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One of the most important philosophers in the Imperial University of Vilnius in the age of Entightenment was Jan Sniadecki (1756-1830), a graduate of the University of Cracow, mathematician, astronomer, philosopher, and Rector of the Imperial University of Vilnius. Jan Sniadecki was the author of various treatises on algebra, trigonometry, geography, and philosophy. The Professor was probably the first who broadly analysed the functions of the human mind and clearly associated it with the activity of the nervous system in the beginning of the 19 th century in Vilnius. In this paper we anatyse “The Phitosophy of the Human Mind" by Jan Sniadecki (Filozofia umyslu ludzkiego czyli rozwazny wywod sit, i dziatan umyslowych, published in 1822 in Vilnius) and overview the principles of investigations on human cognition until the first half of the 19th century in Europe. [ABSTRACT FROM AUTHOR]

Although cognitive impairment is the most common symptom of Alzheimer's disease, sensory systems including visual system are also affected. Also, a visual variant of Alzheimer's disease exists. In this article, anatomical and functional changes of the visual system related to Alzheimer's disease are discussed. Also, the most typical visual disturbances connected to Alzheimer's disease are described. These impairments include decreased visual acuity, colour discrimination and contrast sensitivity, impaired motion processing, and other associated abilities. [ABSTRACT FROM AUTHOR]

Introduction. Frontotemporal dementia (FTD) is a heterogenous disease with the main feature of frontotemporal lobular degeneration. This disorder is divided into smaller subtypes that barely have anything in common apart from the simmilar brain lesion. In order to clarify the difficult diagnostics of FTD we enrolled a detailed article search on the subject. To illustrate the information found we present 3 clinical cases that each represents each subtype of FTD. In 80% of cases of the behavioural subtype of FTD these symptoms can be found: disinhibition, apathy, and lack of empathy. Other symptoms mentioned in the International consortium diagnostic criteria are common in 50% of cases. Semantic subtype can be characterized with: the difficulty in finding the right word, incomprehension of words, superficial dyslexia, and prosopagnosia. While non-fluent progressive aphasia can be diagnosed from these symptoms: agrammatical speech, difficulty in repeating words, and orobucal apraxia. Patients in suspect of FTD must undergo a detailed neuropsycological evaluation and have some radiological examination done. All patients must do an MRI of the brain which would display the degeneration process. If MRI does not show any significant changes in the brain yet sever clinical features are present, a PET scan should be considered. Only radiological testing without the neuropsycological evaluaiion is absoiutely not valid as symp-oms must correiate with the results of a MRI scan or any other radiological test. Conclusion. Our clinical cases clearly represent that each subtype has some features of another subtype. If the differentiation is too difficult, a mixed FTD diagnosis should be considered. The differential diagnostics of FTD subtypes might be useful in the future if a treatment for this disorder appears. [ABSTRACT FROM AUTHOR]

The article presents four pathomorphologically verified cases of sporadic Creutzfeldt-Jacob disease in the Neurology Department of Vilnius University Hospital Santariskiu Klinikos since 2004. The short case analysis and review of the literature are also included. Two of these cases were already published in the Journal "Neurologijos seminarai" 2004 and 2007. The diagnoses of Creutzfeldt-Jacob disease were initially suspected clinically and verified postmortem by histopathological immunohistochemical assay using monoclonal antibodies against protease resistant prion protein (PrP). The article presents clinical features, course, diagnostic examination, and preventive recommendations of sporadic Creutzfeldt-Jacob disease. [ABSTRACT FROM AUTHOR]

Normal pressure hydrocephalus (NPH) is characterized by a progressive neurological syndrome accompanied by a triad of symptoms: gait disturbances, cognitive impairment, and urinary dysfunction associated with ventriculomegaly in the absence of elevated cerebrospinal fluid pressure. NPH is one of the few causes of dementia that is potentially reversible. Not many epidemiological studies on INPH are available, so the incidence and prevalence of this disorder are difficult to determine. Several studies have reported that it was between 0 and 5 %. We report the case of normal pressure hydrocephalus and discuss clinical aspects, di agnostic procedures and treatment options. The described case demonstrates that excellent shunting results can be achieved if the duration of the disease is short and surgery is done without delay. [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]

The article describes a case of a frontotemporal dementia with parkinsonism (FTD-P). A spectrum of these neurodegenerative disorders can present as sporadic or familial FTD-P. Mutations in the gene encoding the microtubule-associated protein tau (MAPT) on chromosome 17 have been found in many kindreds with familial FTD-P. Several other kindreds with FTD-P had been linked to chromosome 17, but they had ubiquitin-positive inclusions rather than tauopathy and were associated with mutations in the gene encoding progranulin (PGRN). [ABSTRACT FROM AUTHOR]

Background. Alzheimer's disease in early stages is known as mainly amnestic disorder. Common paper-pencil tests usually don't show frontal dysfunction in mild Alzheimer's dementia, but PET studies indicate heavy beta-amyloid load in temporal and frontal lobes even in early Alzheimer's disease. Having in mind that frontal dysfunction could have even more disastrous effect on daily activities than medial temporal amnestic syndrome, there is need for more sensitive frontal functions testing which could allow to assess mild decline in frontal cognitive functions. Possible methods for this purpose are computerized cognitive tests. Aim. To evaluate frontal functions in both, Alzheimer's disease (AD) patients and healthy individuals, compare them and relate to demographic characteristics, severity of dementia and depression. Materials and methods. A prospective research was performed in Vilnius University Hospital, Santari~kiq Klinikos, Centre of Neurology in 2009 -2010. There were 66 subjects participating, 30 of which had mild or moderate AD (76.93 ± 5.01 year old; 40% men, 60% women) and 36 were control subjects (74.81 ± 5.51 year old; 39% men, 61% women). Every subject was given CANTAB (Cambridge Neuropsychological Test Automated Battery) tests, evaluating visual memory, learning (PAL, PRM tests) and frontal functions (SOC test). The degree of dementia was assesed using MMSE, severity of depression Yesavage geriatric depression scale. Statistical analysis was made using Student t test, χ² test, Pearson correlation. Results. MMSE score in AD and control groups (C) was 20.1 ± 2.8 and 28.2 ± 1.9 points respectively (p < 0.00 1). The measures of visual memory, recognition and new learning (PAL, PRM tests) were significantly worse in AD group (p < 0.05). The significant difference between groups in Soc test (spatial planning and spatial working memory) was found for these measures: mean moves made by the subject to solve problems where the solution could be reached in a minimum number of 3 moves (AD: 3.71 ± 0.59; C: 3.43 ± 0.52; p = 0.0464) and problems solved in minimum (2) moves (AD: 1.67 ± 0.55; C: 1.92 ± 0.28; p = 0.0201). A significant positive correlation of MMSE score with problems solved in minimum (4) moves (SOC test) was deterniined in AD group (p = 0.002, r = 0.55 197). There was no significant relation of frontal function and age of the subjects. Severity of depression significantly correlated with these frontal measures (SOC test): problems solved in minimum (4) moves (r = -0.35 97; p = 0.003) and mean moves made by the subject to solve problems where the solution could be reached in a minimum number of 4 moves (r = -0.2568; p = 0.0439). Conclusions. Episodic, visual recognition memory and new learning were significantly worse in AD group. Impairment of spatial planning and decision making frontal functions in AD gronp was detected only for some of the measures when compared with the control group. Further and more detail investigations of greater sample size are necessary to assess the characteristics of early frontal dysfunction in AD. [ABSTRACT FROM AUTHOR]

Conceptions of consciousness and various aspects of the term "consciousness", fundamental mind - body problem, empirical and conceptual problems of consciousness research are shortly reviewed in the first part of this article. Notions about possibble neural substrate of consciousness and cognitive and hybrid models of conscious processes are presented. Some clinical neurological disorders are indicated, which highlight the uncertainty of the notion of consciousness as indivisible unity. The question about possibility of empirical investigation of consciousness is posed and promissing experimental cognitive methods, allowing to distinguish conscious and unconscious aspects of cognitive processing are reviewed. Empirical data on possible functional utility and relevance of consciousness in cognitive processing are analysed. In the future, experimental and clinical investigations of such kind may provide an adequate explanation for nowadays vague conceptually and quite scanty empirically understanding of consciousness and its place in cognitive functions and disorders. Final part of the article is concerned with interesting and provoking data indicating that subtle disorders of conscious information processing may be accountable for some peculiarities of clinical and cognitive symptomatology in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background. Cognitive event-related potentials (in particular P300 potential) have been used in clinical practice as objective marker of cognitive function in patients with Alzheimer's disease (AD). In general, P300 potential is considered a measure of the analysis of information in human brain related to the cognitive functions. Also it is an additional objective tool for the evaluation of the response to specific treatment. The aim of our study was to assess the electrophysiological differences of P300 potential profile in two groups of patients with AD - either treated with stable dose of donepezil or treatment-naïve. Materials and methods. 68 patients with AD were enrolled into the study and divided into two groups: 1) patients recently diagnosed with AD and still treatment-naiïve (N=44); 2) patients treated with stable dose of donepezil at least for 3 months (N=24). Also 46 healthy elderly controls were enrolled into the study. Various cognitive tests were performed as well as P300 potential recording was performed for all subjects. Results. There was no statistically significant difference for P300 potential latency found between two groups of patients with AD. The statistically significant difference for P300 potential amplitude recorded at Fz position was found: the P300 potential amplitude at Fz was larger in patients treated with donepezil (p<0.02). The ratio of interpeak P300-N200 latency and P300 amplitude and P300 response time were significantly lower in patients treated with donepezil compared with treatment-naïve patients. Conclusions. The change in P300 potential latency correlates with improvement of cognitive functions in patients treated with donepezil. Cholinergic stimulation reduces the recognition time of target stimulus and enhances neural activity. Donepezil has an impact on the patients' behavior; it accelerates some neurophysiological processes and reduces response time to target stimulus. P300 potential is objective, simple and reliable instrument for the assessment of cognitive function in demented patients and cognitive response to specific treatment. [ABSTRACT FROM AUTHOR]

Background. Diagnosis of dementia is based on the cognitive dysfunction. Various neuropsychological tests are used as indexes of cognitive function. However these tests are subjective and are often difficult to interpret. Cognitive event-related potentials (in particular P300 potential) have been used in clinical practise as objective marker of cognitive function. The aim of our study was to compare the P300 potential profile in healthy elderly controls and in patients with Alzheimer's disease (AD) and to assess correlation between various cognitive tests and the P300 potential profile in patients with AD. Materials and methods. 46 healthy elderly controls and 46 patients with AD were enrolled in the study. Various cognitive tests were performed and P300 potential examination was performed (P300 peak latency and amplitude were calculated) for all patients. Results. Statistical significant difference was found between P300 potential latency and amplitude in healthy elderly controls and patients with AD (in the AD group, patients had longer P300 latency and smaller amplitude). Significant correlation was found between healthy controls age and P300 latency. Significant relationship was found between P300 latency and the following test scores: MMSE, overall ADAS-Cog scale score and also ADAS-Cog word recognition, ADAS-Cog memory total and ADAS-Cog language total score. Conclusions. P300 potential latency and amplitude significantly differs in healthy elderly controls and patients with AD. There is significant relationship between P300 latency and over-all cognitive dysfunction and working memory tests. The P300 potential is objective and simple method and can be used for the evaluation of cognitive functions. [ABSTRACT FROM AUTHOR]

Differential disorders of sensory-discriminative, affective-motivational, and cognitive-evaluative aspects of pain perception in Alzheimer's disease patients are reviewed in this article. While disfunctions of lateral and medial pain systems and corresponding sensory and affective components of pain are more thoroughly investigated in Alzheimer's disease, the role of cognitive factors of pain perception in Alzheimer's disease and even conceptual questions concerning the place of cognition in pain remains quite unclear. Results of recent fMRI, psychophysical, electrophysiological, and neuropathological studies in this field are discussed. Emerging impression from quite scanty cognitive research of pain in Alzheimer's disease is that cognitive aspects of pain could not be analysed as paralel with sensory and affective components with corresponding distinct neurobiological systems but more likely dysfunctional cognition may reveal itself at a higher level of integration of pain processing and therefore requires more subtle and intricate study designs and novel conceptual approaches to be elucidated adequately. In any case this is the problem of exceptional importance for understanding of the nature of pain experience as such, as well as for high quality and evidence based clinical management of Alzheimer's disease patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease and vascular dementia are the most common causes of dementia syndrome. These patomorphologically distinct entities are interrelated not only by dementia syndrome, but also by some risk factors, frequent and clinically significant comorbidity. ApoE ϳ4, hypercholesterolemia, arterial hypertension, diabetes meilitus, hyperhomocysteinemia are known vascular risk factors. Large longitudinal, clinico - pathological studies and autopsy series had proven the relationship between these risk factors, associated cerebrovascular pathology and Alzheimer's disease. Mechanisms by which particular vascular risk factors contribute to the pathology of Alzheimer's disease are still unknown and remain the object of experimental studies. The reduction of the cognitive potential of the brain is the most presumable role of vascular pathology in Alzheimer's disease. Mixed Alzheimer's type and cerebrovascular pathology may contribute up to 40% of dementia cases. However, there is no consensus neither regarding the diagnostic criteria of this mixed pathology nor the terminology. In clinical practice the differentiation between Alzhemier's disease, vascular dementia and Alzheimer's disease with cerebrovascular disease is difficult enough and still remains a significant problem. The correct diagnosis is important not only in choosing an appropriate therapy but also for the prognosis and prophylaxis. The relationship between Alzhemier's disease and cerebrovascular pathology as well as the most important differential issues of Alzheimer's disease and vascular dementia are discussed in this paper. [ABSTRACT FROM AUTHOR]

Averaged evoked potentials have been widely used to record the changes in electrical potential within the nervous system in response to an external stimulus. There is another distinct class of evoked potentials used in clinical practise: the endogenous or event-related potentials. These potentials can be recorded in response to an external stimulus or event but occur only when the subject is selectively attentive to the stimulus and when the subject is required to distinguish one target stimulus from another (non-target). These event-related potentials depend on the cognitive functions of the subject, thus can be used in the evaluation of cognitive functions and their disorders. Use of event-related potentials in clinical neurological practise for the evaluation of patients with dementia (particularly Alzheimer's disease) both as aid in the diagnosis and management of patients, also correlation with other external factors are reviewed in this article. [ABSTRACT FROM AUTHOR]

COVID- 19 infection isaffecting more and morc people around the world. and as the number of rocovered patients increases, so does the knowledge on the potential clinical signs of the disease. Although SARS-CoV-2 virus is commonly associatcd with damage to the respiratory system, it has been obsen•d that about half of patients with COVID-19 infec-tion may also develop various neurological symptoms such as anosmia, dysgeusitt. head-ache. myalgia. or dizzincss. Encephalopathy is šnglcd out as onc of the most severe compli-cations of thc central nenous system caused by SARS-CoV-2 virus and associatod with lon-ger duration of the disease. increascd disability, and mortality. Acute encephalopathy is a disorder of the brain that clinically occurs with a sudden ehange in the levelof consciousness in othcrwise hcalthy patients bcforc thc OfISCI of symptoms. Risk factors include older age, male gender. quicker hospitalization aftcr the onset of symmorns. and chronic illnesses. In cxccptional cascs, cnccphalopathy may be an early or even a mayor symptom of COVID-19 in young paticnts. The pathogcncsis of COVID- 19 encephalopathy is not fully understood. However, the most likely ctiology of encephalopathy is multifactorial: systemic discase re-spoose. inflammation,coagulopathy.direct viral neuroinvasion. endoartheritis. and possibly post-infectiousautoimmune mechanisms. For patients with suspectedchanges in thc levelof consciousnessduc to coronavirus infection. it is recommended toperform a thorough exarni-nation of the ccrcbrospinal tluid (CSF), head imaging with a preference for magnetic reso-nance imaging (MRI),and elecuoencephalography (EEG) It isworth noting that bloodor im-aging tests often do not show specific changcs in patients with encephalopathy. As revealed by some studics of CSF examinations. cytosis is usually atsan or very low while thc protein coacentration remains normal.lt is important to note that SARS-CoV-2 isdetected in the ce-rebral fluid only in isobted cascs. Although the EEG of paticnts with COVID-19 are often normal, they sometimes show spccific encephalopathic changcs including excessive gener-alized frontal delta waves, triphask wavcs and lower amplitudc alpha and bcta waves. The MRI dcseribes a spectrum of neurovisual abnormalities. the most common of which arc foci of leulcoencephalopathy, changes in diffusion restriction imaging in the white, nrcly in the gray matter, signs of microhaemorrhage and leptomcningitis. Trcatmcnt for COVID-19 cnccphalopathy includes supportive carc and symptomatic treatmcnt. Some studics have shown that immtme modulation therapy. including high-dose conicostcroids and intrave-nous immtmoglobulins, is effective in some severely ill patients. [ABSTRACT FROM AUTHOR]

Lewis-Sumner syndrome (LSS) is a multifocal acquired demyelinating sensory and motor neuropathy considered as an asymmetric variant of chronic inflammatory demyelinating polyneuropathy affecting the upper and/or lower extremities. The most common clinical presentations of Lewis-Sumner syndrome are asymmetrical or multifocal sensory disturbances and weakness, electrophysiologically characterized by the presence of motor conduction blocks. In the case report, L-SS affected only the upper limbs, laboratory and electrophysiological testing was normal. Lewis-Sumner syndrome was diagnosed after brachial plexus magnetic resonance imaging. Since Lewis-Sumner syndrome is a rare disorder, its diagnosis and treatment are complicated as studies with a small number of patients and the results are often controversial. [ABSTRACT FROM AUTHOR]

The first or prominent manifestation of frontotemporal dementia (FTD) can be psychosis. In recent years, new genetic mutations have been discovered which arc associated with higher prevalence of psychotic symptoms and are useful for the diagnosis of FTD. According to recent studies, psychotic symptoms of FTD arc significantly more frequent when progranulin (GRN) or chromosome 9 open reading frame 72 (C9orf72) mutations arc detected and often occur before the diagnosis of dementia. Since the symptoms of FTD and primary psychiatric diseases overlap, in the event of a late onset of newly emerging psychotic symptoms, it is necessary to assess the gradual decline of cognitive function associated with FTD, as these patients may be misdiagnosed for primary psychiatric illness. [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]

Alzheimer's disease is a chronic progressive neurodegenerative disorder which affects memory and other cognitive functions. Millions of elderly people around the world suffer from this disease and the number of patients is increasingly growing. Studies on pathogenesis of Alzheimer's disease have identified certain pathophysiological mechanisms that link this disorder to diabetes mellitus; they include insulin resistance, inflammation, oxidative stress, accumulation of advanced gly cation end products, obesity, and others. It is proved that diabetes increases risk of developing cognitive dysfunction and even Alzheimer's disease. Some research has been conducted on antidiabetic drugs for treatment of Alzheimer's disease. Hence, these two diseases are closely connected. Alzhek mer's disease is sometimes even called “type three diabetes". [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]

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]

Background. An assessment of cognitive functioning is considered to be valuable in differential diagnostics of movement disorders. Several studies showed that Addenbrooke's Cognitive Examination-Revised (ACE-R) is an accurate tool in detecting dementia in Parkinson's and related diseases. It is still quite difficult to distinguish between Dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). The aim of this study is to investigate the ability of Addenbrooke's Cognitive Examination-Revised to differentiate mild-moderate dementia with Lewy bodies from Parkinson's disease with mild-moderate dementia in Lithuanian-speaking population. Methods. The Lithuanian version of Addenbrooke's Cognitive Examination-Revised (ACE-RLT) was applied individually to 30 patients with mild-moderate dementia with Lewy bodies, 34 patients with Parkinson's disease dementia, and 64 controls, who were matched for age, gender and education. By using ACE-RLT, the following cognitive domains were evaluated: orientation, attention, memory, verbal fluency, language, and visuospatial abilities; the higher score, the better performance. For statistitical analysis, one-way ANOVA, Mann-Whitney U test, and binary logistic regression were done. Results. The statistical analysis yielded no significant difference among three groups of participants in age (p=0.036), years of education (p=0.401), and gender (χ², p=0.048). The ACE-RLT appeared to be good enough in prognosticating dementia (Ex(B)=0.828, χ²=84.171, p=0.000), with 84% of overall correct cases. While comparing two groups with different diseases, DLB patients had lower scores in overall cognitive performance on ACE-R (DLB average score was 58 and PDD average score was 70, p=0.000). The DLB group had lower scores compared to PDD in those particular cognitive domains: orientation (6.8 points for DLB and 8.7 for PDD), attention (5.4<6.7), verbal fluency (3.3<7.2), and visuospatial abilities (7.5< 12.4); for each domain, p=0.000. Conclussions. The ACE-RLT, an accurate tool in prognosticating dementia, showed only mild differences between DLB and PDD. In line with former studies, the only difference between the DLB and PDD cognitive functioning was that DLB had more severe impairments. Whether DLB and PDD is the same entity or not, remains an open question suggesting the need for more research in this field using different tasks for the cognitive evaluation. [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]

Introduction. Nowadays, succesfull treatment in cardiac surgery is determined not only by the absence of complications, but rather by the guality of post operative life of the patient. Returntonor malactivity post operativelly is of tendisturbed by the worsening of neuro psychological status of the patient. Cognitive declineis one of the most controversal complications following cardiac surgery, widely discussed in modern medical literature. The aim of our study was to determine preoperative risk factors associated with neuro cognitive complications and investigate whether asymptomaticcarotidarterystenos is has an impact on post operative cognition. Methods. We collected data of 127 consecutive patients, under going on pump CABG at our institution. Neuropsychological testing was conducted preoperatively and 7-10 days after surgery. Ultra sound examination of carotidarteries was performed forevery patient as a part of preoperative examination. Results. Early post operative cognitive decline (POCD) was detected in 46%of patients. Patients in POCD group were older (p=0.03), had higher preoperative risks core(p=0.009).Cognitive decline was associated with such factors as longer operation time(p=0.02), low cardiac output syndromeperioperativelly (p<0.05), postoperative bleeding (p=0.03) andeventuallylongermechanical ventilation and intensive care unit stay (p<0.05). Carotidartery lesion was detected in 42 (68.8% patients. Multi variate regression analysis showed that carotidartery stenosis of more than 50% was an independent predict or of POCD (OR26.89,CI6.44-112.34). Conclusions. Postoperativecognitive decline is afrequent complication following coronary artery by pass grafting. The incidence of POCD was associated with perioperative hemo dynamic in stability, post operative bleeding, delirium or cardiac arrhythmias. Increasedage, carotidarterystenosis, longer operation and mechanical ventilationtime, were independent predictors of post operative cognitive impairment. [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]

In case of Parkinson's disease (PD) there is neurodegeneration in various areas of the central nervous system, and this manifests with motor and non-motor symptoms. Some non-motor symptoms make the biggest impact on patients' quality of life and cause huge costs related to the healthcare. Some non-motor symptoms may become obvious in the beginning of the disease, the other are more pronounced in advanced stages of the disease. Non-motor symptoms may be explained by Braak hypothesis - Lewy bodies may be found in various brain structures. Most common symptoms are neuropsychiatric disorders (depression, dementia, psychosis), sleep disorders (insomnia, rapid eye movement sleep disorders), autonomic, and gastrointestinal disorders. Non-motor symptoms usually do not improve with dopaminergic treatment. Article is based on the review of the related material. Non- motor symptoms, their pathogenesis and treatment basis are discussed in the article. [ABSTRACT FROM AUTHOR]

The article presents the second pathomorphologically verified case of sporadic Creutzfeldt-Jacob disease (CJD) in Lithuania. Patient G. K., 54 years old woman, was treated in Vilnius University Santariškių Hospital from 2007 01 04 till 2007 01 16. Clinical features, EEGof this patient were typical for the sporadic Creutzfeldt-Jacob disease. The diagnosis of Creutzfeldt-Jacob disease was verified postmortem by histopathological imunohistochemical assay using monoclonal antibodies against protease resistant prion protein (PrP). Specific for the CJD accumulation of this protein in cerebral cortex and less in cerebellar cortex was found. We compared the clinical features, EEG findings and imunohistochemical data of this case with the first pathomorphologically verified case of Creutzfeldt-Jacob disease in Lithuania (2004). [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]

Tlie recommendations for dementia caregi vers and health care professionals in long-term care facilities during the COVID-19 pandemic published by the Alzheimer's Association, the European Academy of Neurology Dementia Scientific Panel, and Alzheimer Europe are presented in this review article. The main aspects of care and the emerging difficulties that should be taken into account when caring for dementia patients at home and in nursing homes in this rapidly changing emergency are highlighted. [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]

There is a strong necessity to develop new treatments for Alzheimer's disease (AD) as its frequency is rapidly growing with the ageing population. There were 25 pharmacological agents involved in phase I trials, 52 in phase II, and 28 agents in phase III clinical trials in 2017. More than two thirds (70%) of these agents are developed as disease-modifying therapies. Their mechanisms of action are targeted mainly to amyloid and tau related pathology. Almost one third (27%) of the agents comprise the group of symptomatic treatment. There is a number of factors that determine the current failure of the research. The factors include incomplete understanding of AD pathophysiology, limited agent access to the central nervous system, and lack of diagnostic and predictive biomarkers. Although AD treatment studies have given no clear positive results in recent decades, research is actively continued due to the growing economic and social burden of the disease. [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]

Background. The verbal fluency test is a brief and accurate examination of the patients cognitive and executive functions. It is very sensitive to frontal and temporal lobe disorders which are often reported in atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). The verbal fluency test has been included in Addenbrooke’s Cognitive Examination, primarily used for screening of various types of dementia. In this study we sought to evaluate how we could differentiate between PSP, CBD and MSA ustng the verbal fluency test adapted to the Lithuanian - speaking population. Patients and Methods. 8 patients with PSP, 5 patients with CBD, and 7 patients with MSA were recruited to participate in our study. The verbal fluency test consisting of two tasks adapted to the Lithuanian - speaking population was administered to each patient and total words generated for each task were evaluated. We compared the results between each patient group. Mean values with 95% Confidence Intervals and a one - way ANOVA with a post - hoc Bonferroni was used for statistical analysis. Results. Mean values of total words generated with a 95%CIfor each group respectively were: PSP - 4.87 (4.18; 5.57), CBD - 6.20 (5.64; 6.75) and MSA - 9.28 (8.26; 10.31) for phonemic fluency; and PSP - 7.00 (6.22; 7.77), CBD - 8.40 (7.71; 9.08) and MSA - 12.86 (12.03; 13.69) for semantic fluency. Statistically significant differences were noticed between and within groups in both phonemic (F=48.422, p<0.01) and semantic (F=94.991, p<0.01) fluency. Post - hoc Bonferroni analysis revealed that significant differences were in PSP group compared to MSA (p<0.01) and MSA group compared to CBD (p<0.01) for phonemic (letter) fluency and PSP group compared to MSA (p<0.01), MSA group compared to CBD (p<0.01) for semantic (category) fluency. Conclussions. The MSA group had significantly better results in both phonemic and semantic fluency than the CBD and PSP groups and should be differentiated accordingly. Even though the fluency comparison between CBD and PSP groups held no statistical value, the score of total words generated for phonemic and semantic fluency was lower in the PSP group, which may be helpful in differentiating between these conditions. We also determined, that phonemic (letter) fluency impairement was greater in all three patient groups than the semantic (category) fluency impairement. [ABSTRACT FROM AUTHOR]

Neurological symptoms that cannot be explained by known physical disease are called dissociative movement disorder. This disorder is misdiagnosed more often if a patient experiences gait and movement disorders. Stiff person syndrome (SPS) is a very rare autoimmune disease, the diagnosis of which requires "suspiciousness" and specific tests. Patients with SPS experience muscle rigidity and sudden contractions which can be exacerbated by sudden emotional stressors, auditory, visual and tactile stimuli. This article reviews dissociative motor disorder and SPS and presents a clinical case of SPS which has been misdiagnosed as a dissociative motor disorder for many years. [ABSTRACT FROM AUTHOR]

Background. Currently, it is recognised that movement disorders, such as Parkinson's and related diseases, also have a cognitive component and those diseases can even progress in some patients to dementia. Therefore, a cognitive assessment is useful in evaluating movement disorders. There is a need for having more clinical tools for differential diagnostics between DLB and AD. The Addenbrooke's Cognitive Examination-Revised can meet this need as it is a brief sensitive dementia screening test. The Lithuanian version of ACE-R (ACE-RLT) was shown to be able to detect dementia, but further research is still lacking in establishing the use of the ACE-R for differential diagnostics of AD and DLB. Accordingly, the aim of this study was to investigate the ability of the ACE-R to accurately differentiate mild-moderate Alzheimer's disease from mild-moderate dementia with Lewy bodies. Participants and methods. Seventy three patients with early mild-moderate AD and 30 patients with mild-moderate DLB were evaluated with the ACE-R, the test which consists of the following domains: orientation, attention, memory, verbal fluency, language and visuospatial ability, with maximum total score 100. The results were compared with those obtained in 86 healthy controls. The one-way ANOVA, logistic-regression analysis, ROC analysis and Mann-Whitney U-test were done for statistical analysis. Results. In AD group neither age (p=0.060), nor gender (p=0.466) or education (p=0.206) had an effect on ACE-R scores. In DLB group neither age (p=0.249) nor gender (p=0.615) or education (p=0.360) had an effect on ACE-R scores. In control group both age (p<0.001) and education (p<0.001) had an effect, while gender did not (p=0.438). At 74, the previously recommended cut-off score for clinical use in the detection of dementia, the ACE- RLT showed a sensitivity of 100%, and a specificity of 90.5 % for AD in our study. The Cronbach's alpha for the ACE- RLT was 0.912. AD group was significantly more likely to score below the recommended cut-off scores for memory and language subtests than the DLB group (chi-square; p<0.0001). The DLB group was significantly more likely to score below the recommended cut-off scores for verbal fluency and visuospatial abilities subtests than the AD group (chi square; p<0.0001). Conclusions. The ACE- RLT appears to be a reliable and valid tool for differential diagnostics of DLB and AD in Lithuanian speaking population. The cognitive assessment using ACE- RLT indicated that in DLB verbal fluency and visuospatial abilities were more impaired compared to AD. And in AD memory and language performance were worse than in DLB. [ABSTRACT FROM AUTHOR]

Background: Addenbrooke's Cognitive Examination - Revised (ACE-R) is a cognitive screening test, reportedly sensitive for many types of dementia, including Alzheimer's Disease (AD) and frontotemporal Dementia (FTD). Studies investigating the specificity of ACE-R have not yielded a unanimous solution that would allow clinicians to make a more accurate differential diagnosis of AD and FTD. In this study we aimed to validate the Lithuanian version of ACE-R (ACE-RLT) as a test, which can differentiate AD from FTD in Lithuanian-speaking population. Methods: ACE-RLT is a 100-score test battery that allows to assess six cognitive domains. A total of 115 patients with dementia (30 with mild-moderate FTD, and 85 mild-moderate AD) and 95 healthy age, gender and education matched controls were included in the study. Results: Patients with AD can be differentiated from FTD by lower scores on orientation, attention and, memory, while patients with FTD can be differentiated from AD by lower scores on verbal fluency, language, and naming. It was found that VLOM ratio was able to differentiate AD from FTD. The sensilivity for diagnosing AD of VLOM ralio >3.2 was 64.7% with specificity of 90.2%, while the sensitivity for diagnosing FTD of VLOM ratio <2.2 was 76.7% with specificity of 67.1%. Conclusions: The results of this study provide objective validation of the ACE-RLT as a tool for differential diagnostics of FTD and AD in Lithuanian-speaking population. [ABSTRACT FROM AUTHOR]

Background. Alzheimer's disease (AD) is the most common cause of dementia. Nevertheless, diagnosis is usually delayed. In recent studies attention is drawn to the impairment of visual perception, which could be useful in early diagnosis of the disease. There are known various visual disorders related to AD. However, colour perception of patients with AD is not clearly understood. There are some studies with minor extent and the results remain controversary. Purpose of the study. To evaluate colour naming, colour memory and colour-emotion associations in patients with AD. Materials and methods. The study was conducted in the department of Neurology at Vilnius University Hospital Santariškių Klinikos. We enrolled 19 patiens with mild and moderate AD and 20 cognitively normal control subjects, matched for age, sex and level of education. Cognitive functions were assessed using Mini-Mental State Examination (MMSE). Results. Patients with AD named significantly less colours than control group (p=0.009). There were significantly more mistakes in colour naming among subjects of AD group (p=0.01). AD patients made significantly more mistakes naming longer wavelength colours (p=0.002), but there were no significant diference naming colours of shorter wavelength (p=0.4). Remembering the sequence of three colours patients with AD made significantly more mistakes than control group (p=0.02). Significant differences in remembering two colours combination were found in one of two tasks (p=0.09 ir p=0.04), in one of two four colour binding tasks (p=0.51 and p=0.02) and in both tasks of three colour combination (p=0.001 ir p=0.03). The most favourite colours in AD group were green, blue and yellow, while control group preferred green, blue and pink. The least favourite colour were grey in AD and yellow in control group. The evaluation of grey colour differed significantly between groups (p=0.009). There was reliable negative connection of middle strenght between MMSE and grey colour preference. No difference was recorded in the frequence of picked positive and negative emotional descriptors between AD and control subjects (p=0.82). Patients with AD were susceptible to choose few controversial descriptors to one colour (p<0.001). Conclusions. Patiens with AD have selective deficit in naming colours of longer wavelenght. Colour memory is also impaired (it is observed in remembering colour sequence and simultaneous colour combinations). Three colour binding task is the most specific to distinguish AD and control subjects. Colour preferences also vary between groups. The most significant differences are in grey colour evaluation. It is the least favourable colour for patient with AD and the correlation between grey colour evaluation and cognitive performance is observed. There are also differences in colour-emotion associations for patients with AD. They frequently associate colour with several contradictory emotional descriptors. [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]

Background. Prevalence of Alzheimer's disease (AD) is increasing due to the aging of the population. As a result the economic burden of AD is increasing as well. Early diagnosis and timely interventions are needed in order to reduce the cost of care for patients with AD. Visuospatial perception has recently drawn attention as one of the earliest symptoms of AD that could be useful in early diagnosis of the disease. There are some aspects of visual cognition that have not been studied extensively in patients with AD. There are still some uncertainties regarding impairment in visuospatial functions in AD such as the exact nature of these symptoms and the time of on set in the course of the disease. Purpose of the study. To evaluate visual perception and susceptibility to optical illusions in patients with mild and moderate AD. Materials and methods. The study was conducted in the department of Neurology at Vilnius University Hospital Santariškių Klinikos. We en rolled 23 patients with mild to moderate AD and 25 cognitively normal control subjects, matched for age, sex, level of education and type of occupation. Visual perception and susceptibility to optical illusions were assessed using a set of 32 pictures that were divided into six groups according to mechanisms of perception. Cognitive functions were assessed using Mini-Mental State Examination (MMSE). Results. Patients with AD were significantly less susceptible than control subjects to 2 out of 4 geometrical illusions (p<0.001). They were also less susceptible to 1 out of 3 colour illusions (p=0.046). De creased susceptibility to optical illusions was present in the stage of mild dementia (MMSE>20 pts.). Performance in embedded images tasks was significantly (p<0.05) worse in AD patients in 7 out of 8 cases. Patients with mild dementia were significantly worse than control subjects in evaluating 3 of these pictures. Patients with AD identified both possible meanings less frequently than control subjects in 1 out of 3 pictures of ambiguous figures (p=0.001). AD patients made significantly more mistakes than control subjects in 4 out of 8 optical paradoxes tasks (p 0.02 -- <0.001). Mild dementia patients' performance was significantly different from control group in 2 of these tasks. There were no significant differencies between patients with AD and control subjects in perception of motion illusions. Conclusions. Visual perception is impaired in AD. Deficits in visual perception occur early in the course of the disease. They are present in patients with mild dementia. [ABSTRACT FROM AUTHOR]

Back ground and purpose. The development of neutralizing antibodies (NAbs) against interferon beta (IFN-β) during IFN-β treatment in multiple sclerosis (MS) patients has been a significant clinical problem. Persistent, high-titer NAbs-IFN-β reduce or eliminate biological activity of IFN-β therapies for MS and are associated with reduction in efficacy. Therapeutic plasma exchange (TPE) removes the circulating antibodies that are thought to be active in the diseases, so we hypothesized that TPE can restore the ability of IFN-β to induce the Myxovirus Resistance Protein A (MxA) mRNA expression and the maintenance plasmapheresis can sustain the bioavailability of IFN-β. Methods. Eligible patients under went primarily four separate plasma exchange sessions and after the induction TPE sessions they were transferred to the maintenance plasma pheresis. Bioactivity of interferon beta was expressed as in vivo MxA mRNA induction in whole blood using real time PCR. Results. Six patients with RRMS and low IFN-β bioavailability detected by the MxA mRNA response were included. Four patients after induction plasmapheresis be came biological responders. In two patients an in crease of MxA mRNA expression was found, but the values persisted be low the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was quite transient: MxA mRNA expression values reverted to the base line levels after one or two months. Conclusion. Plasma exchange may restore the bioavailability of IFN-β in some patients, but the effect of maintenance plasmapheresis on the bioavailability of IFN-β is transient. [ABSTRACT FROM AUTHOR]