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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]

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).)

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti-titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions., (© 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.)

The clinical course of Lyme neuroborreliosis (LNB) is highly variable. Delayed diagnosis and treatment still remain actual challenges. Moreover, there is a lack of studies analyzing the factors associated with different LNB syndromes. We aimed to analyze clinical and epidemiological features of LNB in hospitalized adults in eastern Lithuania. A retrospective study was performed for patients presenting in the years 2010-2021. A total of 103 patients were included in the study, 100 with early, and three with late LNB. Patients with early LNB most often presented polyradiculitis [75/100, (75%)], which was also the most common initial neurological syndrome. Peripheral facial palsy was diagnosed in 53/100 (53%) patients, in 16/53 (30.2%) cases both facial nerves were affected. Encephalitis or myelitis was diagnosed in 14% of patients with LNB. A total of 76/103 (73.8%) patients were discharged with residual symptoms or signs. One patient presenting encephalomyelitis died because of bacterial complications. The absence of observed erythema migrans (EM) was the predictor of peripheral facial palsy, while female sex and EM untreated with antibiotics were predictors of isolated polyradiculitis. A fever of ≥ 38 ° °C and pleocytosis of ≥ 300 × 10 6 /l were associated with the development of encephalitis or myelitis in patients with early LNB., (© 2023. The Author(s).)

Introduction: Olfaction is impaired in Alzheimer's disease (AD). However, olfactory memory has rarely been examined. As the pathogenesis of AD remains largely unknown, collecting more data regarding the occurrence and progression of its symptoms would help gain more insight into the disease., Objective: To investigate olfactory memory and its relationship with verbal memory and other clinical features in patients with early-stage AD., Methods: Three groups of participants were enrolled in this study: patients with mild dementia due to AD (MD-AD, N  = 30), patients with mild cognitive impairment due to AD (MCI-AD, N  = 30), and cognitively normal older participants (CN, N  = 30). All participants underwent cognitive evaluation (Clinical Dementia Rating scale, Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, delayed verbal recall, and verbal fluency tests) and assessment of olfactory immediate and delayed recognition memory., Results: Olfactory immediate and delayed recognition memory scores were significantly lower in the MD-AD group than in the MCI-AD and CN groups. The MCI-AD and CN groups did not differ significantly [in both cases, Kruskal-Wallis test, p  < 0.05; post hoc analysis revealed significant differences between the MD-AD and MCI-AD groups and between the MD-AD and CN groups ( p  < 0.05), and no significant difference between the MCI-AD and CN groups ( p  > 0.05)]. Verbal immediate recall, delayed recall after 5 min, and delayed recall after 30 min scores were significantly worse in the MD-AD and MCI-AD groups than in the CN group. MD-AD and MCI-AD groups did not differ significantly [in all cases Kruskal-Wallis test, p  < 0.05; post hoc analysis revealed significant differences between MD-AD and CN groups, and MCI-AD and CN groups ( p  < 0.05) and no significant difference between MD-AD and MCI-AD groups ( p  > 0.05)]. Duration of AD symptoms was a strong predictor of both immediate and delayed olfactory recognition memory scores., Conclusion: Olfactory memory impairment was observed in patients with AD. The changes progress during the course of the disease. However, unlike verbal memory, olfactory memory is not significantly impaired in the prodromal stage of AD., 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 Audronyte, Sutnikiene, Pakulaite-Kazliene and Kaubrys.)

BACKGROUND Olfactory impairment is an early symptom of Alzheimer disease (AD). However, it is rarely assessed in clinical practice. This study aimed to assess the identification and discrimination of specific odors in patients with early-stage AD using the Sniffin' Sticks test and determine the items that would be most valuable in the diagnosis of early-stage AD in order to create a brief test of olfactory dysfunction. MATERIAL AND METHODS Three groups of participants were enrolled, including 30 patients with mild cognitive impairment due to AD (MCI-AD group), 30 with mild dementia due to AD (MD-AD group), and 30 older participants with normal cognition (NC group). All participants underwent cognitive (Clinical Dementia Rating, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, and verbal fluency tests) and olfactory (Burghart Sniffin' Sticks odor identification and odor discrimination tests) assessments. RESULTS The MD-AD group scored significantly lower than the MCI-AD group and the MCI-AD group scored significantly lower than the NC group in both the odor identification (P<0.001) and discrimination (P<0.05) tasks. The shortened versions of the odor identification and discrimination tasks showed good diagnostic properties in differentiating patients with AD from the NC participants (receiver operating characteristic [ROC] area under the curve [AUC]=0.912 and 0.954, respectively) and differentiating patients with MCI-AD from the NC participants (ROC AUC=0.871 and 0.959, respectively). CONCLUSIONS The brief versions of olfactory tests, containing selected items that were found to differ the most between cognitively normal participants and early-stage AD patients, have good diagnostic qualities and can aid clinicians in screening for early-stage AD.

Odor identification (OI) is impaired in the early stages of Alzheimer's disease (AD). However, data regarding the diagnostic properties of OI tests are lacking, preventing their clinical use. We aimed to explore OI and determine the accuracy of OI testing in screening for patients with early AD. In total, 30 participants with mild cognitive impairment due to AD (MCI-AD), 30 with mild dementia due to AD (MD-AD), and 30 cognitively normal elderly participants (CN) were enrolled, and cognitive examination (CDR, MMSE, ADAS-Cog 13, and verbal fluency tests) and assessment of OI (Burghart Sniffin' Sticks odor identification test) were performed. MCI-AD patients scored significantly worse in OI than CN participants, and MD-AD patients had worse OI scores than MCI-AD patients. The ratio of OI to ADAS-Cog 13 score had good diagnostic accuracy in differentiating AD patients from CN participants and in differentiating MCI-AD patients from CN participants. Substitution of ADAS-Cog 13 score with the ratio of OI to ADAS-Cog 13 score in a multinomial regression model improved the classification accuracy, especially of MCI-AD cases. Our results confirmed that OI is impaired during the prodromal stage of AD. OI testing has a good diagnostic quality and can improve the accuracy of screening for early-stage AD., (© 2023. The Author(s).)

Background: Brain atrophy, which is associated with cognitive impairment and retinal nerve fiber layer (RNFL) atrophy, is the main biomarker of neurodegeneration in multiple sclerosis (MS). However, data on the relationship between inflammatory markers, such as oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF), and cognition, RNFL atrophy, and brain atrophy are scarce. The aim of this study was to assess the influence of RNFL thickness, brain atrophy markers, intrathecal OCBs, and the immunoglobulin G (IgG) index on cognitive decline over a 5-year period in patients with MS. Methods: This prospective, single-center, observational cohort study included 49 patients with relapsing MS followed up over 5 years. At baseline, the patients underwent brain magnetic resonance imaging (MRI). Cognitive evaluation was performed using the Brief International Cognitive Assessment for MS (BICAMS), and RNFL thickness was assessed using optical coherence tomography (OCT). OCBs and IgG levels in the CSF were evaluated at baseline. The BICAMS, OCT, and MRI findings were re-evaluated after 5 years. Results: A significant reduction in information processing speed, visual learning, temporal RNFL thickness, the Huckman index, and third ventricle mean diameter was found in all 49 patients with relapsing MS over the observation period ( p < 0.05). Of the patients, 63.3% had positive OCBs and 59.2% had elevated IgG indices. The atrophy of the temporal segment and papillomacular bundle and the presence of OCBs were significantly related to a decline in information processing speed in these patients ( p < 0.05). However, brain atrophy markers were not found to be significant on the general linear models. Conclusions: RNFL atrophy and the presence of OCBs were related to cognitive decline in patients with MS over a 5-year follow-up period, thereby suggesting their utility as potential biomarkers of cognitive decline in MS., 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 © 2021 Giedraitiene, Drukteiniene, Kizlaitiene, Cimbalas, Asoklis and Kaubrys.)

Introduction: In recent decades, the incidence of Tick-borne encephalitis (TBE) has been increasing and posing a growing health problem because of the high costs to the healthcare system and society. The clinical manifestations are well studied but there is a lack of research analyzing the severity of the disease., Objective: The aim of this study was to analyze the epidemiology and clinical presentation of severe TBE, to identify the predictors for a severe disease course, and also predictors for meningoencephalomyelitic and severe meningoencephalitic/encephalitic forms., Methods: A retrospective study was conducted in the Center of Infectious Diseases and the Center of Neurology at Vilnius University Hospital Santaros Klinikos in the years 2005-2017 to describe the clinical and epidemiological features of TBE in adults., Results: 1040 patients were included in the study. A total of 152/1040 (14.6%) patients had a severe course. The highest proportion of severe cases, reaching 41.2%, was reported in the 70-79 year-old age group. A total of 36/152 (23.7%) severe patients presented meningoencephalomyelitis. Myelitic patients were older, were frequently infected in their living areas, and usually reported a monophasic disease course compared with severe meningoencephalitic/encephalitic patients. Severe meningoencephalitic/encephalitic patients, compared with non-severe meningoencephalitic/encephalitic, were older, less often noticed the tick bite, and often had a monophasic course. The sequelae on discharge were observed in 810/1000 (81%) of patients., Conclusions: The prognostic factors associated with a severe disease course and severe meningoencephalitic form are: older age, comorbidities, a monophasic course, a fever of 40˚C and above, CRP more than 30 mg/l, CSF protein more than 1 g/l, delayed immune response of TBEV IgG, pathological findings in CT. Age above 60 years, presence of CNS disease, bulbar syndrome, pleocytosis 500x106/l and above, and delayed immune response of TBEV IgG are predictors of the most severe myelitic form., Competing Interests: The authors have declared that no competing interests exist.

Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin ( CP ) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint efforts are needed to better understand the pathophysiology of this potentially disabling disease.

Background: Cognition may be affected at least as seriously as physical function during multiple sclerosis (MS) relapse, however MS relapse related cognitive disorders are still underdiagnosed and poorly characterized. The limited number of paper-pencil tests were used for assessment, and nevertheless, some significant changes were found. Unlike the paper-pencil tests, computerized batteries and tests are more sensitive and highly standardized, produce instant scoring and can minimize the learning and practice effects on follow-up. We investigated the cognition during MS relapse with the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has shown sensitivity to cognitive dysfunction across different clinical groups, including patients with MS. Objective: The objective of the study was to assess the cognitive functions with CANTAB battery in MS patients during relapse, in stable MS patients, and healthy controls, and to establish the timing and pattern of cognitive recovery after relapse. Methods: Sixty relapsing, thirty stable MS patients, and thirty controls were assessed with CANTAB. The relapse group was assessed during multiple sclerosis relapse and 1 and 3 months after the first assessment. Results: The score of the difficult task of spatial planning was worse in MS relapse group than in MS stable group ( p < 0.05). The scores of medium difficulty tasks of spatial planning, episodic visual recall and working memory were worse in the relapse group than in the control group ( p < 0.05), while in stable MS and control groups, the scores of these tasks didn't differ. The most significant improvement of speed of response, spatial planning, episodic visual recall memory and spatial working memory, was established at 1 month after the first assessment, additional improvement of spatial planning and working memory was observed at 3 months after the first assessment. Conclusions: The results of this study indicate that cognitive function is affected during MS relapse. The difficult task of CANTAB battery, which assesses the spatial planning, showed MS relapse related cognitive dysfunction. The changes in scores of episodic visual recall and working memory may be related to MS relapse. A significant improvement in the speed of response, spatial planning, episodic visual recall and working memory was established at 1 month after MS relapse. The additional improvement in spatial planning for the most difficult task and working memory was observed at 3 months after MS relapse. It may be possible that the practice effect had the impact on the improvement of cognitive scores that was noted in relapsing MS patients.

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.)

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

BACKGROUND 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 Alzheimer disease (AD) primarily affects cognition. A variety of visual disorders was established in AD. Fechner illusory colors are produced by a rotating disk with a black and white pattern. The purpose of our research was to explore the perception of illusory colors in AD. MATERIAL AND METHODS W recruited 40 AD patients (MMSE ≥14) and 40 normal controls (CG group) matched by age, education, gender in this prospective, cross-sectional, case-control study. An achromatic Benham's disk attached to a device to control the speed and direction of rotation was used to produce illusory colors. Primary, secondary, and tertiary RGB system colors were used for matching of illusory and physical colors. RESULTS Subjects in the AD group perceived less illusory colors in 5 arcs (p<0.05) of the 8 arcs assessed. The biggest difference was found between AD and CG groups for pure blue (χ²=26.87, p<0.001 clockwise, χ²=22.75, p<0.001 counter-clockwise). Groups did not differ in perception of pure yellow opponent colors (p>0.05). Mixed colors of the blue-yellow axis were perceived less often in AD, but more frequently than pure blue (#0000FF). The sequence of colors on Benham's disk followed a complex pattern, different from the order of physical spectral colors and opponent processes-based colors. CONCLUSIONS AD patients retained reduced perception of illusory colors. The perception of pure blue illusory color is almost absent in AD. The asymmetrical shift to the yellow opponent is observed in AD with red prevailing over green constituent. This may indicate cortical rather than retinal impairment., Competing Interests: Conflicts of interests The authors have no conflicts of interest to declare.

BACKGROUND The primary manifestation of Alzheimer's disease (AD) is decline in memory. Dysexecutive symptoms have tremendous impact on functional activities and quality of life. Data regarding frontal-executive dysfunction in mild AD are controversial. The aim of this study was to assess the presence and specific features of executive dysfunction in mild AD based on Cambridge Neuropsychological Test Automated Battery (CANTAB) results. MATERIAL AND METHODS Fifty newly diagnosed, treatment-naïve, mild, late-onset AD patients (MMSE ≥20, AD group) and 25 control subjects (CG group) were recruited in this prospective, cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth cognitive assessment. Comparisons were performed using the t test or Mann-Whitney U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R. Statistical significance was set at p<0.05. RESULTS AD and CG groups did not differ according to age, education, gender, or depression. Few differences were found between groups in the SOC test for performance measures: Mean moves (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all SOC test time measures differed significantly between groups: SOC Mean subsequent thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001. Correlations were weak between executive function (SOC) and episodic/working memory (PAL, SWM) (R=0.01-0.38) or attention/psychomotor speed (CRT) (R=0.02-0.37). CONCLUSIONS Frontal-executive functions are impaired in mild AD patients. Executive dysfunction is highly prominent in time measures, but minimal in performance measures. Executive disorders do not correlate with a decline in episodic and working memory or psychomotor speed in mild AD., Competing Interests: The authors declare they have no conflicts of interest.

BACKGROUND Ability to predict the efficacy of treatment in Alzheimer disease (AD) may be very useful in clinical practice. Cognitive predictors should be investigated alongside with the demographic, genetic, and other predictors of treatment efficacy. The aim of this study was to establish whether the baseline measures of CANTAB tests and their changes due to the first donepezil dose are able to predict the efficacy of treatment after 4 months of therapy. We also compared the predictive value of cognitive, clinical, and demographic predictors of treatment efficacy in AD. MATERIAL AND METHODS Seventy-two AD patients (62 treatment-naïve and 10 donepezil-treated) and 30 controls were enrolled in this prospective, randomized, rater-blinded, follow-up study. Treatment-naïve AD patients were randomized to 2 groups to take the first donepezil dose after the first or second CANTAB testing, separated by 4 hours. Follow-up Test 3 was performed 4 months after the initial assessment. RESULTS The groups were similar in age, education, gender, Hachinski index, and depression. General Regression Models (GRM) have shown that cognitive changes after the first dose of donepezil in PAL (t-values for regression coefficients from 3.43 to 6.44), PRMd (t=4.33), SWM (t=5.85) test scores, and baseline results of PAL (t=2.57-2.86), PRM (t=3.08), and CRT (t=3.42) tests were significant predictors of long-term donepezil efficacy in AD (p<0.05). CONCLUSIONS The cognitive changes produced by the first donepezil dose in CANTAB PAL, PRM, and SWM test measures are able to predict the long-term efficacy of donepezil in AD. Baseline PAL, PRM, and CRT test results were significant predictors.

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

Background: The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to explore which tests and their measures are able to detect cognitive change after a single dose of donepezil in Alzheimer disease (AD) patients. The aim of this study was to establish the ability of CANTAB tests and their measures to detect cognitive change after a single 5-mg dose of donepezil in treatment-naïve AD patients., Material and Methods: We enrolled 62 treatment-naïve AD patients and 30 healthy controls in this prospective, randomized, rater-blinded study. AD patients were randomized to 2 groups: the AD+ group received donepezil after the first CANTAB testing and the AD- group remained treatment-naïve at second testing. The time period between repeated testing was 4 hours. Parallel versions of CRT, SOC, PAL, SWM, and PRM tests were used., Results: All groups did not differ according to age, education, gender, or depression (p>0.05). AD+ and AD- groups did not differ according to MMSE. SOC, PAL, PRM, and SWM tests distinguished AD from controls. Eight measures of PAL and PRM had a strong correlation with MMSE (r>0.7). Repeated-measures ANOVA with Bonferroni post-hoc test showed the difference of change in AD+ and AD- groups between first and second CANTAB testing in 7 PAL measures. AD+ and AD- groups differed in the second testing by 7 PAL measures. Four PAL measures differed in first and second testing within the AD+ group., Conclusions: The CANTAB PAL test measures, able to detect cognitive change after a single dose of donepezil in AD patients, are: PAL mean trials to success, total errors (adjusted), total errors (6 shapes, adjusted), and total trials (adjusted).

Background: Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function., Material and Methods: We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed., Results: All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004)., Conclusions: The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.

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

Background: One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD)., Methods: This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group., Results: The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74)., Conclusions: ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.