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Multiple Sclerosis (MS) is often seen in young adults and known to cause both physical and cognitive disability, and it is quite important to make an objective assessment of the physical-cognitive disability status of the patients. The first scale that assesses the physical disability in MS cases, the Disability Status Scale (DSS) elaborated in 1983 and transformed into the Expanded DSS (EDSS). It has been in use since 1983 without much change, which is one of its most significant advantages. It includes all functional systems (although with some shortcomings) that may be affected in MS and reflects the clinical status as a number, which is quite valuable. Although there may be differences between EDSS practitioners, it has been in use for more than 30 years and it can objectively display the difference between a patient's clinical picture 20 years ago and today, which can be said for only a small number of scales. This shows the importance of using the same scale for diseases that require long-term monitoring such as MS. In conclusion; it is a consensus that EDSS will not undergo major changes so that its greatest advantage can be preserved. Also, the consensus in the available literature is that EDSS will never lose its value.

While neurofilament light chain (NfL) measurement in serum is a well-established marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial markers in serum are missing. In our study, glial fibrillary acid protein (GFAP) and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and patients with other non-inflammatory neurological diseases (OND) using the Simoa technology. Clinical data like age, gender, expanded disability status scale (EDSS) and MRI findings were correlated to neurochemical markers. We included 80 MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p < 0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups). Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p = 0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p = 0.01). in summary, we report elevated levels of GFAP in the serum of MS patients. Since serum levels of GFAP correlate with the clinical severity scores and MRI lesion count, especially in PMS patients, it might be a suitable disease progression marker.

Background There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments – EDSS and MSFC – meet methodological standards and the value they have in clinical trials. Methods We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed. Results For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments. For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC). Conclusions Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.

Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as a focal inflammatory disease of the central nervous system (CNS). We provide a range of evidence to argue that the ‘real MS’ is in fact driven primarily by a smouldering pathological disease process. In natural history studies and clinical trials, relapses and focal activity revealed by magnetic resonance imaging (MRI) in MS patients on placebo or on disease-modifying therapies (DMTs) were found to be poor predictors of long-term disease evolution and were dissociated from disability outcomes. In addition, the progressive accumulation of disability in MS can occur independently of relapse activity from early in the disease course. This scenario is underpinned by a more diffuse smouldering pathological process that may affect the entire CNS. Many putative pathological drivers of smouldering MS can be potentially modified by specific therapeutic strategies, an approach that may have major implications for the management of MS patients. We hypothesise that therapeutically targeting a state of ‘no evident inflammatory disease activity’ (NEIDA) cannot sufficiently prevent disability accumulation in MS, meaning that treatment should also focus on other brain and spinal cord pathological processes contributing to the slow loss of neurological function. This should also be complemented with a holistic approach to the management of other systemic disease processes that have been shown to worsen MS outcomes.

Background and purpose The validity, reliability, and longitudinal performance of the Patient‐Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS. Methods We included relapsing–remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4. Validity and test–retest reliability was examined. Longitudinal data were analysed with mixed‐effect modelling and Cohen's kappa for concordance in confirmed disability progression (CDP). Results We recruited a total of 1093 participants, of whom 904 had complete baseline data. The baseline correlation between PDDS and EDSS was weak (ρ = 0.45, p < 0.001). PDDS had stronger correlations with patient‐reported outcomes (PROs). Conversely, EDSS had stronger correlations with age, disease duration, Kurtzke's functional systems and processing speed test. PDDS test–retest reliability was good to excellent (concordance correlation coefficient = 0.73–0.89). Longitudinally, PDDS was associated with EDSS, age and depression. A higher EDSS score was associated with greater PDSS progression. The magnitude of these associations was small. There was no concordance in CDP as assessed by PDDS and EDSS. Conclusion The PDDS has greater correlation with other PROs but less correlation with other MS‐related outcome measures compared to the EDSS. There was little correlation between PDDS and EDSS longitudinally. Our findings suggest that the PDDS scale is not interchangeable with the EDSS.

Background and purpose Higher latitude has been associated with increased occurrence of multiple sclerosis (MS) and with more severe disease. The aim was to study the impact of sun exposure habits on MS disease progression and health‐related quality of life. Methods Patients from a population‐based case–control study were categorized based on sun exposure habits at diagnosis and were followed up to 15 years post‐diagnosis through the Swedish MS registry (n = 3314) with regard to changes in Expanded Disability Status Scale (EDSS). Linear mixed models were used to analyse long‐term changes, while Cox regression models, with 95% confidence intervals, were used to investigate outcomes, including 24‐week confirmed diasability worsening, EDSS3, EDSS4, and physical worsening as measured by the physical component of the Multiple Sclerosis Impact Scale 29. Results Compared to average sun exposure (median value), low exposure to sunlight was associated with faster EDSS progression, increased risk of confirmed disability worsening (hazard ratio [HR] 1.48, 95% CI 1.21–1.81), increased risk of reaching EDSS 3 (HR 1.35, 95% CI 1.02–1.79), EDSS 4 (HR 1.47, 95% CI 1.01–2.20) and self‐reported physical worsening (HR 1.27, 95% CI 1.00–1.62). Significant trends revealed a lower risk of unfavourable outcomes with increasing sun exposure. Conclusions Very low levels of sun exposure are associated with worse disease progression and health‐related quality of life in patients with MS.

•DTI carried out over several months on phantom (100 measurements), 50 healthy control (HC) volunteers and 50 multiple sclerosis (MS) patients proved.•The existence of systematic errors with repetitive spatial characteristics and their statistically significant impact on diffusion tensor metrics (DTMs).•The effective elimination of their impact on DTMs by means of the BSD method.•DTMs statistically significantly differentiate the HC and MS groups in both the standard and BSD approaches,however, the latter provides more realistic values. Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1–3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics. [Display omitted]

Background Neuromyelitis optica (NMO) is a severe inflammatory autoimmune disorder of the central nervous system and often results in paralysis or blindness. Rituximab (RTX) is a mouse–human chimeric monoclonal antibody specific for the CD20 antigen on B lymphocytes and used to treat many autoimmune diseases. Disability and relapses were measured using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR) ratio to evaluate the effectiveness of RTX. This review performed a meta-analysis of the efficacy of RTX in NMO. Methods We searched through the databases of PubMed, Embase, and Cochrane Library. We compiled 26 studies, in which 18 used ARR ratio, 22 used EDSS score, and 14 used both variables. Differences in the ARR ratio and EDSS score before and after RTX therapy were used as the main efficacy measures. Publication bias was evaluated after the consistency test, and a sensitivity analysis was performed with mean difference (MD) of the efficacy of RTX. Results A meta-analysis of 26 studies with 577 participants was conducted. Antibodies against aquaporin-4 autoantibody were recorded in 435 of 577 (75.39%) patients with NMO. RTX therapy resulted in a mean (WMD) − 1.56 (95% CI, − 1.82 to − 1.29) reduction in the mean ARR ratio and a mean (WMD) − 1.16 (95% CI, − 1.36 to − 0.96) reduction in the mean EDSS score. A total of 330 of 528 patients (62.9%) reached the relapse-free state. A total of 95 of 577 (16.46%) patients had adverse reactions. Conclusions RTX has acceptable tolerance, reduces the relapse frequency, and improves disability in most patients with NMO. Future studies should focus on reducing the health-care costs, improving the functional outcomes, and reducing the adverse effects associated with RTX treatment.