Seronegative myasthenia gravis

Six to 20 p.cent of patients with generalized myasthenia gravis and 30 to 50 p.cent of those with ocular myasthenia gravis do not have anti AchR antibodies. Strict clinical, pharmacological and electrophysiological criteria are needed for the diagnosis of sero-negative myasthenia gravis. Sero-negative myasthenia gravis is an autoimmune disorder. But thymic hyperplasia is generally absent. Antibodies directed against the muscle receptor of tyrosine kinase (anti MuSK antibodies) were recently demonstrated in 40 to 70 p.cent of patients with sero-negative myasthenia gravis. Sero-negative and sero-positive myasthenia gravis may be clinically very similar. But sero-negative myasthenia gravis may express predominantly severe oculobulbar weakness or mainly neck, shoulder and respiratory muscle weakness. Sero-negative myasthenia gravis is never associated with thymoma. Sero-negative myasthenia gravis responds to immunodulation but perhaps less well than sero-positive myasthenia gravis.     

Familial autoimmune myasthenia gravis and thymoma: occurrence in two brothers

At ages 31 and 42 years, two brothers presented with clinical, pharmacologic, electrophysiologic, and immunologic characteristics of autoimmune myasthenia gravis. At thymectomy, both had histologic findings of epithelial thymoma. HLA analysis revealed A2, A3, B7, and B39 antigens in one patient and A3, A24, B7, and B40 antigens in the other. Familial myasthenia gravis with thymoma has not been described previously. Familial thymoma has been rarely reported, but never with myasthenia gravis.     

Predictive value of serum anti-C1q antibody levels in experimental autoimmune myasthenia gravis

Components of the complement cascade and circulating immune complexes play important roles in both experimental autoimmune myasthenia gravis and myasthenia gravis in humans. Thus far, no serological factor has been identified to predict the clinical severity of either myasthenia gravis. Upon immunization with acetylcholine receptor, levels of complement factors C1q, C3 and CIC increase with time in sera from C57BL/6 (B6) mice. Both these and plasma samples from myasthenia gravis patients also contain anti-C1q antibodies. The serum levels of anti-C1q antibodies but not C1q, C3 and CIC are significantly correlated with the clinical severity in the experimental myasthenia mice. However, this correlation is not observed in myasthenia gravis patients.     

Atypical ocular myasthenia gravis

The diagnosis of ocular myasthenia gravis is rarely in doubt in patients with a proper history and typical clinical findings. However, myasthenia gravis can mimick any pupil-sparing eye movement disorder and several diseases may masquerade myasthenia gravis. We review the atypical presentations and differential diagnoses in ocular myasthenia gravis, describing four patients with some of these conditions (4th nerve palsy, near spasm reflex, one-and-a-half syndrome, orbital meningioma). The correct interpretation of the clinical findings associated with appropriate neuro-imaging studies allowed the appropriate diagnosis in these cases.     

Myasthenia gravis and myotonic dystrophy in a 13-year-old girl. G. Milton Shy Award Essay, 1976

A 13-year-old girl demonstrated clinical, pharmacologic, and electromyographic evidence of myasthenia gravis, as well as clinical, electromyographic, and genetic evidence of myotonic dystrophy. Although myotonic dystrophy was documented in the family, no other family members were found to have myasthenia gravis.     

家族性重症肌无力临床特点及其与人类白细胞抗原DQA1基因多态性的相关性研究

目的探讨家族性重症肌无力(MG)的临床特点及其与人类白细胞抗原(HLA)DQA1基因多态性的相关性。方法对15例家族性、36例散发性MG患者的临床特点进行研究,并运用聚合酶链反应序列特异性引物(PCR SSP)对HLA DQA1基因多态性进行分型。结果与散发性MG相比,家族性MG患者发病年龄较早(两者分别为18 7、34 4岁,P=0 006),病情较轻,预后较好;与散发MG组及健康对照组比较,家族性MG患者的DQA1 0301基因频率增高(三者分别为40 0%、19 4%和20 2% ),差异有统计学意义(P<0 05),这种差异在眼肌型的患者中同样存在,但未发现患者性别与DQA1相关。结论家族性MG有其独特的临床特点,DQA1 0301是家族性尤其是眼肌型MG的易患基因,提示家族性MG与散发MG可能有着不同的免疫遗传机制。     

Prematurity and early-onset juvenile myasthenia gravis.

A child manifested ocular myasthenia gravis at age 16 months which progressed to bulbar and mild systemic weakness over a 3-year period. The medical history was significant for premature birth at 32 weeks gestation and birth weight 940 gm. A review of reported patients with juvenile myasthenia gravis with adequate documentation of the birth history, noncongenital onset, typical clinical course and diagnostic findings, and elevated titers of antiacetylcholine receptor antibodies revealed that 55% with onset before age 3 years had a history of prematurity. This association of myasthenia gravis and prematurity may provide insights to the pathogenesis of the disease.     

Prednisolone-sparing effect of cyclosporin A therapy for very elderly patients with myasthenia gravis

Three very elderly (over 80 years old) patients having generalized myasthenia gravis without thymoma were treated with cyclosporin A and followed for up to 24 months. Cyclosporin A therapy quickly improved myasthenia gravis symptoms in all cases, which allowed a rapid reduction in the prednisolone dose and improvement of prednisolone-related hyperglycemia and hypertension. Combination therapy with prednisolone and low-dose cyclosporin A not only improved the clinical symptoms of the very elderly myasthenia gravis patients but also resulted in a rapid reduction in prednisolone dosage and prednisolone-related side effects. Attention should be paid to cyclosporin A-related renal dysfunction.     

Management of Juvenile Myasthenia Gravis

Juvenile myasthenia gravis is an uncommon autoimmune disorder. Its management is not standardized. Juvenile myasthenia gravis is pathophysiologically similar to myasthenia gravis in adults. However, a number of significant particularities related to race, age at onset, severity, and antibody status complicate the management. We summarize the unique clinical features of juvenile myasthenia gravis and review the therapeutic options.     

Myasthenia gravis and peripheral neuropathy in an Amazon indigenous female.

A 15 year-old female presented with anti-acetylcholine receptor antibody-positive myasthenia gravis and electrophysiological signs of sensory peripheral neuropathy. The repetitive stimulation test showed decremental response of 31% in the median nerve. The clinical picture improved with prostigmine, corticosteroids, plasmapheresis and thymectomy. This is the first case report of an Amazon indigenous patient with myasthenia gravis.     

Myasthenia gravis with inflammatory myopathy without elevation of creatine kinase

Cases of myasthenia gravis with inflammatory myopathy usually show elevated creatine kinase (CK) levels. There are few case reports of myasthenia gravis with inflammatory myopathy without elevated CK levels, and clinical features and useful diagnostic methods for these patients are little known. We describe the case of a 79-year-old man with myasthenia gravis that was complicated with inflammatory myopathy without elevated CK levels and successfully treated with immunological treatment. Initially, he was diagnosed with ocular myasthenia gravis and treated with pyridostigmine, but dysphagia and weakness in the neck and bilateral upper limb without fatigability gradually developed. Needle electromyography revealed myopathic changes, and the results of muscle biopsy were consistent with inflammatory myopathy. Blood tests showed normal CK levels throughout the clinical course and elevated myoglobin levels alone. The possibility of developing inflammatory myopathy in patients with myasthenia gravis cannot be excluded, even if CK levels are normal.     

Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis

PURPOSE OF REVIEW: Some of the 20% of myasthenia gravis patients who do not have antibodies to acetylcholine receptors (AChRs) have antibodies to muscle specific kinase (MuSK), but a full understanding of their frequency, the associated clinical phenotype and the mechanisms of action of the antibodies has not yet been achieved. Moreover, some patients do not respond well to conventional corticosteroid therapy. Here we review recent clinical and experimental studies on MuSK antibody associated myasthenia gravis, and summarize the results of newer treatments for myasthenia gravis. RECENT FINDINGS: MuSK antibodies are found in a variable proportion of AChR antibody negative myasthenia gravis patients who are often, but not exclusively, young adult females, with bulbar, neck, or respiratory muscle weakness. The thymus histology is normal or only very mildly abnormal. Surprisingly, limb or intercostal muscle biopsies exhibit no reduction in AChR numbers or complement deposition. However, patients without AChR or MuSK antibodies appear to be similar to those with AChR antibodies and may have low-affinity AChR antibodies. A variety of treatments, often intended to enable corticosteroid doses to be reduced, have been used in all types of myasthenia gravis with some success, but they have not been subjected to randomized clinical trials. SUMMARY: MuSK antibodies define a form of myasthenia gravis that can be difficult to diagnose, can be life threatening and may require additional treatments. An improved AChR antibody assay may be helpful in patients without AChR or MuSK antibodies. Clinical trials of drugs in other neuroimmunological diseases may help to guide the treatment of myasthenia gravis.     

Cancer occurrence following azathioprine treatment in myasthenia gravis patients: A systematic review and meta-analysis

Treatments of myasthenia gravis (MG) usually include immunosuppressants such as glucocorticoids, tacrolimus, and azathioprine (AZA). In clinical practice, azathioprine therapy is thought to have a potential risk for developing secondary malignancies in myasthenia gravis patients. However, published data on the long-term safety of azathioprine in myasthenia gravis patients are limited and not consistent among studies. To explore cancer occurrence following azathioprine therapy in myasthenia gravis patients in the long term, we searched Medline, EMBASE, and the Cochrane Library for terms related to azathioprine, myasthenia gravis and cancer occurrence. Two investigators independently extracted trial data. A pooled estimate was calculated from fixed-effects meta-analysis. Our analysis included 1650 azathioprine-treated patients and 2481 non-azathioprine-treated patients. All five studies showed some concerns regarding the risk of bias. In a meta-analysis of 5 studies, we observed no significantly elevated risk of cancer occurrence among individuals with prior myasthenia gravis diagnosis who received long-term azathioprine treatment (OR 1.09; 95% CI 0.86–1.38, p = 0.46). Prospective studies are needed to observe the safety of azathioprine.     

Myasthenia gravis: A personal view of pathogenesis and mechanism,part 2

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in the January/February issue of MUSCLE & NERVE, dealt with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of the disease. Part 2, which appears in this issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.     

Infantile myasthenia gravis: report of a case diagnosed clinically

A rare case of infantile myasthenia gravis (congenital type) is reported. The child was 16 months old at the time of the diagnosis, although she presented signs suggestive of the disease since two months earlier. The diagnosis was based solely upon clinical criteria, including immediate response to a therapeutic test with Neostigmine, followed by excellent response to treatment with Mestinon. A review of the different types of myasthenia gravis in infancy is made, with emphasis on the clinical criteria for differential diagnosis of these cases.     

Myasthenia induced by D-penicillamine. Apropos of 2 case reports

Two cases of penicillamine-induced myasthenia gravis in rheumatoid polyarthritis are reported. A complete recovery was obtained in both cases. The authors discuss the clinical presentation and the pathogenetic mechanisms of that drug-induced myasthenia gravis. The presence in both cases of both the HLA antigens DR1 and BW35 is emphasized.     

A very late onset AChR and MuSK double positive myasthenia gravis: a case description and literature review

AChR and MuSK double positive myasthenia gravis has been rarely reported. Generally, it occurs in children and adults after thymectomy or immunotherapy. Furthermore, in a few patients with bulbar or respiratory involvement, MuSK antibodies might be detected after clinical deterioration. We report a man with a very late onset myasthenia gravis (86-year-old) and the coexistence of both antibodies at the time of the diagnosis. Despite the presence of MuSK antibodies, he manifested no bulbar symptoms and had a favorable clinical outcome. However, side effects related to low dose pyridostigmine were evident. Hence, double positivity can also occur in elderly and in more benign forms of myasthenia gravis. Other cases of AChR and MuSK double positive myasthenia gravis could allow a better definition of this condition.     

Three cases of myasthenia gravis from one family with variations in clinical features and serum antibodies

Myasthenia gravis, an autoimmune disorder affecting neuromuscular transmission, is mainly sporadic while familial cases are very rare. Usually familial myasthenia gravis cases have uniform clinical symptoms as well as serum anti-acetylcholine receptor antibodies. Interestingly, in our cases varying clinical types of myasthenia gravis and seropositive/seronegative anti-acetylcholine receptor antibodies coexisted in the same family. The mother and her daughter both had ocular myasthenia gravis, detectable anti-acetylcholine receptor antibodies and non-detectable anti-muscle-specific kinase antibodies, and good responses to medications. The son displayed ocular symptoms at the onset, and then progressed into a generalized form after 1 year. His serum anti-acetylcholine receptor antibodies and anti-muscle-specific kinase antibodies were both negative. Neither corticosteroids nor thymectomy alleviated his symptoms. Human leukocyte antigen DQA1*0301 allele sharing by the three patients may be involved in their genetic susceptibility to myasthenia gravis, and subtle differences in human leukocyte antigen DQB1 alleles may be associated with their variations in clinical features and serum antibodies.     

Role of virus for the induction of myasthenia gravis

Virus has been suggested as an etiological agent in myasthenia gravis. In this investigation 36 patients with the clinical diagnosis of myasthenia gravis were tested for antibodies against ornithosis, mycoplasma pneumoniae and 16 viral antigens. Rabbits with experimentally induced autoimmune myasthenia gravis were similarly tested. There was no overall correlation to any microorganism, which might have suggested the involvement of a viral infection in the pathogenesis of the disease. Neither was there any difference in incidence of antibodies in female patients carrying the HLA B8 antigen, an antigen which is associated with myasthenia gravis, as compared to HLA B8 negative individuals.     

Maximal bite force and surface EMG in patients with myasthenia gravis

Masticatory muscle strength was quantified in patients with bulbar myasthenia gravis and compared with that of patients with ocular myasthenia gravis, patients in clinical remission (whether or not pharmacological) who previously suffered from bulbar myasthenia gravis, and healthy subjects. Maximal bite force and maximal activity of the masseter and temporalis muscles and of the submental muscle complex were measured. Bite force was decreased in the patients with bulbar myasthenia gravis, but was normal in the patients in the clinical remission group and in the ocular group. These findings were consistent with the results of electromyographic data. Although subjective reports of masticatory muscle weakness provide valuable information, quantitative measurements provide more information about the degree of muscle weakness of individual muscles. This is especially important for longitudinal evaluation of therapy in individual patients and for pharmacotherapeutic research.