心血管领域-心律失常方向

METHODS::We herein to describe the response and the potential treatment mechanism of low dose rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against neurofascin-155 (NF-155). Patients received 100 mg rituximab once weekly for 4 weeks followed by 100 mg per month for 2 additional doses. Clinical function scores, Fahn- Tolosa-Marin Tremor Rating Scale (FTMTRS) and flow cytometry of peripheral blood were scheduled before and at 1, 3, 6 months after rituximab treatment. All clinical function score including MRC, INCAT, Hughes, mRS, ODSS and FTMTRS scores showed obvious improvement at the post-treatment follow-up 1,3,6 months in comparison with baseline values. The proportion of CD19 + CD27+, CD19 + CD38+ and CD138 in lymphocytes of all patients declined at 1,3,6 month and the proportion of CD19 + CD24hiCD38hi in one patient was increased at 6 months after rituximab treatment. Low dose rituximab can significant improve disease severity and disabling tremor of CIDP patients with anti-NF155 antibody by the powerful role of B cell depletion within six months and subsequent reestablishment of B-cell subsets including increasing regulatory B cells, inhibiting memory B cells and reducing plasmablasts.

METHODS:Importance:Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective:To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants:The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures:COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures:The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results:A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance:In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

METHODS::Goal setting is a core component of physical therapy in multiple sclerosis (MS). It is unknown whether and to what extent goals are set at different levels of the International Classification of Functioning, Disability and Health (ICF), and whether, and to which, standardized outcome measures are used in real life for evaluation at the different ICF levels. Our aim was to describe the real-world use of goal setting and outcome measures in Europe. An online cross-sectional survey, completed by 212 physical therapists (PTs) specialized in MS from 26 European countries, was conducted. Differences between European regions and relationships between goals and assessments were analyzed. PTs regularly set goals, but did not always apply the Specific, Measurable, Achievable, Realistic, Timed (SMART) criteria. Regions did not differ in the range of activities assessed, but in goals set (e.g., Western and Northern regions set significantly more goals regarding leisure and work) and outcome measures used (e.g., the Berg Balance Scale was more frequently used in Northern regions). Quality of life was not routinely assessed, despite being viewed as an important therapy goal. Discrepancies existed both in goal setting and assessment across European regions. ICF assists in understanding these discrepancies and in guiding improved health-care for the future.

METHODS::A 70-year-old man presented with dizziness and unsteadiness when standing and was hospitalized in another hospital. Magnetic resonance imaging (MRI) of the brain on Day 1 showed no abnormalities. The patient developed respiratory failure on Day 1and flaccid tetraplegia on Day 3, and was transferred to our hospital. Progressive upper and lower limb weakness and bulbar symptoms suggested Guillain-Barré syndrome or its variant. Diffusion-weighted MRI on Day 6 disclosed high signal intensities in the bilateral medial portion of the medulla, and the patient was diagnosed with bilateral medial medulla infarction. Bilateral medial medulla infarction should be considered when a patient shows progressive tetraplegia, and bulbar palsy and follow-up MRI is important to confirm the diagnosis. (Received January 23, 2020; Accepted April 21, 2020; Published August 1, 2020).

METHODS:BACKGROUND:Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS:We evaluated the serum levels of IL-36 (IL-36α, IL-36β and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS:Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS:The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.

METHODS::Health communication offers an important means for patients to make informed decisions for illness self-management. We assessed how the level of engagement with selected health information at baseline is associated with the adoption and maintenance of lifestyle behaviours at a 5-year follow-up in people with multiple sclerosis (MS). Non-engagers were compared to engagers of information delivered online and print (medium), and with engagers who additionally attended a live-in workshop (high). Engagement was assessed against lifestyle behaviours by log-binomial regression. Information engagers had higher education, and were less likely to have severe disability, clinically significant fatigue, or obesity. Medium and high baseline engagement was associated with adopting healthy behaviours for omega 3 supplementation (RR = 1.70; 95%CI: 1.02-2.84), physical activity (RR = 2.16; 95%CI: 1.03-4.55), and dairy non-consumption (RR = 3.98; 95%CI: 1.85-8.56) at 5 years; associations were stronger among high engagers. Only high baseline engagement was associated with maintaining behaviours from baseline to 5 years, specifically for omega-3 (RR = 1.26; 95%CI: 1.06-1.49) and vitamin D supplementation (RR = 1.26; 95%CI: 1.04-1.54) and dairy non-consumption (RR = 1.47; 95%CI: 1.03-2.10). Health communication that includes face-to-face information delivery and practical tools for implementation in daily living may be optimal for adopting and maintaining lifestyle behaviours in people with MS.

METHODS::The confinement forced by COVID-19 can have repercussions on the health of people diagnosed with multiple sclerosis. The objective of this study is to analyze the relationships between physical activity, a sense of coherence, resilience and coping among people diagnosed with Multiple Sclerosis during the health emergency situation. To achieve this goal, this transversal descriptive study included 84 patients that belonged to multiple sclerosis associations during the period of confinement. Participants filled out the Physical Activity (IPAQ-SF), Sense of Coherence (SOC-13), Resilience Scale (ER-14) and coping (COPE-28) questionnaires. The results showed that the average age was 46.9 and that 67.9% had Relapsing Remittent Multiple Sclerosis diagnosed on average 13.9 years ago. They had a high degree (33.3%) and moderate degree (34.5%) of physical activity, high levels of resilience, while the level of a sense of coherence was average and the most commonly used strategies for coping were active confrontation and religion. Physical activity was not related to the rest of the studied variables, but there were correlations between the other variables. The people with multiple sclerosis who belong to patient associations have remained physically active during the obligatory confinement period and have elevated degrees of resilience and an average sense of coherence, as well as using suitable coping strategies, which is why the social-health resource of belonging to a patient association could be boosting these variables that are beneficial to their health.

METHODS::Optic neuritis (ON) is a frequent manifestation of aquaporin-4 (AQP4) antibody-mediated neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disorders, MOGAD). The past few years have seen major advances in the diagnosis and treatment of these two relatively new entities: international diagnostic criteria for NMOSD and MOG-EM have been proposed, improved antibody assays developed, and consensus recommendations on the indications and methodology of serological testing published. Very recently, the results of four phase III trials assessing new treatment options for NMOSD have been presented. With eculizumab, a monoclonal antibody inhibiting complement factor C5, for the first time a relapse-preventing long-term treatment for NMOSD - which has so far mostly been treated off-label with rituximab, azathioprine, and other immunosuppressants - has been approved. Data from recent retrospective studies evaluating treatment responses in MOG-ON suggest that rituximab and other immunosuppressants are effective also in this entity. By contrast, many drugs approved for the treatment of multiple sclerosis (MS) have been found to be either ineffective or to cause disease exacerbation (e.g., interferon-β). Recent studies have shown that not only NMOSD-ON but also MOG-ON usually follows a relapsing course. If left untreated, both disorders can result in severe visual deficiency or blindness, though MOG-ON seems to have a better prognosis overall. Acute attacks are treated with high-dose intravenous methylprednisolone and, in many cases, plasma exchange (PEX) or immunoadsorption (IA). Early use of PEX/IA may prevent persisting visual loss and improve the long-term outcome. Especially MOG-ON has been found to be frequently associated with flare-ups, if steroids are not tapered, and to underlie many cases of "chronic relapsing inflammatory optic neuropathy" (CRION). Both NMOSD-ON and MOG-ON are often associated with simultaneous or consecutive attacks of myelitis and brainstem encephalitis; in contrast to earlier assumptions, supratentorial MRI brain lesions are a common finding and do not preclude the diagnosis. In this article, we review the current knowledge on the clinical presentation, epidemiology, diagnosis, and treatment of these two rare yet important differential diagnoses of both MS-associated ON und idiopathic autoimmune ON. :Die Optikusneuritis (ON) ist vielfach die erste Manifestation einer AQP4-Antikörper-vermittelten NMOSD (AQP4: Aquaporin-4, NMOSD: Neuromyelitis-optica-Spektrum-Erkrankung, Engl.: neuromyelitis optica spectrum disorders) oder einer Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierten Enzephalomyelitis (MOG-EM; auch MOG antibody associated disorders, MOGAD). Für beide Erkrankungen wurden in den vergangenen Jahren internationale Diagnosekriterien und Empfehlungen zu Indikation und Methodik der serologischen Testung vorgelegt. Seit Kurzem liegen zudem Ergebnisse aus 4 großen, internationalen Phase-III-Studien zur Behandlung der NMOSD vor. Mit dem den Komplementfaktor C5 blockierenden monoklonalen Antikörper Eculizumab wurde 2019 erstmalig ein Medikament zur Langzeitbehandlung der NMOSD, die bislang vornehmlich Off-Label mit Rituximab, Azathioprin und anderen Immunsuppressiva erfolgt, auf dem europäischen Markt zugelassen. Für die erst vor wenigen Jahren erstbeschriebene MOG-EM stehen inzwischen Daten aus mehreren retrospektiven Studien zur Verfügung, die eine Wirksamkeit von Rituximab und anderen Immunsuppressiva in der Schubprophylaxe auch in dieser Indikation nahelegen. Viele der zur Therapie der MS zugelassenen Medikamente sind entweder unwirksam oder können, wie z. B. Interferon-β, eine Verschlechterung des Krankheitsverlaufes bewirken. Beide Erkrankungen werden im Akutstadium mit hochdosierten Glukokortikoiden und Plasmapherese oder Immunadsorption behandelt. Diese Behandlung sollte möglichst rasch nach Symptombeginn eingeleitet werden. Insbesondere die MOG-EM ist durch eine oft ausgeprägte Steroidabhängigkeit gekennzeichnet, die ein langsames Ausschleichen der Steroidtherapie erfordert, und schließt viele Fälle der bislang meist als „idiopathisch“ klassifizierten „chronic relapsing inflammatory optic neuropathy“ (CRION) ein. Unbehandelt kann sowohl die NMOSD- als auch die MOG-EM-assoziierte ON zu schweren, persistierenden und oft bilateralen Visuseinschränkungen bis hin zur Erblindung führen. Beide Erkrankungen verlaufen meist relapsierend. Neben den Sehnerven sind häufig das Myelon sowie der Hirnstamm und, vor allem bei NMO-Patienten, das Dienzephalon betroffen; supratentorielle Hirnläsionen im kranialen MRT sind, anders als früher gedacht, kein Ausschlusskriterium, sondern häufig. In der vorliegenden Arbeit geben wir einen Überblick über Klinik, Diagnostik und Therapie dieser beiden wichtigen Differenzialdiagnosen der MS-assoziierten und idiopathischen ON.

METHODS::The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.

METHODS::Aims: The aim of this study was to quantify how multiple sclerosis (MS) phenotypes differ from each other in respect of costs and quality-of-life.Materials and methods: The study is based on survey data from Finnish patients with MS (n = 553). The information contained disease type, disease severity according to self-reported Expanded Disease Severity Scale (EDSS), healthcare resource use, and medication use. In addition, information related to employment and early retirement was collected. EQ-5D-VAS and Multiple Sclerosis Impact Scale-29 (MSIS-29) instruments were used to collect quality-of-life data, and Fatigue Severity Scale (FSS) instrument for evaluating fatigue. Patients were stratified based on their disease type (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS)) and disease severity. The data were primarily analyzed using summary statistics.Results: SPMS had the highest annual total cost (71,177€) followed by PPMS (51,082€) and RRMS (36,492€). Early retirement covered the greatest share of costs in RRMS (39%) and SPMS (43%). In PPMS, early retirement and professional care were the two most equally important cost drivers, contributing together 56% of the total costs. Direct healthcare costs were responsible for 33%, 19%, and 18% of total costs in RRMS, SPMS, and PPMS. The mean EDSS in RRMS, SPMS, and PPMS were 2.5, 5.5, and 5.9, respectively. Differences in the quality-of-life were observed with both disease specific (MSIS-29) and generic (EQ-5D-VAS) instruments. The mean utility value from EQ-5D among patients with RRMS, SPMS, and PPMS was 0.76, 0.52, and 0.49, respectively. In addition, patients with SPMS and PPMS were more likely to report fatigue than patients with RRMS.Conclusions: MS phenotype has an impact on costs and quality-of-life of the patients. Early retirement seems to be one of the most important contributors to MS-related costs.