Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case–control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing–remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

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Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance

Journal of Neurology ◽

10.1007/s004150050407 ◽

1999 ◽

Vol 246 (7) ◽

pp. 578-586 ◽

Cited By ~ 75

Author(s):

P. Flachenecker ◽

Annalaska Wolf ◽

Miriam Krauser ◽

H.-P. Hartung ◽

Karlheinz Reiners

Keyword(s):

Multiple Sclerosis ◽

Autonomic Dysfunction ◽

Orthostatic Intolerance ◽

Cardiovascular Autonomic Dysfunction

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

Journal of Clinical Medicine ◽

10.3390/jcm10102173 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2173

Author(s):

Łukasz Rzepiński ◽

Monika Zawadka-Kunikowska ◽

Julia L. Newton ◽

Paweł Zalewski

Keyword(s):

Multiple Sclerosis ◽

Myasthenia Gravis ◽

Autonomic Dysfunction ◽

Left Ventricular ◽

High Frequency Component ◽

Cardiac Inotropy ◽

Cardiac Autonomic Dysfunction ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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.

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Cardiac Autonomic Dysfunction in Relapsing-Remitting Multiple Sclerosis during a Stable Phase

European Neurology ◽

10.1159/000117250 ◽

1996 ◽

Vol 36 (4) ◽

pp. 211-214 ◽

Cited By ~ 4

Author(s):

Franco Giubilei ◽

Agnese Vitale ◽

Claudia Urani ◽

Marco Frontoni ◽

Marina Fiorini ◽

...

Keyword(s):

Multiple Sclerosis ◽

Autonomic Dysfunction ◽

Stable Phase ◽

Cardiac Autonomic Dysfunction ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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Letter to the Editor: Re: “Is heart rate variability a valuable method to investigate cardiac autonomic dysfunction in subjects with leukemia? A systematic review to evaluate its importance in clinical practice” by Kirizawa et al

Supportive Care in Cancer ◽

10.1007/s00520-019-05103-6 ◽

2019 ◽

Vol 28 (2) ◽

pp. 419-420 ◽

Cited By ~ 1

Author(s):

Maxime Caru ◽

Daniel Curnier

Keyword(s):

Systematic Review ◽

Heart Rate ◽

Heart Rate Variability ◽

Clinical Practice ◽

Autonomic Dysfunction ◽

Letter To The Editor ◽

Cardiac Autonomic Dysfunction ◽

Valuable Method

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The effectiveness of behavioural and psychosocial HIV/STI prevention interventions for MSM in Europe: A systematic review

Eurosurveillance ◽

10.2807/ese.14.48.19430-en ◽

2009 ◽

Vol 14 (48) ◽

Cited By ~ 13

Author(s):

R Berg

Keyword(s):

Systematic Review ◽

Current Knowledge ◽

Relevant Literature ◽

Risk Behaviour ◽

Evidence Base ◽

Risk Of Bias ◽

Effect Estimate ◽

Sti Prevention ◽

Prevention Interventions ◽

Outcome Evaluations

Given the need of programme planners and policy makers for descriptions of specific interventions and quantitative estimates of intervention effects to make informed decisions concerning prevention funding and research, there is a need for a systematic review that updates the current knowledge base about HIV/STI preventive interventions targeted at men who have sex with men (MSM) in Europe. The aim was to summarise and assess the effectiveness of HIV/STI prevention interventions for MSM living in Europe, and to identify intervention characteristics associated with effectiveness as well as potential gaps in the evidence base. A systematic search for relevant literature in eight international databases and in reference lists of relevant reviews and included studies was performed. Studies were selected according to pre-specified criteria and appraised for risk of bias. We summarised results using tables and calculated effect estimates for sexual behaviour outcomes. Results from six controlled studies, involving a total of 4,111 participants at entry from four different European countries were summarised. The results showed that there was 'high' or 'unclear' risk of bias in one or more of the assessed domains in all studies. The pooled effect estimate of the four interventions for which data were available suggested that MSM who participate in HIV/STI prevention initiatives may be somewhat less likely to report unprotected anal intercourse (UAI). The evidence base was insufficient to examine characteristics of interventions most closely associated with magnitude of effect and to draw solid conclusions about unique gaps in the evaluation literature. Despite the maturity of the HIV epidemic, rigorous outcome evaluations of any form of behavioural HIV/STI intervention for MSM in Europe are scarce. The results point to possible short term effects of interventions in terms of reductions in the proportion of MSM who engage in UAI, but the paucity of controlled studies demonstrates the need for research in this area. There is an overall deficit in outcome evaluations of interventions aimed at reducing HIV/STI risk behaviour among MSM in Europe. Designing behavioural HIV/STI preventive strategies to avert new infections, and the evaluation of such prevention programmes for MSM is an important component of a comprehensive HIV/STI containment strategy across the continuum of prevention and care.

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Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review

Multiple Sclerosis Journal ◽

10.1177/1352458515601513 ◽

2015 ◽

Vol 21 (12) ◽

pp. 1485-1495 ◽

Cited By ~ 23

Author(s):

Jason R. Plemel ◽

Camille A. Juzwik ◽

Curtis A. Benson ◽

Michael Monks ◽

Chelsea Harris ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Ginkgo Biloba ◽

Neurological Impairment ◽

Evidence Base ◽

Exclusion Criteria ◽

Over The Counter ◽

Conflicting Evidence ◽

Anti Oxidant ◽

Future Work

Background: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. Objective: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. Methods: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. Results: Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. Conclusion: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients.

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Is heart rate variability a valuable method to investigate cardiac autonomic dysfunction in subjects with leukemia? A systematic review to evaluate its importance in clinical practice

Supportive Care in Cancer ◽

10.1007/s00520-019-05047-x ◽

2019 ◽

Vol 28 (1) ◽

pp. 35-42 ◽

Cited By ~ 3

Author(s):

Jociele M. Kirizawa ◽

David M. Garner ◽

Claudia Arab ◽

Vitor E. Valenti

Keyword(s):

Systematic Review ◽

Heart Rate ◽

Heart Rate Variability ◽

Clinical Practice ◽

Autonomic Dysfunction ◽

Cardiac Autonomic Dysfunction ◽

Valuable Method

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A deep transcriptome meta-analysis reveals sex-based molecular differences in Multiple Sclerosis

10.1101/2021.08.31.21262175 ◽

2021 ◽

Author(s):

José Francisco Català-Senent ◽

Zoraida Andreu ◽

Francisco Jose Roig Molina ◽

Marta R. Hidalgo ◽

Natalia Yanguas-Casás ◽

...

Keyword(s):

Gene Expression ◽

Multiple Sclerosis ◽

Systematic Review ◽

Nervous System ◽

Sex Differences ◽

Nervous Tissue ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Meta Analysis ◽

Men And Women

Background: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory, and degenerative disease of the central nervous system that affects both women and men but the risk of developing MS is higher in women (2-3:1 ratio compared to men). Current knowledge does not allow a precise definition of the sex-related factors intervening in MS. Here, we explore the role of sex in this neurodenegerative disease to identify molecular mechanisms underlying sex-based diferences that can guide novel therapeutics approaches aimed for men and women. Methods: We performed a rigorous and systematic review of MS whole transcriptome studies that included sex patient information in Gene Expression Omnibus and ArrayExpress databases, following PRISMA statment guidelines. A differential gene expression (DGE) was performed for each selected study. Then, three meta-analyses based on genes and different contrasts were addressed to evaluate common features and sex bias in all scenarios: one meta-analysis in nervous tissue studies (4), another in blood studies (5), and a third that integrated the studies from both tissues, blood and nervous system (9). Finally, a gene set analysis (GSA) was performed on the meta-analyzed differential transcriptomic profile between women and men, to study their involvement in biological pathways and phenotypes (physiological and pathological states) sex related. Results: After screening 122 publications, the systematic review provided a selection of nine studies (5 in blood and 4 in nervous tissue) with a total of 653 samples (269 MS women, 152 control women, 116 MS men, 116 control men). The blood sex-differences gene meta-analysis identified 1 gene overexpressed in women (KIR2DL3) while gene meta-analysis in the nervous tissue resulted in 5 genes differentially expressed (4 overexpressed in women: C7orf73, CECR7, TRAF3IP2-AS1, ZNF117; and 1 overexpressed in men: HIST1H2AE). In the global meta-analysis (blood and nervous tissue), 1 gene involved in sex differences were detected (more expressed in women: LOC102723701). 9 MS biomarkers were also identified in both sexes (4 overexpressed genes in MS patients: HIST1H2BC, SMEK2, STBD1, TMEM140) and 5 down-regulated in MS patients: C16orf59, C20orf177, C9orf23, FAM65B, PKI55). Additionally, the GSA related to gene meta-analysis revealed a set of functions differentially enriched in men and women, in the different analysed tissues. Conclusion: These findings provide valuable opportunities for better understanding of MS related sex differences and develop effective and sex-specific interventions down further studies.

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A Systematic Review of the Impact of Dietary Sodium on Autoimmunity and Inflammation Related to Multiple Sclerosis

Advances in Nutrition ◽

10.1093/advances/nmz032 ◽

2019 ◽

Vol 10 (5) ◽

pp. 902-910

Author(s):

Yasmine Probst ◽

Erin Mowbray ◽

Erika Svensen ◽

Keats Thompson

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Immune Response ◽

Risk Factor ◽

Sodium Intake ◽

Evidence Base ◽

Dietary Sodium ◽

Eating Pattern ◽

The Central Nervous System ◽

The Impact

ABSTRACT Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Current research into potential causes, risk factors, and treatment is largely based around the immune response involved in the pathophysiology of the disease, including factors that contribute to the augmentation of this immune response. This review aimed to determine the role of sodium as a risk factor for increased autoimmunity and inflammation in relation to MS pathogenesis. This systematic review searched the Scopus, MEDLINE, and PubMed scientific databases for studies related to MS and sodium. Studies were included if they addressed sodium intake and MS but were not limited to a disease type or to a study design. Study quality was assessed through the use of the quality rating checklist of the Academy of Nutrition and Dietetics. A total of 12 studies were included in the review, including human, animal, and cellular studies. The studies related to the proinflammatory effect of sodium, the blood-brain barrier, and an effect on autoimmunity. The data presented throughout this review provide insight into the emerging evidence base for sodium intake as a risk factor for MS disease progression and potentially onset of disease. More studies are needed to determine if the influence of sodium is as a single nutrient or has a combined effect as part of an overall eating pattern. This review was registered at PROSPERO as CRD42016039174.

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