Decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternal thymectomies.

BACKGROUND: We studied the incidences and evaluated the management of early postoperative complications after thymectomy for myasthenia gravis. METHODS: During the period between 1987 and 1996, 324 thymectomies were performed through median sternotomy access under general anesthesia. Postoperative management was administered according to a standardized protocol of anticholinesterase medication, which was withdrawn for the 48 hours of obligatory postoperative mechanical ventilation. The mean age of patients was 34 years (range, 8 to 71 years). RESULTS: One hundred forty-nine patients made an uneventful recovery; 104 patients had only minor complications, whereas 71 patients had major complications. The mortality rate was 0.6% (2 patients). The major surgical complications were recorded as sternal bleeding (1 patient) and sternal disruption (1 patient). The major general complications were recorded as tracheal stenosis (1 patient), pneumonia (3 patients), heart failure (1 patient), gastric hemorrhage (1 patient), and respiratory insufficiency (71 patients). Forty-six reintubations were performed on 40 patients and 19 tracheostomies (6%) were performed postoperatively. CONCLUSIONS: The excessive incidence of respiratory insufficiency and airway-associated morbidity was potentially related, at least partially, to prolonged mechanical ventilation and withdrawal of anticholinesterase medication. Earlier weaning of patients with revision of 48-hour withdrawal of anticholinesterase medication is necessary.

Dominantly inherited familial myasthenia gravis as a separate genetic entity without involvement of defined candidate gene loci.

Myasthenia gravis (MG) is a sporadic autoimmune disorder affecting neuromuscular transmission. Very rarely autoimmune myasthenia gravis may be inherited within a family. We present here the genetic analysis of a Hungarian family where nine members from two generations are affected by myasthenia gravis. Genetic characterisation of this unique Hungarian family using linkage analysis and mutation screening excludes the involvement of defined candidate gene loci. These findings point to familial MG as a separate genetic entity. Identification of the underlying genetic defect in this family may greatly enhance our understanding of the pathogenesis of myasthenia gravis.

Altered polyamine levels in skeletal muscle of patients with myasthenia gravis.

Forty patients with myasthenia gravis were tested for polyamine content of the musculus sternothyreoideus removed during thymectomy. Cases with slight muscle alteration were found to show elevated values for all the three polyamines (putrescine, spermidine and spermine) examined with an increased spermidine/spermine ratio. In severe muscular atrophy, however, the high spermidine and spermine levels were accompanied by unchanged putrescine content and spermidine/spermine ratio. Denervational changes in polyamine levels parallel to the degree of muscular damage are useful indicators of the actual grade of muscle atrophy associated with myasthenia gravis. In histologically intact samples, without apparent signs of muscular atrophy the spermidine level and spermidine/spermine ratio were increased in comparison to the control. In addition to being very early signs of denervation, these higher values are possibly the biochemical expression of some adaptive, compensatory hyperfunction of the muscle fibers.

Myasthenia gravis: effect of immunoactive therapies.

New immunoactive therapies, plasmapheresis, intravenous steroid pulse infusion and intravenous immunoglobulins were examined for efficacy on the basis of large casuistics of myasthenia gravis. The best results were achieved with combination of these procedures. Indications of the new methods: (i) respiratory crisis of any character (myasthenic, cholinergic or mixed oscillating crisis); (ii) the patients' preparation for thymectomy; (iii) post-thymectomy therapy aimed at improving the patients condition, at avoiding relapses, at shortening the time of steroid therapy and at repressing cholinergic drug therapy; (iv) patients of old age in crisis-prone state. The new methods, together with thymectomy, steroid therapy and immunosuppression, represent a very efficient and promising new way toward modern therapy of myasthenia gravis.

[Tumor-associated myasthenia gravis and myasthenia syndrome]. / Tumorhoz társult myasthenia gravis és myasthenia syndroma.

Out of 700 patients operated on account of myasthenia gravis, 144 cases with tumours (20.57%) were evaluated. Classification took place in five groups: 1. Thymoma and myasthenia gravis; 2. Thymic cysts and myasthenia gravis; 3. Thymoma and latent myasthenia gravis; 4. Paraneoplastic myasthenia-syndrome; 5. Thymoma, myasthenia gravis and myasthenia-syndrome. Up-to-date classification of thymomas is: epithelioma with minimal, marked or overwhelming lymphatic reaction. Dark-cell and light-cell epitheliomas equally associate with myasthenia. Concerning prognosis, location of the tumour to thymic capsula, surrounding, perithymic tissue is more important than the histologic structure of the tumour. Previous examination in the case of mediastinal tumour can reveal latent, mild myasthenia which was not known till that time. Term of postthymectomic myasthenia can be excluded on the basis of these examinations. Heterogeneity is considerable among myasthenia-syndromes concerning both histopathologic and clinical features. There is a double indication of operation in the case of myasthenia with tumour: the tumour and the disease. Good results can be achieved in myasthenia gravis associated with tumour by means of total operation, post-operative radiation and by other up-to-date therapeutical procedures. The results are hardly beyond those of non-tumours myasthenia gravis.

Examinations of the relative fluidity in cerebrovascular disease patients.

Parallel with the increasing incidence of cerebrovascular diseases, and the limitations of possible surgical methods, the importance of drug therapy has significantly increased. Due to our knowledge of haemorheology the effectiveness of therapies may be measured by means of useful circulatory markers. In course of our research activities of one and a half decades the changes in blood viscosity were measured during vinpocetine therapy, and were compared to the changes of haematocrit and mean corpuscular volume (MCV) values. The effect of vinpocetine and secale alkaloids or vinpocetine and pentoxifylline were compared by sequential analysis in other cases. The results of these examinations proved that vinpocetine is effective in both short and long-term therapy.

Myasthenia gravis: prognostic significance of clinical data in the prediction of post-thymectomy respiratory crises.

Medical records of 170 patients who had undergone thymectomy for myasthenia gravis were reviewed from the point of view of respiratory disturbances. In the group of patients requiring mechanical ventilation for over 24 hours after operation the incidence of high preoperative cholinesterase inhibitor intake, severe bulbar symptoms and severe myasthenia gravis with anamnestic respiratory crisis and cardiorespiratory disease were much higher than in the group of patients who could have their trachea extubation within 24 hours. The presence of a thymic tumour, patients' age over 50 years and the so-called precrisis have revealed differences between the two groups, while the patient groups were identical in mean age, duration of myasthenia gravis and sex distribution. The above clinical data are recommended to be considered in the evaluation of the need for postoperative mechanical ventilation or extubation and preparation of preventive tracheotomy.

Familial myasthenia gravis: nine patients in two generations.

In two generations of a family followed up for 15 years, nine patients suffering from myasthenia gravis were observed. The family, being of special genetic importance, is unique in the literature.

Myasthenia gravis: treatment with plasma exchange experiences over 10 years.

Evaluation of the results of plasmapheresis therapy is reviewed on 160 patients suffering from myasthenia gravis. This new therapeutical procedure is considered very valuable: improvement can be achieved in 63% of the patients during the therapy, a further improvement in 30% after it. Plasmapheresis is especially effective for patients in respiratory crisis-prone state, for drug-resistant cases and for preparation patients for surgery. Plasma exchange therapy may be combined with other forms of immunosuppression with benefit. Thymectomy and plasma exchange are considered to be the main therapeutical procedures in myasthenia gravis.

[Myasthenia gravis: results of thymectomy in 550 patients]. / Myasthenia gravis: thymectomia eredménye 550 betegen.

Report is giving on 550 myasthenic patients who underwent thymectomy during the last 18 years. Results of thymectomy are analysed in separate groups and according to different aspects, including thymic tumours (13.63%), operations in childhood (9.64%), and combined cases (11.1%). The results are evaluated according to Disability Status Scale based on a point-system. Successive improvement was observed in the three series concerning the results of operation. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined group, in long-lasting myasthenia and in tumourous cases, too. There are quite a few factors influencing the results, such as the interval between the disease onset and thymectomy, the patients' age, thymoma, crisis-danger and the activity of the thymus gland reflecting in the number of the germinative centres. The more active the thymus, the better the results.

Myasthenia gravis: effect of thymectomy in 425 patients. A 15-year experience.

We report 425 myasthenic patients who underwent thymectomy during the last 15 years. The authors analyse the results of thymectomy in separate groups, including thymomas (12.7%), childhood myasthenia (9.4%) and combined cases (12.4%). They evaluate the results according to the Disability Status Scale based on a points system. Three series were evaluated: patients operated upon between 1972-1977, 1977-1982 and 1982-1987. Although the results in all three series were good, there has been steady improvement over the years. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined (immunological) group, in long-lasting myasthenia and in thymomas. Factors influencing the results of thymectomy were patients' age, time interval between onset of disease and thymectomy, resistence to therapy and thymic tumour. Thymic activity as reflected in germinal centres can also influence the results: the more active the thymus, the better the results.

Treatment of multiple sclerosis.

Data referring to the pathogenesis, pathomechanism, pathology, clinical symptoms and immunological changes which are important considering the treatment of multiple sclerosis have been reviewed. On the basis of published data and own experiences of 37 years of conventional drug therapy, steroid therapy required in acute forms and cytostatic, immunosuppressive therapy used in chronic forms have been discussed. A survey has been given on the theoretical basis and clinical use of the therapeutic methods still under investigation. Relaxation therapy and physiotherapy of primary importance and psychopathological phenomena and the tasks to be fulfilled within the frames of an extended after-care of patients have been outlined.

Myasthenia gravis: familial occurrence. A study of 1100 myasthenia gravis patients.

Eleven-hundred myasthenia gravis cases observed by the author in a period of 37 years are reviewed. The ratio of familial incidence was 4.23%. Transitory (neonatal) myasthenia in new-born babies should be separated from the familial cases. In familial myasthenia gravis both maternal and paternal line can occur. The majority of the cases are similar to the generalized, acquired myasthenia gravis, still there are some myasthenic familial congenital patients, too. Some rare instances are reported, among them a unique family with six sisters suffering from myasthenia gravis. Genetic line and HLA antigens' role are dealt with. Observation of familial myasthenia cases may contribute to the knowledge of the immunologic and clinicopathologic background of the disease.

Myasthenia gravis in childhood and adolescence. Report on 209 patients and review of the literature.

Authors review the different theoretical and practical problems of childhood and adolescent myastenia gravis, including the heterogeneous group of congenital myasthenia and the big casuistics of the literature. There are reports on 113 cases with childhood myasthenia gravis and 96 cases of adolescent myasthenia. Ratio of these forms ranged 10.76% in childhood myasthenia and 9.14% in adolescent age, resp., 19.9% of the whole patient material. A classification is given concerning juvenile myasthenia: 1. Neonatal (transitory) myasthenia. 2. Congenital (local, non-progressive) form. 3. Congenital form with late generalized symptoms. 4. Myasthenia simulating brain-stem process. 5. Generalized childhood myasthenia. 6. Adolescent type myasthenia (juvenile form). 7. Associated myasthenia, myasthenic syndrome or reaction. A new form of the disease is described in which the congenital myasthenia changes into generalized form in the later course of the disease. Report is given on thymectomies in childhood and adolescence which produce in general excellent results. Thymic pathology and activity are dealt with.

Myasthenia gravis: demonstration of membrane attack complex in muscle end-plates.

The membrane attack complex (MAC) assembles from C5b-9 complement components and has neoantigenic properties. Antihuman-MAC rabbit immunserum was applied in order to localize the MAC in myasthenic muscles. Using the indirect immunoperoxidase method MAC was demonstrated at the motor end-plates in eleven myasthenic patients who underwent thymectomy. This result provides direct evidence of antibody-dependent complement-mediated injury of acetylcholine receptors in myasthenia gravis.

Myasthenia gravis: 75seleno-methionine scanning of thymus gland.

The 75Se-seleno-methionine isotope thymus scanning was examined in a series of patients with myasthenia gravis. The method proved useful and informative in the diagnostics of myasthenia. Prior to thymectomy, the thymic tumour or a large gland could be observed and some hints could be gained concerning the biological activity of the gland. After the operation, the success of thymectomy could be checked and later a possible recidive could be shown or excluded. In non-operative cases the change in thymic activity could be followed which is an important sign of a malignant or tumorous growth of the thymus.

Myasthenia gravis: influence of thymic changes on clinical parameters. A study on the basis of 364 thymectomies.

In 364 patients with myasthenia gravis the morphology of thymus glands, thymomas and muscle samples was studied and compared to different clinical, therapeutic and prognostic parameters of the disease. The role of active thymus as the most outstanding finding, was considered for the result of thymectomy and for the prognosis to be positive: The more active the thymus the better the outcome of thymectomy and the final and lasting prognosis of the disease.