Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.
Antibodies ; Complement System Proteins ; Cytokines ; Humans ; Myasthenia Gravis ; diagnosis ; pathology ; therapy ; Oculomotor Muscles ; pathology

Strabismus is a pathologic condition in which the eyes do not properly align with each other forming different images on the corresponding retinal points. Early diagnosis and appropriate management of strabismus in the sensitive period of visual maturation is critical for the development of normal binocular vision in children. Therefore, it is important to perform ophthalmologic examinations including cycloplegic refraction and ocular alignment as early as possible to detect risk factors for amblyopia and strabismus. Strabismus could also be a sign of intraocular pathology, brain diseases or myasthenia gravis which may require urgent treatment. Strabismus can be treated by surgical and non-surgical methods. The first step in the management of strabismus is to correct amblyogenic refractive errors and prescribe glasses if necessary. Bifocal lenses, prism glasses, occlusion therapy, and botulinum toxin injection could also be considered. Surgery is usually performed if non-surgical treatments are unsuccessful. Making an accurate diagnosis and setting practical goals and limitations of treatment is the key to success in the treatment of strabismus.
Amblyopia ; Botulinum Toxins ; Brain Diseases ; Child ; Diagnosis ; Early Diagnosis ; Eyeglasses ; Glass ; Humans ; Myasthenia Gravis ; Pathology ; Refractive Errors ; Retinaldehyde ; Risk Factors ; Strabismus ; Vision, Binocular

Myasthenia gravis (MG) is a chronic autoimmune disease of neuromuscular blockade, characterized by muscle weakness and fatigue, and is associated with the production of autoantibodies against the skeletal muscle acetylcholine receptor, muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and other muscle endplate proteins. In addition, MG may be classified according the location of the affected muscles (ocular vs. generalized), patient age at symptom onset, and thymic pathology. Subgroup classification based on serum antibodies and clinical features include early-onset, late-onset, thymoma-associated, MuSK and LRP4 antibody-negative, and ocular forms of MG, and can help with therapeutic decisions and prognosis. Pyridostigmine is the chosen symptomatic treatment. For patients who do not adequately respond to symptomatic therapy, corticosteroids, other immunomodulating agents, and thymectomy are the first-line immunosuppressive treatments. The treatment of MG is highly individualized and depends on the age of the patient, the type and severity of the disease, and the pace of progression.
Acetylcholine ; Adrenal Cortex Hormones ; Adult ; Antibodies ; Autoantibodies ; Autoimmune Diseases ; Child ; Classification* ; Fatigue ; Humans ; Lipoproteins ; Muscle Weakness ; Muscle, Skeletal ; Muscles ; Myasthenia Gravis* ; Neuromuscular Blockade ; Pathology ; Phosphotransferases ; Prognosis ; Pyridostigmine Bromide ; Thymectomy

Myasthenia gravis (MG) is a chronic autoimmune disease of neuromuscular blockade, characterized by muscle weakness and fatigue, and is associated with the production of autoantibodies against the skeletal muscle acetylcholine receptor, muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and other muscle endplate proteins. In addition, MG may be classified according the location of the affected muscles (ocular vs. generalized), patient age at symptom onset, and thymic pathology. Subgroup classification based on serum antibodies and clinical features include early-onset, late-onset, thymoma-associated, MuSK and LRP4 antibody-negative, and ocular forms of MG, and can help with therapeutic decisions and prognosis. Pyridostigmine is the chosen symptomatic treatment. For patients who do not adequately respond to symptomatic therapy, corticosteroids, other immunomodulating agents, and thymectomy are the first-line immunosuppressive treatments. The treatment of MG is highly individualized and depends on the age of the patient, the type and severity of the disease, and the pace of progression.
Acetylcholine ; Adrenal Cortex Hormones ; Adult ; Antibodies ; Autoantibodies ; Autoimmune Diseases ; Child ; Classification* ; Fatigue ; Humans ; Lipoproteins ; Muscle Weakness ; Muscle, Skeletal ; Muscles ; Myasthenia Gravis* ; Neuromuscular Blockade ; Pathology ; Phosphotransferases ; Prognosis ; Pyridostigmine Bromide ; Thymectomy

Pure red cell aplasia (PRCA) and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.
Agammaglobulinemia ; Humans ; Middle Aged ; Myasthenia Gravis ; Paraneoplastic Syndromes ; Pathology ; Red-Cell Aplasia, Pure* ; Thymectomy ; Thymoma

BACKGROUNDSingle-fiber electromyography (SFEMG) abnormality in the extensor digitorum communis (EDC) was reported in ocular myasthenia gravis (OMG), which indicated subclinical involvement beyond extraocular muscles in OMG patients. The relationship between the abnormal findings of SFEMG in EDC and the probability for OMG to develop generalized myasthenia gravis (GMG) is unknown. This retrospective study aimed to determine the predictive value of abnormality of SFEMG in EDC of OMG patients.

METHODSOne-hundred and two OMG patients underwent standard clinical diagnosis process and SFEMG test in EDC muscle when diagnosed and were clinically followed up for 5 years. The SFEMG data were compared between different clinical groups according to thymus status, onset age, and different outcome of OMG developing. Chances of progressing to GMG were compared between two different groups according to SFEMG and repetitive nerve stimulation (RNS) results, acetylcholine receptor antibody (AchRAb) titer, thymus status, and onset age.

RESULTSAbnormal SFEMG results were observed in 84 (82.4%) patients. The mean jitter, percentage of jitter >55 μs (%), and blocking were higher in OMG patients than in healthy volunteers. There were no statistical differences in jitter analysis between thymoma group and non-thymoma group (P = 0.65), or between the later OMG group and the later GMG group (P = 0.31), including mean jitter, percentage of jitter >55 μs (%), and blocking. Elderly group (≥45 years old) had a higher mean jitter than younger group (t = 2.235, P = 0.028). Total 55 OMG developed GMG, including 47 in abnormal SFEMG group while 8 in normal SFEMG group. There was no statistical difference in the conversion rates between the two groups (χ2 = 0.790, P = 0.140). RNS abnormality, AchRab titer, or onset age had no correlation with OMG prognosis (P = 0.150, 0.070, 0.120, respectively) while thymoma did (χ2 = 0.510, P = 0.020).

CONCLUSIONSFEMG test in the EDC showed high abnormality in OMG, suggesting subclinical involvement other than extraocular muscles. Nevertheless, the abnormal jitter analysis did not predict the prognosis of OMG according to clinical follow-up.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Electromyography ; methods ; Humans ; Middle Aged ; Myasthenia Gravis ; metabolism ; pathology ; physiopathology ; Prognosis ; Receptors, Cholinergic ; metabolism ; Retrospective Studies ; Young Adult

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; diagnosis ; pathology ; Phenotype ; Prognosis ; Young Adult

OBJECTIVETo evaluate the different pathological and clinical characteristics of thymomas with and without myasthenia gravis (MG) and to determine whether the presence of MG influences the prognosis in thymoma patients.

METHODSThe clinical data from 228 consecutive patients (median sternotomy were used in 153, video-assisted thoracoscopic themectomy were used in 75) operated on from January 1992 to December 2007 was analyzed retrospectively. These thymoma patients had been subdivided into two groups: thymoma with MG (n = 125) and thymoma without MG (n = 103). All thymic epithelial tumors were classified according to the WHO histologic classification and the Masaoka clinical staging system. The result was evaluated according to the Myasthenia Gravis Foundation of America's criterion. The clinical features of the 2 test was compared between the two groups by χ² test, and the survival were compared between the two groups by Cox analysis.

RESULTSThere were no peri-operative deaths. 19 cases were inoperable (6 in the group with MG, 13 without MG (χ² = 4.52, P = 0.035)). The proportions of type A and thymic carcinoma were 0 in the group with MG, 10.5% (11/103) and 11.6% (12/103) respectively in the group without MG. According to the Masaoka's clinical staging, in the group MG, 24.8% (31/125) patients were stage III and IV; in the group without MG, 33.0% (34/103) patients were stage III and IV. There was a significant difference between hyperplastic paraneoplastic thymus coexisting in 28.8% (36/125) patients with MG and only 5.8% (6/103) in patients without MG (χ² = 20.91, P = 0.000) Microthymoma was identified in the paraneoplastic thymus of 3 patients with MG. There were 198 patients followed up, the rate was 86.8% (198/228). There was no recurrence in patients with type A and a few patients with type AB, B1, B2, B3 thymoma and thymic carcinoma recurred. The actuarial 5- and 10-year survival rates were 89.3% and 81.2% for patients with MG respectively, and 90.0% and 78.9% for patients without MG respectively. Within 5 years postoperatively, 6 of 9 patients with MG died of myasthenia crisis, while 6 out of 7 deaths in patients without MG were attributable to inoperable tumors (stage IV) and thymic carcinoma.

CONCLUSIONSThe existence of myasthenia gravis has little influence on the prognosis of thymomas, but it is good for early diagnosis and treatment. Extended thymectomy should be performed to all patients with thymoma, no matter they have myasthenia gravis or not. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and (or) thymic carcinoma for patients without MG.

Humans ; Myasthenia Gravis ; complications ; pathology ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; complications ; pathology ; surgery ; Postoperative Period ; Prognosis ; Retrospective Studies ; Sternotomy ; Survival Rate ; Thoracic Surgery, Video-Assisted ; Thymectomy ; Thymoma ; complications ; pathology ; surgery ; Thymus Neoplasms ; complications ; pathology ; surgery

BACKGROUNDAntibodies against acetylcholine receptor, acetylcholinesterase, ryanodine receptor and titin have been found in patients with myasthenia gravis. However, the relations between these antibodies and character of myasthenia gravis are unknown. This study aimed to detect multiple antibodies in myasthenia gravis and to investigate its clinical significance.

METHODSThese antibodies were detected by enzyme-linked immunoabsorbent assay in 89 cases of myasthenia gravis, 66 cases of other neurological diseases and 66 healthy controls. The incidences of antibodies were compared using the chi-square test.

RESULTSAcetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies were detected in 53.9%, 20.2%, 64.0% and 55.0% of myasthenia gravis patients respectively, higher than in patients of other neurological diseases and controls groups. The combination of the four antibodies assays provided 94.4% sensitivity and 84.0% specificity for the diagnosis of myasthenia gravis. Acetylcholinesterase antibody occurred more frequently in acetylcholine receptor antibody negative patients with adverse reactions to neostigmine test. Titin antibody provided 82.1% sensitivity and 52.5% specificity for myasthenia gravis with thymoma. Incidences of titin and of ryanodine receptor antibody were higher in late onset myasthenia gravis than in early onset myasthenia gravis. The proportion of titin antibody positive patients increased with the severity of myasthenia gravis as graded by a modified Osserman scale.

CONCLUSIONSTesting for acetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies can offer a better diagnostic method for myasthenia gravis than each antibody test alone. Titin antibody combined with computed tomography was better for the diagnosis of thymoma. Titin antibody occurred most frequently in severe myasthenia gravis.

Adult ; Age of Onset ; Antibodies ; metabolism ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; immunology ; metabolism ; pathology ; Thymoma ; immunology

OBJECTIVETo study the expression of CD20 in thymomas and its clinical significance.

METHODSOne hundred and seventy-nine cases of thymoma were enrolled into the study. The histologic diagnosis was reviewed by two experienced pathologists on the basis of the 2004 WHO classification. One hundred and two cases were selected for immunohistochemical study for CD20, pancytokeratin, TdT, CD3, CD43, CD99 and S-100 protein. The cases were further categorized into two groups, according to the association with clinical evidence of myasthenia gravis. The immunostaining pattern was then statistically analyzed.

RESULTSAmongst the 102 cases studied, 7 cases belonged to type A thymoma, 32 cases type AB thymoma, 17 cases type B1 thymoma, 15 cases type B2 thymoma, 17 cases type B3 thymoma and 14 cases thymic carcinoma. The expression rates of CD20 in neoplastic epithelial cells of type A, type AB, type B1, type B2 and type B3 thymomas and thymic carcinomas were 3/7, 84.4% (27/32), 1/17, 2/15, 0/17, 0/14, respectively. The proportions of CD20-positive lymphocytes in the background were 3/7, 18.8% (6/32), 14/17, 11/15, 11/17, 6/14, respectively. The proportion of CD20-positive intra-tumoral B lymphocytes in the group of thymomas with myasthenia gravis was 67.5% (22/40), in contrast to 35.5% (22/62) in those without myasthenia gravis.

CONCLUSIONSThe neoplastic epithelial cells in cases of type A and type AB thymoma, as well as few cases of type B1 and B2 thymoma, express CD20. The immunostain highlights the presence of oval, stellate or spindly cells. Thymomas associated with myasthenia gravis contain a significant population of CD20-positive intra-tumoral B lymphocytes. Type AB thymomas may be originated from different populations of cells, rather than a simple admixture of type A and B thymoma cells.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; B-Lymphocytes ; immunology ; pathology ; Child ; Epithelial Cells ; immunology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; complications ; immunology ; pathology ; Thymoma ; classification ; complications ; immunology ; pathology ; Thymus Neoplasms ; classification ; complications ; immunology ; pathology ; Young Adult