including disease-modifying therapies, and medical services for MS patients during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic inflammatory autoimmune demyelinating disease of the central nervous system affecting myelin of the gray and white matter and causing axonal loss. Multiple sclerosis is the leading cause of acquired neurological disability in the group of young patients. As the incidence of the disease is increasing, the most common signs (optic neuritis, pyramidal, cerebellar, and other common symptoms manifesting during the relapses) are easily recognized by the medical professionals. However, there are symptoms nonspecific for multiple sclerosis: sensory (Lhermitte sign, Oppenheim hand), visual phenomena (of Pulfrich and Uhthoff), paroxysmal symptoms, movement disorders, epilepsy, sleep, and thermoregulation disorders that are associated with demyelinating lesions in the central nervous system (cervical segments of the spinal cord, hypothalamus, temporal lobe, etc). We review these unusual symptoms of multiple sclerosis, analyze pathophysiological mechanisms and clinical features, and shortly introduce some treatment options. We also present two clinical cases with unusual multiple sclerosis symptoms that were diagnosed in Vilnius Multiple Sclerosis Centre in 2011. [ABSTRACT FROM AUTHOR]

Introduction. Most of patients with multiple sclerosis are initially diagnosed with relapsing-remitting form of the disease. It is characterized by clearly defined attacks that are followed by periods of partial or complete recovery (remissions). The presence of a relapse, its clinical presentation, severity, and occurrence rate of relapses are the main indicators of the disease activity as well as the effect iveness of the treatment whereas the rel at ionship between the relapse and its severity, rate of progression, and other indicators of long-term disability is still debatable. Aim of the study. To evaluate the ef-ect of re-apses and immunomodulatory treatment on the neurological disability in multiple sclerosis patients. Materials and methods. We investigated 60 multiple sclerosis patients treated for a multiple sclerosis relapse in Vilnius University Hospital Santariskiu Clinics and 30 multiple sclerosis patients in a remission stage. The disability was assessed using the Extended Disability Status Scale (EDSS). The choice of relapse treatment was based on the international recommendations. Results. The relapse increased the mean EDSS score by 0.49 points assessing EDSS 3 months before the relapse and 3 months after its treatment. 48.3% of patients were treated with methyl- prednisolone, 41.7% with both methylprednisolone and plasmapheresis, and 10% only with plasmapheresis. Pa tients treated with methylprednisolone pulse therapy had EDSS score by 0.92±0.31 points lower than patients treated with methylprednisolone pulse therapy and plasmapheresis (p<0.05). A significant decrease of EDSS score was observed administering 5 g of methylprednisolone while the administration of 3 g and 4 g of methylprednisolone decreased EDSS score by 0.85±0.08 and 0.67±0.21 points respectively (p<0.05). The increase of EDSS score in patients who had used immunomodulatory therapy before the relapse was 1.28±0.61 points compared to 1.91± 1.24 points in patients who had not used immunomodulatory therapy (p<0.05). No significant differences in EDSS scores before, during, and after the relapse were found between the patients who had biologically active interferon beta and the patients who had partly active/ inactive interferon beta (p>0.05). Conclusions. In Vilnius University Hospital Santariskiu Clinics, clinically milder relapse episodes were treated only with methylprednisolone pulse therapy, while more severe cases were treated with methylprednisolone pulse therapy combined with plasmapheresis. More prominent disability regression was observed in patients treated with higher dosages of methyl- prednisolone. Re -apses were milder in patients who had used immunomodulatory therapy before the relapse. Biological activity of interferon beta had no significant effect on the severity of the relapse and the rate of disability regression after the relapse. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic inflammatory autoimmune demyelinating disease of the central nervous system, affecting myelin of the gray and white matter and causing axonal loss. Multiple sclerosis is the leading cause of acquired neurological dis ability in the young persons' group. Long-term studies of the natural disease course showed that the average time of relapsing-remitting disease progression to secondary progressive course is about 10 years and approximately half of untreated patients will require ambulatory assistance within 15 years of disease. The etiology of multiple sclerosis is still unknown, therefore the treatment that could cure the disease has not been established yet. Nevertheless, the discovery of disease-modifying therapy pro vides many benefits: prevents new relapses, progression of dis ability, etc. Relapsing-remitting multiple sclerosis patients are successfully being treated with the I-line therapy (interferons beta and glatiramer acetate parenterally) for more than 15 years. In 2011 the first oral drug fingolimod was approved by European Medicines Agency and is available as II-line therapy for multiple sclerosis patients with very active disease despite treatment with interferons, as well as those with rapidly progressive disease course. This article presents the algorithm of multiple sclerosis treatment and introduces the new drug fingolimod: mechanism of action, pharmacodynamics, pharmacokinetics, efficacy and safety in clinical trials, treatment initiation, first dose monitoring recommendations and its place in multiple sclerosis treatment algorithm. The new oral therapy (teriflunomide, BG-12, laquinimod and cladribine) created for multiple sclerosis treatment is also introduced and new treatment perspectives are dis cussed, brief summary of patients treated with fingolimod in VUH Santariskiu klinikos, indications of drug prescription, monitoring of the drug efficacy and safety are also presented in this paper. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that is the major course of the disability of young adults. The relapsing-remitting multiple sclerosis can be treated with immunomodulatory drugs - interferon-beta (IFN-β) and glatiramer acetate. One of the major clinical problems with the interferon-beta is the development of binding (BAB's) and neutralizing antibodies (NAB's). It is probable that the presence of Nabs, especially in persistently high titers, is associated with a reduction in the radiographic and clinical effectiveness of IFN-β treatment. We review the features of the development of NAB's, the factors influencing the development, clinical importance of NAB's and EFNS, and AAN guidelines regarding the assessment of their clinical and radiographic impact. We describe the results of our pivotal trial that studies the binding antibodies against IFN-β and their clinical impact. [ABSTRACT FROM AUTHOR]