Myasthenia gravis and thymoma. Evaluation of 41 patients.

We evaluated the epidemiological, clinical, laboratory and therapeutical aspects of 41 patients with thymomatous myasthenia gravis. Thirty five patients (85.36%) were submitted to thymectomy. Follow-up ranged from two to 18 years. Diagnosis of thymoma was based upon clinical investigations and CT scan of the anterior mediastinum and in 11 patients supported by immunological tests of anti-striated muscle antibodies with a positive result in more than 80% of cases. Histopathologic examination of all thymomectomized patients confirmed the diagnosis of thymoma. There was a significant predominance of benign over malignant thymoma. Occurred higher prevalence of male patients and of patients over 40 years of age. The therapeutical strategy to control myasthenic clinical findings was the same as that for non-thymomatous myasthenia gravis. The corticosteroids associated to cytotoxic drugs were less often used. Radiotherapy of the anterior mediastinum was more often used in patients having invasive tumors submitted to surgery or not. With regard to survival and control of myasthenia gravis, especially in younger patients and in those submitted to early surgery, results of treatment were surprisingly favorable.

Evaluation of the respiratory function in myasthenia gravis. An important tool for clinical feature and diagnosis of the disease.

Myasthenic gravis may affect both inspiratory and expiratory muscles. Respiratory involvement occurred in almost all patients with myasthenia gravis in all clinical forms of the disease: 332 lung function tests done in 324 myasthenic patients without respiratory symptoms (age 34.6 +/- 18.3 years) were examined. Lung volumes analysis showed that all the patients of both sexes with generalized or ocular myasthenia gravis showed "myasthenic pattern". Male patients with "ocular" form only presented the "myasthenic pattern" with lung impairment and had, from the lung function point of view, a more benign behaviour. Female patients with the "ocular" form exhibited a behaviour of respiratory variables similar to that of the generalized form. It was not observed modification of the variables that suggested obstruction of the higher airways. The "myasthenic pattern" was rarely observed in other neuromuscular diseases, except in patients with laryngeal stenosis.

[History of the study of myasthenia gravis at the Neurologic Clinic of the Hospital of Medical School Clinics of the University of São Paulo]. / História do estudo da miastenia grave no Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina de Universidade da São Paulo.

It is synthetized the evolution of the researches on myasthenia gravis at the Department of Neurology of the Hospital das Clínicas of the Faculty of Medicine, Medical School of the University of São Paulo (Brazil) between 1950 and 1992. The most important results observed about therapeutical, clinical and pathophysiological researches are reviewed. Immunologic studies and advances on molecular biology are emphasized.

Atrophy of the tongue with persistent articulation disorder in myasthenia gravis: report of 10 patients.

Ten patients with atrophy of the tongue, from a group of 752 with generalized acquired myasthenia gravis (MG), were studied. Tongue atrophy developed late in the majority of patients and was accompanied by tongue paresis (70% of the cases) and eventually associated to atrophy of other muscles of the palate, especially the uvula. All the patients exhibited severe forms of MG with bulbar involvement, mainly persistent dysphonia and dysphagia, almost always refractory to treatment. There is no correlation among atrophy of the tongue, sex, and thymus pathology. There is correlation between severeness of symptoms and early, persistent and treatment refractory dysphonia and dysphagia.

Thymectomy in over 50 years-old patients with myasthenia gravis: long and short-term results in 21 patients.

Thymectomy is considered to be an important method for the treatment of myasthenia gravis in older patients when the improvement cannot be achieved with the use certain drugs such as anticholinesterasic, corticosteroids and immunosuppressive agents. In our series of 281 thymectomized patients, 13 were male and 8 female, varying their age between 50 and 73 years. The duration of the disease prior to the thymectomy varied between 30 days and 15 years; in 12 of them (57%) it lasted already 2 years. Eleven patients had the severe and eight the moderate clinical form of the disease. Nine patients were treated with corticosteroids before submitted to thymectomy. In 11 patients the histopathological changes in the thymus were evaluated: eight had thymomas, one atrophic changes, one lipomatosis and one a normal thymus. The short-term follow-up revealed important improvement in 12 patients, slight improvement in four and worsening in two; two patients died. It is concluded that thymectomy may be indicated in older patients when their condition worsens in spite of the use of corticosteroids and immunosuppressive agents, in the presence of serological markers or computerized tomography image indicating thymoma, and intolerance for corticosteroids.

Juvenile myasthenia gravis and thymectomy: report of ten cases.

Ten patients from 7 to 12 years of age presented generalized acquired myasthenia gravis: six had a severe form and four a moderate one. All patients showed progressive worsening and poor response to the medical treatment; all of them were submitted to thymectomy by median sternotomy. Long-term results were beneficial for 60% of the patients who experimented a marked improvement or even complete remission. One patient improved without medication being followed for two years. Another patient has been in remission taking only a minimal dose of anticholinesterase drug for seven years. In most cases prednisone has been used as long-term maintenance in the postoperative phase. Short-term results were not favorable: one death occurred and 30% of the patients worsened.

Thymectomy for myasthenia gravis: evaluation of results in 282 patients.

The results of thymectomy in 282 patients with acquired and generalised myasthenia gravis are presented. The study includes patients submitted to surgical treatment in the period between 1958 and 1990. Remission or marked improvement was obtained in 70% of the patients with follow-up extending from one to 25 years. The total post-operative mortality rate was 8% dying predominantly patients with thymoma. Median sternotomy was made in 278 patients, transcervical thymectomy in two patients and thyroidectomy with concomitant thymectomy in other two. Surgical methods, operatory phases, previous treatment with prednisone and long term evolution with final results are discussed.

[Myasthenia gravis: critical evaluation of the treatment]. / Miastenia grave: avaliação crítica dos tratamentos.

The author emphasizes the difficulty of the subject since on the one hand there is no assurance about the value of the treatment methods performed commonly at the moment, and on the other hand there is an evident lack of prospectively controlled trials and double-blind studies. Mostly this dilemma occurs by the lack at the moment of any specific treatment. The author deals with the four therapeutic methods most commonly used: cholinergic drugs, thymectomy, immunosuppressive drugs and plasmapheresis. At last, the experimental specific immunotherapy by the use of antibodies and suppressive cells and the irradiation methods are discussed.

Mitochondrial dysfunction in myasthenia gravis. Report of a case.

The case of an 11-year-old boy with external ophthalmoparesia, tetraparesia and bilateral eyelid ptosis is reported. He was 7-years-old when first symptoms appeared. Anticholinesterasic drugs were used. He was submitted to muscle biopsy. The results of histochemistry analysis showed storage of granulous material at the subsarcolemmal region of muscle fibers by SDH. Increase in the number of mitochondria with electron dense bodies was found at electron microscopy. Anticholinesterasic drugs administration was interrupted and consequently he got worse, and bouts of dyspnea occurred. Due to this worsening anticholinesterasic agents were reintroduced together with prednisone, and he improved. Due to clinical and histological expressions we think it is possible that morphological mitochondrial alterations may occur also in myasthenia gravis.

Nervous system involvement in systemic lupus erythematosus: report of three cases.

Central nervous system involvement in systemic lupus erythematosus is rather frequent whereas peripheral nervous system involvement is much less common. The three patients studied by us had isolated manifestations uncommon in nature. The first one developed a sensory-motor polineuropathy with signs of axonal degeneration. It responded to the therapeutic association of corticosteroids with an immunosuppressive agent. Satisfactory recovery took place over a time span of a year. The second patient had encephalic and cerebral trunk involvement from which an irreversible dementia resulted. The third patient, who had recurrent aseptic meningitis, is asymptomatic for six months now. Patients one and two had no systemic manifestations at the time of nervous system involvement. Suspicion of systemic lupus erythematosus was made on the basis of past inspecific articular symptoms. The neurological and systemic manifestations may be sometimes simultaneous; they are usually followed by serologic changes. Isolated nervous system involvement may be seen with and without sorologic changes, and there may be found antibodies reactive with phospholipids (anticardiolipin, antigangliosides and anticerebrosides). The employment of nonsteroid immunosuppressive drugs associated with corticosteroids in small doses seems to be useful in cases of systemic lupus erythematosus with nervous system involvement.

Failure of treatment of myasthenia gravis by cyclosporin-A: A case report.

Recently, cyclosporin-A (Cy-A) has been used in the treatment of myasthenia gravis (MG). This drug could be employed in some patients refractory to classic treatments or that develop undesirable side effects. It is reported the case of a 22 year-old woman with generalized and severe MG, and diabetes mellitus. She had been submitted to thymectomy and reoperated, to the classic ethiopathogenic methods of therapy, and to total body irradiation. No therapeutical results were observed. Also, she developed transient and slow bone marrow depression, and liver dysfunction. Owing to these limitations and to the absence of response to treatments mentioned. Cy-A use was attempted in this case. Unfortunately, Cy-A did not influence the myasthenic symptomatology. Cy-A also failed in suppressing anti-AChR production, which increased during Cy-A therapy. Results observed in this case are in disagreement with literature data on the subject.

[Study of circulating lymphocytes by monoclonal antibodies in myasthenia gravis]. / Estudo dos linfócitos circulantes por anticorpos monoclonais na miastenia grave.

A significant decline of CD3 cell detected by rosettes and a significant increased of B cell populations were observed. The total CD3+, helper CD4+ and suppressor CD8+ T-cell subsets showed no significant variation em relation to sex, age thymectomy and corticotherapy by monoclonal antibodies.

[Conservative treatment and thymectomy in myasthenia gravis: short- and long-term evaluated results]. / Tratamento conservador e timectomia na miastenia grave: resultados avaliados a curto e longo prazos.

A retrospective survey of the records of 33 patients with generalized acquired myasthenia gravis treated at Hospital das Clínicas, Medical School of The University of São Paulo, Brazil and in private practice, with and without thymectomy, is reported. Nineteen were thymectomized and 14 non operated. Both groups were demographically homogeneous and were followed from 8 to 24 years. Parameters for evaluating the natural history of disease and other ones for a comparative analysis of the improvement or remissions were established. The influence of the individualized therapy was evaluated by McNemar test (chi 2); the U-Mann-Whitney was used for evaluation of the populational behavior groups; variable parameter with possible influence in the useful life were studied by multivariate analysis. The difference of distance between both groups was not significant: (D2 = 0.08894); T2 = 7.17 (Hottelling test). There were differences of the isolate clinic parameter response in both groups, but the global analysis of the parameters did not permit to discriminate them, possibly because of interaction of the parameters influencing the analytic result. Inspite of the fact that superposition of the parameter occurred when analysed for a long period, we believe the early thymectomy to be beneficial. Our patients who had their operation at a younger age and specially those with recent disease had a maximum improvement.

[Dermatopolymyositis: evaluation of 63 patients]. / Dermatopolimiosite: avaliação de 63 pacientes.

Sixty-three patients with dermatopolymyositis were evaluated from the clinical, laboratory and therapeutical aspects during a period of 15 years: 39 are women and 24 men. The mean age was 36.8 +/- 15.6 years. No correlation was observed between clinical and isolated therapeutics employed; when corticosteroids and cytolytic drugs were used simultaneously, the clinical response was satisfactory. No special fact was seen that can predict the therapeutical response.

[Myasthenia gravis. Evolution of research at the Neurologic Clinic of the Clinical Hospital of the University of São Paulo Medical School]. / Miastenia grave. Evolução das pesquisas na Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da USP.

The evolution of investigations in Myasthenia gravis in the Division of Neurology, University of São Paulo Medical School, during the period from 1956 to 1986 is reported. The most important findings in the therapeutical, clinical and immunological researches are showed.

[Treatment of myasthenia gravis by immunosuppressive non-steroidal drugs]. / Tratamento da miastenia grave mediante imunossupressão medicamentosa não esteróide.

Fourteen patients (twelve of them were women) with severe myasthenia gravis who had not responded to any treatment at all, were treated by cytostatic drugs. Both azathioprine and cyclophosphamide single or in combination are used. All patients except two were thymectomized and almost all were treated by plasmapheresis and corticosteroid before and during the cytostatic treatment. All patients take cholinesterase inhibitors. No serious complications were observed. The patients received 100-200mg of azathioprine and/or 100-200mg of cyclophosphamide daily by oral route, the first during 20 months and the second one during 6 months. Three patients received cyclophosphamide 1g daily by venous route during 6 months at 15-20 days intervals. The preliminary results were favourable occurring important improvement in 71.4% of the cases. Their performance increased considerably. The progress of the disease was generally stabilized. Exacerbations and crises did not recur, except in one case. Only three patients had not responded to the treatment, one responded poorly but better later and one had an exacerbation after the 24th month. This patient returned to azathioprine.