Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment.

Background: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. Objectives: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. Design: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. Methods: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. Results: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). Conclusion: The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.

Suicidal ideation in people with multiple sclerosis and its association with coping self-efficacy.

BACKGROUND: Chronic neurological disease such as multiple sclerosis (MS), is a significant risk factor for psychological distress, which can result in suicidal behaviour. Suicidal ideation (SI) is considered a harbinger of suicide-related mortality. However, so far, little is known about the role of protective factors against SI in MS. OBJECTIVE: This study aims to assess the association between coping self-efficacy and SI when controlled for sociodemographic variables, clinical variables, sleep-related problems, and depression. METHODS: The study sample consisted of 162 people with MS, was predominantly female (75.9 %), the mean age was 40.9 ± 11.4 years, the mean disease duration was 11.7 ± 7.1 years, and the mean functional disability score was 3.55 ± 1.1. We used the Coping Self-Efficacy scale (CSE), the General Health Questionnaire-28 (GHQ-28), the Expanded Disability Status Scale (EDSS), the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), and the Multidimensional Fatigue Inventory (MFI). Multiple linear regressions were utilized to statistically analyse the data. RESULTS: All assessed coping self-efficacy dimensions were significantly associated with SI in MS when controlled for sociodemographic variables, clinical variables, sleep-related problems, and depression. Furthermore, all assessed coping self-efficacy dimensions were able to alleviate the negative association between income, depression and SI. CONCLUSION: People with MS may significantly benefit from psychological support aimed at promoting coping self-efficacy and utilization of various coping strategies. Problem-focused coping, coping focused on getting support, and coping focused on stopping unpleasant thoughts and feelings seem to have comparable associations with SI, and thus interventions aimed at empowering any of these dimensions may be beneficial in diminishing the severity of SI.

Clinical and demographic characteristics of patients with NMOSD: a longitudinal retrospective analysis of a Slovak cohort of 63 patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoantibody-mediated inflammatory diseases of the central nervous system predominantly targeting optic nerves and the spinal cord. Two distinct phenotypes are recognized based on the presence of serum aquaporin-4 (AQP4-IgG) antibodies. However, contrasting clinical course patterns have been identified between AQP4-IgG-positive and AQP4-IgG-negative patients. AIMS: This study aimed to present demographic and clinical characteristics of patients with NMOSD in Slovakia and to evaluate the significance of differences between AQP4-IgG-seropositive and AQP4-IgG-seronegative patients. METHODS: We performed a longitudinal multi-centric retrospective study and analysed the clinical and demographic characteristics of a cohort of 63 Slovak NMOSD patients. RESULTS: Eighty-six percent of patients were women, and ninety-four patients were Caucasian. The median age at diagnosis was 37 years. The most frequent initial manifestations were optic neuritis (47.6% of patients) and transverse myelitis (39.7% of patients). The median EDSS score deteriorated from the initial 3.0 to 4.0 at the last follow-up. Sixty-eight percent of patients were AQP4-IgG positive; 10% of patients were MOG-IgG positive; 27% of patients had no NMOSD-specific antibodies detected. There was a higher prevalence of autoimmune thyroiditis among AQP4-IgG-positive patients (25.6%) compared to AQP4-IgG-negative patients (0%) (p = 0.01). CONCLUSION: This study provides a detailed overview of the clinical and demographic characteristics of NMOSD based on a retrospective analysis of a Slovak cohort of 63 NMOSD patients and extends information provided by similar recently published studies. The most important finding is that there is a high prevalence of autoimmune thyroiditis among AQP4-IgG-negative patients (25%).

Annual Plasma Neurofilament Dynamics Is a Sensitive Biomarker of Disease Activity in Patients with Multiple Sclerosis.

Background and Objectives: Neurofilament light chain (NfL) is a sensitive biomarker of neuroaxonal damage. This study aimed to assess the relationship between the annual change in plasma NfL (pNfL) and disease activity in the past year, as defined by the concept no evidence of disease activity (NEDA) in a cohort of multiple sclerosis (MS) patients. Materials and Methods: Levels of pNfL (SIMOA) were examined in 141 MS patients and analyzed in relationship to the NEDA-3 status (absence of relapse, disability worsening, and MRI activity) and NEDA-4 (NEDA-3 extended by brain volume loss ≤ 0.4%) during the last 12 months. Patients were divided into two groups: annual pNfL change with an increase of less than 10% (group 1), and pNfL increases of more than 10% (group 2). Results: The mean age of the study participants (n = 141, 61% females) was 42.33 years (SD, 10.17), and the median disability score was 4.0 (3.5-5.0). The ROC analysis showed that a pNfL annual change ≥ 10% correlates with the absence of the NEDA-3 status (p < 0.001; AUC: 0.92), and the absence of the NEDA-4 status (p < 0.001; AUC: 0.839). Conclusions: Annual plasma NfL increases of more than 10% appear to be a useful tool for assessing disease activity in treated MS patients.

Associations of optical coherence tomography with disability and brain MRI volumetry in patients with multiple sclerosis.

AIM OF THE STUDY: To investigate in a cross-sectional study the correlations of optical coherence tomography (OCT) with clinical and magnetic resonance imaging (MRI) parameters in multiple sclerosis (MS) patients. MATERIAL AND METHODS: OCT parameters include the peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell complex (GCC). Brain magnetic resonance volumetry (T2- and T1- lesions volume, whole brain volume and grey matter volume) was evaluated using the Icobrain program. Clinical data was compared according to the history of optic neuritis (HON). Correlations were determined between OCT parameters and demographic (age, gender), clinical (disease duration, Expanded Disability Status Scale score [EDSS]), and MRI data. RESULTS: Out of 83 recruited people with MS, 27 had HON. The mean age of 75 patients with non-ON eyes was 42.08 ± 10.36 years, and 70.67% of the sample were females. Significant correlations were found between pRNFL and disability, along with several brain MRI-volumetry variables (Fluid-attenuated Inversion Recovery lesions volume [FLAIR]; T1-hypointense lesions volume; T1-lesions volume change; T1-volume lesions enlarging; whole brain volume; whole brain volume normative percentile; and volume of periventricular lesions). Multivariable linear regression analysis showed that age, pRNFL and GCC were significantly associated with T1-hypointense lesions volume change (the model explained 24% of the overall variance of the dependent variable). CONCLUSIONS: The pRFNL value correlates with disability and brain MRI-volumetric parameters in MS patients, serving as a useful neurodegeneration and inflammation surrogate marker.

Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis.

BACKGROUND: Neurofilament light chain is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (MS). Its role in progressive MS is less clear. AIM: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA-3 (No Evident Disease Activity), and brain volumetry, in a cohort of patients with the progressive disease form (PMS). METHODS: Levels of pNfL (SIMOA technology) were examined in 52 PMS patients and analysed in relationship to NEDA-3 status and annual brain volume loss (BVL) during the last 12 months. The statistical model was developed using logistic regression analysis, including demographic, clinical and magnetic resonance imaging (MRI) data as independent variables. Dependent variables were NEDA-3 status and BVL. RESULTS: The mean age of the study participants (n=52, 50% females) was 45.85 (SD, 9.82) and the median disability score was 5.0 (IQR: 5.0-5.5). ROC analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 77.8% and 87.6%, respectively, P<0.001) and abnormal BVL (the sensitivity and specificity were 96.6% and 68.2%, respectively, P<0.001). CONCLUSIONS: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-3 status, including brain MRI-volumetry, in patients with the progressive form of MS.

Cognitive Event-Related Potentials-The P300 Wave Is a Prognostic Factor of Long-Term Disability Progression in Patients With Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) is a chronic disorder with a variable course. The aim of our study was to find out whether cognitive event-related potentials are prognostic for patient disability at the 15-year follow-up. METHODS: In the observed cohort of patients with MS, we examined the event-related potentials at baseline (2003). Functional status (Expanded Disability Status Scale score) was then assessed 15 years later, and the prognostic model was developed using binary logistic regression analysis. The independent variables included demographic (age, sex, and education), clinical (disability in 2003), radiologic (MRI lesion load), and event-related potentials parameters. The prognostic accuracy of the proposed model was evaluated by calculating the area under the receiver-operating characteristics curve. RESULTS: The study sample consisted of 85 patients with MS. The mean age was 35.5 (SD, 11.2) years, and the median disability score was 3.0 (1-7) in 2003 and 5.0 (1.5-9.5) in 2018. The significant prognostic factors of poor Expanded Disability Status Scale are higher baseline Expanded Disability Status Scale, longer MS duration, and prolonged P300 latency. The sensitivity and specificity of the cutoff at 5.0 for the disability score were 94% and 89%, respectively, with the area under the receiver-operating characteristics curve 0.94 (95% confidence interval, 0.889-0.984; P < 0.001). CONCLUSIONS: The results show that out of event-related potentials, the P300 wave latency is a prognostic of long-term disability progression in patients with MS.

Incidence and prevalence of neuromyelitis optica spectrum disorders in Slovakia.

OBJECTIVE: : Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare, inflammatory, demyelinating diseases that affect the central nervous system. Neither the incidence nor the prevalence of NMOSD has been determined in Slovakia thus far. The aim of this study was to determine both the incidence and the prevalence of NMOSD in Slovakia using the 2015 International Panel of NMOSD diagnosis (IPND) criteria. METHODS: : We performed a population-based study in Slovakia to estimate both the incidence and the prevalence of NMOSD during the period from 1 January 2006 through 31 December 2019. NMOSD cases were reported from multiple sources and the diagnosis was subsequently verified using the IPND criteria by a joint commitee of three neurologists. The prevalence is reported as number of cases per 100,000 inhabitans and the incidence as number of new cases per 1,000,000 person-years. Age-adjusted rates to the WHO standard population 2005-2025 were also calculated. RESULTS: : We identified 63 NMOSD cases. The crude point-prevalence rate was 1.37 (95% CI 1.03-1.71) per 100,000 inhabitants. The crude indidence rate was 0.88 (95% CI 0.65-1.12) per 1,000,000 person-years. The age-adjusted point-prevalence rate was 1.42 (95% CI 1.07-1.84) per 100,000 persons and the age-adjusted incidence rate was 0.96 (95% CI 0.72-1.25) per 1,000,000 person-years. CONCLUSION: : The NMOSD epidemiological situation in Slovakia is comparable to those reported from other Caucasian populations.

Psychological well-being in people with multiple sclerosis and its association with illness perception and self-esteem.

BACKGROUND: Illness perception and self-esteem were found to improve adjustment to disease in many chronic conditions. However, so far, little is known about the role of illness-appraisal and self-appraisal factors in psychological well-being in people with multiple sclerosis (MS). Thus, we aimed to assess the association between illness perception, self-esteem and psychological well-being in people with MS while controlling for sociodemographic variables, clinical variables, and sleep-related problems. METHODS: The General Health Questionnaire-28, the Brief Illness Perception Questionnaire, the Rosenberg Scale of Self-esteem, the Expanded Disability Status Scale, the Pittsburgh Sleep Quality Index, and the Multidimensional Fatigue Inventory were used. Multiple linear regressions and mediation analyses were utilized to analyse the data. RESULTS: Positive illness perception (p<0.001) and self-esteem (p<0.05) were significantly associated with psychological well-being in MS. Low income (p<0.05) and sleep-related problems (p<0.001) were significantly associated with lower level of psychological well-being in people with MS. Positive illness perception and self-esteem were able to diminish the association between low income (p>0.05), poor sleep quality (p<0.01), fatigue (p>0.05), and low level of psychological well-being. Self-esteem also mediated the association between illness perception and psychological well-being. DISCUSSION: People with MS may benefit from psychological support aimed at promoting self-esteem and diminishing negative illness perception.

Self-management, self-esteem and their associations with psychological well-being in people with multiple sclerosis.

BACKGROUND: Optimal self-management seem to be protective factor of health-related quality of life and psychological well-being in many chronic conditions. However, the results in people with multiple sclerosis (MS) are still inconclusive. Thus, the aim of this study is to assess the associations between self-management, self-esteem and psychological well-being in people with MS when controlled for sociodemographic and clinical variables. METHODS: A total of 165 people with MS filled in The Multiple Sclerosis Self-Management Scale, Rosenberg Self-Esteem scale, and General Health Questionnaire-28, to assess main variables under study. Functional status was measured by Kurtzke disability Status Scale. RESULTS: We found significant associations between self-esteem and somatic symptoms, anxiety/insomnia, social dysfunction and severe depression. Explained variance of the models ranged from 16% to 38% for somatic symptoms and severe depression, respectively. Self-management significantly contributed to the explained variance in all models sans GHQ social dysfunction. Self-esteem was significant contributor to overall variance in all models. DISCUSSION: According to our results, self-management and self-esteem were found to be associated with multiple domains of psychological well-being. These findings may be used in neurological practice, to help people with MS who report psychological distress in one or more domains.

Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients.

INTRODUCTION: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). METHODS: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). RESULTS: Levels of pNfL were significantly higher in MS patients than in healthy controls (p <  0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). CONCLUSION: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

Approaches and challenges in the diagnosis and management of secondary progressive multiple sclerosis: A Central Eastern European perspective from healthcare professionals.

Secondary progressive multiple sclerosis (SPMS) is a debilitating condition characterized by gradual worsening after an initial relapsing disease course. Despite the recent advances in our understanding of the disease, the diagnosis and treatment of SPMS continue to be challenging in routine clinical practice. The aim of this review article is to present the views of leading MS experts on the challenges in the diagnosis and management of SPMS and clinicians' perspectives in Central and Eastern Europe. This article also provides recommendations of MS experts to improve the situation with diagnosis and management of SPMS. Many countries within Central and Eastern Europe have high prevalence of MS (>100 per 100,000 population). Consistent with the global trend, in the absence of reliable tests or biomarkers, SPMS at early stage remains undiagnosed. Due to diagnostic uncertainty and lack of a universally accepted disease definition, clinicians rely more on retrospective analysis of the clinical symptoms to confirm the diagnosis. With the lack of awareness and poor understanding of the timing of the onset of SPMS, clinicians may tend to direct attention to relapses than the symptoms of progression, which leads to underestimation of SPMS. Although several predictors of progression to SPMS have been identified, their predictive value is highly variable. Therefore, defining the transitioning period as a separate stage of MS is essential. According to experts' opinion, frequent follow-up of patients and periodic assessment of progression are recommended for the timely identification of patients transitioning from RRMS to SPMS. MSProDiscuss Tool is an example of a quick assessment tool for identifying patients progressing from RRMS to SPMS. MS progression is usually assessed by changes in Expanded Disability Status Scale (EDSS) scores. As EDSS scores tend to fluctuate when measured in the short term (3-6 months), a longer period (≥12 months) may be needed to confirm the progression. Assessment of cognitive function is also important for evaluating secondary progression. Compartmentalization of inflammation within the central nervous system is an important reason behind the limited success of disease-modifying therapies (DMTs) for treating SPMS. Most of the DMTs fail to cross the blood-brain barrier; only 38% of the tested DMTs achieved their primary endpoint in SPMS. In Europe, siponimod is the first oral treatment for adults with active SPMS. Particularly, in Central and Eastern Europe, patients with SPMS are still being prescribed less efficacious DMTs and interferons. The absence of alternative treatments in SPMS supports the use of new products (siponimod and others); however the decision to initiate siponimod therapy in more severe patients (EDSS score of 7 or higher) should be individualized in consultation with the payers. The focus should be on early treatment initiation to delay disease progression.

Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss.

BACKGROUND: The research is focused on sensitive biomarkers in multiple sclerosis (MS). OBJECTIVE: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA (no evident disease activity), including brain volumetry, in a cohort of MS patients treated with disease-modifying treatment (DMT). METHODS: Levels of pNfL (Single Molecule Array (SIMOA) technology) were examined in 95 RRMS (relapsing-remitting multiple sclerosis) patients and analyzed in relationship to NEDA-3 status and NEDA-BVL (brain volume loss; NEDA-3 extended by brain volumetry) during the last 12 months. The statistical model was developed using logistic regression analysis, including the independent variables: demographic, clinical, and magnetic resonance imaging (MRI) data. Dependent variables were NEDA-3 and NEDA-BVL status. RESULTS: The mean age of the study participants (n = 95, 62% females) was 37.85 years (standard deviation (SD) = 9.62) and the median disability score was 3.5 (2.5-4.1). Receiver operating characteristics (ROC) analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 92% and 78%, respectively, p < 0.001) and NEDA-BVL status (the sensitivity and specificity were 80% and 65%, respectively, p < 0.001). CONCLUSION: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-BVL status, including brain MRI-volumetry in patients with RRMS.

Sexual functioning in patients with multiple sclerosis and its association with social support and self-esteem.

Sexual dysfunction is very commonly reported by people with multiple sclerosis (MS). However, this problem often remains under-diagnosed and under-treated. Furthermore, still very little is known about protective psychosocial factors that may help to improve sexual functioning in MS patients. Thus, we aimed to assess the associations between social support, self-esteem and sexual functioning in MS patients when controlled for clinical and sociodemographic variables. The Expanded Disability Status Scale (EDSS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Rosenberg Scale of Self-esteem (RSE) were used to assess the independent variables. Sexual functioning was assessed by the Incapacity Status Scale (ISS). We found a significant association between social support and sexual functioning (p = 0.01). However, this association attenuated (p < 0.05) when self-esteem (p < 0.01) was added to the model. Furthermore, we found that sexual dysfunction in MS patients was associated with older age (p < 0.001). Self-esteem was associated with sexual functioning more strongly compared to social support and sexual functioning, even though both of these variables were associated with sexual functioning as well. Our findings support the biopsychosocial model of treatment of sexual dysfunction in MS patients.

Factors influencing daily treatment choices in multiple sclerosis: practice guidelines, biomarkers and burden of disease.

At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.

Fatigue and Suicidal Ideation in People With Multiple Sclerosis: The Role of Social Support.

Fatigue and poor sleep quality are among the most common patient-reported problems associated with multiple sclerosis (MS). Social support, on the other hand, is often found to be positively associated with quality of life in patients with neurological diseases. Studies also show that suicidal ideation (SI) levels in MS are elevated compared to the general population. Thus, the aim of this study is to assess the associations between fatigue, social support, and SI in patients with MS. Out of 184 MS patients asked to participate in this cross-sectional study, 156 agreed (RR 69.8%; 75% female; mean age: 39.95 ± 9.97 years). Patients filled-in the Multidimensional Fatigue Inventory-20, the Pittsburgh Sleep Quality Index, the Multidimensional Scale of Perceived Social Support and the subscale of the General Health Questionnaire-28 focused on assessing SI. Models were controlled for age, gender, disease duration, functional disability, and sleep quality. Data were analyzed using multiple linear regressions. SI was positively associated with lower sleep quality and four types of fatigue: general, mental, reduced activity, and reduced motivation (p < 0.05). Physical fatigue was not significantly associated with SI. Social support was negatively associated with SI in all models. The final models under study explained from 24.3 to 29.7% of the total variance in SI. SI yielded associations with both sleep quality and fatigue, with the exception of physical fatigue. Information provided by physicians on sleep management, and a psychosocial intervention focused on people who provide support for patients with MS (family, friends, and significant others) may reduce levels of SI.

Identification of new phosphorylation sites of CD23 in B-cells of patients with chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease. Here we report changes in the phosphorylation of CD23 on threonine (pThr314) and two serine residues (pSer254, pSer265) in B lymphocytes of B-CLL patients, using a flow cytometry approach. The majority of tested patients with active forms of B-CLL presented a notable overexpression of CD23 along with pThr314, pSer254, and pSer265 CD23 phosphorylation positivity. Moreover, we have experimentally stimulated the CD23 phosphorylations in a subset of peripheral blood lymphocytes of healthy controls by phorbol-12-myristate-13-acetate treatment. This affects the activation of competent phosphorylation mediating kinases, resulting in the enhanced phosphorylation pattern. Together, these data confirm that CD23 protein is phosphorylated in B cells of B-CLL patients, report the identification of new CD23 phosphorylation sites, and suggest a possible role(s) of such phosphorylations in the activation of CD23 during the process of lymphocytic activation in B-CLL.

Management of multiple sclerosis patients in central European countries: current needs and potential solutions.

Multiple sclerosis (MS) experts in Europe are facing rapidly rising demands of excellence due to the increasing complexity of MS therapy and management. A central European expert board of MS experts met to identify needs and obstacles with respect to raising quality of MS care in central and Eastern European countries. There are substantial variations across countries regarding delivery of care and its cost structure, as well as access to treatment. To date, Eastern European countries are often less able to afford reimbursement of immunomodulatory agents than Western countries. Overall, approximately 40% of working-age patients are not working due to MS. Costs rise steeply with increasing disability; indirect costs constitute the bulk of the financial burden in patients with severe MS. Magnetic resonance imaging (MRI) assessment is meanwhile obligatory as the diagnostic interface in the management of MS patients. Recommended measures directed at improving quality of care include the collection of patient data in registries, enhanced education of healthcare professionals, implementation of national strategies aiming at reducing regional variation, optimization of approval processes, and removal of administrative barriers. Local partnerships with authorities such as those that represent the interests of employees can contribute to leverage the importance of epidemiological data. The need for education extends to (neuro)radiologists who are responsible for reporting MRI findings in expert quality. Dissemination of the Magnetic Resonance Imaging in MS (MAGNIMS) protocol would be an important step in this context. Also, clinical freedom of choice is rated as essential. Physicians should have access to a range of treatment options due to the complexity of disease. Guidelines such as the upcoming EAN-ECTRIMS clinical practice guideline also aim at providing a basis for argumentation in negotiations with national health authorities.

Management of multiple sclerosis: the role of coping self-efficacy and self-esteem.

Patients with multiple sclerosis (MS) engage in various coping behaviours in order to manage their disease. The aim of this study is to find out if the self-esteem of patients is associated with coping strategies - problem-focused (e.g. making a plan of action when confronted with a problem); emotion focused (e.g. get emotional support from community); and focused on stopping unpleasant emotions and thoughts (e.g. keeping oneself from feeling sad), and if it can enhance or hinder coping efforts in the disease management. We collected data from 155 consecutive MS patients who completed the Coping Self-Efficacy Scale (CSE) and the Rosenberg Self-esteem Scale (RSE). Explained variance for problem-focused coping, emotion-focused coping, and coping focused on stopping unpleasant emotions and thoughts was 33, 24, and 31%, respectively. Self-esteem seems to be associated with coping strategies indicating that feelings of self-worth are linked with the ability to handle difficult life situations and can be helpful in chronic disease management.