Dissertation
Dissertation > Medicine, health > Neurology and psychiatry > Neurology > Neuromuscular disease > Myasthenia gravis

The Clinical and Animal Experimental Studies of Myasthenia Gravis in Children

Author LiWenHui
Tutor ChenChao;ZhouShuiZhen;SongYiQing
School Fudan University
Course Pediatrics
Keywords Child Myasthenia gravis (MG) Seropositive myasthenia gravis ( SPMG ) Seronegative myasthenia gravis ( SNMG ) Acetylcholine receptor antibody ( AchRab ) Anti - presynaptic membrane receptor antibodies ( PsmRab ) Anti- connection antibody ( Titinab ) Experimental autoimmune myasthenia gravis animal model (EAMG) Passive transfer of Glucocorticoid
CLC R746.1
Type PhD thesis
Year 2007
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PART 1 The clinical studies of myasthenia gravis inchildrenObjectives: Depending on having or not detectable AchR antibodies, myasthenia gravis were divided into seropositive myasthenia gravis and seronegative myasthenia gravis. In this part we compared the clinical problems of seropositive myasthenia gravis with seronegative myasthenia gravis. We did serological antibody tests during clinical follow-up and studied the correlation between the changes of serological classification and the clinical states.Methods: The data from 81 cases with myasthenia gravis treated in our hospital from 2002 to 2006 were analyzed. The levels of AchRab, PsmRab and Titinab in the sera were estimated. The clinical characteristics (including gender, the clinical classification, the image changes of thoracic gland and the positive results of repetitive nerve stimulation) were compared and the positive percents of PsmRab and Titinab between SPMG and SNMG were compared. During the clinical follow-up, the serological antibodies tests were done again when the clinical states had been changed. During the clinical follow-up, the differences of relapsed times between SPMG and SNMG were compared.Results: Eighty-one patients (41 were male and 40 were female), onset median aged 3.03 years. According to the modified Osserman’s criteria, type I MG was found in 63 patients, typeⅡin 18.Two female patients had hyperthyroidism. Two patients had family histories of myasthenia gravis. According to the serological classification, SPMG was found in 36 patients and SNMG in 45.The positive percents of AchRab, PsmRab and Titinab were 44.4, 43.2 and 21.7.The Patients positive for Titinab had not thymoma in imaging. There were no differences in the clinical characteristers (including gender, the clinical classification, the image changes of thoracic gland and the positive results of Repetitive nerve stimulation) between SPMG and SNMG. There were significant differences in the percents of positiveness of PsmRab and Titinab between SPMG and SNMG. The positive percents of PsmRab and Titinab of SPMG were higher than SNMG. Thirty-two patients were followed up. The percents of changes of AchRab, PsmRab and Titinab were 25, 25 and 19.2.Eight patients relapsed after the therapies were finished and eight patients relapsed in the treatment. There were no relation between the clinical states and the transfer of AchRab.Conclusions: Recently the cases of myasthenia gravis admitted in our hospital had been increased. The onset ages were young. SNMG accounted for a considerable proportion of the cases. There were no differences in the clinical characteristics (including gender, the clinical classification, the image change of thoracic gland and the positive results of Repetitive nerve stimulation) between SPMG and SNMG. It may be helpful to make the correct serological classification for doctors that the sera of patients are estimated several times and the method of detecting the AchRab is improved. There were correlations among AchRab, PsmRab and Titinab. There was no correlation between positiveness of Titinab and thymoma. The percent of positiveness of Titinab was lower than those of adult reports. It is very worthy of studing of the correlation between relapses and the courses of treatment of glucocorticoid.PART 2 The animal experimental studies of myastheniagravis in childrenObjectives: We performed passive transfer studies using sera from the initial patients with myasthenia gravis including SPMG and SNMG and from the released patients who had taken glucocorticoid for different courses. We compared the groups of passive transfer models of SPMG and SNMG. We investigated the pathological mechanism of SPMG and SNMG. We investigated the appropriate course of treatment of glucocorticoid for MG.Methods: Passive transfer studies were performed using sera from the initial SPMG, the initial SNMG, the released patients who had taken glucocorticoid for different courses (three months, six months, twelve months) and non-MG control donors. The sera were injected intraperitoneally into female C57BL/6 mice (8 weeks) at a dose of 0.5ml/d for 7 consective days. On the seventh day from the start of injection, manifestation of muscle weakness was observed and classificated according on Lennon’s criteria. Twelve hours after the seventh day from the start of injection, electrophysiologic studies were performed and the amplitude of action potencial was recorded. The results of electrophysiology were demonstrated by D5.α-BGT-HRP was used for the localization of the AchR in the endplate of mice. When electrophsiologic studies had been finished, mice were executed. Gastrocnemius muscles were obtained from the mice and then light microscope and electron microscope studies were performed. The blank control mice were bred in identical environment. Classification of muscle weakness, elecrophysiologic studies, light microscope studies and electron microscope studies were also performed in the blank control group.Results: Both the groups of passive transfer of the sera of SPMG and SNMG had significant muscle weakness, the control groups had no significant muscle weakness. There were significant differences in muscle weakness among the groups of SPMG, SNMG and the control groups. There were significant differences in D5 among the groups of SPMG, SNMG and the control groups. There were no differences in muscle weakness and D5 between the group of SPMG and the group of SNMG. The yellow lines of AchR deposition in sarcolemma were observed by the light microscope. The yellow lines of the group of SPMG and the group of SNMG were lighter and more discontinous than the lines of the non-MG control group and the blank control group. The construction of synapses of the group of SPMG was abnormal and the construction of synapses of the group of SNMG was also abnormal. Both the reductus of postsynaptic membranes of the group of SPMG and the group of SNMG were shorter and fewer than the control groups. The groups of the initial patients and released patients for taking glucocorticoid for different courses had significant muscle weakness, the control groups had no significant muscle weakness. There were significant differences of muscle weakness and D5 among the groups of the initial patients, the groups of the released patients and the control groups. There were no differences of muscle weakness and D5 among the initial groups and three released groups. The yellow lines of the initial groups and three released groups were lighter and more discontinous than the control groups. The constitution of synapses of the initial groups was abnormal and three released groups was abnormal too. The reductus of postsynaptic membrane of the initial groups and the released groups were shorter and fewer than the control groups.Conclusions: It was suitable to make the animal model through passive transfer of the sera of MG to female C57BL/6 mice (8 weeks). There were no differences of muscle weakness and the decremental responses to repetitive nerve stimulation between the group of SPMG and the group of SNMG. Both the pathological changes of the group of SPMG and the pathological changes of the group of SNMG were the breakdown of AchR in postsynaptic membranes. The pathological mechanism of SNMG in childhood may be the direct or indirect breakdown of AchR in postsynaptic membranes. In the future we will focus on the pathological factors which result in the indirect breakdown of AchR in postsynaptic membrane. Glucocorticoid played a role on curing myasthenia gravis. Our data implied that the child patients of myasthenia gravis might need the longer courses of treatment of glucocorticoid.

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