Анализа на факторите кои влијаат на изборот на терапискиот модалитет кај болни од Мијастенија гравис

Abstract

Introduction: Myasthenia gravis (MG) is an autoimmune disease which occurs due to impaired neuromuscular synapse function (NMS), which causes weakness and fatigue of various, specific muscle groups with characteristic distribution. Weakness increases with activity and improves with rest. The principal abnormality is found at the postsynaptic part of the neuromuscular synapse, and is due to the action of antibodies, leading to a reduction in the number of available acetylcholine receptors (AChR), and impaired neuromuscular transmission. The thymus plays a central role in the pathophysiology of MG due to the presence of the key elements of the myasthenic autoimmune process, such as antigen-presenting cells, T and B cells. The pathophysiological role of the thymus in MG is supported by histological observations. Approximately 80% of patients with MG have thymic abnormalities. The diagnosis of the disease is made on the basis of a typical clinical presentation of the disease in the majority of patients (clinical examination); a pharmacological test (prostigmine test); laboratory tests: a) neurophysiological (electromyography), b) serological (immunological) and radiological investigations (computed tomography or nuclear magnetic resonance imaging of the anterior mediastinum and lungs). The treatment of acquired autoimmune MG ensues from the pathogenesis of the disease, and encompasses several different etiologically conditioned approaches: symptomatic, immunomodulatory and immunosuppressive therapy, surgical treatment (thymectomy). Aim: 1. analysis of the demographic, clinical characteristics, and disease evolution; 2. analysis of the factors relevant for determining the therapeutic modality; 3. a) analysis of the correlation between the thymectomy outcome and the demographic characteristics of this subgroup of patients, and b) determining the correlation between thymectomy outcome and clinical presentation, the time between the initial symptoms and the thymectomy, and the histopathological finding of the thymus; 4. analysis of the outcome of all therapeutic procedures applied. Methods: a combined retrospective and prospective, observational study of 127 patients with MG, diagnosed according to a generally accepted and recommended diagnostic protocol. The clinical manifestation is classified according to the modified scale of Osserman-Genkins. According to the intensity of the symptoms at different stages of the disease, patients were treated with symptomatic therapy (cholinesterase inhibitor), immunosuppressive therapy (corticosteroids and cytostatics), rapid immunomodulatory treatment (plasmapheresis and intravenous immunoglobulins), surgical treatment (thymectomy), and oncological treatment in patients with thymoma. Statistical analysis is performed using the statistical programs STATISTICA 7.1 and SPSS 20.0. Results: predominance of females in the total number of patients (1.76: 1), as well as the distribution by age groups and distribution by early and late onset. Statistically significant difference in age at the onset and diagnosis of the disease in favor of female patients. The initial presentation in most patients is a generalized form of the disease (class II according to the modified Osserman classification); the generalized form of the disease is predominant in the thymectomised patients; in the non-thymectomised patients the ocular form of the disease is predominant (class I according to the modified Osserman classification). Immunological tests, i.e. antibodies show no correlation with the clinical presentation of the disease, but antiAChRat show statistically significant association with the histological finding. In thymectomised patients, thymic hyperplasia is the predominant histopathological finding, and less frequent are thymoma, thymic atrophy with fatty degeneration, persistent thymus, and thymic cyst. Thymic hyperplasia is more frequent in the younger group. The correlation between histological findings and clinical presentation (Osserman) at the time of diagnosis of the disease is statistically significant. There is no statistical significance between the average time between the initial presentation of the disease and thymectomy nor a statistically significant correlation between sex and outcome in thymectomised patients. A moderate positive correlation between the age at the onset of the initial symptoms and the outcome was observed. A statistically significant correlation was observed between the Osserman class distribution and the outcome after thymectomy, as well as between the distribution by class of conservative treatment and the outcome in non-thymectomised patients. Improvement was reported in 59.8% of the total number of patients; in 40.6% of the non-thymectomised and 86.7% of the thymectomised patients. Conclusion: The results confirm that the combined approach is a safe and effective way of treating MG. The most important objective is determining the factors (age, clinical picture, immune profile, patient’s condition) and the time of initiation of the therapeutic approach that will somewhat predict the outcome of the surgical or pharmacological treatment. Thymectomy has a beneficial effect on the clinical course and intensity of the disease, but combined with pharmacological treatment, appropriately applied, produces a favorable therapeutic response.