Cardiac involvements in myasthenia gravis associated with anti‐<scp>K</scp>v1.4 antibodies

Suzuki, Shigeaki; Baba, Akira; Kaida, K.; Utsugisawa, Kimiaki; Kita, Yasushi; Tsugawa, Jun; Ogawa, Go; Nagane, Yuriko; Kuwana, Masataka; Suzuki, Norihiro

doi:10.1111/ene.12234

Cited by 82 publications

(54 citation statements)

References 30 publications

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“…Such antibodies occur in thymoma and late onset MG, the same subgroups where clinical cardiomyositis has been reported. In a Japanese MG report, suspected myocarditis was found in eight of 650 MG patients, all of them with Kv1.4 muscle antibodies . Giant cell myocarditis should be paid special attention.…”

Section: Heart Diseasementioning

confidence: 97%

Myasthenia gravis and risks for comorbidity

Gilhus

Nacu

Andersen

et al. 2014

Euro J of Neurology

125

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Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle-specific tyrosine kinase or lipoprotein receptor-related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG-related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side-effects. Thymectomy is regarded as a safe procedure both short and long term. Non-MG-related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow-up is necessary to identify and treat all types of coexisting disease in MG.

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Section: Heart Diseasementioning

confidence: 97%

Myasthenia gravis and risks for comorbidity

Gilhus

Nacu

Andersen

et al. 2014

Euro J of Neurology

125

View full text Add to dashboard Cite

show abstract

“…13) In cardiovascular system, Kv1.4 channels have critical roles in ventricular arrhythmias and atrioventricular blocking. 14,15) Thus, these channels are one of the targets of drugs for treatment of pathological conditions including human nervous system disease and cardiac diseases.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Human Kv1.4 Channel Activity by the Antidepressant Metergoline

Yeom

Lee

2016

Biological & Pharmaceutical Bulletin

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Metergoline is an ergot-derived psychoactive drug that is a ligand for various serotonin and dopamine receptors. Little is known about the effect of metergoline on different types of receptors and ion channels. Potassium channels are the most diverse group of ion channels. Kv1.4, a shaker family K channel alpha subunit, is one of a family of voltage gated K channels that mediates transient and rapid inactivating A-type currents and N-type inactivation. We demonstrated previously that metergoline inhibited the activity of neuronal voltage-dependent Na(+) channels in Xenopus laevis oocytes (Acta Pharmacol. Sin., 35, 2014, Lee et al.). In this study, we sought to elucidate the regulatory effects underlying metergoline-induced human Kv1.4 channel inhibition. We used the two electrode voltage-clamp (TEVC) technique to investigate the effect of metergoline on human Kv1.4 channel currents in Xenopus laevis oocytes expressing human Kv1.4 alpha subunits. Interestingly, metergoline treatment also induced inhibition of peak currents in human Kv1.4 channels in a concentration-dependent manner. The IC50 of peak currents of hKv1.4 currents was 3.6±0.6 µM. These results indicate that metergoline might regulate the human Kv1.4 channel activity that is expressed in X. laevis oocytes. Further, this regulation of potassium currents by metergoline might be one of the pharmacological actions of metergoline-mediated psychoactivity.

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“…In TAMG, anti‐Kv1.4 antibodies are possible markers for bulbar involvement, myasthenic crisis, myocarditis and QT prolongation on electrocardiogram …”

Section: Tipsmentioning

confidence: 99%

Management of myasthenia gravis in daily practice for general neurologists and healthcare professionals

Yokoyama

2017

Clinical & Exp Neuroim

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A characteristic feature of myasthenia gravis (MG) is the fluctuating weakness of the muscles. MG is an autoimmune neuromuscular junction disorder mediated by autoantibodies against nicotinic acetylcholine receptor and muscle-specific tyrosine kinase. If the commercially available acetylcholine receptor and muscle-specific tyrosine kinase antibody test is negative, MG patients are termed as having double-seronegative MG. Although the clinical phenotype is not yet defined, antibodies for lipoprotein receptor-related protein 4 and agrin, involved in clustering of acetylcholine receptors within the postsynaptic membrane and in structural maintenance of the neuromuscular synapse, have been found. The updated 2014 Guidelines in Japan state that the management of MG should be individualized, and earlier aggressive treatment using steroid pulse, plasma exchange and intravenous immunoglobulin therapy, before long-term steroid therapy, should be used in order to minimize manifestation, with fewer adverse effects achieved by co-administering immunosuppressants. In 2016, thymectomy was shown to be efficacious in non-thymomatous MG in a single-arm randomized clinical trial. The continuous update and modification in MG management makes it difficult for the general neurologist to decide on a treatment strategy. The present review aims to improve the understanding of current MG diagnosis, specific immunotherapy and clinical management tips, not only for the general neurologist, but also for other medical staff.

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Cardiac involvements in myasthenia gravis associated with anti‐Kv1.4 antibodies

Abstract: It has been demonstrated that anti-Kv1.4 antibodies are possible markers for cardiac involvements in MG patients.

Cited by 82 publications

References 30 publications

Myasthenia gravis and risks for comorbidity

Myasthenia gravis and risks for comorbidity

Regulation of Human Kv1.4 Channel Activity by the Antidepressant Metergoline

Management of myasthenia gravis in daily practice for general neurologists and healthcare professionals

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