Onset Of Myasthenia Gravis Research Articles

Clinical, electrophysiological and immunological remissions after thymectomy in myasthenia gravis

Objectives: Approximately 50% of patients treated with thymectomy have a chance for symptom-free life. However, immunological and neurophysiological abnormalities may be detected in patients with clinical remission. Although improvement usually parallels decrease in acetylcholine receptor antibody (AChRAb) levels and jitter values, there is a question what factors influence immunological and electrophysiological remission in a population of myasthenia gravis (MG) patients. Methods: We analyzed retrospectively clinical data of 32 MG patients operated for generalized MG, followed-up at our department for 17.2 (4–31) years. They were in clinical remission for 12.8 (2–25) years. All of them had single fiber electromyograhy (SFEMG) of extensor digitorum communis muscle (EDC) muscle and estimation of AChRAb level at the end of follow-up. Their age at onset of MG was 17 years (6–48) and at thymectomy 19 (6.4–58) years. Tensilon test was positive in 30, repetitive nerve stimulation in 29 cases. Results: Clinical remission was reached on average 4.2 years after thymectomy. SFEMG jitter value normalized in 60% of cases. AChRAb were negative only in 34% of patients. Jitter values correlated with AChRAb levels ( P=0.006, r=0.5) but were not related to clinical factors. Only time to thymectomy correlated with time from thymectomy to clinical remission ( P=0.001, r=0.5). Conclusions: Clinical remission is not always accompanied by normalization of SFEMG and AChRAb. Although normalization of neuromuscular transmission in patients with remission of MG is individual, short duration of MG before thymectomy increases the chance of early remission.

PROGNOSIS AFTER THYMECTOMY IN OLDER PATIENTS WITH MYASTHENIA GRAVIS

To the Editor: The management of older patients (onset after age 60) with myasthenia gravis (MG) is frequently troublesome, and definite guidelines for treatment of these patients have not yet been established. The article by Evoli et al.,1 reporting the clinical characteristics and prognosis of 172 older patients with MG, was of great interest. The number of older patients with MG has been increasing in Japan. We evaluated 135 unrelated Japanese patients with MG who were seen at Keio University Hospital from January 1991 through December 2000, and identified 24 (17.7%) in whom the onset of MG was at or after the age of 60. There were 13 men and 11 women (M/F = 1.18), and age at onset ranged from 60 to 87 years (mean, 69.0). At maximum disease severity, eight patients (33.3%) had the ocular form of MG, whereas 16 (66.6%) had the generalized form. Anti-acetylcholine receptor antibody, measured by conventional assay, was positive in 21 patients (87.5%). The frequency of older patients with MG and the clinical characteristics of in-series were therefore compatible with recent published series describing Caucasians.1–3 In Japan, prednisone was the only approved immunosuppressive agent for MG treatment until September 2000, when tacrolimus (FK-506) received approval as a medication for MG from the Ministry of Welfare. Of 24 patients, only nine (37.5%) required immunosuppressive therapy with prednisone (starting dose of 0.5–1.0 mg/kg/day). This frequency was much lower than that in the report by Evoli et al. (80.5%).1 This is attributable to seven patients (29.1%) with the ocular form in our series whose symptoms could be controlled with anticholine esterase agents alone. Good results, as defined by Evoli et al.,1 were obtained in 17 patients (70.8%). Better outcomes might have been obtained in our series had we chosen the combination treatment with prednisone plus azathioprine, as proposed by Evoli et al.1 In particular, some older patients with bulbar symptoms experienced ongoing deterioration, and it was difficult to control the disease. Side effects of prednisone were observed in four patients (44.4%), although no cancers other than thymoma were found during follow-up. The four side effects were tuberculosis, myopathy, diabetes mellitus, and osteoporosis. This frequency was similar to that in the series by Evoli et al. (46.2%).1 The indications for and benefits of thymectomy in older patients with generalized MG remain controversial. We question whether the prognosis of older patients in whom thymectomy was performed was actually good in the series of Evoli et al.1 We conducted the following comparisons in our series. Statistical analysis was performed by chi-square and Student's t-tests. First, we divided older patients with generalized MG into two groups, a thymectomized group (n = 7) and a nonthymectomized group (n = 9). According to the general consensus,4 transsternal extended thymectomy was generally performed in our hospital when thymoma was detected on computed tomography or magnetic resonance images. Thymectomy could not be performed in one patient because of an old myocardial infarction. Prednisone treatment was required in four patients (57%) in the thymectomized group and in four patients (44%) in the nonthymectomized group (P = .6). Rates of good results were 57% in the thymectomized groups and 66% in the nonthymectomized group (P> 1.0). These data suggest that the prognosis of older patients with MG does not depend on thymectomy. Second, we compared prognosis after thymectomy in older patients to that in younger patients. Thymectomy was performed in 70 patients with onset of MG before the age of 60. To exclude any bias associated with pathological differences, we selected 34 patients (48.5%) with thymoma from this younger group. The clinical characteristics and prognosis of these two groups (the younger group (n = 34) and the older group (n = 7)) are summarized in Table 1. The prognosis tended to be worse in the older than in the younger group. The higher frequency of invasive thymoma in older patients appears to contribute to their poorer prognosis. Although Tsuchida et al. reported that thymectomy was effective for older patients with MG,5 even if no thymoma was detected, most of their patients required prednisone treatment after thymectomy. In fact, they showed the remission rate to be 40% in younger patients, but 8% in older patients.5 Considering these observations together, we emphasize that the prognosis after thymectomy in older patients is not as good as in younger patients, and that their clinical features constitute a particular challenge in treating older patients with MG.

Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis

With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [ p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients ( p<0.005; RR=6.2), more frequent in females ( p<0.005; RR=7.8) and most frequent in EOMG female patients ( p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.

Double filtration plasmapheresis in the treatment of myasthenic crisis--analysis of prognostic factors and efficacy.

To examine the prognostic factors and outcome of myasthenia gravis (MG) patients in crisis with double filtration plasmapheresis (DFP) treatment. A total of 15 patients experienced 20 episodes of crisis during the study period. Plasmapheresis was carried out using a double filtration Demographic information, clinical features of crisis, and associated complications were analyzed. The median duration of crisis was 9 days. Chest infection was the most common precipitant of crisis. Twelve out of the 20 episodes (60%) responded well to DFP and mechanical ventilation was discontinued after the third session of DFP in 8 of them. Three significant predictors for prolonged crisis were shorter intervals between the onset of MG and the first crisis (P=0.04), higher serum bicarbonate levels at baseline (P=0.03) and the thymic pathology of thymoma (P=0.03). DFP can ameliorate the profound weakness in crisis and seems to be a rational therapy for patients with myasthenic crisis.

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.

A Case of Myasthenia Gravis Preceded by Major Depression

Back to table of contents Previous article Next article LetterFull AccessA Case of Myasthenia Gravis Preceded by Major DepressionKoji Shinkai, M.D., Osamu Ohmori, M.D., Ph.D., Nobuhisa Ueda, M.D., Jun Nakamura, M.D., Ph.D., Tomoko Amano, M.D., and Sadatoshi Tsuji, M.D., Ph.D., Koji ShinkaiSearch for more papers by this author, M.D., Osamu OhmoriSearch for more papers by this author, M.D., Ph.D., Nobuhisa UedaSearch for more papers by this author, M.D., Jun NakamuraSearch for more papers by this author, M.D., Ph.D., Tomoko AmanoSearch for more papers by this author, M.D., and Sadatoshi TsujiSearch for more papers by this author, M.D., Ph.D., Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Fukuoka, JapanPublished Online:1 Feb 2001AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: In some reports on the relationship between myasthenia gravis (MG) and depression, the relationship has been discussed mainly from the viewpoint that depression may occur secondarily in MG patients reacting to having a chronic disability.1,2 The possibility that the involvement of the central nervous system in MG may play a pathogenic role in depression has been less examined and remains unclear.We here report a case of MG occurring with depression, in which the symptomatology and progress suggested that depression stemmed from the same pathology as MG.Case ReportA 39-year-old man developed symptoms of depression, including a depressed mood, guilt feelings, appetite loss, insomnia, and general fatigue in 1998. At this time, he had not yet experienced symptoms of MG.Four months later, he began to feel drooping in both eyelids. Two months thereafter, he suddenly experienced difficulty with speech and, around the same time, complained of a suicidal tendency. After another two months, the patient was admitted to our psychiatry unit. A diagnosis was made of major depression according to DSM-IV, and his score on the Hamilton Rating Scale for Depression (Ham-D) was 22 points. A brain CT and an EEG were normal.The patient was prescribed fluvoxamine 50 mg/day. However, he soon began to experience dysphagia repeatedly and suffered from aspiration pneumonia. Consequently, the medication was discontinued. He also had marked weakness of the upper limbs, which got worse in the afternoons. The diagnosis of MG was established by a consultant neurologist, in consideration of a positive result on an edrophonium (Tensilon) test. The serum titer of anti-AchR antibody was very high (25.5 pmol/ml); the level in cerebrospinal fluid was not examined.The patient was treated with anticholinesterase drugs. At the same time, thymoma was found and a thymectomy was performed. Since then, he has shown gradual improvement in both MG and depressive symptoms. The score on Ham-D gradually decreased (from 17 at admission to 13, 10, and 9 in successive months), simultaneous with a reduction of the serum titer of anti-AchR antibody (from 25.5 to 18.7, 14.2, and 15.2 pmol/ ml).CommentIn the present case, findings suggest that depression was not caused by the patient's reaction to disability resulting from MG, but by a pathology in common with MG. Onset of depression preceded onset of MG, and depressive symptoms associated with anxiety about MG symptoms were obscure; on the contrary, guilt feelings toward subordinates and regret over life choices, such as choosing an occupation and getting married, were more prominent. In addition, the score on Ham-D decreased parallel to decrease in the serum titer of anti-AchR antibody. This progress suggests that MG and depression in this patient had the same immunological basis.The potential pathogenic role of anti-AchR antibody in depression has been controversial.3 This case, however, suggests that increased attention should be paid to the complications of MG with depression. Further research on the autoimmune pathology of depression may help us understand the relationship between these two diseases.References1 Magni G, Micaglio GF, Lalli R, et al: Psychiatric disturbances associated with myasthenia gravis. Acta Psychiatr Scand 1988; 77:443–445Crossref, Medline, Google Scholar2 Brolley M, Hollender MH: Psychological problems of patients with myasthenia gravis. J Nerv Ment Dis 1955; 122:178–184Crossref, Medline, Google Scholar3 Keesey JC: Does myasthenia gravis affect the brain? J Neurol Sci 1999; 170:77–89Google Scholar FiguresReferencesCited byDetailsCited ByPsychopharmacological Treatments for Mental Disorders in Patients with Neuromuscular Diseases: A Scoping Review28 January 2022 | Brain Sciences, Vol. 12, No. 2Depression in myasthenia gravis: a heterogeneous and intriguing entity5 March 2020 | Journal of Neurology, Vol. 267, No. 6Clinical characteristics of patients with myasthenia gravis accompanied by psychiatric disorders10 January 2019 | Neurology and Clinical Neuroscience, Vol. 7, No. 2The Lancet, Vol. 375, No. 9711Neuroscience & Biobehavioral Reviews, Vol. 29, No. 4-5 Volume 13Issue 1 February 2001Pages 116-a-117 Metrics History Published online 1 February 2001 Published in print 1 February 2001

Altered expression of costimulatory molecules in myasthenia gravis.

To characterize the involvement of costimulatory pathways in the pathogenesis of myasthenia gravis (MG), a multiparameter flow cytometry assay was adopted to enumerate blood mononuclear cells (MNC) expressing CD28, CD80, CD86, CD40, and CD40L molecules in patients with MG and healthy subjects. Patients with MG had lower percentages of CD8(+)CD28(+) cells, augmented percentages of CD4(+)CD80(+), CD4(+)CD86(+), CD8(+)CD80(+), CD8(+)CD86(+), CD14(+)CD80(+), and CD14(+)CD86(+) cells, and similar levels of cells expressing CD40 and CD40L and of B cells expressing CD80 and CD86 compared to the controls. Patients with early onset of MG (<40 years) had lower percentages of CD3(+)CD86(+), CD4(+)CD86(+), CD8(+)CD86(+) T cells and CD20(+)CD86(+) B cells compared to those with late onset (>40 years). There was a positive correlation between the patients' age and percentages of CD86(+) cells. The data indicate that the CD28/CD80-CD86 costimulatory pathway is involved in MG. The high percentages of CD80 and CD86 positive T cells and monocytes may reflect persistent activation of T and B cells, whereas the low CD28 expression may be the result of chronic exposure to CD80 and CD86. These molecules could be the focus for new and improved immunomodulating therapies of MG.

TNFA and TNFB polymorphisms in myasthenia gravis.

Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammatory cytokines thought to be involved in the pathogenesis of myasthenia gravis (MG). To examine whether TNF polymorphisms are associated with MG, MG subgroups, and the presence of titin and ryanodine-receptor antibodies. We did genotyping on 30 patients with MG and 92 healthy blood donors for 2 biallelic TNFA polymorphisms (G to A at positions -238 and -308) and 1 TNFB polymorphism (NcoI digestive site) using methods based on the polymerase chain reaction. Patients with thymoma were typically homozygous for both the TNFA*T1 and the TNFB*2 alleles, but patients having an early onset of MG without thymoma were carriers of the TNFA*T2 and TNFB*1 alleles. Patients without thymoma who had the titin antibody had the same high frequency of TNFA*T1 and TNFB*2 as patients with thymoma, whereas patients without the titin antibody carried the same allele, TNFA*T2 and TNFB*1, regardless of age and thymic disease. No association was found with acetylcholine-receptor levels or disease severity for any of the TNFA or TNFB polymorphisms. Patients having MG, including those with thymoma, who have the titin antibody are most often homozygous for the TNFA*T1 and TNFB*2 alleles, whereas the presence of the TNFA*T2 and TNFB*1 alleles correlates with early-onset MG and the absence of titin antibodies.

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.

Tumour necrosis factor-α polymorphism and secretion in myasthenia gravis

The mechanism behind the association between MHC genes and myasthenia gravis (MG) is not fully understood. In the present study we studied the associations with polymorphisms at HLA-DR3, HLA-B8 and TNF-α genes in Swedish patients and healthy individuals. The TNF-α-308 allele 2 was associated with female patients having disease onset before the age 40 and with thymic hyperplasia. Analysis of strongest associations between MG and alleles close to TNF-α indicated that the association of TNF-α was possibly stronger than for HLA-DR3 and nearly the same as for HLA-B8. Peripheral blood mononuclear cells from patients positive for TNF-α -308 allele 2 had higher secretion of TNF-α when stimulated by anti-CD3 antibodies. Our results indicate that a subgroup of MG patients who have been previously shown to be associated with MHC genes may have a higher inducible TNF-α level in vivo, thus resulting the pathological changes in the thymus and the early onset of MG.

Late-onset myasthenia gravis: a changing scene.

The prevalence of myasthenia gravis (MG) among middle-aged and older patients has increased. Patients with early-onset MG live longer than before, but there is also an increase in late-onset MG (onset of the disease after the age of 50 years in patients with no clinical or paraclinical evidence of a thymoma). Epidemiological data support using the age of 50 years to separate early- and late-onset MG. The main immunological difference between early- and late-onset MG is the presence of antibodies to muscle titin, which are detected in approximately 50% of patients with late-onset MG. Treatment of late-onset MG has to be tailored both to the age of the patient and to the immunological findings of that particular form of MG.

Thymectomy in myasthenia gravis--an analysis of current status

Between May 1992 and June 1997, 11 patients with myasthenia gravis and 1 asymptomatic patient with thymoma underwent extensive thymectomy through a median sternotomy. Seven patients were male and 5 female. The mean age at onset of myasthenia gravis was 46.5 (13-73) years. The interval between the first symptom and diagnosis was 3.6 months (1 week-7 months), between the first symptom and thymectomy 8.3 months (2 weeks-36 months) and the mean follow-up period was 28.4 months (3-57 months). Clinical improvement after extensive thymectomy was noted in 80% of patients. Four patients became asymptomatic under decreased medication. Thymectomy was found to be beneficial even in older patients or patients with the purely ocular type of myasthenia gravis. There was no perioperative mortality or long-term morbidity.

Molecular analyses of HLA class II-associated susceptibility to subtypes of autoimmune diseases unique to Asians

It is well known that individuals positive for particular HLA-class II alleles show high risks for the development of Takayasu arteritis and other diseases caused by immunological disorders such as autoimmune diseases and allergies. HLA class II molecules present antigenic peptides to CD4 +T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. To better understand the mechanisms for association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many autoimmune diseases are observed in all ethnic groups, whereas the incidences of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoimmune self-peptides and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in determining the pathogenesis of the diseases. In this paper, we describe our recent findings on: (1) the uniqueness of both clinical manifestations and HLA-linked genetic background of Asian-type (optico-spinal form) multiple sclerosis; (2) the structural characteristics of peptides bound to HLA-DQ molecules susceptible to insulin-dependent diabetes mellitus; (3) the identification of a disease-related autoantigenic peptide presented by disease-susceptible HLA-DQ molecules in Asians-specific infant onset myasthenia gravis; and (4) a manipulation of human T cell response by altered peptide ligands, as a possible candidate for new and antigen-specific immuno-suppressive therapy against autoimmune diseases.

Glomerulonephritis associated with myasthenia gravis

In a follow-up study of 128 myasthenic patients from a neurological center in Northern Italy, three were found to have developed glomerulonephritis at variable intervals after the onset of myasthenia gravis, thymoma (two patients), and thymectomy. By renal biopsy, two patients (cases 1 and 3) were found to have membranous nephropathy; and one (case 2), pauciimmune extracapillary glomerulonephritis. At follow- up, patient 1 was persistingly nephrotic and developed renal failure, and patient 3 only had urinary abnormalities. Patient 2 developed end- stage renal disease. The review of the literature showed 10 other cases of glomerulonephritis associated with myasthenia gravis with or without thymoma and thymectomy. Therefore, it is likely that these conditions are pathogenetically linked. The role of autoantibodies, thymoma, and thymectomy in favoring glomerulonephritis in myasthenic patients is discussed. (Am J Kidney Dis 1998 Feb;31(2):350-5)

Prognosis of myasthenia gravis: a retrospective study of 380 patients.

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.

Late onset myasthenia gravis

Late onset myasthenia gravis (MG) is defined as the onset of the disease after the age of 50 in a patient with no clinical or paraclinical evidence of a thymoma. Myasthenia gravis has a bimodal appearance for both sexes with a peak age of onset located in the early onset group and another peak for late onset of MG. Early onset of MG in men is approximately 10 years later than in females. In late onset MG, the thymus is smaller than in early onset and much of the lymphoid tissue has been substituted with fat. There is no morphological evidence that the thymus atrophy seen in late onset MG is any different from the thymus involution which is age‐related. The AChR antibody concentration is lower in cases with late onset MG than it is in early onset and in thymoma‐associated MG. Sera from late onset MG patients can be divided in 2 groups; those with and those without striated muscle (MGT 30) antibodies. Their presence is not an effect of age since they are not detected among old healthy individuals. Nor is it an effect of long MG duration, since there is no relation between titre and duration. Non‐thymoma MG patients who demonstrate an immune response to titin identical to that observed in thymoma, have a worse prognosis and seem to do less well after thymectomy than late onset MG patients without muscle antiboides.

Myasthenia gravis and hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infections are often associated with extrahepatic immunological manifestations, including various autoimmune disorders. The aims of this study were to determine the prevalence of HCV markers in patients with myasthenia gravis (MG) and to determine any relationship with HCV infection. Eighty-three patients with MG. 40 men aged 20-93 years and 43 women aged 13-87 years (mean age 54 years) were studied. The MG patients were positive for antibody to acetylcholine receptor in addition, their sera was analysed for antibody to HCV (HCVAb) and HCV RNA, HCVAb was detected in two of the 83 patients (2.4%). Four patients were repeatedly HCV RNA positive. They were infected by HCV genotype 1 (one patient), HCV genotype 2a (two patients) and an undetermined HCV genotype in one patient. They received plasmapheresis or intravenous immunoglobulin treatment. Among the four patients, one was infected after the onset of MG without receiving a blood transfusion or using intravenous drugs. The other three had chronic hepatitis C which was discovered at the same time as MG and only one patient had been exposed to blood products. The prevalence of HCV markers in patients with MG (4.8%) was higher than that reported for the general French population, about 1%. This prevalence is similar to that occurring in patients exposed to plasmapheresis or intravenous immunoglobulin. In conclusion, HCV appears to play little, if any, role in causing MG. The higher prevalence of infection among MG patients may be related to transmission in the course of therapy.

Expression of acetylcholine receptor genes in human thymic epithelial cells: implications for myasthenia gravis.

The intrathymic presence of the muscle acetylcholine receptor (AChR) is controversial, and the nature of the cell(s) expressing it is unclear. We thus analyzed the molecular expression of muscle AChR in human thymi. mRNA studies indicated that the two isoforms (P3A+ and P3A-) of the alpha-subunit were present in thymic extracts and in cultured thymic epithelial cells (TEC), while expression in thymocytes was low and not consistently detectable. The amount of mRNA coding for the alpha-subunit, evaluated by means of quantitative PCR, was about 20 times less in TEC than in muscle, and was similar in TEC from normal subjects and from patients with myasthenia gravis (MG). The beta- and epsilon-subunits present in adult AChR were also expressed in TEC (but not in thymocytes), while the embryonic subunit (gamma) was absent. In TEC cultures, the AChR alpha- and epsilon-subunit mRNA levels were down-regulated by forskolin, as also observed in the TE671 rhabdomyosarcoma cell line, suggesting similar regulation of AChR subunits in thymus and muscle. Protein expression was evidenced on TEC (but not on thymocytes), by Western blotting as well as by immunofluorescence, thus demonstrating AChR expression on human thymic epithelial cells. There was no difference in the expression of AChR between TEC from MG patients and controls, meaning that the expression of AChR subunits alone is not sufficient to explain the onset of MG.

P161 Comparative study of late results of thymectomy in myasthenia gravis of onset at older and younger age (clinical at electrophysiological studies)

P161 Comparative study of late results of thymectomy in myasthenia gravis of onset at older and younger age (clinical at electrophysiological studies)

The association of systemic lupus erythematosus and myasthenia gravis

Two women with the rare association of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are reported. The first patient developed SLE (arthritis, severe thymectomy for MG. The second patient developed SLE (oral ulcers, arthritis, serositis, leukopenia, high titres of anti-DNA and anti-nuclear antibodies) 4 years prior to the clinical and serological onset of MG. Lymphocyte subsets and in vitro proliferative responses of peripheral blood mononuclear cells to mitogens were normal in both patients. A review of the literature revealed 26 additional patients with definite SLE coexisting with MG. Besides the theoretical interest of this association, the differential diagnosis of fatigue in patients with SLE should always include the possibility of MG.