Course Of Myasthenia Gravis Research Articles

Effect of pregnancy and birth on the course of myasthenia gravis before or after transsternal radical thymectomy☆

Myasthenia gravis (MG) affects women at childbearing age. Therefore, the question arises if these patients should become pregnant and if thymectomy has a positive effect on the course of MG in pregnant patients. Fifteen pregnancies had been followed retrospectively. All patients underwent transsternal radical thymectomy for MG. The course of MG in the period before, during, and after the pregnancy was scored according to Ossermann's classification. The effect of thymectomy on delivery and on the newborns was evaluated. Patients were divided in two groups: pregnancies before (group I, n=8) and after (group II, n=7) thymectomy. During pregnancy, in group I, one deterioration was observed and in seven patients the disease was unchanged. In group II, one deterioration, five unchanged courses, and one improvement were observed. In the postpartum period, in group I, seven patients did not change and one improved. In group II, two deteriorations, three unchanged courses, and two improvements were observed. Before pregnancy, group II patients were in a better Ossermann stage in comparison with those in group I. Eight of the 12 deliveries were spontaneous (three abortus). Myasthenic symptoms were observed in two newborns in group I. Our data suggest that MG is not prohibitive to have children. The course of MG after transsternal radical thymectomy is often ameliorated. A better MG-stage, reached after thymectomy, before pregnancy seems to be correlated with a better course during pregnancy.

Myasthenia gravis and pregnancy: clinical implications and neonatal outcome

BackgroundThe myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients.MethodsTo describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome.ResultsFrom January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11%) had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39%) had clinical worsening of the condition of 9 other patients (50%) remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns.ConclusionsThe clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population.

A population based epidemiological study on myasthenia gravis in Estonia

Objective: To describe the occurrence of myasthenia gravis in the Baltic area. Methods: Data were obtained from hospital files recorded during the period 1942 to 1996 from neurologists and the...

Treatment Principles in the Management of Autoimmune Myasthenia Gravis

The pathogenesis of myasthenia gravis (MG) involves a T cell-directed antibody-mediated autoimmune attack on the nicotinic acetylcholine receptor (AChR) or, occasionally, on other postsynaptic antigens. The antibodies induce their effects through complement-mediated destruction of the postsynaptic endplate membrane with resultant reduction in endplate AChR, and to a lesser degree by increased turnover of endplate AChR or blockade of AChR function. Considerable progress in the treatment of MG has accrued from so-called symptomatic treatments, including improved critical care of seriously ill patients and medications (e.g., cholinesterase inhibitors) increasing the concentration of acetylcholine at the remaining endplate AChRs. Information from other autoimmune diseases and from the response of the normal immune system to invading pathogens supports the view that the course of MG is characterized by exacerbations and remissions. Therefore, the goal in MG treatment is to induce and maintain a remission. This usually involves combinations of short-term and long-term immunosuppressive agents. Selection of the particular combinations of agents in a given patient is guided by the goal of minimizing the cost/benefit ratio of the regimen in an individual patient. In general, the plan involves an initial forceful attack followed by a slow and measured withdrawal.

Myasthenia Gravis in Pregnancy: Report on 69 Cases

Obstetrical & Gynecological Survey 58(3):p 156-157, March 2003. | DOI: 10.1097/01.OGX.0000055745.76455.47

Myasthenia gravis with ocular involvement in older patients

Background: There has been little previous study reporting the eye findings and presentation of elderly patients with myasthenia gravis. The purpose of this study was to review the findings and course of myasthenia gravis after the sixth decade of life.Methods: Retrospective observational case series. The authors reviewed the clinical records of 27 patients with onset of myasthenia gravis at age 60 years or more who were seen at a tertiary care academic ophthalmology centre in Houston between January 1992 and March 1999. The diagnosis of myasthenia gravis was based on conventional clinical and laboratory criteria.Results: Twenty patients (74%) were men. Of the 16 patients who underwent testing for anti-acetylcholine receptor antibodies, I I (69%) were seropositive. Concurrent thyroid disease was found in seven patients (26%), including five (71 %) of the seven women. No patient had thymoma. Sixteen patients (59%) manifested generalized symptoms during follow-up; 12 did so within I year of disease onset. Patients responded well to both anticholinesterase and corticosteroid therapy. At the most recent follow-up visit 18 patients (67%) were clinically improved, and no patient was clinically worse.Interpretation: Myasthenia gravis in this study was characterized by a male predominance, high rate of concurrent thyroid disease, high rate of progression to mild generalized symptoms, absence of thymoma, good response to medical therapy and minimal life-threatening complications. Clinicians should consider the diagnosis of myasthenia gravis in an older patient presenting with diplopia or ptosis.

The third-dimensional structure of the complex between an Fv antibody fragment and an analogue of the main immunogenic region of the acetylcholine receptor: A combined two-dimensional NMR, homology, and molecular modeling approach

Binding of autoantibodies to the acetylcholine receptor (AChR) plays a major role in the autoimmune disease Myasthenia gravis (MG). In this paper, we propose a structure model of a putative immunocomplex that gives rise to the reduction of functional AChR molecules during the course of MG. The model complex consists of the [G(70), Nle(76)] decapeptide analogue of the main immunogenic region (MIR), representing the major antigenic epitope of AChR, and the single chain Fv fragment of monoclonal antibody 198, a potent MG autoantibody. The structure of the complexed decapeptide antigen [G(70), Nle(76)]MIR was determined using two-dimensional nmr, whereas the antibody structure was derived by means of homology modeling. The final complex was constructed using calculational docking and molecular dynamics. We termed this approach "directed modeling," since the known peptide structure directs the prestructured antibody binding site to its final conformation. The independently derived structures of the peptide antigen and antibody binding site already showed a high degree of surface complementarity after the initial docking calculation, during which the peptide was conformationally restrained. The docking routine was a soft algorithm, applying a combination of Monte Carlo simulation and energy minimization. The observed shape complementarity in the docking process suggested that the structure assessments already led to anti-idiotypic conformations of peptide antigen and antibody fragment. Refinement of the complex by dynamic simulation yielded improved surface adaptation by small rearrangements within antibody and antigen. The complex presented herein was analyzed in terms of antibody-antigen interactions, properties of contacting surfaces, and segmental mobility. The structural requirements for AChR complexation by autoantibodies were explored and compared with experimental data from alanine scans of the MIR peptides. The analysis revealed that the N-terminal loop of the peptide structure, which is indispensable for antibody recognition, aligns three hydrophobic groups in a favorable arrangement leading to the burial of 40% of the peptide surface in the binding cleft upon complexation. These data should be valuable in the rational design of an Fv mutant with much improved affinity for the MIR and AChR to be used in therapeutic approaches in MG.

Course and treatment of myasthenia gravis during pregnancy.

To evaluate the influence of myasthenia gravis (MG) on pregnancy and potential treatment risks for infants and mothers. MG frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Knowledge of the potential effects of 1) pregnancy on the course of MG and 2) the use of immunosuppressive drugs during pregnancy is limited, rendering decision-making difficult for both patient and physician. We studied 47 women who became pregnant after the onset of MG. Immunosuppressive drugs were administered when MG symptoms were not controlled with anticholinesterases. Sixty-four pregnancies resulted in 55 children and 10 abortions. During pregnancy, MG relapsed in 4 of 23 (17%) asymptomatic patients who were not on therapy before conception; in patients taking therapy, MG symptoms improved in 12 of 31 pregnancies (39%), remained unchanged in 13 (42%), and deteriorated in 6 (19%). MG symptoms worsened after delivery in 15 of 54 (28%) pregnancies. Anti-acetylcholine receptor antibody (anti-AChR ab) was positive in 40 of 47 mothers and was assayed in 30 of 55 newborns; 13 were positive and 5 of 55 (9%) showed signs of neonatal MG (NMG). All affected babies were seropositive. Pregnancy does not worsen the long-term outcome of MG. The course of the disease is highly variable and unpredictable during gestation and can change in subsequent pregnancies. The occurrence of NMG does not correlate with either maternal disease severity or anti-AChR antibody titer. Immunosuppressive therapy, plasmapheresis, and i.v. human immunoglobulins can be administered safely if needed.

Follow-up of myasthenia gravis. Results of a longitudinal study of the significance of psychosocial predictors

Forty-two patients suffering from myasthenia gravis were examined in a longitudinal study design. The aim of the study was to investigate possible psychosocial predictors for the course of the disease. At the time of the first examination (T1) the diagnosis myasthenia gravis had been established for no longer than 1 year. Two further examinations were done at 6 months (T2) and 18 months (T3) after T1. Methods consisted of a personality questionnaire (FPI), a coping questionnaire (FKV), an assessment of neurotic symptoms by interviewers (PSKB) and an assessment of the doctor-patient relationship by the attending physicians. Two different severity scores (Oosterhuis Index, Myasthenia Score) served as criteria for the course of the disease. There was no connection between the course of myasthenia gravis and neurotic symptoms like anxiety or depression and the quality of the doctor-patient relationship (both assessed at T1). Also demographic data were independent from the development of severity scores. The personality factor extraversion was associated with a positive course of the disease, aggressiveness and worrying about health with a negative one. Among the coping behaviors religiousness and looking for sense were associated with a favorable course but that was shown only regarding the Oosterhuis Index and not the Myasthenia Score. As several T1 personality factors were predictive for the severity scores at T3, these results may suggest a causal influence of personality factors on the severity of the illness. Whether or not this relationship is actually in operation, however, remains ellusive. Further studies using an experimental design are needed to strengthen this hypothesis.

Análisis de los resultados de la timectomía a largo plazo en el control de la miastenia gravis

We studied 77 patients with myasthenia gravis (MG) in whom thymectomy had been done between 1968 and 1992. The mean follow-up period was 7.3 years. Our aim was to analyze their clinical courses with regard to various parameters: demographic, clinical and the anatomo-pathology of the thymus. We classified the patients according to three possible situations: in remission without treatment, in remission with some type of treatment and not in remission. We did not find any data which significantly affected the subsequent course of MG. However, there was a statistically significant improvement (p = 0.008) when the pre-thymectomy and post-thymectomy conditions of the patients were compared. Overall, our series of cases is comparable to the majority of those presented. It should be remembered that although thymectomy has a place in the treatment of MG, and the technique is of low morbidity, precise indication for it has not yet been established. There are a considerable number of patients in whom no improvement is seen after this operation, although in 30% improvement may be expected.

Indications and value of thymectomy in myasthenia gravis

The therapeutic impact of thymectomy on the clinical course of myasthenia gravis is still a matter of debate. Issues in this discussion that are clinically relevant are reviewed. While the surgical procedure is accepted for thymomas its performance is controversial in cases with no thymomatous tissue. Outcome studies show a weak correlation between clinical course and thymus histology, but there is some doubt about the maximum age for thymectomy and about the therapeutic regimen following surgery. Retrospective studies show that thymectomy has a beneficial influence on the natural course of myasthenia. This positive effect is enhanced by appropriate immunosuppressive therapy together with anticholinesterase inhibitor substitution. Unfortunately, the different forms of myasthenia do not all respond in the same manner. Studies have shown that thymoma-associated myasthenia is more difficult to control than non-thymoma-associated myasthenic states. In both groups some patients go into remission after thymectomy alone, and the majority of patients with the institution of additional immunosuppression. In clinically mild cases thymectomy should not immediately be followed by immunosuppression. This will help to identify those patients responding with remission to thymectomy alone. Mostly these are young women with a hyperplastic thymus. Overall, thymectomy is beneficial and should be considered in all patients with generalized myasthenia who are still under 60 years of age.

To the course of myasthenia gravis in elderly patients

To the course of myasthenia gravis in elderly patients

Augmented interferon-γ, interleukin-4 and transforming growth factor-β mRNA expression in blood mononuclear cells in myasthenia gravis

The abnormal T lymphocyte-dependent production of antibodies to the nicotinic acetylcholine receptor (AChR) in myasthenia gravis (MG) suggests a role for immunoregulatory cytokines. We examined the T helper type 1 (Th1) cell-associated interferon-γ (IFN-γ) that promotes cell-mediated immunity, the Th2 cell-related interleukin-4 (IL-4) that augments B cell immunity, and transforming growth factor-β (TGF-β) that downregulates immune responses but enhances isotype switching. Blood mononuclear cells (MNC) expressing cytokine mRNA were enumerated after in situ hybridization with labelled complementary DNA oligonucleotide probes for IFN-γ, IL-4 and TGF-β. MG patients had elevated numbers of cells expressing IFN-γ and IL-4 compared to patients with non-inflammatory neurological diseases and healthy controls, implying that both Th1- and Th2-like cells are involved in MG. TGF-β-positive cells were also elevated in MG. The levels of cytokine-positive MNC were similar in MG and in control patients with other inflammatory neurological diseases. There were no associations between numbers of cytokine-positive blood MNC and clinical variables of MG, but individual patients need to be studied over the course of MG to clarify a relation between the cytokines under study and clinical or laboratory variables of MG.

Factors influencing the clinical type and course of myasthenia gravis

Myasthenia gravis is considered to be an autoimmune disease in which several factors reciprocally influence the clinical type and course. We investigated the relative importance of the following factors: anti-acetylcholine receptor antibody (AChR Ab), HLA, age at onset, autoimmunity, thymic abnormality, duration of treatment, change in AChR Ab titer and immunosuppressive therapy. The pretreatment-AChR Ab titer and HLA were shown to significantly influence the clinical type. On the other hand, the age at onset significantly influenced the clinical course. The finding that with an onset at less than 5-year-old there was a tendency for a good prognosis suggests an association between the immaturity of the muscle and immune systems, and the clinical course.

T-cell subsets in the long-term course of myasthenia gravis

T-cell subsets in the long-term course of myasthenia gravis

Epidemiology of Myasthenia Gravis in Denmark A Longitudinal and Comprehensive Population Survey

The incidence of myasthenia gravis (MG) was found to be constant in calendar time. The mean annual incidence rate was 4.4 per million population. Age- and sex-specific incidence rates disclosed a bimodal appearance for both sexes, with a peak age at onset located in the early-onset group and another peak for late onset of MG. Early onset of MG appeared 10 years later for male individuals than for female individuals, whereas the peak for late onset of MG was located at the same age for both sexes. It is suggested that the separation between early onset and late onset of MG should be at the age of 50 years for both sexes, rather than at 35 to 40 years as accepted in most studies. The prevalence of MG has increased in time. On January 1, 1988, the point prevalence rate was 77 per million population (female subjects, 96, and male subjects, 57). This reflects an improvement in prognosis despite the fact that life expectancy was found to be significantly lower for MG patients than that of the sex- and age-matched population. The factors causing increased mortality were found to be operative throughout the duration of the disease. Maximum severity of disease was reached within 2 years from onset in 78% of the cases, and more than 50% of all MG-related deaths occurred during the same period. In the course of MG, 70% of all patients experience generalized muscular weakness, and 30% to 40% also suffer from respiratory problems.

A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy

A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.

Immunogenetics, thymic morphology and clinical course of myasthenia gravis

Immunogenetics, thymic morphology and clinical course of myasthenia gravis

The natural course of myasthenia gravis: a long term follow up study.

A long term follow up study is presented of 73 patients with myasthenia gravis, living in Amsterdam between 1926 and 1965. In the period 1961-65 the annual incidence was 3.1, the prevalence 53 per million. Maximum severity of the disease occurred during the first seven years after onset in 87%. Eighteen (29%) patients died, of whom eight had a thymoma (TH). Spontaneous improvement or remission occurred at any time during the follow up. At the end of the study (1985) 16 (22%) patients were in a complete clinical remission, 13 (18%) had improved considerably (3 with prednisone), 12 (16%) had improved moderately, 12 (16%) had remained unchanged and two had deteriorated. If the early deaths are excluded the outcome is similar in the early and the late onset group without TH. Patients with TH had a less favourable course. Associated autoimmune diseases were diagnosed in 25% (n = 58). Because most of these patients were treated with anticholinesterases only, the evolution of their clinical state represents the natural course of MG.

Involvement of HLA in clinical courses of myasthenia gravis

The relationship between the histocompatibility leukocyte antigen (HLA) phenotypes and the clinical course of myasthenia gravis (MG) was studied in 53 Japanese patients with MG. The frequency of HLA-DRw9 antigen was high in the MG patients who did not need immunosuppressive therapy but only anticholinesterase agents ( RR = 4.52; CP < 0.02), who achieved remission of the disease ( RR = 2.98; CP < 0.05) or two showed a decrease in AChR antibody (Ab) titer ( RR = 6.32; CP < 0.0002) whereas the frequency of HLA-DRw8 antigen was increased in MG patients who underwent immunosuppressive therapy ( RR = 4.03; CP < 0.01), who did not have remission ( RR = 4.75; CP < 0.1) or who showed an increase in AChR Ab titer ( RR = 6.48; CP < 0.01). These data suggest that immunogenetic heterogeneity in MG might be reflected in its clinical course.