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  • 1
    Online Resource
    Online Resource
    Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis
    SAGE Publications ; 2019
    In:  Multiple Sclerosis Journal Vol. 25, No. 5 ( 2019-04), p. 661-668
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 25, No. 5 ( 2019-04), p. 661-668
    Abstract: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Methods: Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. Results: Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. Conclusions: Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients’ counseling upon initial diagnosis of MS.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458518763541
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
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  • 2
    Online Resource
    Online Resource
    Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Neurological Disorders Vol. 14 ( 2021-01), p. 175628642110396-
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 14 ( 2021-01), p. 175628642110396-
    Abstract: Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/17562864211039648
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 3
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    Dietary fatty acids and susceptibility to multiple sclerosis
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 1 ( 2018-01), p. 12-16
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 1 ( 2018-01), p. 12-16
    Abstract: The gut microbiome as well as dietary habits have recently been established as environmental contributors to the pathogenesis of multiple sclerosis (MS), a T-cell-mediated autoimmune disease of the central nervous system (CNS). Objective: To summarize recent findings on the Janus-faced effects of dietary short-chain fatty acids (SCFAs) and long-chain fatty acids (LCFAs) on T-cell immunity with a special focus on the gut and the microbiome as an interface linking diet and T-cell responses during MS. Methods: Review article. Results: The autoimmune basis of MS most likely stems from an imbalance between pro-inflammatory T helper cell (Th)1 and Th17 cells and anti-inflammatory or regulatory mechanisms including regulatory T cells (Treg). Hence, the rationale of currently available therapeutic interventions is to either suppress pathogenic Th1/Th17 and/or to foster Treg responses. Dietary fatty acids are often discussed for their detrimental role in MS. However, recent studies investigating saturated fatty acids in animal models of MS revealed harmful as well as beneficial effects depending on their aliphatic chain length. Conclusion: Dietary SCFAs constitute interesting candidates as safe and potent add-on therapy in the immunomodulatory treatment armamentarium for relapsing-remitting MS.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517737372
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 4
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    Online Resource
    Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder
    SAGE Publications ; 2014
    In:  Multiple Sclerosis Journal Vol. 20, No. 7 ( 2014-06), p. 882-888
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 20, No. 7 ( 2014-06), p. 882-888
    Abstract: Longitudinally extensive transverse myelitis is characteristic but not pathognomonic for neuromyelitis optica spectrum disorders (NMOSDs) and may mimic local tumors. In this retrospective study based on a cohort of 175 NMOSD patients we identified seven patients who initially presented with a longitudinally extensive spinal cord lesion and underwent spinal cord biopsy due to magnetic resonance imaging (MRI)-suspected malignancies. Remarkably, routine neuropathology was inconclusive and did not guide the diagnostic process to anti-aquaporin-4 (AQP4)-seropositive NMOSD. Serious postoperative complications occurred in 5/7 patients and persisted during follow-up in 2/7 patients (29%). Considering these sequelae, AQP4-antibody testing should be mandatory in patients with inconclusive longitudinally extensive spinal cord lesions prior to biopsy.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458513510981
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 5
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    Online Resource
    Influence of female sex and fertile age on neuromyelitis optica spectrum disorders
    SAGE Publications ; 2017
    In:  Multiple Sclerosis Journal Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Abstract: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p  〈  0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at 〉 40 years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458516671203
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 6
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    Online Resource
    Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis
    SAGE Publications ; 2023
    In:  Multiple Sclerosis Journal - Experimental, Translational and Clinical Vol. 9, No. 4 ( 2023-10)
    Details
    In: Multiple Sclerosis Journal - Experimental, Translational and Clinical, SAGE Publications, Vol. 9, No. 4 ( 2023-10)
    Abstract: Ofatumumab is approved for treating relapsing multiple sclerosis (RMS). Examining tolerability will enable understanding of its risk–benefit profile. Objective Report the tolerability profile of ofatumumab in RMS during treatment of up to 4 years and the effect of pre-medication. Methods Cumulative data from the overall safety population included patients taking continuous ofatumumab or being newly switched from teriflunomide. Injection-related reactions (IRRs) by incidence and severity, and post-marketing surveillance data, with an exposure of 18,530 patient-years, were analyzed. Results Systemic IRRs affected 24.7% of patients (487/1969) in the overall safety population; most (99.2% [483/487]) were mild (333/487) to moderate (150/487) in Common Terminology Criteria for Adverse Events severity; most systemic IRRs occurred after first injection. Local-site IRRs affected 11.8% (233/1969) and most (99.6% [232/233] ) were mild/moderate. Incidence and severity of systemic and localized IRRs were similar between continuous and newly switched patients across repeated injections. Systemic IRR incidence and severity were not substantially affected by steroidal or non-steroidal pre-medication. Post-marketing surveillance identified no new tolerability issues. Conclusion Ofatumumab is well tolerated, displays a consistent safety profile during continuous use or after switching from teriflunomide and does not require pre-medication. This enables home management of RMS with a high-efficacy treatment.
    Type of Medium: Online Resource
    ISSN: 2055-2173 , 2055-2173
    URL: Article
    DOI: 10.1177/20552173231203816
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2841884-0
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  • 7
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    Online Resource
    Review: Innovative monoclonal antibody therapies in multiple sclerosis
    SAGE Publications ; 2008
    In:  Therapeutic Advances in Neurological Disorders Vol. 1, No. 1 ( 2008-07), p. 33-42
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 1, No. 1 ( 2008-07), p. 33-42
    Abstract: The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis (MS), especially for relapsing—remitting disease courses. In particular, the application of monoclonal antibodies provide innovative approaches allowing for blocking or depleting specific molecular targets, which are of interest in the pathogenesis of MS. While natalizumab received approval by the US Food and Drug Administration and the European Medicines Agency in 2006 as the first monoclonal antibody in MS therapy, rituximab, alemtuzumab, and daclizumab were successfully tested for relapsing-remitting MS in small cohorts in the meantime. Here, we review the data available from these recent phase II trials and at the same time critically discuss possible pitfalls which may be relevant for clinical practice. The results of these studies may not only broaden our therapeutic options in the near future, but also provide new insights into disease pathogenesis.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/1756285608093945
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
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  • 8
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    Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 5 ( 2018-04), p. 590-603
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 5 ( 2018-04), p. 590-603
    Abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS), most likely autoimmune in origin, usually beginning in early adulthood. The aetiology of the disease is not well understood; it is viewed currently as a multifactorial disease which results from complex interactions between genetic predisposition and environmental factors, of which a few are potentially modifiable. Improving our understanding of these factors can lead to new and more effective approaches to patient counselling and, possibly, prevention and management of the disease. The 2016 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) addressed the topic of environmental, modifiable risk factors for MS, gathering experts from around the world, to collate experimental and clinical research into environmental factors that have been associated with the disease onset and, in a few cases, disease activity and progression. A number of factors, including infections, vitamin D deficiency, diet and lifestyle factors, stress and comorbidities, were discussed. The meeting provided a forum to analyse available evidence, to identify inconsistencies and gaps in current knowledge and to suggest avenues for future research.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458516686847
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 9
    Online Resource
    Online Resource
    Fingolimod initiation in multiple sclerosis patients is associated with potential beneficial cardiovascular autonomic effects
    SAGE Publications ; 2017
    In:  Therapeutic Advances in Neurological Disorders Vol. 10, No. 4 ( 2017-04), p. 191-209
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 10, No. 4 ( 2017-04), p. 191-209
    Abstract: Fingolimod slows heart rate (HR) due to vagomimetic effects and might cause additional cardiovascular autonomic changes. While the time course of HR changes is well described, the extent and course of cardiovascular autonomic changes upon fingolimod initiation has not yet been evaluated. This study, therefore, intended to assess cardiovascular autonomic changes during the first 6 h after fingolimod initiation. Methods: In 21 patients with relapsing-remitting multiple sclerosis (RRMS), we recorded respiration (RESP), electrocardiographic RR interval (RRI), systolic and diastolic blood pressure (BPsys, BPdia) at rest, before and 0.5, 1, 2, 3, 4, 5, and 6 h after fingolimod initiation. We calculated parameters of total autonomic modulation [RRI standard deviation (RRI-SD), RRI coefficient of variation (RRI-CV), RRI-total powers], mainly sympathetic cardiac modulation [RRI low frequency (LF) powers] , sympathetic BP modulation (BPsys-LF powers), parasympathetic modulation [square root of the mean squared difference of successive RRIs (RMSSD), RRI high frequency (HF) powers], sympatho-vagal cardiac balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). We compared parameters between the eight measurements [analysis of variance (ANOVA) or Friedman test with post-hoc analysis; significance: p 〈 0.05]. Results: After fingolimod initiation, RESP, BPsys, and BPsys-LF powers remained unchanged while RRIs, RRI-CV, RRI-SD, RRI-total powers, RRI-LF powers, RMSSD, RRI-HF powers, and BRS increased after 1 h and rose to peak values occurring after 5, 1, 2, 2, 1, 4, 4, and 4 h, respectively. After 3 h, BPdia had decreased significantly and was lowest after 5 h. RRI-LF/HF ratios decreased to a nadir after 4 h. Conclusions: The increases in parasympathetic and overall cardiac autonomic modulation and in BRS seen with fingolimod initiation are theoretically beneficial for the MS patient’s cardiovascular system. However, long-term studies must show whether these effects persist or are attenuated (e.g. due to S1P1 receptor down-regulation upon continued fingolimod therapy).
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/1756285616682936
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 10
    Online Resource
    Online Resource
    Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies
    SAGE Publications ; 2016
    In:  Therapeutic Advances in Neurological Disorders Vol. 9, No. 4 ( 2016-07), p. 269-280
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 9, No. 4 ( 2016-07), p. 269-280
    Abstract: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing–remitting MS (RRMS) treated with DMTs over 1 year. Methods: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients ( n = 41) corresponds to the stability in healthy individuals ( n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod ( n = 22) with patients treated with natalizumab ( n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. Results: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. Conclusions: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/1756285616643892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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