Clinical Course Of Myasthenia Gravis Research Articles

Repetitive nerve stimulation as a predictor of treatment response in myasthenia gravis

Background and objectives. The clinical course of myasthenia gravis (MG) varies and may adversely affect quality of life and limit daily activities. Repetitive nerve stimulation (RNS) can be used to diagnose MG and may predict disease progression. We aim to establish the correlation between RNS and pharmacological treatment response. Materials and methods. We conducted a cross-sectional study evaluating the correlation between RNS result and pharmacological treatment response as evaluated using the Myasthenia Gravis-Activities of Daily Living (MG-ADL). Results. RNS positive patients possess greater severity on pre-treatment (9 [5-11] vs. 4 [2-5], p<0.001) and post-treatment (2 [1-4] vs. 1 [0-2], p=0.007) MG-ADL scores. ΔMG-ADL was also significantly greater in RNS positive patients (-6[-7 - -3) vs. -2 [-5 - -1], p=0.004). Spearman’s rank-order correlation conducted evaluating the correlation between RNS and ΔMG-ADL demonstrates a significant moderate positive correlation between RNS and ΔMG-ADL (rs=0.495, p<0.001). Conclusions. A moderate significant correlation was found between RNS and pharmacological treatment response. RNS positive patients are more responsive towards treatment compared to RNS negative patients. Higher fatigability in muscles translates to greater RNS decrements and clinical severity, lending itself to a greater opportunity for improvement following pharmacological. However, this must not be confused with long-term prognosis.

Clinical features of myasthenia gravis with neurological and systemic autoimmune diseases.

Multiple reports on the co-existence of autoimmune diseases and myasthenia gravis (MG) have raised considerable concern. Therefore, we reviewed autoimmune diseases in MG to explore their clinical presentations and determine whether the presence of autoimmune diseases affects the disease severity and treatment strategies for MG. We reviewed all the major immune-mediated coexisting autoimmune conditions associated with MG. PubMed, Embase and Web of Science were searched for relevant studies from their inception to January 2023. There is a higher frequency of concomitant autoimmune diseases in patients with MG than in the general population with a marked risk in women. Most autoimmune comorbidities are linked to AChR-MG; however, there are few reports of MuSK-MG. Thyroid disorders, systemic lupus erythematosus, and vitiligo are the most common system autoimmune diseases associated with MG. In addition, MG can coexist with neurological autoimmune diseases, such as neuromyelitis optica (NMO), inflammatory myopathy (IM), multiple sclerosis (MS), and autoimmune encephalitis (AE), with NMO being the most common. Autoimmune diseases appear to develop more often in early-onset MG (EOMG). MS coexists more commonly with EOMG, while IM coexists with LOMG. In addition, MG complicated by autoimmune diseases tends to have mild clinical manifestations, and the coexistence of autoimmune diseases does not influence the clinical course of MG. The clinical course of neurological autoimmune diseases is typically severe. Autoimmune diseases occur most often after MG or as a combined abnormality; therefore, timely thymectomy followed by immunotherapy could be effective. In addition, thymoma-associated AChR MG is associated with an increased risk of AE and IM, whereas NMO and MS are associated with thymic hyperplasia. The co-occurrence of MG and autoimmune diseases could be attributed to similar immunological mechanisms with different targets and common genetic factor predisposition. This review provides evidence of the association between MG and several comorbid autoimmune diseases.

Clinical characteristics and prognosis of very late-onset myasthenia gravis in China

Alteration in onset-age distribution in myasthenia gravis (MG) and its increasing prevalence among the elderly underscores the need for a better understanding of the clinical course of MG and the establishment of personalized treatment. In this study we reviewed the demographics, clinical profile, and treatment of MG. Based on onset age, eligible patients were classified as early-onset MG (onset age ≥18 and <50 years), late-onset MG (onset age ≥50 and <65 years), and very late-onset MG (onset age ≥65 years). Overall, 1160 eligible patients were enrolled. Patients with late- and very late-onset MG showed a male predominance (P=0.02), ocular MG subtype (P=0.001), and seropositivity for acetylcholine receptors and titin antibodies (P<0.001). In very late-onset MG, a lower proportion of patients retained minimal manifestations status or better, a higher proportion of patients had MG-related deaths (P<0.001), and a shorter maintenance time of minimal manifestation status or better was seen at the last follow-up (P=0.007) than that in patients with early- and late-onset MG. Non-immunotherapy may associated with a poor prognosis in patients in the very late-onset group. Further studies on very late-onset MG patients should be performed to evaluate the relationship between immunotherapy and prognosis.

Fecal Incontinence as a Symptom of Myasthenia Gravis

I report three cases of fecal incontinence during the clinical course of myasthenia gravis. Fecal incontinence developed after withdrawal from the pyridostigmine and improved after re-administration of the pyridostigmine. Myasthenia gravis could affect external anal sphincter and puborectalis function. Myasthenia gravis is presumably one of the causes of fecal incontinence. We must check for fecal incontinence in the patients with myasthenia gravis.

Anti‐lipoprotein receptor‐related protein 4 antibody titer correlates with the clinical course of myasthenia gravis

Anti‐lipoprotein receptor‐related protein 4 antibody titer correlates with the clinical course of myasthenia gravis

Myasthenia gravis exacerbation in association with antibody overshoot following plasmapheresis.

Antibody overshoot following therapeutic plasmapheresis (PLEX) is defined by subsequent increase in antibody to levels exceeding those prior to removal. It has been infrequently described in the past, and its influence on the clinical course of myasthenia gravis (MG) remains unclear. This was a retrospective analysis of five patients with generalized MG treated with PLEX. All five patients possessed antibodies against acetylcholine receptor (AChR-Ab). After undergoing 3 to 12 PLEX treatment sessions, AChR-Ab titer increased to a median of 1292% of the baseline level. The median interval from the last PLEX session to peak AChR-Ab detection was 6wk. In four patients, AChR-Ab overshoot was associated with a clinical deterioration. The AChR-Ab overshoot may occur following PLEX. In patients who deteriorate following PLEX treatment, the presence of antibody overshoot may serve as additional guidance for treatment adjustment.

SARS-CoV-2 in pre-existing autoimmune myasthenia gravis: An institutional experience

The impact of SARS-CoV-2 on pre-existing chronic neuromuscular junction disorders like myasthenia gravis (MG) is not known. We report three patients with pre-existing acetylcholine receptor autoantibody-positive myasthenia gravis who were infected with SARS-CoV-2. We observed the clinical course of these patients during hospitalization, none of the three patients had an exacerbation of peripheral myasthenia syndromes like ptosis, extra-ocular muscle weakness, bulbar or limb weakness during hospitalization. Therapy for MG was not altered during hospitalization for any of the patients. While two of the patients had a favorable outcome, one succumbed to the complications of SARS-CoV-2. Our findings suggest that the clinical course of MG remains unaffected during course, however outcome is variable depending on severity of SARS-CoV-2. Further large observations are needed to define best management and treatment principals and determinants of outcomes in this unique patient population of co-occurrence of SARS-CoV-2 and myasthenia gravis.

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients’ sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.

Clinical course of myasthenia gravis at the department of neurology in Antananarivo Madagascar

Introductionla myasthénie auto-immune est une maladie rare, agissant au niveau de la jonction neuromusculaire. Elle peut engager le pronostic vital surtout lors d´une atteinte respiratoire. La rémission complète est possible sous traitement. Nos objectifs étaient de décrire l'évolution clinique sous traitement de nos patients myasthénique pour améliorer ultérieurement notre prise en charge et pour obtenir une première base de données malgaches.Méthodesune étude rétrospective descriptive fut menée au sein du Service de Neurologie de l´Hôpital Universitaire Befelatanana entre janvier 2010 et décembre 2017, incluant tout patient diagnostiqué comme myasthénie auto-immune après un test à la prostigmine positif.Résultatsvingt-cinq patients (0,42%) sur 5814 hospitalisés étaient inclus. Seule l´évolution de 16 patients était connue (64%) dont 14 étaient sous traitement médical et 3 d´entre eux avaient une thymectomie. La durée moyenne de suivi était de 24 mois. Parmi les patients traités, 8 s´étaient améliorés, 2 étaient décédés. Chez les patients thymectomisés, 2 s´étaient améliorés, 1 était décédé.Conclusionla myasthénie reste une pathologie rare, grave, mais l´amélioration sous traitement est possible même en absence d´un plateau technique adéquat pour sa prise en charge à Madagascar. En ce moment, un projet avec l´association des patients myasthéniques à Madagascar est en cours pour pouvoir bénéficier des appareils respiratoires utiles surtout lors des crises myasthéniques.

The evaluation of approaches to the treatment of myasthenia gravis.

Myasthenia gravis is a relatively rare autoimmune disease with an undetermined aetiology which affects neuromuscular junctions. Currently, the following approaches to the treatment of myasthenia gravis are mainly distinguished: symptomatic treatment with anticholinesterase inhibitors (AChEIs), immunomodulatory therapy (“basic” therapy) with glucocorticoids, cytostatics, monoclonal antibodies; surgical treatment — thymectomy; short-term treatment with plasmapheresis and intravenous administration of immuno­globulin. The efficiency of treatment approaches to myasthenia gravis in Ukraine remains insufficiently studied. The purpose of this work is to analyse the therapeutic approaches in patients with myasthenia gravis depending on the clinical form and severity of the disease. Between 2014 and 2017, 182 patients with myasthenia gravis have been examined, out of which 147 (80.8%) were the patients with the generalized form of the disease and 35 (19.2%) — with its ocular form. The clinical neurological examination included the collection of complaints, an anamnesis of disease and life as well as a neurological examination. In all the patients, the level of antibodies to acetylcholine receptors (AchR) and to muscle-specific tyrosine kinase (MuSK) has been measured, in terms of quantity as well, using the enzyme-linked immunosorbent assay (ELISA), and the presence of antibodies to titin and SOX1 has also been detected by means of indirect immunofluorescence. Of the total sample, less than a third (28.0%) of the patients examined received basic therapy; among them, there were no patients with the ocular form and only 34.7% — with the generalized form (p&lt;0.001). Basic therapy is found more often among the patients with class II myasthenia gravis (51.9%), with a statistically significant (p&lt;0.001) higher share of the patients receiving such a therapy than in classes III and IV (26.6% and 22.6% respectively). The structure of therapy in patients with classes III and IV has not shown any statistically significant difference (p=0.658), with symptomatic treatment being the predominant type of therapy. Undergoing basic therapy reduces the chances of a severe clinical course of myasthenia gravis (the QMG score of 17 and higher) — OR=0.52 (95.0% CI 0.14-0.90), p=0.032; fatal cases of the disease — OR=0.36 (95.0% CI 0.02-0.70), p=0.049. When basic therapy is used, the survival rate of the patients (Figure 2) is 42.0 years on average (95% CI 42.0-42.7) which is considerably higher (p=0.021) compared to that of the patients receiving symptomatic treatment only — 33.0 years (95% CI 30.9-36.7). Immunomodulatory therapy was prescribed for only 28% of the patients in the total sample, for none of the patients with the ocular form of myasthenia gravis, and for 34.7% of the patients with the generalized myasthenia gravis. The prescription of immunomodulatory therapy reduces relative risks of a severe clinical course of myasthenia gravis — OR=0.52 (95.0% CI 0.14-0.90), p=0.032. The prescription of immunomo­dulatory therapy decreases the probability of a fatal outcome of the disease — OR=0.36 (95.0% CI 0.02-0.70), p=0.049). With the use of immunomodulatory therapy, the patient survival rate rises considerably reaching an average of 42.0 years (95% CI 42.0-42.7), which is much higher compared to that in the group of the patients receiving symptomatic treatment only — 33.0 years (95% CI 30.9-36.7), p=0.021.

Myasthenia gravis and pregnancy: retrospective evaluation of 27 pregnancies in a tertiary center and comparison with previous studies.

To share our experience with the management of pregnancies in women with myasthenia gravis (MG) in a tertiary center. The study retrospectively evaluated 27 pregnancies in 12 patients. The pregnancies were divided into 3 groups on the basis of the clinical course of MG during pregnancy: improvement (n = 7), disease-stable (n = 9), and deterioration (n = 11). The groups were compared with respect to patient characteristics, clinical features, and obstetric outcomes. There were 4 miscarriages (14.8%), 3 preterm births (11.1%), and 4 cases of preterm premature rupture of the membranes (PPROM) (14.8%). Exacerbation was observed in 25.9% of the cases; the remission rate during the postpartum period and after miscarriage was 37%. The cesarean section (CS) rate was 78.3%. Pregnancies with deterioration of MG were statistically more likely to have higher miscarriage, preterm birth, PPROM, CS, and transient neonatal MG rates, in addition to a lower gestational age at birth, birth weight, and 5-min Apgar score than pregnancies with improved or stable disease (p values < 0.001, 0.04, 0.03, 0.009, 0.02, < 0.001, 0.002, and 0.043, respectively). Physicians who manage pregnant women with MG must be familiar with the clinical features of the condition; a multidisciplinary approach is necessary for a better prognosis.

Management of Myasthenia Gravis During Pregnancy: A Report of Eight Cases.

BackgroundThe clinical course of myasthenia gravis (MG) during pregnancy is highly variable and unpredictable. The management of MG in pregnancy has not been standardized.MethodsEight cases of MG in pregnancy, who were treated and gave birth in our hospital between 2004 and 2012, were retrospectively reviewed.ResultsIn three patients, MG deteriorated during pregnancy. Three patients discontinued their medication for MG during their pregnancy, and the other five patients continued on corticosteroid or pyridostigmine. None of the infants showed any congenital abnormalities. Interestingly, there was a trend towards lower birth weight in infants born to women who had an exacerbation of MG during pregnancy. One patient who had unstable MG before pregnancy and voluntarily discontinued the medication for MG at the beginning of pregnancy, experienced MG exacerbation at the 30th week of pregnancy and gave birth prematurely to an infant with transient neonatal MG at the 34th week. The other seven patients had uneventful full-term pregnancy.ConclusionWomen with unstable MG should postpone pregnancy to avoid potential risk of MG exacerbation and adverse effects on the fetus. Medication for MG should not be stopped abruptly during pregnancy, particularly for women with unstable MG. MG during pregnancy should be closely monitored and properly controlled.

Single fiber EMG as a prognostic tool in myasthenia gravis.

Single fiber electromyography (SFEMG) is the most sensitive diagnostic tool for diagnosis of myasthenia gravis (MG). Its prognostic value is not known. We retrospectively analyzed the clinical course of 232 MG patients who presented with only mild symptoms and had SFEMG of the orbicularis oculi muscle. We correlated their SFEMG results with the severity of their later clinical course. During the observation period 39 patients (17%) developed severe disease exacerbations, and 193 (83%) remained stable. Patients with severe disease exacerbation had a significantly higher mean jitter value (P < 0.0001), a greater percentage of fibers with increased jitter (P < 0.0001), and/or impulse blocking (P < 0.0001) on SFEMG. The extent of the SFEMG abnormalities in this study correlated with the later clinical course of MG. Muscle Nerve 54: 1034-1040, 2016.

Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG.

Anaesthesia in a Parturient with Myasthenia Gravis- Transient Myasthenia in newborn

Myasthenia gravis is an acquired chronic autoimmune disorder caused by decrease in functioning of acetylcholine receptors at the neuromuscular junctions owing to their destruction or inactivation by circulating antibodies. Disease manifests in the form of easy fatigability, weakness, difficulty in swallowing and even paralysis of respiratory muscles necessitating assisted ventilation. The clinical course of myasthenia gravis and its effect on pregnancy outcome is unpredictable. Worsening of symptoms can occur at any stage during pregnancy and also in post operative period. We are reporting a case of maternal myasthenia gravis who underwent caesarean section and developed respiratory distress after 20 minutes of spinal anaesthesia. Her baby also had a weak cry, hypotonia and tachypnoea. Baby was shifted to neonatal intensive care unit with continuous oxygen supplementation. Baby was kept under close observation and recovered well after two weeks.

Taste disorders in myasthenia gravis: a multicenter cooperative study

The purpose of the present study was to investigate the prevalence and clinical characteristics of taste disorders in patients with myasthenia gravis (MG). We studied 371 Japanese patients with MG (127 men and 244 women; mean age, 56.6±16.9years) consecutively evaluated between May and September 2010 in six neurological centers comprising the East Japan MG Study Group. Ninety-three patients (25%) had thymoma. We interviewed all patients to determine whether they had taste disorders during the clinical course of MG and then further evaluated the patients with MG, who reported having taste disorders, using a questionnaire. Taste disorders were observed in 16 (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of patients with MG excluding other factors were associated with MG itself. All patients had thymoma with seropositivity for anti-acetylcholine receptor antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage IVa required radiation therapy or chemotherapy. Five patients noticed taste disorders 2-3 months before the onset of MG. Sweet taste loss was more common than salty, bitter, and sour taste loss. This was the first systematic survey of taste disorders in patients with MG by a multicenter study. Taste disorders were more common in the present sample of patients with MG than in the general population.

Successful use of rocuronium and sugammadex in a patient with myasthenia

Successful use of rocuronium and sugammadex in a patient with myasthenia

Course and prognosis of myasthenia gravis: a systematic review

The clinical course of myasthenia gravis (MG) is variable, and spontaneous remission is still uncommon. Knowledge of the prognostic factors may help understand the course of MG and thus optimize its management. A systematic review search was conducted in MEDLINE and EMBASE for English language studies from 1985 through 2009. We identified additional studies by reviewing bibliographies of retrieved articles and hand search main journal of neurology. Studies evaluating variables associated with or predictive of remission in adult patients with MG were included. Because of methodological heterogeneity, we refrained from statistical pooling, instead, a best evidence synthesis was used for summarizing the results. From 1810 potentially relevant studies, 13 cohort studies met the inclusion criteria. The included studies were heterogeneous considerably in sample size, disease duration, follow-up years, definition of remission, and analysis. Study quality was limited by retrospective design in most studies and lack of multivariate analysis. Time of diagnosis from onset (<1 year) showed strong evidence of predicting a better remission. In studies using completely stable remission outcomes, there was strong evidence that age at onset (<40 years) was of prognostic importance. Furthermore, gender showed no association with remission. Time of diagnosis from onset and age at onset were found to be predictors of remission. Gender does not seem to predict the course of MG. Our findings should be interpreted with caution because of the clinical and methodological heterogeneity of included studies.

Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia (1983-1992).

This is the first epidemiological study of myasthenia gravis (MG) in the area of Belgrade. During the survey period (1983 1992), 124 incidental cases of MG were observed, producing an average annual incidence rate of 7.1 per million population (women, 8.3; men, 5.8). Age and sex specific incidence rates for females demonstrated a bimodal pattern, with the first peak in the age group between 20 and 40, and the second peak in the age group 70-80. The age-specific rates for males showed unimodal pattern, reaching a maximum in the age group between 60 and 80. There was a tendency of more frequent disease appearance in the urban as opposed to the suburban districts. On the prevalence day, December 31, 1992, the point prevalence rate was 121.5 per million (women, 142.5; men, 98.8). Only for incidental cases, the point prevalence rate was 77.1 (women, 83.2; men, 70.4). The average annual mortality rate was 0.47 per million (females, 0.52; males, 0.42), while cumulative lethality was 5.6 (women, 5.6; men, 5.7). Most frequently initial symptoms were ocular, occurring in 58% patients. Through the period of investigation ocular symptoms were generalized in 68%, most frequently in the first 2 years (62.5%). Thymoma was confirmed in 11.3% of patients. In this group there was equal presence of both sexes, older median age at onset, and more severe clinical course of MG. Associated autoimmune disease was found in 17 out of 124 incidental cases (13.7%). The most common were thyroid diseases (7.3%). Family history of MG was recorded in 2 cases belonging to 1 family (1.6%).

Miastenia gravis y gestación: caso clínico

Myasthenia gravis is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness and fatigue of ocular, facial, bulbar and voluntary muscles. It has a bimodal peak of incidence with first peak in the third decade in women. The diagnosis is possible with the current test, electromyography and the presence of antibodies to acetylcholine receptors. Treatment may include anticholinesterase drugs, corticosteroids, plasmapheresis, immunosuppressive drugs and thymectomy. The clinical course of myasthenia gravis during pregnancy is variable, with an increased risk for complications during delivery. We analyse the clinical presentation, diagnosis, treatment and evolution of a patient in our hospital because of the slight number of cases we can find in the scientific literature.