Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome

Myasthenia gravis can present with rapid respiratory failure as the first manifestation of disease. In the Lambert-Eaton myasthenic syndrome (LEMS), such a manifestation has rarely been reported. We are reporting a patient who developed respiratory failure as the first manifestation of LEMS without associated carcinoma.     

Myasthenia gravis

Adult-onset myasthenia gravis is an acquired autoimmune disorder of neuromuscular transmission in which acetylcholine receptor antibodies attack the postsynaptic membrane of the neuromuscular junction. Although the cause of this disease is unknown, the role of immune responses in its pathogenesis is well established. Circulating acetylcholine receptor antibodies are present in 80% to 90% of patients with the generalized form of myasthenia gravis. Most patients have ptosis, diplopia, dysarthria and dysphagia. The weakness and fatigue worsen on exertion and improve with rest. Respiratory muscle and limb weakness are rare at the onset of the disease. For the past two decades, there has been considerable progress in understanding the diagnosis and management of myasthenia gravis. The diagnosis is based on clinical presentation, neurologic examination, and confirmation by means of electrophysiologic testing and immunologic studies. Myasthenia gravis mimics many neuromuscular diseases and even illnesses such as depression and chronic fatigue syndrome. One should always exclude drug-induced myasthenia gravis for all patients. With the introduction of new modalities of treatment, particularly immunosuppressive or immunomodulating drugs, plasma exchange and thymectomy, the morbidity and mortality of myasthenia gravis have decreased dramatically to the point that myasthenia gravis should not be considered as serious a disease as it once was. Although the several therapeutic options are usually effective and have meant independence in daily life to many patients with myasthenia gravis, well-designed, controlled, prospective studies are still lacking.     

Clinical and electrophysiological evaluation of dysphagia in myasthenia gravis

OBJECTIVE: To evaluate dysphagia at the oropharyngeal stage of swallowing and to determine the pathophysiological mechanisms of dysphagia in patients with myasthenia gravis. METHODS: Fifteen patients with myasthenia gravis with dysphagia and 10 patients without dysphagia were investigated by a combined electrophysiological and mechanical method described previously. Laryngeal movements were detected by a piezoelectric transducer and the related submental EMG (SM-EMG) and sometimes the EMG of cricopharyngeal muscle of the upper esophageal sphincter (CP-EMG) were recorded during dry or wet swallowing. The results of these electrophysiological variables were compared with those of normal age matched control subjects. RESULTS: In patients with myasthenia gravis with dysphagia, it was found that the time necessary for the larynx to remain in its superior position during swallowing and swallowing variability in successive swallows increased significantly compared with normal subjects and with patients with myasthenia gravis without dysphagia. The total duration of SM-EMG activity was also prolonged in both groups but more severely in the dysphagic patients. Electromyographic activity of the CP sphincter was found to be normal in the dysphagic patients investigated. All the patients with myasthenia gravis with dysphagia had pathological dysphagia limits (<20 ml water) whereas other patients except two, were within normal limits. CONCLUSIONS: Because the electrophysiological variables related to oropharyngeal swallowing were prolonged even in patients with myasthenia gravis without dysphagia, it is concluded that the submental and laryngeal elevators are involved subclinically in myasthenia gravis and, because of compensating mechanisms, the patient may not be dysphagic. As the CP-EMG behaviour was found to be normal, a coordination disorder between normal CP sphincter muscle and the affected striated muscles of the laryngeal elevators may be one of the reasons for dysphagia in myasthenia gravis. This method also made it possible to investigate the myasthenic involvement in the laryngeal elevators that cannot be evaluated by other electrophysiological methods in myasthenia gravis.     

Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value

Elevated amounts of antibodies specific for acetylcholine receptors were detected in 87 percent of sera from 71 patients with myasthenia gravis but not in 175 sera from individuals without myasthenia gravis, including those with other neurologic or autoimmune diseases. Antireceptor antibodies were not directed at the acetylcholine binding site of the receptor. Presence or titer of antibody did not appear to correlate with age, sex, steroid therapy, or duration of symptoms. Myasthenia gravis patients with only ocular symptoms had lower antibody titers, while the majority of titers in myasthenia gravis patients with thymoma exceeded the median titer of the myasthenia gravis group as a whole. Assay of antireceptor antibody should prove a useful test in the diagnosis of myasthenia gravis.     

Recurrence of thymoma and myasthenia gravis after 19 years. A case report

Myasthenia gravis developed in a 51-year-old woman in 1956; she was found to have a thymoma. Complete remission of the myasthenia gravis occurred within 18 months of thymomectomy. In 1975, myasthenia gravis recurred in association with recurrence of the thymoma. Remission of the myasthenic state once more followed the thymomectomy. The asymptomatic period of 18 years is, to our knowledge, the longest reported interval for recurrence of a thymoma-associated myasthenia gravis; 15 years is the longest reported interval for recurrence of a thymoma.     

Electroglottographic studies in myasthenia gravis patients--swallowing in exacerbation and remission stage]

We quantitatively evaluated the electroglottographic changes in swallowing in patients with generalized myasthenia gravis during exacerbation and remission stages. Five patients with myasthenia gravis (Osserman's stage IIB, 55.3 +/- 3.1 years old) and 6 healthy control subjects (55.3 +/- 1.1 years old) were examined. The instrument delivered a 450 microA. 52 kHz carrier signal to a pair of surface electrodes on each side of the larynx at the level of the thyroid lamina. Tissue impedance across the neck was recorded via electroglottography (EGG) while swallowing 10 ml of water. Four trials were performed for each subject, and the EGG waveform was analyzed. The EGG waveform during the exacerbation stage exhibited a more significantly increased number of phases and longer duration than that during remission. In myasthenia gravis patients, the number of phases and the duration from exacerbation to remission was more significantly reduced than those in controls at an interval of 3 years (p < 0.001, p < 0.02). These findings suggest that changes in the number of phases and duration of the EGG waveform are objective and quantitative parameters for measuring therapeutic effectiveness in treating swallowing disturbance due to myasthenia gravis. EGG is a useful and noninvasive technique for evaluating swallowing change in myasthenia gravis patents.     

Current management of Barrett''s esophagus

A number of drugs have been reported to cause neuromuscular blockade and/or to increase weakness in myasthenia gravis. We report on two patients, treated with felodipine and nifedipine for arterial hypertension, who presented with an exacerbation of their myasthenia gravis and a myasthenic syndrome or exacerbation of myasthenia gravis, respectively. The mechanism of action of calcium antagonist drugs at the neuromuscular junction is not yet well established, but it could be located at both presynaptic and postsynaptic levels.     

Solar UVR exposures of primary school children at three locations in Queensland

OBJECTIVES: To study mortality and survival of patients with myasthenia gravis. METHODS: 290 patients with myasthenia gravis were studied, including 212 incident cases identified during a comprehensive epidemiological study of myasthenia gravis in western Denmark 1975-89. Follow up was performed on 31 December 1994. Survival curves were constructed using the life table method. Patient data were compared with data from the public Danish population statistics. Death certificates were provided from the National Registry of Death. RESULTS: The annual average crude mortality rate was 1.8 per million (range 1.5-2.2). The myasthenia gravis related mortality rate (myasthenia gravis as underlying or contributory cause) was 1.4 per million (range 1.1-1.8). The age specific mortality rates were low below 50 years. After this age the mortality increased with age in both sexes; after 60 years more rapidly in men than in women. The overall survival rates three, five, 10, and 20 years from diagnosis were 85%, 81%, 69%, and 63% respectively. The survival of both sexes was shorter than that of the corresponding Danish population. Old age at diagnosis, a classification in Osserman-Genkins group IIB or III, and the presence of a thymoma were associated with a less favourable prognosis. The three, five, 10, and 20 year survival rates of thymectomised patients were 94%, 94%, 86%, and 79% respectively. The corresponding figures for the non-thymectomised patients were 78%, 71%, 56%, and 51%. A Cox regression analysis showed that this apparently significant effect of thymectomy was because the thymectomised patients were younger than the non-thymectomised patients. Furthermore, at the time of diagnosis of myasthenia gravis the non-thymectomised patients had a higher frequency of serious conditions associated with myasthenia gravis than the thymectomised patients. CONCLUSION: Patients with myasthenia gravis generally have a relative good prognosis although their survival is shorter than that of the corresponding population. Old age, a classification in Osserman-Genkins group III, and the presence of a thymoma are associated with a less favourable prognosis. In this study, the apparently significant effect of thymectomy was because the thymectomised patients were younger than non-thymectomised patients and because the non-thymctomised patients had a higher frequency of serious conditions associated with myasthenia gravis.     

Failure of intravenously administered immunoglobulin in the treatment of neonatal myasthenia gravis

Neonatal myasthenia gravis is uncommon and life threatening. We describe the use of intravenously administered immunoglobulin, in addition to conventional modalities, in a neonate with severe neonatal myasthenia gravis. However, despite this aggressive management, the child had a prolonged period of weakness requiring intensive care.     

Myasthenia gravis: recognition of a human autoantigen at the molecular level

The symptoms of myasthenia gravis are primarily or exclusively due to an autoimmune response against the muscle nicotinic acetylcholine receptor (AChR) and this has been the object of intensive investigations for almost 20 years. A detailed picture at the molecular level of the interaction of this autoantigen with the key elements involved in the autoimmune response, such as anti-AChR antibodies, the T-cell receptor and restricting major histocompatibility complex molecules, is now emerging for both human myasthenia gravis and its experimental model, experimental autoimmune myasthenia gravis. Here, Maria Pia Protti and colleagues focus on the molecular interactions occurring in human myasthenia gravis and summarize recent information on pathogenic mechanisms of the autoimmune response, and the structure of epitopes recognized by B cells and CD4+ T cells of myasthenic patients on the AChR molecule.     

Stapedius reflex decay in myasthenia gravis

Stapedius reflex decay, in response to a one-minute sound stimulus of 500 Hz occurred in six patients with myasthenia gravis. This decay is analagous to the decremental response of muscle action potentials to rapid nerve stimulation. Edrophonium chloride decreases the degree of decay. This represents a useful test in the diagnosis of myasthenia gravis.     

Drug-induced neuromuscular blockade and myasthenia gravis

Myasthenia gravis is an uncommon disorder of the neuromuscular junction resulting in weakness of all striated voluntary muscles. Therapeutic advances have increased patients' age and survival. Older patients with myasthenia gravis may have additional medication needs. Numerous drugs have experimental and clinical evidence of neuromuscular blockade. A MEDLINE search of the English literature from 1966 to the present pertinent to drug-induced myasthenia gravis was performed. Additional literature was obtained from reference citations of relevant articles. Drugs with several reports of neuromuscular blockade were assessed for causality by a recognized probability scale. Prednisone was most commonly implicated as aggravating myasthenia gravis, and D-penicillamine was most commonly associated with myasthenic syndrome. The greatest frequency of drug-induced neuromuscular blockade was seen with aminoglycoside-induced postoperative respiratory depression. However, drugs most likely to impact myasthenic patients negatively are those used in the treatment of the disease. These include overuse of anticholinesterase drugs, high-dose prednisone, and anesthesia and neuromuscular blockers for thymectomy.     

The new pathological anatomy]

We report a 14-year-old girl who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia gravis, which was clinically of ocular type, but with waning phenomenon of the extremities, occurred at 2 years and 4 months of age. Muscle weakness of the lower extremities gradually developed over the next 6 years. The electrophysiological and pathological findings fulfilled the criteria of "possible CIDP" with severe axonal involvement. The signs of myasthenia gravis and CIDP fluctuated synchronously. A common immunological abnormality was suggested to underlie this rare association of myasthenia gravis and CIDP in childhood.     

Immunoadsorption therapy for myasthenia gravis

The results of a multicentre trial were analysed to evaluate the efficacy of immunoadsorption therapy for severe generalised myasthenia gravis. Twenty patients with myasthenia gravis who were concurrently receiving high dose prednisolone and azathioprine therapy were treated with an affinity-type adsorbent, using tryptophan-linked polyvinyl alcohol gel (IM-TR), according to a standardised treatment protocol. The 20 patients received five adsorption treatments within a period of 10 days. In 11, pronounced improvement of myasthenic weakness was seen and long-term remission was maintained. The treatment was especially effective in patients with thymic hyperplasia. Circulating acetylcholine receptor (AChR) antibodies were reduced by about 60% by treating one plasma volume. There was no difference in the rate of removal of the AChR antibodies between patients with thymic hyperplasia and patients with thymoma. No serious complications occurred during 100 procedures. It was concluded that the immunoadsorption therapy with IM-TR is useful in controlling symptoms in patients with severe myasthenia gravis who are otherwise unresponsive.     

Myasthenia gravis and primary squamous cell carcinoma of the thymus

Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year-old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature.     

Colon carcinoma metastatic to the trachea. Report of a case and a review of the literature

It is known that myasthenia gravis is improved by cold. In two previously reported studies performed on a limited number of myasthenic patients and controls, local cold application to the eyelid was suggested for use as a diagnostic test for ocular myasthenia gravis. In this study, ice test to the eyelid was evaluated as a diagnostic test on 12 myasthenic patients and 15 controls with blepharoptosis and the results were compared with those of edrophonium test.     

Immunologic studies of a case of myasthenia gravis associated with pemphigus vulgaris after thymomectomy

A case of myasthenia gravis was associated with thymoma and pemphigus vulgaris. The bullous lesions developed after partial thymomectomy, cobalt (60Co) irradiation, and 3 days' extensive sunbathing, although a retrospective study of the patient's sera by quantitative indirect immunofluorescence method indicated that antiepithelial antibody already was positive before the clinical appearance of pemphigus vulgaris. Serial observation of the patient's clinical course and titrations of antiepithelial, antimuscle, and antithymus antibodies suggested a reverse relationship between the severity of myasthenia gravis and titers of antimuscle and anitithymus antibodies, and a parallel relationship between pemphigus vulgaris and antiepithelial antibody. Review of the literature suggests a close relationship between pemphigus vulgaris and myasthenia gravis and thymoma, particularly thymoma injured by medical procedures.     

Anti-idiotypic antibodies against the receptor antibodies in myasthenia gravis

Anti-idiotypic antibodies were prepared against purified acetylcholine receptor antibodies from two patients with myasthenia gravis. The purified idiotypes did not cross-react. Reaction with idiotypes from other patients were found in 8% and 37%, respectively, which suggests that shared idiotypic specificities occur. The anti-idiotypic IgG fractions had no receptor-like activity and did not bind cholinergic ligands. Receptor antibodies from two mothers and their newborn children with neonatal myasthenia gravis showed marked differences in the reactions with an anti-idiotypic antibody. This suggests that not passive transfer of maternal antibodies but a transient synthesis of a receptor antibody with a different specificity is an important factor in the pathogenesis of neonatal myasthenia gravis.     

Myasthenia gravis: another autoimmune disease associated with hepatitis C virus infection

We report on a male Egyptian patient who developed myasthenia gravis with typical symptoms, beneficial response to pyridostigmine, and the presence of anti-acetylcholine receptor antibodies and anti-striated muscle antibodies during the course of a chronic hepatitis C infection complicated by liver cirrhosis. As also reported for the herpes simplex and for the HIV virus, hepatitis C may lead to myasthenia gravis via a mechanism of cross-reactivity between viral epitopes and the acetylcholine receptor.     

Evaluation of nursing care in patients with myasthenia gravis

A retrospective study was made of 35 periods of hospital admission between January 1985 and September 1995, of 17 patients diagnosed in the Hospital Josep Trueta, Girona, as having myasthenia gravis. These were all the patients diagnosed as having myasthenia gravis in this ten year period. We studied the characteristics of their stay in hospital and evaluated the planning and practice of nursing care during these 35 periods. Nursing problems or diagnostic difficulties were found on 15 occasions, probably due to lack of knowledge of myasthenia gravis. When a patient had dysphagia, nursing care was increased and any problems identified. 29.4% of the patients were admitted to the intensive care unit. Since this disorder may be very serious, we consider that special training should be given to the nurses attending these patients. An understanding of this disorder and the possible treatments, complications, drugs, etc. would make it possible to give specific, individualized attention which would result in a higher standard of care.