Importance of thymectomy and prognostic factors in the complex treatment of myasthenia gravis.

BACKGROUND: Thymectomy is indicated in patients with seropositive myasthenia gravis (SPMG) in patients under the age of 50 and in patient with myasthenia gravis (MG) associated with thymoma. METHODS: 345 patients with MG who underwent an extended thymectomy from April 1990 to December 2010. Patients were separated into the 4 groups: group with a complete stable remission, pharmacological remission group, group of patients with significant improvement and the group with mild improvement of symptoms. RESULTS: In our study, we observed 345 patients with MG and thymectomy. 137 patients (39.71 %) attained the complete stable remission (CSR) and 92 patients (26.67 %) the pharmacological remission (PR). The significant improvement of MG symptomatology was achieved in 95 patients (27.54 %). The rest of 21 patients from total 345 (6.08 %) have reached only a mild improvement. Patients after thymectomy with CSR were in the clinical stage I and IIA, in accordance to the modified Osserman classification and most benefited from the thymectomy. CONCLUSIONS: The extended thymectomy combined with immunotherapy is the preferred treatment with an expected satisfactory long-term remission rate. Despite the recent improvements in MG medical therapy, thymectomy plays an important role in the otherwise complex treatment of the disease. Because of early diagnosis with thymectomy performed without a delay, patients can achieve significantly more often favorable outcomes and even stable remissions (Tab. 4, Fig. 7, Ref. 17).

Molecular diagnosis of spinal and bulbar muscular atrophy in Slovakia.

OBJECTIVES: Molecular-genetic analysis is a determining step in setting the diagnosis of spinal and bulbar muscular atrophy (SBMA). We present the first nation-wide study and experience with this disease and its diagnosis in Slovakia. The study is enriched by comparison of genetic findings from Slovak patients to patients from other countries. METHODS: Molecular-genetic analysis was performed for patients suspected of SBMA. Data of patients with confirmed diagnosis were statistically evaluated. In addition, the detection rate and the prevalence of the disease for Slovakia were estimated. RESULTS: In 40 patients with confirmed diagnosis of SBMA, average values were observed at 44.7 CAG repeats and 52.5 years at the time of molecular-genetic diagnosis. The detection rate represents approximately 23% and an estimated prevalence is of 1 : 41,700. CONCLUSION: Concerning the population of Slovakia with 5,420,000 inhabitants, we document a relatively large cohort of SBMA patients. This is obvious when comparing similar studies from other countries, while this is the only study representing the Central Europe. Our findings prove that molecular-genetic analyses for the detection of this neuromuscular disorder show high efficiency. This fact underlines the necessity of such testing and may serve as a guide for clinicians from other countries in setting the right diagnosis for these patients (Tab. 1, Fig. 2, Ref. 29).

Late onset form of Pompe disease.

BACKGROUND: Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by deficiency in lysosomal enzyme α-glucosidase. OBJECTIVES: We present first two patients from Slovakia with confirmed Pompe disease. METHODS: Activity of α-glucosidase was measured using 4-methylumbelliferyl-α-D-glucopyranoside with the presence of acarbose, inhibitor that eliminates isoenzyme interference of maltase-glucoamylase. This methodical approach is substantial for determination of lysosomal enzyme deficiency. Using molecular genetic methods, PCR-RFLP and direct sequencing of coding region α-glucosidase gene (GAA) we have identified causal mutations in our patients. RESULTS: Late-onset type of disease was confirmed by measuring α-glucosidase activity in leukocytes isolated from blood. The presence of common Caucasian mutation c.-32-13T>G was proved by genetic testing in the first patient in homozygous state. Second patient was a compound heterozygote, with mutation c.-32-13T>G on one allele and mutation A486P on the second allele. CONCLUSION: We present a diagnostic algorithm for diagnosing the Pompe disease in patients of European origin. Enzyme replacement therapy has been used as a treatment option for improving the quality of life of patients. Early diagnosis and treatment of Pompe disease are considered to be critical for maximum efficacy of enzyme replacement therapy (Tab. 1, Fig. 3, Ref. 20).

Thymic tumours associated with Myasthenia gravis: a long term observation study of operated patients.

Primary tumours of thymus, thymoma and thymic carcinoma, are very rare, they represent less than 1 % of all neoplasms. The most common manifestation of thymoma with appearance of 40 to 50 % of the neuromuscular autoimmune disease is myasthenia gravis (MG). The performance of a complete resection is the most predictive indicator for long-term survival of patients with thymic tumour, also important prognostic factors are the histological type of thymic tumour and its invasiveness. The aim of our study is to study the long-term survival of patients after the resection of the tumour, as well as enhanced efficiency of radical thymectomy in the complex treatment of myasthenia gravis. From 1989 to 2010 we operated on 369 patients with MG. Out of 49 patients (13.7 %) 38 cases (76.6 %) were thymomas and 11 cases (23.4 %) thymic carcinomas. Complete removal of tumours (stage I, II, and III) were performed in 45 (92 %) cases. Of the 41 living patients (83.7 %), three (7.3 %) were diagnosed with metastatic thymic carcinoma or thymoma, and treated with adjuvant therapy. In one case, the patient died due to generalization of the thymic carcinoma. Statistical analysis with Kaplan-Meier method showed better overall survival of patients with thymoma than patients with thymic carcinoma. The difference in survival curves was not significant. (Mantel-Cox p = 0.479, Generalized Wilcoxon p = 0.326). In terms of treatment of Myasthenia gravis associated with thymoma, we achieved 70 % successful clinical and pharmacological remission. On the other hand, paraneoplastic MGAT has the worst prognosis of all the other forms of MG. The difference between MGAT to every other form of MG was statistically significant (Tab. 6, Fig. 1,Ref. 28).

[First Czech and Slovak domino liver transplantation]. / První Cesko-Slovenská domino transplantace jater.

INTRODUCTION: The study introduces the first international, Czech and Slovak Domino Transplantation performed based on a tight cooperation between the Czech and Slovak transplant centres. MATERIAL AND METHODS: The donor of the cadaveric graft was a young Slovak man with Familial amyloidotic polyneuropathy. The livers of these patients are the predominant source of circulating transthyretin, and liver transplantation is the only treatment available for the disease. The graft was obtained from heart beating deceased donor with brain death. The domino graft was then transplanted to Czech sixty-three years old man with hepatocellular carcinoma and liver cirrhosis based on HCV. RESULTS: Both recipients had an uneventful immediate postoperative course with early graft function. The Czech patient faced early HCV recurrence in a graft which necessitated the reduction of immunosuppressives. CONCLUSION: The domino liver transplantation represents a suitable way for addressing graft shortage and reducing waiting list time. A well-organized cooperation between the two international centres is required to complete successful domino transplantation.

[Simultaneous occurrence of acute myasthenia gravis and acute polymyositis in 3 patients and in 2 patients also associated with a thymoma]. / Kombinovaný výskyt akútnej myasténie gravis a akútnej polymyozitídy u troch pacientov, u dvoch v asociácii s tymómom.

In the Slovak Centre for Neuromuscular Diseases 768 patients with myasthenia gravis are on the records. 112 myasthenics (14.5%) have another associated autoimmune disease. Most frequently a combination with an autoimmune disease of the thyroid gland or rheumatoid arthritis is involved. Extremely rare is the concurrent manifestation of the acute form of mysthenia gravis and acute polymyositis, observed by the authors in three patients,incl. two associated with a thymoma. In all three patients the disease had a serious clinical picture which called for controlled ventilation and a nasogastric tube. From the prognostic aspect rapid and correct diagnosis and early adequate treatment--combined immunosuppressive treatment (prednisone, azathioprin) is most important, incl. large i.v. doses of methylprednisone, repeated plasmaphereses, i.v. administration of human immunoglobulin, 0.4 g/kg body weight for a period of five days and optimally timed thymectomy with removal of the thymoma.

[Determination of prognostic factors in surgical treatment of myasthenia gravis]. / Stanovenie významu prognostických faktorov pri chirurgickej liecbe myasténia gravis.

The authors evaluated, using statistical analysis, the importance of prognostic factors in patients subjected to thymectomy on account of myasthenia gravis. The results revealed a better prognosis of the disease, if the history was less than 6 months, preoperative treatment less than 1.5 years, a histological finding of thymus hyperplasia, second clinical stage according to Ossermann and the patients age below 30 years. From the statistical analysis ensues that the prognosis of myasthenia gravis is more favourable when the case-history is shorter as a result of rapid diagnosis and when preoperative treatment is reduced to a minimum.

[Development of myasthenia gravis after thymectomy for thymoma]. / Vznik mysténie gravis po tymektómii pre tymóm.

Impaired neuromuscular transmission in myasthenia gravis is caused by autoimmune mechanisms. The association of myasthenia gravis with pathological abnormalities of the thymus has been known for a long time and was the reason why thymectomy was used in the treatment of myasthenia gravis before the immunocompetent impact of the thymus and the autoimmune pathogenesis of myasthenia was known. Forms of myasthenia refractory to thymectomy, and in particular the development of myasthenia gravis after thymectomy on account of a thymoma, indicate the fact that in case of destruction of postsynaptic acetylcholine receptors an important part is played by extrathymic humoral and cellular autoimmune mechanisms. In the submitted paper the authors describe three patients where myasthenia gravis was manifested several months to 14 years after thymectomy on account of a thymoma. The presented facts emphasize the importance of immunosuppressive treatment of patients with myasthenia gravis.

[Myasthenia gravis and 93 thymectomies. Therapeutic strategies and results 1990-1994]. / Myasténia gravis a 93 tymektómií. Stratégia liecby a výsledky v rokoch 1990-1994.

The authors evaluate 93 thymectomies they performed in the course of five years. Indication for surgery was in all instances myasthenia gravis. Surgery was used only after conservative treatment, the patients had to be asymptomatic or have only minimal myasthenic manifestations. Thymectomy was associated with a 6.4% morbidity and zero mortality. On long-term follow-up the results were excellent or very good in 66.7% of patients and marked improvement was recorded in 30.1%. Thymectomy is part of comprehensive treatment of patients with myasthenia gravis.