Myasthenia in elderly patients: a series of 23 cases

PURPOSE: There is evidence that myasthenia gravis is substantially underdiagnosed in older people, for which diagnosis and treatment may be difficult. METHOD: We report on a series of 23 cases of myasthenia gravis diagnosed after the age of 65. Diagnosis was ascertained by compatible symptoms, associated with electrophysiological evidence and/or presence of antibodies to the acetylcholine receptor (AchRAb) and/or positive prostigmine test. RESULTS: Twelve female and 11 male patients were identified, with a mean age of 77 (range: 66-89). Initial symptoms were ocular in 8 cases (35%), bulbar and ocular in 9 cases (39%), generalized in 6 cases (26%). Diagnosis was delayed in many patients (mean delay 31+/-47 months). Prostigmine test was positive in 16 cases (100%), AchRAb were positive in 19/23 cases (83%). Only one thymoma was found. Other diagnoses than myasthenia gravis, mainly stroke, were often considered. Treatment with anticholinesterase drugs, prescribed in all cases, has been able to control symptoms in only 3 cases. Corticosteroids were used in 10 cases, azathioprine or mycophenolate mofetil in 14 cases, intravenous immunoglobulins in 8 cases, and plasma exchanges in 2 cases. Thymectomy was performed on one patient with thymoma. Three patients were hospitalized in intensive care units for several weeks, and 3 patients died from their myasthenia. CONCLUSION: Diagnosis of myasthenia gravis is often missed or delayed in the elderly, because of a broad differential diagnosis in older people, and because the high incidence of the disease in middle and old age is often overlooked. The outcome of myasthenia gravis in older people is far from simple, and immunomodulation proves to be necessary in most cases. However, quality of life of surviving patients appears good.     

The co-existence of myasthenia gravis in patients with myositis: A case series

ObjectiveMyositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients.MethodsWe identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features.ResultsAll 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%) patients. High-dose steroids were associated with worsening weakness in 2/6 (33%) patients.ConclusionsProminent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis–MG overlap, high-dose steroids may exacerbate symptoms and pyridostigmine may play an important therapeutic role.     

Myasthenia gravis and hyperthyroidism: two cases

It is well known that hyperthyroidism occurs in approximately 2 to 17.5% of patients with myasthenia gravis. Hyperthyroidism may influence the clinical course of myasthenia gravis. We report the cases of two patients, a 53-year-old man and an 18-year-old woman, who had both severe myasthenia gravis and hyperthyroidism due to Graves' disease. Myasthenia gravis affected in particular facio-ocular areas with diffuse myopathy and signs of neuromuscular block on the electromyogram. In one patient, the diagnosis of thyroid disease was made three months before the diagnosis of myasthenia gravis while in the other, thyroid disease was recognized four months after myasthenia gravis. Myasthenia gravis worsened after the development of hyperthyroidism in the second patient. Both patients were given anti-cholinesterase drugs. One underwent thymectomy. Radioiodine used for the treatment of hyperthyroidism improved the symptoms of myasthenia gravis in the first patient. The association of myasthenia gravis and hyperthyroidism is more than a coincidence; our cases illustrate the difficult diagnosis and management of these diseases. Clinicians should look for myasthenia gravis in hyperthyroid patients and vice versa, especially when symptoms of myasthenia gravis or hyperthyroidism worsen.     

A comparative clinical and pathological study on the classification and prognostic features of 57 thymomas. II. prognostic features (author's transl)]

The most important prognostic determinants of the thymomas are the gross findings at operation (equal to the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas. Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymoma-associated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.     

Klinisch-pathologische Studie zur Klassifikation und Prognose von 57 Thymustumoren

Summary The most important prognostic determinants of the thymomas are the gross findings at operation (= the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas.Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymomaassociated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.

     

The co-existence of myasthenia gravis in patients with myositis: A case series

Objective

Myositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients.

Methods

We identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features.

Results

All 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%) patients. High-dose steroids were associated with worsening weakness in 2/6 (33%) patients.

Conclusions

Prominent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis–MG overlap, high-dose steroids may exacerbate symptoms and pyridostigmine may play an important therapeutic role.     

Myasthenia gravis

Myasthenia gravis is an autoimmune disease, which leads to load-dependent weakness of voluntary skeletal muscles with recovery of function after resting. The disease is caused by autoantibodies directed against the postsynaptic nicotinic acetylcholine receptors (AChR) leading to a reduction of neuromuscular transmission. Muscles and nerves are not affected. Disorders of the thymus play a role in the pathogenesis of AChR antibody-positive myasthenia. The clinical symptoms include exercise-induced fatigue either of the ocular muscles alone (ocular myasthenia) or striated skeletal muscle and the ocular, facial and bulbar musculature (generalized myasthenia). Treatment of myasthenia gravis involves administration of acetylcholine esterase inhibitors and immunosuppressive drugs. A myasthenic crisis is characterized by life-threatening complications with severe weakness, swallowing difficulties and respiratory failure, which requires intensive care treatment.     

A case of post-thymomectomy myasthenia gravis after extrapleural pneumonectomy for invasive thymoma which necessistated long-term mechanical ventilation]

The patient was a 58-year-old male with invasive thymoma which had disseminated in the left thorax and was histologically a polygonal cell type lesion. While the serum value of anti-acetylcholine receptor antibody was high before surgery, there were signs of myasthenia gravis. After preoperative chemotherapy, a thymectomy and left panpleuropneumonectomy were conducted. Forty days after surgery, the patients suffered post-thymomectomy myasthenia gravis, which necessitated mechanical ventilation for 6 months. Despite steroid therapy and 17 plasmapheresis procedures the tidal volume increased by little more than 200-250 ml during that time. The causes of ventilatory failure, therefore, were probably decreased pulmonary function due to extrapleural pneumonectomy and the myasthenia gravis. According to the literature, polygonal cell type thymomas with high serum levels of anti-acethycholine receptor antibody have higher incidences of post-thymomectomy myasthenia gragvis than other ones. Therefore, the risk of post-thymomectomy myasthenia gravis should be kept in mind when extrapleural pneumonectomy for invasive thymoma is being considered, especially in the cases of this type.     

Acute Respiratory Failure Induced by Magnesium Replacement in a 62-Year-Old Woman with Myasthenia Gravis

Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient''s neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature.     

Rapidly progressive polymyositis with elevated antiacetylcholine receptor antibody activity

We report a 51-year-old woman with polymyositis accompanied by a high titer of antiacetylcholine receptor antibody. The patient presented with weakness of grip strength followed by rapidly progressive dyspnea, which required mechanical ventilation. She was treated with a glucocorticoid and came off the respirator one week later. Antiacetylcholine receptor antibody activity was elevated in the acute phase and decreased during recovery, although other signs of myasthenia gravis were negative. This patient suggested that in cases of rapidly progressive bulbar palsy and limb muscle weakness, it is necessary to include polymyositis associated with elevated antiacetylcholine receptor antibody activity in the differential diagnosis.     

Changes in respiratory muscle function after neostigmine injection in patients with myasthenia gravis

In sixteen patients with myasthenia gravis, the weakness of respiratory muscles, especially of expiratory, caused some disturbances in lung function. Thirty minutes after injection of neostigmine, general improvement of muscle function was accompanied by an increase of strength and endurance of respiratory muscles. The mean value of maximal inspiratory mouth pressure (PImax) increased by 33%, maximal expiratory mouth pressure (PEmax) by 23.5% and maximal voluntary ventilation (MVV) by 21%. As a consequence of these changes amelioration of lung function indices was found, vital capacity increasing on average by 13% and residual volume decreasing by 12.5%. We concluded that patients with generalized myasthenia gravis have disturbances in lung function which may be partially improved by neostigmine injection or other anticholinesterase agents.     

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a glutenfree diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 （or, about 4.3%） was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.     

Myasthenia gravis--a rare presentation with tongue atrophy and fasciculation

We report the case of an unusual presentation of myasthenia gravis with tongue atrophy and fasciculation. Myasthenia gravis is an autoimmune condition associated with weakness and fatigability of voluntary muscles. In >50%, the initial symptoms and signs are related to extraocular muscle weakness, such as diplopia or ptosis [Tsung K, Seggev JS. An unusual cause of dysphagia. West J Med 1995; 163: 159-60]. Rarely, it is known to affect bulbar muscles and can lead to dysphagia and respiratory compromise.     

Cricoarytenoid arthritis may be a case of emergency

Summary Cricoarytenoid arthritis is a frequent complication of rheumatoid arthritis. In most cases it is an insidious, progressive disorder which does not produce early symptoms. A bilateral fixation can lead to a considerable stenosis; exertional dysponea, however, may not be noted because mobility of most patients is restricted. We report a case of severely symptomatic cricoarytenoid arthritis in a woman known to have myasthenia gravis and rheumatoid arthritis. Initially exacerbation of the myasthenia gravis, leading to severe inspiratory insuffiency was suspected. On indirect laryngoscopy, however, the correct diagnosis was made. Early diagnosis might have prevented an emergency in our patient.     

Pancreatic Cancer in a Patient with Myasthenia Gravis

Myasthenia gravis has been associated with several diseasessuch as hyperthyroidism and malignancy (thymoma,lung carcinoma) but so far no reports have demonstrated arelationship between this disease and pancreatic disease.We report a 66-year-old man with myasthenia gravis diagnosedon the basis of clinical symptoms (eyelid ptosis),typical abnormalities on repetitive nerve-stimulation tests,and the presence of Ach-R antibodies in the serum. The responseto anticholinesterasic agents (pyridostigmine) wasgood, but after 1 year, he developed pancreatic cancer andmyasthenia gravis symptoms recurred. After surgery andchemotherapy, myasthenia gravis symptoms disappeared.Some months later, the patient had a recurrence of pancreaticcancer after relapse of myasthenia gravis.     

Early and late results after thymectomy in myasthenia gravis: a retrospective study [correction of analysis]

BACKGROUND: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy. METHODS: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively. RESULTS: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma. CONCLUSIONS: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.     

Mediastinal thymolipoma: an analysis of 10 cases

Thymolipoma is a benign tumour composed of thymic elements and adipose tissue. It may be associated with myasthenia gravis or immune disorders. We aimed to evaluate the clinical and radiological features of thymolipoma. The clinical data from 10 cases of thymolipoma, diagnosed at our centre between 2002 and 2004, were analysed retrospectively. There were six female and four male patients, whose ages ranged from 16 to 67 years, with a mean age of 34.1 years. All but two patients had pulmonary or extrapulmonary symptoms. Five patients also had myasthenia gravis. All thymolipomas were localized in the anterior superior mediastinum. The surgical approach was sternotomy in nine cases and thoracotomy in one case. Thymectomy was performed on all patients. Thymolipomas are unusual tumours and may be associated with myasthenia gravis. Surgical resection is the most appropriate treatment modality.     

Studies in myasthenia gravis: Early thymectomy: Electrophysiologic and pathologic correlations

Indications for thymectomy in myasthenia gravis have been recently expanded to include all cases with extraocular symptoms as a result of the minimal morbidity and negligible mortality of the transcervical approach.As increasing numbers of patients with myasthenia gravis, covering the entire spectrum of generalized disease, have been added to the thymectomy population, a more accurate evaluation of the effects of the operation is possible.Our experience with 353 patients who have undergone thymectomy indicates that early thymectomy, particularly in patients who do not have thymic germinal centers, is followed by early remission of the disease. Delayed remission after thymectomy is related to the duration and severity of the disease, and to presence of thymic germinal centers. Germinal centers were found more frequently in patients with long duration of the disease and in patients in whom the disease had progressed to respiratory involvement. Marked improvement in electromyographic findings immediately after thymectomy was observed in the majority of patients who had had the disease for 1 year or less and where germinal centers were absent. The percentage of malignant thymomas was higher in patients who underwent thymectomy 1 year or more after the onset of symptoms of myasthenia gravis.These data indicate the importance of early thymectomy while the disease is still in the mild stages. Transcervical thymectomy is the treatment of choice as it is followed by a higher percentage of remissions and by less morbidity than other forms of treatment.     

Thymectomy for myasthenia gravis: prognostic factors in 70 patients

Thymectomy has become increasingly accepted as an efficacious procedure for myasthenia gravis, with high rates of complete clinical remission. Predictors of the response to thymectomy for myasthenia gravis vary in the literature. We retrospectively reviewed the clinical records of 70 patients (63% female; mean age, 38 years) diagnosed with myasthenia gravis from August 1993 to August 2004, to determine the factors predicting outcome. Complications occurred in 20%, but there was no hospital mortality. Complete clinical remission was obtained postoperatively in 47%. Our results indicate that patients with less than 1 year's duration of disease have a better prognosis, and Osserman stages I, IIa, and IIb are also associated with higher clinical remission rates. Female patients have a better prognosis than males, and the younger the patient the better the outcome. Thymectomy is indicated for myasthenia gravis as early as possible in the course of the disease.     

Steroids induce acetylcholine receptors on cultured human muscle: implications for myasthenia gravis.

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.