High-dose intravenous immunoglobulin in the management of myasthenia gravis.

Intravenous immunoglobulin, 400 mg/kg, was administered daily for five days to 12 patients with exacerbation of generalized myasthenia gravis. Degree of weakness, duration of illness, use of prednisone, and history of thymectomy or thymoma did not affect the response to intravenous immunoglobulin. Eleven patients improved, beginning 3.6 +/- 2.7 (mean +/- SD) days after the start of treatment and becoming maximal in 8.6 +/- 4.6 days, with sustained improvement lasting 52 +/- 37 days. Vital capacity increased from 1748 +/- 510 to 2700 +/- 614 mL at peak effect. Decreases in strength occurred in four patients beginning on day 3.2 +/- 2.5, lasted 1.5 +/- 0.6 days, and were mild in three patients. Other effects were minimal. There was no significant change in acetylcholine receptor antibody titers, which were elevated in all patients. Immunoglobulin seemed to produce a more rapid improvement than corticosteroids and is recommended as an adjunct in the management of myasthenia gravis exacerbations.

High-dose intravenous methylprednisolone in myasthenia gravis.

Corticosteroids have been useful in the management of myasthenia gravis (MG), but their efficacy has been limited by the slow onset of improvement, initial worsening of MG, refractoriness of some patients, and side effects of large daily doses. High-dose intravenous methylprednisolone pulses have been reported to produce rapid improvement in several immunologic disorders. In this study we administered 2 g of methylprednisolone intravenously every five days to 15 consecutive patients who had exacerbation of generalized MG. Satisfactory improvement occurred in ten of 15 patients after two courses and in two of five patients after a third course. Onset of improvement began a mean (+/- SD) of 3 +/- 1.1 days after the first infusion, 2.1 +/- 1 days after the second, and 2.4 +/- 1 days after the third, and reached its maximum level 8.9 +/- 6.1 days after the last infusion. A decrease in strength occurred in three patients 1.43 +/- 1.30 days after each infusion, was not marked, and lasted three days, following which improvement generally occurred. Side effects were minimal. After improvement, a daily dose of prednisone (30 mg) was used to maintain improvement. Use of pulse therapy at five-day intervals for the management of severe MG seems to have an advantage in that it produces less initial worsening and more rapid improvement in MG, enabling smaller daily maintenance doses to be employed, with fewer side effects.

Ophthalmoplegia, ptosis, and miosis in temporal arteritis.

Ophthalmoplegia occurred in 7 of 14 patients with biopsy proved temporal arteritis. Only one patient had diplopia. In six of the seven patients, the pattern of ophthalmoplegia did not conform to the distribution of one of the ocular motor nerves. Impairment of upward gaze was most common. In five patients the ophthalmoplegia was accompanied by ptosis, and in five it was accompanied by a miotic pupil. Ophthalmoplegia and ptosis were the major manifestations of temporal arteritis in one patient. Oculomotor signs and symptoms responded to corticosteroid therapy in all seven patients, but in two patients prolonged therapy was necessary. Ophthalmoplegia or ptosis may be early manifestations and may precede visual loss, so that frequent examination is recommended in patients suspected of temporal arteritis, with prompt administration of adequate doses of corticosteroid as soon as any ocular manifestations of temporal arteritis are noted.

The course of myasthenia gravis and therapies affecting outcome.

The course of 1,487 patients with myasthenia gravis followed between 1940 and 1985 for a mean of 18 years provides further evidence that the distribution, severity, and outcome of the disease are determined during the first 1 to 3 (occasionally 5) years after onset, suggesting that injury to acetylcholine receptors occurs mainly during this time. In 14%, the disease remained clinically localized to the extraocular muscles, and in the remaining 86% became generalized, in 87% within a year, with the disease reaching maximum severity within the first year after onset of symptoms in 55%, during the first 3 years in 70%, and during the first 5 years in 85%. Male patients tended to have more rapid progression of disease, higher mortality, and lower rates of remission and improvement than females. From 1940 to 1957, when management relied on anticholinesterase compounds, endotracheal intubation or tracheostomy and negative pressure assisted ventilation for respiratory failure, and thymectomy in 26% of patients and thymomectomy in 8%, 31% of patients with generalized myasthenia gravis died of the disease (29% of these during the first year after onset, 27% during the second and third years, and 17% during the fourth and fifth years), 32% improved, 23% remained unchanged, 10% went into remission, and only 5% were worse during the last year seen than during the worst of the first 3 years (or 5 years in the minority of patients who reached maximum weakness after 3 years). From 1958 to 1965, during which time the management of respiratory failure was improved by positive pressure and volume controlled ventilation and improved intensive care, mortality fell to 14% (p less than 0.005), and a higher proportion remained unchanged (p less than 0.005). From 1966 to 1985, when over half the patients received adrenal cortical steroids, mortality fell to 7% (p less than 0.005) and the proportion who improved rose to 47% (p less than 0.05). Even though the patients who received steroids usually had more severe myasthenia, they had a higher rate of improvement than those who received no steroid, 54% compared to 39% (p less than 0.005). Thymectomy was performed in one-fourth of patients with generalized myasthenia gravis, more frequently in young females and those with more severe weakness, and less often in older males and those with less severe weakness.(ABSTRACT TRUNCATED AT 400 WORDS)

Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management.

The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.

Adverse cardiovascular effects of anticholinesterase medications.

Anticholinesterase medications (anti-ChEs) play a significant role in the diagnosis and treatment of myasthenia gravis (MG). The primary effect on the heart produced by a surfeit of ACh is bradyarrhythmias with consequent fall in cardiac output and hypotension; yet, adverse cardiac reactions to these agents have been reported relatively infrequently. The authors describe 12 patients with MG from a pool of more than 1,000 who suffered hypotensive episodes related to use of anti-ChEs. The 12 patients (seven male, five female) had a mean age of 62.6 years; of these, eight adverse reactions occurred after edrophonium, two after neostigmine, and two after pyridostigmine. Seven patients had a recent increase in anti-ChEs and none had a decrease in dosage. Nine patients suffered either from severe sinus bradycardia, (20 beats/min), junctional bradycardia, or complete AV dissociation. Two patients had paradoxic sinus tachycardia and all had syncopal or near-syncopal episodes. Evidence for cholinergic stimulation of other organs was generally lacking. No recurrence appeared with reduction of the dose of anti-ChEs or discontinuation of the drug. The authors believe that these agents should be given with caution to patients with inflammatory, infiltrative, or degenerative disease of the conduction systems, patients being treated with digitalis, calcium-channel antagonists or beta blockers, patients with myocardial ischemia, and elderly patients. Appropriate resuscitative equipment should be readily available.

Effects of repeated doses of intravenous immunoglobulin in myasthenia gravis.

The authors administered repeated courses of intravenous immunoglobulin (IVIg) to nine patients at the onset of an exacerbation of generalized myasthenia gravis (MG). Anticholinesterase medication (nine patients) and corticosteroid dosage (six patients) had been kept constant for a 2-month period. Six patients received two courses, two patients received three courses, and one patient received five courses. Twenty of 23 courses resulted in satisfactory improvement beginning 4.3 +/- 1.2 days after start of IVIg and becoming maximal 8.2 +/- 2.0 days, with sustained improvement lasting 106.6 +/- 49.1 days. Vital capacity increased from an average of 1845.1 +/- 489 cc to 2894 +/- 762 cc (p less than 0.01) at peak effect. Four of nine patients had a decrease in strength before improvement. There was no significant change in acetylcholine receptor antibody titers before or after therapy. Side effects were minimal. Of the three patients who had nonsatisfactory course, two responded well to additional IVIg. IVIg can produce repeated beneficial effects in patients with MG and may be useful as an adjunct in the management of MG.

Myasthenia gravis occurring in twins.

Myasthenia gravis in one member each of two sets of twins is described. A 17 year old girl developed generalized myasthenia gravis at the age of 14 years, while her monozygotic twin sister has remained in good health during a three year period of observation. Another patient was a 19 year old woman with the onset of generalized myasthenia gravis at the age of 11 years, and her dizygotic twin sister has been in good health.Myasthenia gravis has been described in 13 sets of monozygotic twins, seven sets of dizygotic twins, and one set of twins with undetermined zygosity. Both members of twins were affected in five sets of monozygotic twins and one set of twins with undetermined zygosity, and only one twin was affected in the remaining sets of twins. Occurrence of myasthenia gravis in both members of monozygotic twins and in none of dizygotic twins, and frequent familial occurrence of the disease suggest the role of a genetic factor in the pathogenesis of this disease.