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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]

Autoimmune encephalitis (AE) is a group of inflammatory brain disorders involving the central nervous system (CNS) that currently includes more than 10 distinct types of the disease. Nowadays, AE has been identified as the second most frequent cause of encephalitis after infectious etiology. Over the past decade, the clinical spectrum of AE has expanded, and new clinicopathological entities are increasingly being identified. Also, our understanding of disease mechanisms and treatment strategies is rapidly evolving. In clinical practice, neuronal antibodies remain the most significant diagnostic marker currently available. Prognosis of AE varies greatly depending on the subtype and the time of immunotherapy initiation. In general, AE patients respond well to immunotherapy, therefore cognitive functions might be fully or at least partially restored. Cumulative research on the AE pathogenesis has resulted in a paradigm shift in clinical decision-making for these patients. In this article, we present two clinical cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-contactin-associated protein-like 2 (anti-CASPR2) encephalitides and focus on the essential aspects of these conditions based on the latest scientific literature. [ABSTRACT FROM AUTHOR]

Bacterial meningitis remains a disease associated with high mortality. Thus, in some hospitals admission of most patients presenting with bacterial meningitis to the intensive care unit (ICU) was a standard procedure. However, ICUs require advanced technologies and highly specialized personnel. Since both economic and human resources are scarce, countries are attempting to develop the most accurate ICU admission criteria that can minimize over- and undertriage. The guidelines designed so far mainly suggest admitting patients to ICU based on their neurological status. However, since neurological condition is not the only factor contributing to the outcomes of bacterial meningitis, over- and undertriage cannot always be avoided. In this article, we present two cases of bacterial meningitis: an elderly man who was denied ICU care since his consciousness was only mildly altered, and a woman who was admitted to ICU because she was diagnosed with meningococcus meningitis. We will also review some literature regarding prognostic factors for bacterial meningitis in an attempt to distinguish valuable criteria for ICU admission. [ABSTRACT FROM AUTHOR]

We present two patients with neuroborreliosis initially considered as demyelinating disease of the central nervous system. The first patient developed facial numbness on the right side, diplopia and dizziness that lasted about half a year. Magnetic resonance imaging of the brain showed confluent hyperintense lesions and visual evoked potentials revealed prolonged latencies of the P wave. The second patient developed weakness, numbness and pain in the left hand that lasted several weeks. Magnetic resonance imaging of the cervical spine demonstrated hyperintense lesions commonly found in multiple sclerosis. In both cases, positive serology for Borrelia burgdorferi was an indicator of past infection. However, the cerebrospinal fluid analysis showed proteinorrhachia and lymphocytic pleocytosis and the presence of specific IgM and IgG antibodies in the cerebrospinal fluid confirmed the diagnosis of neuroborreliosis. The clinical symptoms, abnormal cytological, biochemical and immunological cerebrospinal fluid findings in combination with good response to antibiotic therapy confirmed the diagnosis of neuroborreliosis in our patients. [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]

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]

There are continually produced new generic drugs in the world. When the patent of a classical small molecule drug expires generics may be marketed if their therapeutic equivalence to the original drug has been established. Conventional generics for an orally administered drug are considered to be therapeutically equivalent to the reference once pharmaceutical equivalence and bioequivalence have been established and they do not require formal clinical efficacy and safety studies. Such pathway still does not exist for complex drugs. An extensive comparison of complex drugs follow-on and reference products needs to be performed showing the products to be similar in quality, safety, and efficacy with an emphasis on immunogenicity issues. There are a lot of discussions about the complex drug “families", such as the iron-carbohydrate drugs, low molecular weight heparins, liposomal drugs, and the glatiramoids. These groups are quite different, therefore experts constantly discuss about the new approaches for regulatory evaluation of non-biological complex drug follow-on products. The article particulary examines glatiramoids, their structural features, mechanism of action, generic drug development, manufacturing process, and quality control standards. [ABSTRACT FROM AUTHOR]

The diagnosis of MS requires demonstration of dissemination of demyelinating lesions in both time and space using strict clinical and paraclinical criteria. However, many other diseases exhibit dissemination both in time and space, thus the diagnosis of MS should be questioned when clinical or laboratory findings are unexpected or atypical. Great care must be taken to exclude treatable etiologies (spinal tumors, arteriovenous malformations, cavernous angiomas and other). The patients in these cases were initially misdiagnosed with MS or demyelinating disease of the central nervous system, but the cervical and thoracic spine MRI revealed another disease of the spinal cord: in the first case - epidural arachnoid cyst with spinal cord compression, in the second - spinal cord arteriovenous malformations, in the third-syringomyelia with Arnold-Chiari malformation and the fourth -dysplasia of the central nervous system (syringomyelia, syringo-bulbia and peri ventricular cysts). In the first case the arachnoid cyst was surgically removed and in the following months the patient fully recovered. In the second and third cases - it was too late for surgical treatment due to delayed diagnosis. In the case with syringomyelia surgical treatment was recommended and the patient will undergo planned operation. The patients in the present cases were misdiagnosed with MS or demyelinating diseases of the central nervous system, thereby inducing a therapeutic delay of several months or years that could have been prevented if adequate imaging (spinal MRI) had been carried out after their initial presentation. These cases illustrate that, in order to achieve a correct diagnosis in patients presenting with symptoms similar to MS, a careful interpretation of medical history and signs at the time of physical examination is essential. [ABSTRACT FROM AUTHOR]

The etiology of multiple sclerosis is unknown. It is likely to be multifactorial disease and the genetic factors play a role in it's pathophysiology. Human leucocyte antigen system is known to contribute to disease susceptibility. Its alleles are responsible for the dis ease development and relapses frequency and they are different according to geografic location. As the mode of inheritance is un known, multiple scle rosis was attributed to the multiplex group of non-mendelian diseases. It is determined by the series of genes situated in the different genetic regions, their effects are summarizing and acting with different environ mental factors. Among relatives of multiple sclerosis patients, the risk of be ing affected is influenced by the degree of identity of the ge nome. The age-adjusted life time risk is higher for first-de gree than for sec ond-de gree rel a tives. There is concordance for age at on set for affected parent-child group and siblings and the clinical course of multiple sclerosis is similar between siblings. In this article we discuss two clinical cases of familial multiple sclerosis: in the first case diagnosis of multiple sclerosis was determined for siblings, in the second diagnosis of multiple sclerosis was stated for mother and for her son diagnosis of acute disseminated encephalomyelitis was as certained. [ABSTRACT FROM AUTHOR]

Cladribine is a disease-modifying drug used for the treatment of the highly active relapsing-remitting form of multiple sclerosis. Cladribine is a purine nucleoside analogue which selectively targets lymphocyte subpopulations involved in the pathogenesis of multiple sclerosis, and therefore it is classified as an immune reconstitution therapy drug. Two short courses of cladribine tablets given over two years significantly reduce the multiple sclerosis relapse rate and disability progression. For most patients, the effect persists in the third and the fourth year. This makes cladribine convenient for patients with multiple comorbidities, difficulties in adhering to their prescribed treatment regimen, those planning a pregnancy, or those for whom long-term immunosuppression is undesirable. Cladribine tablets are denoted by good safety characteristics, with the most prominent adverse effect being lymphopenia, which does not lead to an increased risk of infections other than Herpes zoster. However, in clinical practice, there are a number of issues related both to the initial administration of cladribine tablets and the strategy of treatment in different clinical situations during the first-to-fourth years of treatment, and particularly after the fourth year. Although there are no contraindications for additional courses of cladribine tablets, the product information does not provide detailed guidance on their continued use. During more than five years after the approval of the medicinal product, the new clinical trial data and the Real-World Evidence (RWE) on the efficacy and safety of cladribine tablets have become available, based on which, several national and international expert panels, as well as the Lithuanian Association of Neurologists, have issued guidance on the use of cladribine tablets reviewed in this article. Upon reactivation of the disease, additional courses of cladribine tablets or other disease-modifying therapies may be prescribed, depending on various factors related to the severity of the relapse, patient characteristics, and previously used medications. If the patient’s condition remains stable after the fourth year, extension of the treatment-free period with the structured monitoring approach could be appropriate. [ABSTRACT FROM AUTHOR]

Immune reconstitution therapy (IRT) is a relatively new and highly effective treatment option for multiple sclerosis (MS). Uncertainty regarding the development of autoimmune disorders (ADs) after some therapies remains. The aim of this study was to assess new AD development after IRT in MS patients and to describe the nature of those ADs and the time to onset. A total of 179 patients with relapsing multiple sclerosis (37 after autologous haematopoietic stem cell transplantation (AHSCT), 19 after alemtuzumab (ALE) and 123 after cladribine (CLA) treatment) over a ten year period were included in the study. ADs were observed in 6 patients (16.2%) after AHSCT, 8 patients (42.1%) after ALE and 2 patients (1.6%) after CLA treatment. ADs developed earlier after ALE infusions, but later after AHSCT except for cytopenias. Neurologists should be attentive to the development of secondary ADs after ALE and AHSCT in MS patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Approximately half of patients with multiple sclerosis (PWMS) experience sleep disorders or changes in the circadian rhythm, that may further promote the pathogenesis of multiple sclerosis. As the prevalence of chronotypes among PWMS remains unclear, we aimed to evaluate the prevalence of chronotypes among Lithuanian PWMS; to assess the relationship of chronotypes with depression, anxiety, and fatigue symptoms; and to compare these results with those of healthy controls., Methods: We enrolled 101 PWMS and 100 healthy controls. We included 130 (64.7%) and 71 (35.3%) women and men, respectively. The median age of all respondents was 39 [interquartile range (IQR) 20.75] years. Participants were assessed using general questionnaire, Horne-Östberg Morningness-Eveningness Questionnaire (MEQ), Hospital Anxiety and Depression Scale (HADS), and Shortened Fatigue Questionnaire (SFQ). Chronotypes were identified based on the total MEQ score., Results: The average MEQ scores of the PWMS and control groups were 54 (IQR 15.0) and 53.5 (IQR 13), respectively, which indicated the intermediate chronotype. There was no significant between-group difference in the prevalence of chronotypes ( p  = 0.893). In both groups, individuals with moderate evening and intermediate chronotypes showed higher average HADS depression scores ( p  = 0.022). Further, in both groups, the individuals with the evening chronotype showed the highest average HADS anxiety scores ( p  = 0.001). The PWMS group had a higher average SFQ score than the control group ( p  < 0.001). High SFQ scores were more common among PWMS who had the intermediate ( p  < 0.001) and morning chronotypes ( p  = 0.011). The fatigue level was higher among healthy individuals with the evening chronotype ( p  < 0.001)., Conclusion: The most common chronotype for PWMS and healthy controls was the intermediate chronotype. Further, in both groups, higher HADS depression and anxiety scores were associated with the evening chronotype. Fatigue was more commonly found in healthy controls with the evening, and in PWMS - with intermediate and morning chronotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jonušaitė, Sakalauskaitė-Juodeikienė, Kizlaitienė, Giedraitienė, Sereikė, Liutkienė, Kaubrys and Jatužis.)

Background: tumefactive multiple sclerosis (TmMS) is a rare subtype of a demyelinating disease that develops over time. Cases of hyperacute presentations mimicking cerebrovascular disorders have been reported; however, detailed clinical and demographic data are lacking., Methods: this study aimed to systematically review the literature on tumefactive demyelinating disorders presenting as strokes. After screening the PubMed, PubMed Central, and Web of Science databases, 39 articles describing 41 patients were identified, including 2 historical patients from our center., Results: 23 (53.4%) patients were diagnosed with multiple sclerosis variants (vMS), 17 (39.5%) with inflammatory demyelinating variants (vInf), and 3 with tumors; however, only 43.5% of cases were verified histologically. In subgroup analysis, vMS differed from vInf in several aspects. Inflammatory cerebral spinal fluid parameters, including pleocytosis, proteinorachia was more commonly observed in vInf [11 (64.7%) vs. 1 (5.2%), P = 0.001 and 13/17 (76.4%) vs. 6/23 (31.5%), P = 0.02] than that in vMS. Neurological deterioration and fatal outcomes were more commonly observed in vInf [13/17 (76.4%) vs. 7/23 (30.4%), P = 0.003, and 11/17 (64.7%) vs. 0/23 (0%), P = 0.0001] than that in vMS., Conclusions: Clinicodemographic data might aid in recognizing different subtypes of TmMS and warrant consideration of unconventional therapies because outcomes may be poor in the vInf of TmMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Neuromyelitis optica (NMO) is frequently associated with aquaporin-4 autoantibodies (AQP4-Ab); however, studies of NMO in Lithuania are lacking. Therefore, the main objective of our study is to assess positivity for AQP4-Ab in patients presenting with inflammatory demyelinating central nervous system (CNS) diseases other than typical multiple sclerosis (MS) in Lithuania., Materials and Methods: Data were collected from the two largest University hospitals in Lithuania. During the study period, there were 121 newly diagnosed typical MS cases, which were included in the MS registry database. After excluding these typical MS cases, we analyzed the remaining 29 cases of other CNS inflammatory demyelinating diseases, including atypical MS (n = 14), acute transverse myelitis, TM (n = 8), acute disseminated encephalomyelitis, ADEM (n = 3), clinically isolated syndrome, CIS (n = 2), atypical optic neuritis, ON (n = 1), and NMO (n = 1). We assessed positivity for AQP4-Ab for the 29 patients and evaluated clinical, laboratory, and instrumental differences between AQP4-Ab seropositive and AQP4-Ab seronegative patient groups., Results: AQP4-Ab test was positive for three (10.3%) patients in our study, with initial diagnoses of atypical MS (n = 2) and ADEM (n = 1). One study patient was AQP4-Ab negative despite being previously clinically diagnosed with NMO. There were no significant clinical, laboratory, or instrumental differences between the groups of AQP4-Ab positive (3 [10.3%]) and negative (26 [89.7%]) patients., Conclusions: AQP4-Ab test was positive for one-tenth of patients with CNS inflammatory demyelinating diseases other than typical MS in our study. AQP4-Ab testing is highly recommended for patients presenting with not only TM and ON but also an atypical course of MS and ADEM., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

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.