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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management was administered according to a standardized protocol of anticholinesterase medication, which was withdrawn for the 48 hours of obligatory postoperative mechanical ventilation.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.

A 44-year-old male patient was hospitalised with paranoid schizophrenia in 1985. Depot neuroleptic treatment was started which successfully prevented further psychotic relapses for the next ten years. His myasthenia gravis started with bulbar signs in 1997 and the symptoms soon became generalized. The diagnosis of myasthenia gravis was confirmed by electromyography, by positive anticholinesterase test and by the detection of anti-acetylcholine receptor antibodies in the serum. Mediastinal CT examination showed enlarged hilar lymph nodes on the left but no thymic pathology was observed. Mediastinoscopy was performed and biopsies were obtained from the affected nodes. Histology revealed sarcoidosis. The patient suffered respiratory crisis following the thoracic intervention (in September 1998). Combined oral corticosteroid (64 mg methylprednisolone/e.o.d.) and azathioprine (150 mg/day) treatment regimen was initiated and complete remission took place in both the myasthenic symptoms and the sarcoidosis. The follow-up CT scans showed no mediastinal pathology (January 2000). During steroid treatment a transient psychotic relapse occurred which was successfully managed by supplemental haloperidol medication added to his regular depot neuroleptics. The patient currently takes 150 mg/day azathioprine and receives 40 mg/month flupentixol depot i.m. His physical and mental status are stable and he has been completely symptom free in the last 24 months. The association of myasthenia gravis and sarcoidosis is very rare. To our best knowledge no case has been reported of a patient suffering from myasthenia gravis, sarcoidosis, and schizophrenia at the same time.

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.

Up to now the exstirpation of thymus gland stands in the central position of the immuno-therapeutic strategy of myasthenia gravis promising alone the chance of total and definitive recovery in some cases. FIGURE 1. The current antigen-specific therapeutical approaches inducing autoimmune unresponsiveness to acetylcholin receptor are still in experimental phase.(ref. 1) They certainly need a rather long period until one or more of them will be applied in humans. This is the reason why the therapeutic centers elaborated new management for the therapy-resistant patients.(ref. 2, 3, 4, 5). FIGURE 2. In some dubious cases the diagnosis of myasthenia gravis and the indication of thymectomy are difficult and need a long-lasting observation. The benefit from maintaining anticholinesterase therapy, the significant respond to plasma-exchange in crisis, the secondary generalization of ocular symptoms and the electrodiagnostic tests becoming positive after some years all strengthen the indication for thymectomy. FIGURE 3. As you can see on the third figure the indication of immunotherapies other than thymectomy has pro- and contra-arguments. We used to apply these methods at thymectomy unresponders, elderly X-ray unresponders, pregnants in crisis-prone state and in anticholinesterase resistance or intolerance. The crisis tendency is the major reason for applying these expensive therapies, but decreasing the drug doses and making rare the myasthenic relapses in the interest of improving life-quality are not negligible standpoints, either. FIGURE 4. In some severe cases both the plasma-exchange and the high-dose intravenous methylprednisolon infusion as well as the repeated high-dose intravenous immunoglobulin therapy may unfortunately fail.(ref. 6, 7, 8) All these observations induced us preparing new effectual therapeutic pattern.

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.

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.

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.

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.

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.

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.

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.

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.