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Cardiac Autonomic Dysfunction in Myasthenia Gravis and Relapsing-Remitting Multiple Sclerosis-A Pilot Study.

ABSTRACT: This study assessed cardiac autonomic response to head-up tilt test (HUTT) in 23 myasthenia gravis (MG) and 23 relapsing-remitting multiple sclerosis (RRMS) patients compared to 30 healthy controls (HC). Task Force^® Monitor was used to evaluate cardiac inotropy parameters, baroreflex sensitivity (BRS), heart rate (HRV), and blood pressure variability (BPV) during HUTT. MG patients were characterized by reduced BRS (p < 0.05), post-HUTT decrease in high-frequency component (p < 0.05) and increase in sympathovagal ratio of HRV (p < 0.05) when compared to controls indicating parasympathetic deficiency with a shift of sympathovagal balance toward sympathetic predominance. Compared to HC, MG patients also showed lower cardiac inotropy parameters, specifically, left ventricular work index (LVWI) during supine rest (p < 0.05) as well as LVWI and cardiac index values in response to orthostatic stress (p < 0.01 and p < 0.05, respectively). Compared to controls, RRMS patients were characterized by lower HRV delta power spectral density (p < 0.05) and delta low-frequency HRV (p < 0.05) in response to HUTT suggesting combined sympathetic and parasympathetic dysfunction. There were no differences in cardiac autonomic parameters between MG and MS patients (p > 0.05). Our study highlights the possibility of cardiac and autonomic dysfunction in patients with MG and RRMS which should be considered in the pharmacological and rehabilitation approach to managing these conditions.

SUBMITTER: Rzepinski L

PROVIDER: S-EPMC8157285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics. There is no single best treatment strategy, but therapy has to be tailored to the patient. This is a time-consuming task, rich in complexity, and influenced by the attitude towards risk on the parts of both the patient and the clinical team. The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for.

Project description:BACKGROUND: Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce. METHODS: We studied gene expression of a broad panel of cytokines in WB from relapsing-remitting multiple sclerosis (RRMS) patients in remission and healthy controls (HCs). Subsequently we determined the gene expression of the dysregulated cytokines in isolated PBMC subsets (CD4+, CD8+T-cells, NK-cells, B-cells, monocytes and dendritic cells) from RRMS patients and HCs and in CSF-cells from RRMS patients in clinical relapse and non-inflammatory neurological controls (NIND). RESULTS: RRMS patients had increased expression of IFN-gamma (IFNG), interleukin (IL) 1-beta (IL1B), IL7, IL10, IL12A, IL15, IL23, IL27, lymphotoxin-alpha (LTA) and lymphotoxin-beta (LTB) in WB. In PBMC subsets the main sources of pro-inflammatory cytokines were T- and B-cells, whereas monocytes were the most prominent source of immunoregulatory cytokines. In CSF-cells, RRMS patients had increased expression of IFNG and CD19 and decreased expression of IL10 and CD14 compared to NINDs. CD19 expression correlated with expression of IFNG, IL7, IL12A, IL15 and LTA whereas CD14 expression correlated with IL10 expression. CONCLUSIONS: Using a systematic approach, we show that expression of pro-inflammatory cytokines in peripheral blood primarily originates from T- and B-cells, with an important exception of IFNG which is most strongly expressed by NK-cells. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated with expression of pro-inflammatory cytokines; contrarily, monocytes are relatively scarce in CSF from RRMS patients and are associated with IL10 expression. Thus, our findings suggest a pathogenetic role of B-cells and an immunoregulatory role of monocytes in RRMS.

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Cardiac Autonomic Dysfunction in Myasthenia Gravis and Relapsing-Remitting Multiple Sclerosis-A Pilot Study.

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