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Background: Impaired olfactory threshold has been reported in early inflammatory phases of MS, while impaired odor identification was associated with more widespread disability. Objective: To prospectively assess the development of olfactory function and its correlation with relapse and disability progression. Methods: In this prospective, 3-year longitudinal study on 151 MS patients and 30 healthy controls, three different qualities of olfactory function (threshold, discrimination, and identification) were quantified using the Sniffin' Sticks test. The influence of relapses and disability on olfactory function was analyzed at different time points and in a multivariate model. Results: Discrimination and identification capability significantly worsened over 3 years, while threshold did not. Threshold was markedly impaired in patients with relapse activity within 12 months, recovered in the absence of relapse, and was associated with a 2.5-fold increased risk of relapse. Deterioration of discrimination and identification was irreversible and both strongly associated with and predictive of EDSS progression. Conclusion: Olfactory function changes over time in MS. Threshold impairment is transient and predicts inflammatory disease activity, while odor identification and discrimination are associated with disability progression. Olfactory dysfunction might be a useful and easily obtainable parameter to monitor patients with regard to inflammation and neurodegeneration in MS. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. Objective: To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. Methods: We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS (n = 48), relapsing-remitting multiple sclerosis (n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). Results: CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Conclusion: Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB. [ABSTRACT FROM AUTHOR]

Background: Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing–remitting multiple sclerosis (RRMS). Objective: To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making. Methods: We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation. Hazard ratios (HRs) with 95% confidence intervals (CIs) regarding relapse and disability progression after DMT discontinuation were calculated from Cox regression models. Results: Age >45 years at discontinuation (HR = 0.47, CI = 0.23–0.95, p = 0.038), absence of relapses for ⩾4 years on DMT before discontinuation (HR = 0.29, CI = 0.10–0.82, p = 0.020) and absence of contrast enhancing lesions (HR = 0.46, CI = 0.28–0.78, p = 0.004) were independent predictors of absence of relapse after discontinuation. Age >45 years and absence of relapses ⩾4 years on DMT combined had an HR of 0.06 (CI = 0.01–0.44, p < 0.001). Higher Expanded Disability Status Scale (EDSS) at discontinuation, age >45 years and longer disease duration were significantly associated with disability progression after discontinuation. Conclusion: While freedom from further disease activity is generally unpredictable, there is a subset of patients (age ⩾45 years, DMT intake ⩾4 years without evidence of clinical or radiological disease activity) having a high likelihood of remaining relapse-free after DMT discontinuation. However, close clinical monitoring for recurrent disease activity is mandatory after discontinuing treatment. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the frequency and implications of antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) and aquaporin 4 antibodies (AQP4-ab) in adult patients with suspected limited forms of neuromyelitis optica (NMO). The study is investigated by cell-based assays, Mann-Whitney U test, and Chi-square test. Results show that MOG-ab is commonly detected in the serum of patients with NMO, longitudinally extensive myelitis (LETM), and optic neuritis (ON).

We have recently demonstrated the safety and tolerability of a novel therapeutic regimen employing autologous blood cells chemically coupled with seven myelin peptides to induce antigen-specific tolerance in MS (ETIMS study). The aim of the current study was an extended safety analysis to assess the effect of the ETIMS approach on antibodies to common autoantigens, the myelin peptides used and common recall antigens. None of the patients showed induction of autoantibody responses. One patient had a measurable myelin peptide-specific response at baseline, which was reduced after treatment. Total immunoglobulins and recall antibody responses showed no significant change. [ABSTRACT FROM AUTHOR]

The article presents a study which describes the cognitive dysfunction in pediatric transverse myelitis (TM) patients. The study also explores the impact of depression, medication, and fatigue on cognitive functioning. The study uses the neuropsychological screening as the method of the study. Results show that a slight higher frequencies of impairment were observed as compared to processing speed and verbal fluency.

Background: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren’s syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation.Objectives: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms.Methods: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4.Results: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69).Conclusion: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients. [ABSTRACT FROM AUTHOR]

The article discusses a study on the role of rate CYP27BI gene variants in multiple sclerosis (MS) patients in Austria. It examines the potential role of vitamin D deficiency as a risk factor for MS as well as looks at the cause of vitamin D-dependent rickets type 1. The study suggests that rate CYP27B1 variants have no major role in the etiology of MS.