Early-Onset Myasthenia Gravis Following COVID-19 Vaccination.

As coronavirus disease 2019 (COVID-19) has spread worldwide, the rate of COVID-19 vaccination uptake is encouraging. Neurological complications associated with COVID-19 vaccines such as stroke, Guillain-Barré syndrome, and Bell's palsy have been reported. Recently, late-onset myasthenia gravis (MG) following COVID-19 vaccination has been reported. To date, however, there has been no evidence of increased risk of early-onset MG following COVID-19. Here, we report a case of a patient with new-onset MG that arose after receiving a COVID-19 vaccine. A 33-year-old woman suddenly experienced generalized weakness and diplopia on the evening she had received the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal relationship suggests that this new-onset MG is related to the vaccination. It also implies that COVID-19 vaccination could trigger early-onset MG symptoms in patients at risk of MG.

Clinical Genomic, phenotype and epigenetic insights into the pathology, autoimmunity and weight management of patients with Myasthenia Gravis (Review).

Myasthenia Gravis (MG) is an autoimmune disease that affects neuromuscular junctions and is characterized by muscle weakness as a result of autoantibodies against certain proteins. As a heterogeneous disorder, MG presents with different types, including neonatal, ocular and generalized in both juveniles and adults. Different types of antibodies serve a role in how MG presents. The main biological characteristic of MG is the production of antibodies against the muscular acetylcholine receptor; however, other types of antibody have been associated with the disorder. The role of the thymus gland has been established and thymectomy is a possible treatment of the disease, along with traditional medication such as pyridostigmine bromide (Mestinon) and immunosuppresants. In recent years, steps have been made towards developing more sensitive diagnostic methods. Additionally, novel treatments have demonstrated promising results. Developing new assays may lead to an increased understanding of the disease and to unravelling the genetic pathway that leads to the development of neuromuscular diseases.

Congenital thymoma.

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (<18 years of age), the youngest being 4 years old, and no cases in newborns. They represent less than 1% of all mediastinal tumors in children. Due to the limited number of cases in the pediatric population, the diagnosis and treatment in this population is extremely challenging. Thymomas in all age groups may be associated with paraneoplastic syndromes, being myasthenia gravis the most common, which is associated with a worse prognosis in the pediatric population. We present the first case of a newborn infant with congenital thymoma. This case demonstrates a rare tumor in an unusual age group and emphasizes the importance of multidisciplinary teamwork in the decision-making and management of this condition.

Congenital thymoma

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (<18 years of age), the youngest being 4 years old, and no cases in newborns. They represent less than 1% of all mediastinal tumors in children. Due to the limited number of cases in the pediatric population, the diagnosis and treatment in this population is extremely challenging. Thymomas in all age groups may be associated with paraneoplastic syndromes, being myasthenia gravis the most common, which is associated with a worse prognosis in the pediatric population. We present the first case of a newborn infant with congenital thymoma. This case demonstrates a rare tumor in an unusual age group and emphasizes the importance of multidisciplinary teamwork in the decision-making and management of this condition.

Incidental finding of thymic cyst in a newborn baby.

Thymic hyperplasia is a common finding among newborns, but cyst formation might produce mediastinal symptoms. Lethal outcome is reported when accompanied by massive intrathoracic hemorrhage. The clinical picture in our case was characterized from profuse multiple hemorrhagic foci and respiratory distress syndrome, with an unclear role of the thymic cyst.

miR-548k regulates CXCL13 expression in myasthenia gravis patients with thymic hyperplasia and in Jurkat cells.

Myasthenia gravis (MG) is a B cell-mediated and T cell-dependent autoimmune disease. Thymic hyperplasia has great significance for MG pathogenesis and treatment. MicroRNAs (miRNAs) are a newly recognized type of gene expression regulatory factor that regulate gene expression at the post-transcriptional level. Additionally, miRNAs are involved in immune regulation of the thymus and the occurrence and development of autoimmune diseases. In this study, we found 33 miRNAs that were significantly dysregulated in thymic tissues from MG patients with thymus hyperplasia (MGH) compared with thymic tissues from normal controls using a miRNA microarray chip. We found a negative correlation between the miR-548k and CXCL13 mRNA levels in a large set of samples using quantitative real-time polymerase chain reaction (qRT-PCR). We found that the CXCL13 3'-untranslated region (UTR) was a target of miR-548k using bioinformatics analysis. Next, we obtained direct evidence that CXCL13 is a target of miR-548k using a luciferase reporter assay. Finally, we demonstrated negative regulation between mir-548k and CXCL13 in Jurkat cells. Thus, miR-548k regulates the mRNA expression of its target gene CXCL13 in the thymus of MGH patients and plays an important role in MGH pathogenesis.

Miastenia gravis: resultados inmediatos y alejados de la timectomía transesternal extendida / Results of extended transsternal thymectomy for Myasthenia gravis: experience with 58 patients

Background: Thymectomy improves clinical outcomes and decreases the need for medical treatment in patients with myasthenia gravis (MG). Aim: To describe the immediate and long-term results of extended transsternal thymectomy (ETT) in patients with MG. Material and Methods: A review of databases, surgical protocols, clinical records and interviews of patients subjected to extended transsternal thymectomy for MG between 1990 and 2016. Perioperative clinical characteristics, anticholinesterase treatment, immediate and remote surgical results were analyzed and patients were followed from one to 10years. Results: We studied 58 patients aged 35 ± 14years (72%) women. In the preoperative period, according to Osserman classification, nine patients (15,5%) were in grade I, eight (13,8%) in grade IIA 8 and 40 (69%) in grade IIB. The pathological study of the surgical piece showed thymic hyperplasia in 39 cases (67,2%). Four patients had postoperative complications but none died. In the Follow-up at 1, 3, 5, 8 and 10years the Masaoka palliation rate was 71.7, 77.5, 67.7, 70.0 and 70,6% respectively. The figures for remission rate were 13.0, 15.0,19.4, 35.0 and 35,3% respectively. The figures for Zielinski positive results were 79.6, 87.5, 87.1, 90.0 and 82,4% respectively. The DeFilippi score improved by 80.4, 87.5, 87.1, 90.0 and 82.4% respectively. The Myasthenia Gravis Foundation of America Post-Intervention State improved by 67.4, 77.5, 77.5, 75.0 and 70,6% respectively. Mean Myasthenia Gravis Activities of daily living (MGADL) and Myasthenia Gravis Quality of life scale 15 (MGQOL 15) were 1.65 and 6.31 respectively. Conclusions: In selected patients with MG, extended transsternal thymectomy in MG has good immediate and long-term results.

Thymus imaging in myasthenia gravis: The relevance in clinical practice.

INTRODUCTION: The ability to distinguish between normal thymus, thymic hyperplasia, and thymoma should aid clinical management and decision making in patients with myasthenia gravis (MG). We sought to determine the accuracy of routine imaging in predicting thymic pathology. METHODS: We retrospectively analyzed records of patients with MG from the Oxford Myasthenia Centre registry who had undergone thymectomy. Each patient received 1 radiological diagnosis and 1 histological diagnosis. RESULTS: We included 106 patients. Radiological and histological diagnoses agreed in 73 (68.9%) patients. Sensitivity and specificity, respectively, were calculated for each radiological diagnosis as follows: thymoma 90% and 95.5%, hyperplasia 17.6% and 98.6%, and normal 96.9% and 60.8%. DISCUSSION: Routine chest computed tomography and MRI can effectively identify thymoma. However, they are not reliable tools to differentiate between thymic hyperplasia and normal thymus in patients with MG. Muscle Nerve, 2018.

Caracterización clínica de los pacientes miasténicos timectomizados / Clinical Characterization of Thymectomized Myasthenic Patients

Introducción: la miastenia gravis es una enfermedad crónica de la unión neuromuscular, de naturaleza autoinmune y es reconocido que la timectomía es una modalidad terapéutica efectiva en esta entidad clínica. Objetivos: realizar una caracterización clínica de los pacientes miasténicos timectomizados. Métodos: se realizó un estudio observacional descriptivo retrospectivo, en el Servicio de Neurología del Hospital Clínico Quirúrgico Hermanos Ameijeiras en el periodo comprendido de enero de 1984 a diciembre de 2014. Resultados: se reclutaron 393 pacientes, la mayoría fueron del sexo femenino y del grupo de edad de 30-39 años, predominó el grado II b (65,3 por ciento) de intensidad de la enfermedad. La hiperplasia tímica (66,9 por ciento) fue la alteración histológica del timo más común. El hipertiroidismo fue la enfermedad autoinmune más frecuente. La crisis miasténica representó la complicación posoperatoria principal y apareció esencialmente en pacientes con timoma. La mortalidad fue de 1,3 por ciento. Conclusiones: fue más común el grado II b de intensidad de la enfermedad, el tipo histológico de hiperplasia tímica y la mortalidad baja(AU)

Introduction: Myasthenia gravis is a chronic disease of the neuromuscular junction, it is autoimmune by nature and it is recognized that thymectomy is an effective therapeutic modality in this clinical entity. Objectives: Clinically characterize the myasthenic thymectomized patients. Methods: A retrospective, descriptive, observational study was conducted in the Neurology Service at Hermanos Ameijeiras Surgical Clinical Hospital from January 1984 to December 2014. Results: 393 patients were recruited; the majority was female and aged 30-39 years. 65.3 percent of them had grade II b of disease intensity. Thymic hyperplasia (66.9 percent was the most common histological alteration of the thymus. Hyperthyroidism was the most frequent autoimmune disease. The myasthenic crisis represented the main postoperative complication and it essentially showed in patients with thymoma. Mortality was 1.3 percent. Conclusions: Grade II b disease intensity was more common, the histological type of thymic hyperplasia and mortality was low(AU)

Caracterización clínica de los pacientes miasténicos timectomizados / Clinical Characterization of Thymectomized Myasthenic Patients

Introducción: la miastenia gravis es una enfermedad crónica de la unión neuromuscular, de naturaleza autoinmune y es reconocido que la timectomía es una modalidad terapéutica efectiva en esta entidad clínica. Objetivos: realizar una caracterización clínica de los pacientes miasténicos timectomizados. Métodos: se realizó un estudio observacional descriptivo retrospectivo, en el Servicio de Neurología del Hospital Clínico Quirúrgico Hermanos Ameijeiras en el periodo comprendido de enero de 1984 a diciembre de 2014. Resultados: se reclutaron 393 pacientes, la mayoría fueron del sexo femenino y del grupo de edad de 30-39 años, predominó el grado II b (65,3 por ciento) de intensidad de la enfermedad. La hiperplasia tímica (66,9 por ciento) fue la alteración histológica del timo más común. El hipertiroidismo fue la enfermedad autoinmune más frecuente. La crisis miasténica representó la complicación posoperatoria principal y apareció esencialmente en pacientes con timoma. La mortalidad fue de 1,3 por ciento. Conclusiones: fue más común el grado II b de intensidad de la enfermedad, el tipo histológico de hiperplasia tímica y la mortalidad baja(AU)

Introduction: Myasthenia gravis is a chronic disease of the neuromuscular junction, it is autoimmune by nature and it is recognized that thymectomy is an effective therapeutic modality in this clinical entity. Objectives: Clinically characterize the myasthenic thymectomized patients. Methods: A retrospective, descriptive, observational study was conducted in the Neurology Service at Hermanos Ameijeiras Surgical Clinical Hospital from January 1984 to December 2014. Results: 393 patients were recruited; the majority was female and aged 30-39 years. 65.3 percent of them had grade II b of disease intensity. Thymic hyperplasia (66.9 percent was the most common histological alteration of the thymus. Hyperthyroidism was the most frequent autoimmune disease. The myasthenic crisis represented the main postoperative complication and it essentially showed in patients with thymoma. Mortality was 1.3 percent. Conclusions: Grade II b disease intensity was more common, the histological type of thymic hyperplasia and mortality was low(AU)

Imaging of the pediatric thymus: Clinicoradiologic approach.

The thymus is a lymphatic organ that undergoes dynamic changes with age and disease. It is important to be familiar with these physiological changes in the thymus gland to be able to identify pathology and make an accurate diagnosis. The thymus may be involved in multisystem disorders or show focal isolated lesions. The aim of this article is to review the radiological anatomy of the thymus, normal variants, and pathology including hyperplasia and benign/malignant lesions involving the thymus gland in the pediatric age group. We also propose an algorithmic approach for imaging evaluation of a suspected thymic mass on the basis of morphologic features.

Appearance of a thymic mass after treatment of Cushing's syndrome.

A 23-year-old woman was referred to our center with hirsutism, acne, weight gain, weakness, and irregular menses. Laboratory tests revealed increased levels of cortisol and sex hormones, and reduced adrenocorticotropic hormone levels. The patient underwent a right adrenalectomy. Pathology of the resected right adrenal gland showed an adrenal carcinoma. Computed tomography 8 months after the surgery revealed a thymic mass that was not detected preoperatively. The frequency of rebound thymic hyperplasia after normalization of hypercortisolism is not known, but possibly as high as 40%. Physicians must be aware of this phenomenon to avoid unnecessary thoracic surgery.

Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia.

PURPOSE: To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia. MATERIALS AND METHODS: Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups. RESULTS: Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II. CONCLUSION: Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.

Graves' Patient with Thymic Expression of Thyrotropin Receptors and Dynamic Changes in Thymic Hyperplasia Proportional to Graves' Disease Activity.

Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia.

Graves' Patient with Thymic Expression of Thyrotropin Receptors and Dynamic Changes in Thymic Hyperplasia Proportional to Graves' Disease Activity

Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia.

Miastenia grave generalizada: reporte de un caso / Generalized-myasthenia gravis: a case report

Mujer de 17 años de edad, con diagnostico reciente de miastenia gravis, en tratamiento irregular con piridostigmina y prednisona; que acudió por presentar debilidad muscular generalizada, disfagia, diplopía y ptosis palpebral. El examen físico encontró una tiroides aumentada de tamaño. Los exámenes auxiliares mostraron T4 libre y TSH normales, pero los anticuerpos antirreceptor de acetilcolina fueron positivos. Se realizó timectomía, pero en el postoperatorio, la paciente presentó crisis miasténica con insuficiencia respiratoria, por lo que fue sometida a ventilación mecánica. Después de dos semanas, la paciente fue dada de alta sin presentar debilidad muscular, disfagia o ptosis palpebral. El tratamiento al alta fue piridostigmina. La miastenia grave es una enfermedad autoinmune que se caracteriza por debilidad muscular fluctuante. En los casos de inicio temprano (menores de 40 años), esta asociada a hiperplasia del timo y otras enfermedades autoinmunes. La timectomía es el tratamiento de elección en pacientes menores de 50 años.

A 17-year-old woman presented with generalized weakness, dysphagia, ptosis, and diplopia. Recently, she was diagnosed with myasthenia gravis, and her treatment included pyridostigmine and prednisone. Physical examination showed goiter. Thyroid hormones were normal, but the autoantibodies against the postsynaptic acetylcholine receptor were positive. She underwent thymectomy, and developed respiratory insufficiency secondary to myasthenic crisis. After two weeks, she was discharged without complaints. Her long-term treatment included pyridostigmine. Myasthenia gravis is a rare autoimmune disease. The clinical hallmark is fatigable weakness. Patients with early- onset disease (< 40 years), are more often female, have enlarged, hyperplastic thymus glands, and other organ- specific autoantibodies might be present. Thymectomy is the treatment of choice in patients with disease onset before the age of 50 years.

Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case.

Myasthenia gravis (MG) is a devastating autoimmune disease that involves the acetylcholine receptor (AchR) in the postsynaptic membrane of the neuromuscular junction. It is not uncommon for MG to accompany with other autoimmune diseases and complicate with multiple organ dysfunction. Here, we report on an 18-year-old female patient with a rare case of MG concomitant with thymus hyperplasia, diabetes mellitus, and hyperthyroidism. After full excision of the hyperplastic thymus gland, the patient's muscle weakness was greatly improved and her blood glucose level was restored to normal at the 6-month follow-up.

The association between Graves disease with hypokalemic periodic paralysis or thymus hyperplasia / 中国综合临床

Objective To explore the relationship between Graves disease and hypokalemic periodic paralysis or thymus hyperplasia.Methods Sixty-two patients with Graves disease were enrolled in this study.Thirty-three patients without thymus hyperplasia were selected as group A and other 29 patients were group B.In addition,30 healthy volunteers served as control group.Results There were no significant difference between group A and group B in terms of sex,age,illness course,thyroid enlargement,exophthalmos,periodic paralysis and the levels of free triiodothyronine (FT3),free thyroxin (FT4),thyroid stimulating hormone (TSH) (P ＞ 0.05).The incidence rate of hypokalemic periodic paralysis in male Graves disease with thymus hyperplasia was 62％ (8/13),higher than that in female patients (6％ (1/16),x2 =10.24,P ＜ 0.05).The incidence rate of hypokalemic periodic paralysis in male Graves patients was 62％ (16/26),higher than in female Graves patients (6％ (2/36),x2 =22.96,P ＜ 0.05).There was no significant relationship between Graves disease patients combined with thymus hyperplasia and sex,age,illness course,thyroid enlargement,exophthalmos,periodic paralysis and the levels of FY3,FT4,TSH.Conclusion The incidence rate of hypokalemic periodic paralysis in male Graves disease patients combind with thymus hyperplasia is higher than in female,and therefore it should pay more attention of male Graves patients in case misdiagnosis.

A misleading cause of pseudo-thymic tumor in ectopic Cushing's syndrome.

A 27-year-old man was referred with typical features of severe Cushing's syndrome. A bilateral adrenalectomy was performed. Three months later, a triangular nodular mediastinal enlargement, evocative of a right anterior thymic tumor, was discovered. Thymectomy was undertaken. Histological examination revealed diffuse thymic hyperplasia with negative immunostaining for adrenocorticotropic hormone. Five years later, a right endobronchial tumor corresponding to a carcinoid tumor was removed.

CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis / 中华放射学杂志

Objective To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG).Methods The CT findings of thymus area of 134 adult patients with lymphofolficular thymic hyperplasia in MG were reviewed,all of them with surgically and histologically proven diagnosis,and compared with the CT findings of 165 normal subjects.Results In the group of patient,CT showed enlargement of thymus in 31 patients,5 patients had nodule or mass(＜3 cm);thus 36 cases(26.9%)can confirmed diagnose by CT with thymic hyperplasia.CT showed 2 masses(＞3 em) and 9 patients(6.7%)had normal size thymus with soft-tissue density,it can considered with thymic hyperplasia.The spotty or streak shadow showed in other patients,though it could not be certain diagnosed as thymic hyperplasia,but could not be except it.The thymus area tissue complete replacement by fatty density were not found in patient group.The CT findings of patients had marked difference when compared with group of normal subjects(P＜0.01),except the spotty or streak shadows.Conclusion CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult.