Anticorps dans la myasthénie

In autoimmune myasthenia gravis, 75 to 80% of patients have antiacetylcholine receptor antibodies (anti-AChR abs) quantified by immunoprecipitation. Anti-AChR abs are polyclonal, directed against all AChR subunits, with a major fraction against the main immunogenic region, (alpha-subunit, aminoacids 67-76); they cause AChR loss by three mechanisms: blocking of acetylcholine binding; accelerated degradation or AChR due to bridging of two adjacent AChR molecules (antigenic modulation); lysis of postsynaptic membrane induced by complement. Neither anti-AChR ab level nor antigenic repertoire are correlated with disease severity. Studies performed on rat and human myotubes have shown that capacity of myasthenic patients's sera or immunoglobulins to induce AChR loss was correlated with anti-AChR ab titer but not with severity. Highest anti-AChR ab titers are found in young women with hyperplastic thymus, lowest in older patients and atrophic thymus. Ten to fifteen percent of babies born to myasthenic mothers suffer from a transitory neonatal myasthenic syndrome due to passive transfer of maternal anti-AChR abs. There is no correlation between clinical condition of the baby (presence and severity of neonatal myasthenia) and severity of maternal myasthenia. The risk of neonatal myasthenia is high when maternal ab titer is elevated (≥ 100 nM). Very rare and severe cases of foetal neonatal myasthenia gravis with arthrogryposis, hypomobility are due to presence in maternal serum of anti-AChR ab directed against foetal (gamma) AChR. In generalized myasthenia without anti-AChR ab, antibodies directed against MuSK, a postsynaptic molecule involved in AChR aggregation, are detected in around 40% of patients. Features of MuSK+ myasthenia are the following: strong female preponderance, severity (respiratory and bulbar) requiring immunosuppressants, facial and tongue atrophy, poor response to anticholinesterase inhibitors, atrophic thymus and poor response to thymectomy. Low-affinity anti-AChR abs have been recently reported in myasthenia gravis without anti-AChR and anti-MuSK ABS.     

Ocular myasthenia: diagnosis and treatment

Myasthenia gravis is a rare, auto-immune disorder of the neuromuscular junction. Onset signs frequently involve ocular muscles, accounting for ptosis and/or diplopia in more than 75% of cases. Among the cases with purely ocular muscle involvement, less than one half will never progress towards a more general form of myasthenia. However, even if they do not share the potentially life-threatening course of generalized myasthenia, purely ocular forms are often responsible for severe impairment in everyday life. The diagnosis is essentially based on fluctuations in the time and topography of the ocular muscle weakness. It still remains uneasy, as investigations such as electromyography, search for antiacetycholine receptor antibodies (positive in 50% of cases of purely ocular myasthenia), and edrophonium chloride test sometimes yield false negative results. Whereas some patients get better while on anticholinesterasic drugs alone, most of them will experience insufficient improvement and need steroids and/or immunosuppressant drugs. There is no indication for plasma exchanges, intravenous immunoglobulin or thymectomy (except in the presence of thymoma). This treatment could well decrease the risk of an evolution towards generalized myasthenia. The reasons underlying the vulnerability of ocular motor muscles in myasthenia are complex and several factors (linked to immunology, anatomy and function) may combine to bring about their specific involvement. In the future, randomized, controlled trials will be necessary, in order to determine a more rational approach of the treatment of ocular myasthenia, which currently lies mostly on retrospective data and the expertise of reference centers implicated in the management of the disease.     

Sphenoid and optic nerve sheath meningioma revealed by recurrent brain infarctions

Meningioma, though benign, may invade adjacent structures such as bone, soft tissues, dural sinuses and arteries. However brain infarctions secondary to meningioma involving the cavernous sinus and encasing and narrowing the intracranial carotid artery are rare. We report the case of a young man with recurrent left carotid artery infarctions due to a left sphenoid meningioma infiltrating the posterior optic nerve sheath through the optic canal and circumscribing the intracranial carotid artery. The patient had a gradually progressive occlusion of the middle cerebral artery, the distal internal carotid artery and finally the anterior cerebral artery ipsilateral to the sphenoid meningioma.     

Diagnostic utility of stimulated single-fiber electromyography of the orbicularis oculi muscle in patients with suspected ocular myasthenia

Stimulated single-fiber electromyography (SSFEMG) is a valuable diagnostic tool in cases of myasthenia gravis with limited disease. From 1990 to 2008 SSFEMG in the orbicularis oculi muscle (OO) was performed in a cohort of 456 patients referred with clinical suspicion of myasthenia gravis (MG) and exclusively ocular symptoms. A diagnosis of MG was made on clinical grounds in 103 patients. In this patient cohort, the specificity of SSFEMG for myasthenia was 97%, and the sensitivity was 80%. MG patients with a normal SSFEMG had a benign clinical course. This study confirms a high specificity and sensitivity of SSFEMG when it is performed on patients suspected to have ocular MG. In such patients, a normal SSFEMG of the OO predicts a benign clinical course.     

Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas

Introduction

Despite the fact that anti-muscle specific tyrosine kinase (MuSK) antibodies have been discovered for seven years, only a few studies have, until now, focused on myasthenia without acetylcholine-receptors antibodies (ab) (formerly known as “seronegative myasthenia”), and among them, anti-MuSK-antibody-positive and -negative patients.

Method

We retrospectively studied 20 patients with “seronegative” myasthenia gravis, eight of them being anti-MuSK-ab positive, the remaining twelve being negative. We searched for clinical, neurophysiological, and therapeutic differences between the two groups (anti-MuSK-ab positive: anti-MuSK+ versus anti-MuSK-ab negative: anti-MuSK−).

Results

Anti-MuSK+ patients had more predominantly bulbar involvement and had more severe disease (these patients required referral to intensive care more frequently). There was no difference between the two groups concerning treatment efficiency and tolerance. Most of our patients were treated with acetylcholinesterase-inhibitors, and immunomodulatory or immunosuppressive drugs that could indirectly reflect greater severity. However, there was no difference in treatments for anti-MuSK+ versus anti-MuSK− patients.

Conclusion

These results both confirm and complete the preexisting data on RACh-negative myasthenia, and especially on myasthenia associated with MuSK antibodies.     

Traitement de la myasthénie auto-immune

Myasthenia gravis is the most common neuromuscular junction disorder and the best understood autoimmune disease of the nervous system. The autoimmune attack leads to decreased concentrations of the AChR and results in fatigability of skeletal muscles increasing with activity and improving with rest. The treatment of myasthenia has improved dramatically over the last few decades, with an increasing number of immunotherapies used in management although not all of them have been formally tested in double-blind, prospective trials. The principles of treatment consist in optimizing neuromuscular junction function by use of cholinesterase inhibitors, inducing an immunologic remission and then maintaining that remission by long-term immunotherapies. Prednisone and/or azathioprine are the most effective. Short-term immunotherapies, i.e. intravenous immunoglobulin or plasmapheresis, are indicated for disease exacerbation. For patients with nonthymomatous autoimmune myasthenia, the effectiveness of thymectomy remains uncertain. The overall objective of therapy is to enable patients to lead a normal life as rapidly as possible, while limiting side effects and costs if possible. Treatment should be individualized. The aggressiveness of therapy should be balanced against a number of factors including distribution of muscle involvement, rate of progression, degree of functional impairment, lifestyle choice, and coexisting disease. In all cases, adequate education, for the patient and the physician, is most helpful in facilitating management of this chronic disease.     

Prognosis of ocular myasthenia

A retrospective study of 108 patients with myasthenia gravis who had solely ocular symptoms and signs at onset was carried out to identify factors influencing prognosis. Increasing duration of pure ocular myasthenia was associated with a decreasing risk of late generalized symptoms; only 9 (15%) of the observed generalizations occurred after more than 2 years of solely ocular symptoms. Increasing age at onset was associated with greater risk of respiratory crisis or death caused by myasthenia, whereas patients younger at onset had a greater chance of a benign outcome. Neither systemic curare tests nor responses to repetitive nerve stimulation had prognostic value.     

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.     

Combined Guillain–Barré syndrome and myasthenia gravis

Background: Guillain–Barré syndrome and myasthenia gravis both lead to muscle weakness but the two combined is uncommon. Detection of these entities can help identify forms of autoimmune neuromuscular diseases that may respond to immunotherapy. This report sought to characterize the clinical features of these two entities when combined. Methods: This report is of a case of combined Guillain–Barré syndrome and myasthenia gravis. The clinical features were analyzed and correlated to those published in English literature from 1960 to 2012. Ten reports and 12 cases, including the present case, were reviewed. Results: There were 12 patients (4 women and 8 men), aged 17 to 84 years, with combined Guillain–Barré syndrome and myasthenia gravis. Four had post-infectious Guillain–Barré syndrome followed by the development of myasthenia gravis concurrently or concomitantly within one month. All cases had symptoms of ptosis and areflexia. The other common presentations were limb weakness, oculobulbar weakness, and respiratory involvement. Functional outcome was mentioned in 10 patients and seven had good outcome (Hughes scale ?2). Conclusion: Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing combined Guillain–Barré syndrome and myasthenia gravis. The early recognition of this combination of peripheral nervous and neuro-muscular junction inflammation is important for initial treatment and prognosis.     

Recovery from global amnesia during plasma exchange in myasthenia gravis: report of a case

A 47-year old thymectomized woman with myasthenia gravis, receiving prednisone therapy, developed amnesia for recent events during a benign acute febrile illness. Plasma exchange was performed 9 months later, and was followed by a dramatic improvement of the mnemonic dysfunction.     

MYASTHENIA GRAVIS IN CHINESE CHILDREN

A clinical study of 50 Southern Chinese myasthenic children observed for periods of two to 18 years (six years on average) revealed manifestations different from those of caucasian patients. Onset was early, at an average of 4.8 years. 82 per cent had ocular myasthenia. Ophthalmoplegia followed ptosis between three months and 10 years later. Additional facial and isolated limb-muscle fatigability developed in only 6 per cent within three months to 3 1/2 years. Only 12 per cent developed generalized myasthenia. Although extension from ocular to the generalized form did not occur later than 20 months after onset, a deterioration in ocular symptoms, without extension into generalized myasthenia, occurred in nine of 18 children during adolescence. Ptosis and generalized myasthenia responded better to anticholinesterase and/or prednisone. Ophthalmoplegia was difficult to treat. The natural clinical course was benign. Spontaneous remission occurred in 62 per cent of cases, but 54.8 per cent of these relapsed, all confined to ocular muscles. Although there was no familial occurrence of myasthenia gravis, an association was found between myasthenia and thyroid disorders in some patients and their relatives. The association with HLA BW46 antigen was striking. Acetylcholine receptor antibodies were absent in the majority, but mildly elevated titres were found in three of five patients whose ocular symptoms deteriorated during adolescence, without extension into generalized myasthenia.     

Ocular myasthenia mimicking a one-and-a-half syndrome.

A 52-year-old patient developed an eye movement disorder first resembling a left internuclear ophthalmoplegia and subsequently a "one-and-a-half syndrome" as the presenting symptoms of ocular myasthenia gravis. No accompanying myasthenic features were present except for the fluctuation in the amplitude of dissociated nystagmus. This patient shows that an oculomotor disorder considered a typical pontine lesion may instead be caused by myasthenia gravis, even in the absence of other clinical and electrophysiologic features of neuromuscular deficit.     

Acquired rippling muscle disease with myasthenia gravis

Rippling muscle disease (RMD) is a rare disorder that occurs in both familial and sporadic forms. Seven patients have previously been reported with myasthenia gravis and sporadic RMD. There have been conflicting reports of the electrophysiological characteristics of rippling muscles in this acquired form. Another such patient is reported, and the clinical, electrophysiological, and laboratory features of this disorder are described. In addition, this patient had alopecia areata and recurrent metastatic thymoma, years after resection of a benign thymoma. This report emphasizes the clinical manifestations of RMD in association with myasthenia gravis (RMD-MG), and its distinctive features, in this and previously reported patients.     

Cardiac myxoma complicated with cerebral aneurysms and revealed by an ischemic stroke

Introduction

Myxoma is a rare benign primary cardiac tumor. It may cause vascular complications. Neurological symptoms may precede or accompany the diagnosis of myxoma with systemic embolization occurring most often in the cerebral circulation.

Observation

We report a case of cardiac myxoma complicated with cerebral aneurysms and revealed by an ischemic stroke in a 21-year-old patient. The cardiac myxoma was discovered during the transthoracic echocardiography performed as part of the etiological work-up. Because of the high risk of embolism, the mass was resected and mitral valve surgically repaired. The postoperative outcome was uneventful.

Conclusion

Although myxoma is a benign tumor histologically, it can lead to serious complications such as systemic embolism and sudden death.     

Neuromuscular diseases associated with benign monoclonal gammopathy

In over 1200 cases examined by isoelectric focusing of CSF and serum proteins, 4 patients had benign monoclonal gammopathy. These patients were affected by amyotrophic lateral sclerosis of bulbar onset, sensitive neuropathy of Thevenard type, myasthenia gravis and limb-girdle muscular dystrophy, respectively. The difficulty to relate the differences in the clinical features of these cases to a common physiopathological mechanism and the incidence of this finding (0.4% in 873 cases ranging from 21–60 years of age) do not seem to suggest any pathogenetic relationship between benign monoclonal gammopathy and the different neurological disorders encountered in these patients.     

Myasthenia gravis in children: a longitudinal study

BACKGROUND: Juvenile myasthenia gravis (JMG) is an uncommon disease. Unlike adults, clinical characteristics and outcomes of myasthenia gravis (MG) are not well studied in children. PATIENTS AND METHODS: Case records of 77 patients with MG who were 15 years of age or less at disease onset, evaluated over a period of 34 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. Their clinical characteristics and response to therapy was compared with 290 patients with MG onset after 15 years of age. RESULTS: Median age at onset was 8 years and mean period of follow-up was 6.2 years (range 6 months to 25 years). At presentation, 30% of patients had ocular myasthenia and the rest had generalized disease. Twenty-one patients (27%) had disease confined to ocular muscles throughout the course and three had limb girdle myasthenia. Familial myasthenia was more common than adult onset disease, 10 patients had positive family history. Unlike adults, none of the patients had associated autoimmune disease. Fifty-two patients (67%) received corticosteroids, and azathioprine was added in five patients. Thymectomy was performed in 11 patients, six below the age of 15 years. Thymic histology was normal in one and showed hyperplasia in eight and thymoma in one. Four patients had crisis. At the end of follow-up, 25 patients were asymptomatic, 28 had partial improvement, and nine remained unchanged or worsened and two died. Ten patients achieved complete stable remission. CONCLUSIONS: This study shows some distinctive characteristics of JMG, such as higher frequency of ocular myasthenia, benign course, better long-term outcome and lack of association of thymoma and other autoimmune disorders.     

La myasthénie associée aux thymomes : particularités cliniques et résultats chirurgicaux

Objective

The aim of this study was to compare the characteristics of myasthenic patients with and without thymoma, and the results of thymectomy in both types of patients.

Material and methods

A retrospective study was conducted among 66 patients who underwent thymectomy for myasthenia gravis in our department over a 10-year period (2000–2010). The surgical approach was sternotomy or anterolateral thoracotomy. Patients were divided into two groups according to the presence of thymoma: with (T-MG) and without (NT-MG) thymoma. Complete stable remission (CSR) was the primary endpoint.

Results

Median age was 35.09 ± 9.89 years. The NT-MG group had 38 patients (57.57%) and the T-MG group 28 patients (42.43%). There was no difference between the two groups regarding the surgical approach (P = 0.52). T-MG patients were older (40.54 ± 15.16 vs. 31.37 ± 9.46) (P = 0.008) and predominantly male. There were more generalized forms (P = 0.01) and more bulbar involvement (P = 0.02) in the T-MG group. The rate of CSR at 5 years was 7% and 17% in the T-MG and NT-MG patients respectively (P = 0.70). At 10 years, it was 36% and 94.73% respectively (P = 0.03).

Conclusion

Thymomatous myasthenia gravis is characterized by the severity of its clinical features. Remission rate at 10 years was significantly lower in the myasthenia with thymoma group.     

Multiple phenotypic manifestations of X-linked spinobulbar muscular atrophy

Recessive X-linked amyotrophic spinobulbar muscular atrophy (SBMA) or Kennedy disease is a neuroendocrine disorder with a slowly progressive phenotype, caused by an expansion of a polymorphic tandem CAG repeat of the androgen receptor gene. Classical clinical hallmarks include onset in the third decade of life, weakness and wasting predominantly in proximal extremity muscles, variable weakness of bulbar muscles, abundant muscle fasciculations, sensory nerve action potential abnormalities and signs of androgen insensitivity such as gynecomastia and testicular atrophy. The diagnosis has been recently made easier by the availability of genetic testing but Kennedy disease is probably still underdiagnosed because of phenotypic variability. We report 11 new cases, of which seven had atypical initial manifestations presenting respectively with myasthenia, cramps and fasciculation syndrome, polyneuropathy, post-trauma monomelic neuronopathy, effort-dependent muscle intolerance and/or muscular dystrophy, with the aim to enlarge the phenotypic spectrum of the published series.     

脂质沉积性肌病30例临床资料分析

目的总结脂质沉积性肌病(LSM)的临床特点。方法总结30例LSM患者的临床资料并复习文献。结果LSM是脂肪酸代谢异常所致,90.0%以上患者有发作性近端肌无力,不耐受疲劳;73.3%有眼肌、颈肌受累;46.7%有消化道症状。60.0%～86.7%的患者肌酶升高;83.3%有肌电图异常,其中77.0%为肌源性损害;93.1%有脂质沉积;可有血浆肉毒碱降低。泼尼松或能量支持治疗有效率为95.2%。结论LSM是肌无力原因之一,可多系统受累或与其他代谢异常共存,多数预后较好。     

Thymic carcinoma in myasthenia gravis developing years after thymectomy

We report two patients with myasthenia gravis (MG) who underwent thymectomy but developed thymic carcinoma years after the initial surgery. In one patient, the initial thymic pathology was normal, whereas the other had an encapsulated benign thymoma that was found only on pathological assessment. These cases demonstrate that MG may occur as part of a “new” paraneoplastic syndrome even after thymectomy. The late appearance of metastatic thymoma raises questions about monitoring for these patients. Muscle Nerve 40: 137–138, 2009