Search

Background:   Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG., Objective:  This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG., Methods:  This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile., Results:  The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment., Conclusion:  Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).) more...

We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG., (© 2021. Fondazione Società Italiana di Neurologia.) more...

Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG)., Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort., Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool., Results: We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe)., Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended. more...

Myasthenia gravis (MG) is an autoimmune disease in which the peak incidence is among women of childbearing age. For this reason, there is an overlap between the occurrence of this disease and pregnancy. It is known that MG symptoms can worsen during pregnancy and postpartum, and that pregnancy has special characteristics in MG patients. Children born to myasthenic mothers are at risk of having transient neonatal myasthenia. We briefly review the main relationships between MG and pregnancy, and we make recommendations for MG therapy, pregnancy, delivery, breastfeeding and newborns. more...

Azathioprine (AZA) is the most common immunosuppressive drug used to treat myasthenia gravis (MG). To analyses the prevalence of thiopurine S-methyl-transferase (TPMT) genotypes and their association with adverse events due to azathioprine therapy in MG patients. Allele-specific polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP) analysis were carried out to determine the prevalence of the most common TPMT genotypes (*2, *3A, *3B and *3C) in 50 MG patients from Southern Brazilian. The frequency of adverse reactions due to azathioprine therapy was analysed and correlated with different genotypes groups. The prevalence of TPMT gene variants was 12%. The allelic frequency of variant TPMT*2 (C238G), TPMT*3A (G460A/A719G), TPMT*3B (G460A), and TPMT*3C (A719G) genotypes was 1, 3, 2 and 1%, respectively. Adverse events occurred in 44%, of MG patients, of which 86% were minor and 14% were major. One patient, who presented a major adverse event (bone marrow suppression), was homozygous for the TPMT*3A genotype. Our study estimated the prevalence of TPMT genotypes for Brazilian MG patients. The profile of TPMT genotypes was different from other Brazilian populations. Hardy-Weinberg equilibrium and allelic frequencies of TPMT*3A and TPMT*3B, respectively, were different than expected, a finding that suggests a possible founder effect. Major adverse events were statistically significant for TPMT genotypes compared to wild-type. Although TPMT genotype has been associated with AZA-related adverse events, since no statistically significant difference among wild-type and other TPMT genotypes for minor adverse events, our study supports the view that TPMT genotype alone is not enough to adequately personalise the AZA therapy in MG patients. In conclusion, these results were important to characterise the prevalence of TPMT gene variants in MG patients treated with AZA and correlate the adverse events of this therapy in a real-world outpatient clinic from Southern Brazil., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.) more...

Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients. more...

The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG., (Copyright © 2017. Published by Elsevier Ltd.) more...

This study aimed to analyze the outcome and impact of pregnancy in women with myasthenia gravis (MG). Obstetric and clinical data were retrospectively analyzed before, during and after pregnancy. Predictors of outcome were studied. We included 35 pregnancies from 21 MG patients. In the course of MG symptoms in 30 pregnancies with live births, 50% deteriorated (mainly during the second trimester, p = 0.028), 30% improved, and 20% remained unchanged. The deterioration group had more frequent abnormal repetitive nerve stimulation (RNS) (p = 0.028) and lower myasthenia gravis composite (MGC) scores (p = 0.045) before pregnancy. The improvement group was associated with higher MGC scores (p = 0.012) before pregnancy. The no-change group was associated with longer duration of MG (p = 0.026) and normal RNS (p = 0.008) before pregnancy. The course of MG in the second pregnancy was different from that in the previous pregnancy in 65.3% of cases. Obstetric complications were reported in 20 pregnancies; the most common was preterm premature rupture of membranes (PPROM) (25.8%), and the most severe were abortion (11.4%) and fetal death (2.9%). Most of the patients delivered via caesarean section (66.7%). Spinal anesthesia was performed in 73.3%. Transient neonatal myasthenia gravis occurred in 12.9% of live-born infants, and no predictors were found. In conclusion, severity and duration of MG, RNS and treatment influence MG and pregnancy. Pregnant MG patients have greater rates of PPROM and caesarean delivery. Our data suggest that duration of MG, MGC and RNS before pregnancy may be useful in helping to predict the course of MG during pregnancy., (Copyright © 2017 Elsevier B.V. All rights reserved.) more...