Publications by authors named "Refik Pul"

Background: The impact of body weight on disability progression rates among patients receiving ofatumumab was not evaluated yet.

Methods: Among patients from a multicentre prospective cohort, baseline demographics were compared among body mass index (BMI) quartiles as well as proportions of clinical relapses, MRI lesions and disability worsening during follow-up.

Results: 536 patients from four centres were included.

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A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.

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Article Synopsis
  • B-cell-depletion with CD20 antibodies, specifically ocrelizumab (OCR) and ofatumumab (OFA), is an effective treatment for relapsing multiple sclerosis (RMS), but their comparative effectiveness in real-world settings was previously unknown.
  • A cohort study involving 1,138 RMS patients was conducted in Germany, using propensity-score matching to compare the outcomes of OCR and OFA treatment, focusing on clinical relapses, MRI lesion changes, and disability progression.
  • Results showed that OFA was non-inferior to OCR in overall effectiveness, but differences were noted in patients switching from other therapies, highlighting the need for more research on these specific cases.
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  • Diagnosing multiple sclerosis (MS) is complicated by varied symptoms and lack of specific biomarkers, compounded by the presence of concurrent autoimmune diseases (AID) and non-specific antibodies, which can hinder effective management.* -
  • A study conducted on 315 patients from 2010 to 2017 revealed that 13.7% had concurrent AID, with autoimmune thyroiditis being the most common, but these conditions did not significantly affect MS progression or relapse rates over a median follow-up of 9 months.* -
  • The findings suggest that while AIDs are prevalent at the onset of MS, they do not influence neurofilament light (NfL) levels, indicative of similar disease activity, pointing to a need
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Background: Incomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data on apheresis outcomes in MOGAD attacks remain limited.

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  • Cognitive impairment is a significant issue in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD), with a study showing that about 21.9% of patients experience cognitive deficits, particularly in mental flexibility and attention.
  • The study involved 32 MOGAD patients and analyzed clinical factors like age and previous relapses, finding that the overall number of relapses and past episodes of acute disseminated encephalomyelitis (ADEM) were linked to increased cognitive impairment risk.
  • MRI results indicated that patients with MOGAD had reduced white and deep gray matter volumes compared to healthy controls, highlighting potential neurological damage in this condition.
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  • Eculizumab (ECU) has shown effectiveness in preventing attacks in patients with aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (NMOSDs) during a retrospective analysis in clinical settings between 2014 and 2022.
  • A total of 52 patients were studied, with 88% being attack-free during treatment, and the annualized attack rate significantly decreased from 1.0 to 0.
  • While common side effects included serious infections, five patients died from various complications, indicating a need for careful monitoring during long-term ECU therapy.
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Background And Objectives: Accurate diagnosis of secondary progression in multiple sclerosis (MS) remains a challenge since standardized criteria are missing. In 2016, the MSBase registry presented an algorithm that enabled the diagnosis of secondary progressive multiple sclerosis (SPMS) more than three years earlier compared to diagnosis by neurologists. This work aimed to test whether this approach is equally effective in a real-world cohort of MS patients.

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Background: The current approval of oral cladribine covers four years, with two treatment courses in the first two years, followed by two treatment-free years. For decision-making in year 5, experts recommend three scenarios: Extending the treatment-free period, retreatment with cladribine, or therapy switch.

Objective: To assess the implementation of the three year-5-scenarios in clinical practice in a large multicentric real-world cohort in Germany.

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Background And Objectives: Relapse and MRI activity usually decline with aging but are replaced by progression independent of relapse activity (PIRA) in patients with multiple sclerosis (PwMS). However, several older PwMS continue to experience clinical relapses, and the impact on their disease remains undetermined. We aimed to determine the impact of an index relapse on disease outcomes in patients older than 50 years and to identify risk factors of disadvantageous outcomes.

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We analyzed actin cytoskeleton alterations during NET extrusion by neutrophil-like dHL-60 cells and human neutrophils in the absence of DNase1 containing serum to avoid chromatin degradation and microfilament disassembly. NET-formation by dHL-60 cells and neutrophils was induced by Ionomycin or phorbol-12-myristat-13-acetate (PMA). Subsequent staining with anti-actin and TRITC-phalloidin showed depolymerization of the cortical F-actin at spatially confined areas, the NET extrusion sites, effected by transient activation of the monooxygenase MICAL-1 supported by the G-actin binding proteins cofilin, profilin, thymosin ß4 and probably the F-actin fragmenting activity of gelsolin and/or its fragments, which also decorated the formed NETs.

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Background: Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.

Objectives: Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.

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5q-related Spinal muscular atrophy (SMA) is a hereditary multi-systemic disorder leading to progressive muscle atrophy and weakness caused by the degeneration of spinal motor neurons (MNs) in the ventral horn of the spinal cord. Three SMN-enhancing drugs for SMA treatment are available. However, even if these drugs are highly effective when administrated early, several patients do not benefit sufficiently or remain non-responders, e.

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Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g.

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Article Synopsis
  • - A 24-year-old male with an unknown immunodeficiency was ultimately diagnosed with deficiency of adenosine deaminase 2 (DADA2), which caused recurrent brainstem strokes.
  • - The patient initially misdiagnosed with common variable immunodeficiency (CVID) underwent various treatments, including immunosuppressive therapy and plasma exchange, which highlighted the complexity of his condition.
  • - DADA2, a rare cause of recurrent stroke due to vasculitis, should be considered in young patients with unexplained strokes to ensure appropriate and effective treatment.
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Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls.

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Background And Objectives: B cell-depleting antibodies were proven as effective strategy for the treatment of relapsing multiple sclerosis (RMS). The monoclonal antibody ocrelizumab was approved in 2017 in the United States and in 2018 in the European Union, but despite proven efficacy in randomized, controlled clinical trials, its effectiveness in the real-world setting remains to be fully elucidated. In particular, most study patients were treatment naive or switched from injectable therapies, whereas oral substances or monoclonal antibodies made up >1% of previous treatments.

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More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into account the patient's current situation. Therefore, concomitant treatment of various comorbid conditions, including autoimmune mediated disorders such as rheumatoid arthritis, should be considered in MS patients.

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Background: Data on the humoral vaccine response in patients on anti-interleukin-6 (IL-6) receptor therapy remain scarce.

Objective: The main objective of our study was to investigate the humoral response after vaccination against SARS-CoV-2 in neuromyelitis optica spectrum disorder (NMOSD)/myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients treated with anti-IL-6 receptor therapy. Secondarily, we analyzed relapse activity timely associated with vaccination.

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Although the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses.

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Background And Objectives: To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD).

Methods: This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers between July 2021 and March 2022. The effects of the pandemic on immunotherapeutic treatment and access to care, the possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of vaccination against SARS-CoV-2 on disease incidence and relapse risk were assessed using a patient questionnaire.

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Background: Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape.

Methods: We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients.

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Plasmapheresis (PE) is an established form of therapeutic apheresis (TA). Purpose of this longitudinal prospective single center study was to investigate the effect of PE on albumin redox state (ARS), as infusion of commercial albumin during PE may alter albumin oxidation which has an impact on its functional properties and oxidative stress level. 43 subjects with autoimmune-mediated neurological disorders were included.

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Introduction: Fatigue is the most frequent symptom in multiple sclerosis (MS), although it is still poorly understood due to its complexity and subjective nature. There is an urgent need to identify reliable biomarkers to improve disease prognosis and therapeutic strategies. Epstein-Barr virus (EBV) is the major environmental risk factor associated with MS aetiology, and trials with EBV-targeted T cell therapies have reduced fatigue severity in MS patients.

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Background: Cladribine is a synthetic deoxyadenosine analogue approved for the treatment of highly active relapsing multiple sclerosis (RMS). Cladribine is considered to be a semi-selective immune-reconstitution therapy (IRT) that induces long-term remission following short course of treatment. Here, we evaluated the effect of cladribine on immune cell reduction and reconstitution during the first two years of treatment.

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