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Objective: Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia., Methods: PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi 2 test and multivariable linear regression models were run., Results: 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness., Conclusions: We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively., Competing Interests: Declaration of Competing Interest Diem L received travel grants from Merck, Biogen, Roche and Bayer Schweiz. She also received advisory honoraria or speaker's honoraria from Biogen, Novartis and Merck. All not related to that work. Evangelopoulos ME received travel grants and consulting fees from Biogen, Novartis, Genzyme, Teva, Merck, and Roche. All not related to that work. Karathanassis D has no conflicts of interest. Natsis V has no conflicts of interest. Hammer H received research support and travel grants within the last 5 years from Biogen, Merck, Roche & BMS Friedli C has received travel grants from Biogen, travel grants and advisory honoraria from Sanofi Genzyme, as well as speaker honoraria from Biogen, Novartis and Merck and research support from Chiesi, not related to this work. He reports no conflicts of interest related to this manuscript. Kamber N received travel and/or speaker honoraria and served on advisory boards for Alexion, Biogen, Merck, Sanofi Genzyme and Roche and received research support by Biogen. Salmen A received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme and research support by the Swiss MS Society. Chan A has served on advisory boards for, and received funding for travel or speaker honoraria from, Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, and Teva, all for hospital research funds; and research support from Biogen, Genzyme and UCB. Chan A is associate editor of the European Journal of Neurology and serves on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. Helbling A has no conflicts of interest. Penner IK has received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She has received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. Walther S received honoraria from Janssen, Lundbeck, Mepha, Neurolite, Otsuka and Sunovion. He served on advisory boards for Lundbeck and Sunovion in 2019. All interests are unrelated to this work. Dr. Walther is associate editor of the European Archives of Psychiatry and Clinical Neuroscience and Frontiers in Psychiatry, in addition, he serves on the editorial board of Neuropsychobiology. Stegmayer K received honoraria from Janssen, Lundbeck, Mepha, and Sunovion. All interests are unrelated to this work. Hoepner R received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Bristol-Myers Squibb, and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society. All not related to that work., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Interruption of natalizumab (NTM) treatment in multiple sclerosis (MS) patients may be followed by disease reactivation. On the other hand, patients with positive John Cunningham virus (JCV) antibodies treated with NTM over 24 months demonstrate a higher risk for developing progressive multifocal encephalopathy (PML). No established therapeutic approach is available for treating these patients to prevent disease reactivation., Materials and Methods: Of the MS patients treated with NTM at the authors' institution, 30 were found positive for JCV abs. NTM was interrupted followed by a washout period of 6 months. During this period, 20/30 patients received monthly intravenous (i.v.) methylprednisolone (MPD) 1000 mg infusion and regular clinical assessment. On months 3 and 6, brain MRI was performed and 1000 mg MPD was administered for 5 days., Results: All patients were clinically and radiologically stable at the time of NTM break. No clinical relapse was observed during the six-month washout period for the MS patients under monthly MPD treatment, while one patient had a relapse and active lesions in the MRI on month 6. Of the other patients not receiving i.v. MPD regularly after NTM withdrawal, one showed several active lesions in brain MRI and the other had a severe relapse., Conclusions: Despite the limited size of this patients' cohort, the results of this study support that monthly MPD treatment for 6 months may result in a clinically stable disease status, thus ensuring safe transition to another second-line therapy such as fingolimod, following NTM withdrawal.

Introduction: Interleukin-15 (IL-15) is a proinflammatory cytokine. RANTES is a member of the beta chemokines subfamily with strong chemoattractant activity for T lymphocytes and monocytes., Materials and Methods: We measured by enzyme-like immunosorbent assay (ELISA) serum levels of IL-15 and RANTES in 24 patients with MS in relapse, 27 patients with stable MS and 21 healthy subjects. Serum levels of IL-15 and RANTES were also measured before, 5 days and 1 month after onset of treatment with methylprednisolone i.v., Results: IL-15 serum levels were higher in patients with relapse compared with patients in stable stage of the disease and healthy subjects (p=0.001 and p=0.008 respectively). RANTES serum levels were increased in patients with relapse and stable disease as compared to healthy subjects (p=0.01). IL-15 and RANTES levels were not decreased after treatment with corticosteroids., Conclusions: Our findings suggest a possible role of IL-15 and RANTES in MS. Treatment with methylprednisolone in relapse had no effect on serum IL-15 and RANTES levels.

Background/aims: The onset of multiple sclerosis (MS) in Greece has not been systematically studied. We sought to provide data on the onset of MS in Greece with detailed information regarding initial symptoms, and to confirm the prognostic significance of demographic and clinical factors at onset., Methods: We studied 1,034 consecutive patients with MS and independently assessed 265 patients 'seen at onset'. We used the MS severity score and survival analysis (time to reach an Expanded Disability Status Scale score of 4.0) to evaluate the prognostic significance of factors at onset., Results: Female-to-male ratio was 1.9:1 and mean age at onset was 30.7 +/- 9.9 years. MS was primary progressive in 9.6%. Initial symptoms were optic neuritis in 20.1%, brainstem dysfunction in 14.7%, dysfunction of long tracts in 49.3%, cerebral dysfunction in 1% and a combination of symptoms in 14.9%. In 'seen at onset' patients, detailed data on initial symptoms are presented. Female gender, earlier age at onset, 'bout onset' and onset with optic neuritis were associated with less severe disease and longer time to disability., Conclusion: The onset of MS in Greece is similar to Western populations. Initial symptoms are within the expected spectrum. Prognostic significance of factors at onset is as previously identified., (Copyright 2010 S. Karger AG, Basel.)

There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug-free male and female patients with clinically-isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing-remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17–61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Interleukin-12 (IL-12), a proinflammatory cytokine produced by Th1 cells, and interleukin-10 (IL-10), a product of Th2 cells, are involved in the pathogenetic mechanisms of multiple sclerosis (MS). CCL2 chemokine expression is induced by Th2 cytokines and is decreased in MS relapse. The mechanisms responsible for the beneficial effects of IVmethylprednisolone in attacks are not clearly established and the duration of the effect of this treatment remains controversial. Patients and methods: We measured by enzyme-like immunosorbent assay (ELISA) serum levels of IL-12, IL-10 and CCL2 before, 5 days and 1 month after the initiation of treatment with IVMP in 20 patients with MS in relapse. Results: A significant increase of IL-10 and decrease of CCL2 serum levels was observed (p =0.0028 and 0.045 respectively) five days after the onset of steroid treatment but not after one month. Steroid treatment had no influence in serum levels of IL-12. Conclusions: The clinical improvement of our MS patients with relapse following the treatment with methylprednisolone may be associated with an immediate but not a long-term modification of serum levels of IL-10 and CCL2. IL-12 may not be influenced by steroid treatment. [Copyright &y& Elsevier]