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.     

大剂量丙种球蛋白、甲基强的松龙治疗重症肌无力

目的探讨依次采用大剂量丙种球蛋白静滴、大剂量的甲基强的松龙治疗重症肌无力的临床疗效。方法时符合Osserman分型的61例患者,随机分为两组：治疗组（A组）31例,依次采用大剂量丙种球蛋白厦大剂量的甲基强的松龙治疗;对照组（B组）30例,采用传统大剂量地塞米松静滴治疗;观察两组的临床疗效。结果治疗组症状缓解快,激素治疗过程中发生呼吸肌瘫痪、使用呼吸机现象少,住院时间短,疗效好（均P〈0．05）。结论依次采用大剂量丙种球蛋白、大剂量的甲基强的松龙冲击治疗重症肌无力的临床疗效好,值得临床推广。     

High-dose intravenous immunoglobulin in myasthenia gravis

The effects of high-dose intravenous immunoglobulin (i.v.Ig) in 12 MG patients were studied. All patients had severe symptoms. In two cases anti-acetylcholine receptor antibodies (anti-AChR abs) were not detectable. I.V.Ig was administered to 9 patients already on long-term immunosuppressive therapy and to 3 patients at the beginning of azathioprine treatment. 10 patients (83%) improved; the duration of improvement was longer in immunosuppressed patients. Anti-AChR abs generally decreased after infusion but we did not find a constant correlation between reduction in ab titers and clinical improvement. Side effects included one case of severe hemolysis. In our experience i.v.Ig therapy is effective in MG. The chief indication for its use appears to be the treatment of deteriotation of the disease in patients already on immunosuppressive therapy. Paper presented at the National Congress at Sorrento in 1991 and selected by the Editorial Board of the Journal     

Successful response of non-recovering Ramsay Hunt syndrome to intravenous high dose methylprednisolone

Ramsay Hunt syndrome (RHS) is a frequent cause of facial palsy. It is a consequence of the infection of geniculate ganglion by herpes zoster or herpes simplex virus. In the lack of randomized controlled trials, RHS is empirically treated by a combination therapy of antiviral agents and steroids given orally. However, RHS has, per se, a poorer prognosis than idiopathic facial palsy (Bell's palsy). We describe a case series of two patients with RHS unsuccessfully treated with antiviral drugs and oral corticosteroids, showing an almost complete recovery after late administration of intravenous (i.v.) high dose methylprednisolone. Both patients had all recognized negative prognostic factors including age of onset, a high grade facial weakness, absence of R1 and R2 response at blink reflex test, and in the first case, the involvement of greater superficial petrosal nerve. We propose that i.v. high dose methylprednisolone should be considered, even as a late treatment option, in patients with RHS non recovering after standard antiviral and oral steroid therapy as well as presenting clinical features suggestive of a poor prognosis.     

Neurogenic muscle atrophy in myasthenia gravis

Two cases of severe myasthenia gravis are described, with histological findings. Both cases showed severe neurogenic atrophy of the muscles of the tongue, with fatty pseudohypertrophy and a remarkable proliferation of terminal nerve fibres. Similar, but less severe, changes were present in other bulbar muscles. The findings are in keeping with the view that functional interruption at the neuromuscular junctions results first in failure to transmit the contractile impulse, and at a later stage in denervation atrophy. Terminal proliferation of axons is regarded as an attempt, on the part of motor fibres, to compensate for the breakdown of normal neuromuscular interaction.     

大剂量甲基强的松龙治疗重症肌无力疗效及各肌群肌力变化研究

目的探讨甲基强的松龙冲击治疗重症肌无力的临床疗效及治疗中各肌群肌力变化。方法60例重症肌无力患者采用甲基强的松龙冲击治疗，从1000mg／d开始，每3d减半量，减至60mg时改为强的松片口服，21d停用，观察其临床疗效及治疗中各肌群肌力的变化。结果甲基强的松龙治疗重症肌无力临床总有效率98．3％，在冲击早期部分患者肌无力加重，发生率68．3％，以四肢多见，加重多发生在原有肌无力基础上；随着治疗的继续，肌无力渐好转。结论甲基强的松龙治疗重症肌无力疗效肯定，部分肌群肌力可加重，但继续治疗，肌无力渐好转。     

High-dose intravenous immunoglobulin therapy in juvenile myasthenia gravis

Autoimmune neurologic disease management has been significantly modified by the use of high-dose intravenous immunoglobulin (HDIVIG) during the past 15 years. Venous access, readily available IgG (until recently), and the relative lack of serious identifiable complications have prompted its use in myasthenia gravis. In adults, its effectiveness has been inconsistent, with variable acetylcholine receptor (AChR) antibody responses. Ten children were evaluated for clinical responses to, and complications of, HDIVIG. Weekly anti-AChR antibody titers in three patients were obtained. The HDIVIG dosage was 2 gm/kg body weight, infused at variable rates of 2 gm/kg for 1 day, 0.66 gm/kg daily for 3 days, and 0.5 g/kg daily for 4 days; in one patient the total dose was 0.8 gm/kg to correct to the ideal body weight. All children but one tolerated HDIVIG without complications. Eight patients exhibited definite improvement in functional strength after HDIVIG, but a decreasing response to HDIVIG was evident after multiple monthly treatments, warranting the additional use of corticosteroids in two patients. A decrease in anti-AChR antibody levels was observed in the three patients tested, but this decrease was constant in one patient. No correlation was observed between clinical response and antibody titers. HDIVIG is safe and effective in most patients for short-term management of juvenile myasthenia gravis, in myasthenic crises, and in preparing patients for surgery but appears to be of limited long-term benefit.     

Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide

We have treated animals with an ongoing autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), using a strategy designed to eliminate the antibody-producing cells. During well-established EAMG, a single high doese of cyclophosphamide was given because of its known effectiveness against B-lymphocytes. To counteract the lethal effects of the drug, the rats were “rescued” by bone marrow cell transplantation. This treatment produced a rapid and sustained fall of antibody titers against both the immunizing antigen (Torpedo acetylcholine receptor) and the autoantigen (rat acetylcholine receptor). Immunologic memory, as measured by an anamnestic response to the antigen, was partially suppressed. Cyclophosphamide treatment produced improvement in the neuromuscular defect: treated animals had, on the average, twice as many acetylcholine receptors at neuromuscular junctions compared with untreated EAMG animals. This treatment method of short-term high doses of an immunosuppressive drug, such as cyclophosphamide, may eventually prove useful for human myasthenia gravis and other autoimmune diseases.     

High-dose intravenous immunoglobulin therapy for myasthenia gravis

The objective of this open, retrospective study was to investigate whether intravenous immunoglobulin (IVIg) could induce a clinically obvious improvement in patients with generalized myasthenia gravis (MG), as judged by MG functional status. Fourteen patients with generalized MG were treated during at least one episode with 0.4 g IVIg per kilogram body weight per day for 5 consecutive days. Patients with confounding variables were excluded; this left 11 patients (16 episodes) to be further analysed. We defined improvement as at least a one-step improvement in MG functional status (according to the University of Virginia’s Modification of Osserman’s classification). Of the treatment episodes, 56% were classified as positive responses. If improvement occurred, onset of improvement started after 3 (1–12) days and peak effect was reached after 7 (4– 30) days (median and range). All four patients who required artificial ventilation could be weaned from it 8.5 (6–11) days after the start of IVIg (median and range). Of the patients treated on two occasions, only one patient had a positive response during both. In MG functional status 5, improvement was observed during five of seven episodes. None of the patients with MG functional status 3 responded. Patients with an acute relapse of MG seemed to respond equally well to IVIg compared with patients with subacute deterioration/ chronic-static state (50% versus 60%). The MG functional status at the start of IVIg and on the day of maximal improvement was compared for all episodes together, and significant improvement was noted (P = 0.0052). We did not see any serious side-effects after IVIg treatment. This retrospective analysis suggests that high-dose IVIg is an effective therapy in some patients with deterioration of generalized MG. If improvement occurs, it starts within a few days of the onset of IVIg and the effect seems to peak within 2 weeks. Received: 4 March 1997 Received in revised form: 28 August 1997 Accepted: 1 September 1997     

High-dose intravenous immunoglobulin G treatment of myasthenia gravis

Neurological Sciences - IVIg is a safe and effective adjunctive treatment for myasthenia gravis, but there are no well established guidelines for the use of IVIg in this disease, lacking controlled...     

High-dose intravenous immunoglobulin G treatment of myasthenia gravis

IVIg is a safe and effective adjunctive treatment for myasthenia gravis, but there are no well established guidelines for the use of IVIg in this disease, lacking controlled randomized trials to assess its efficacy in homogeneous group of patients. The main advantages of IVIg are the rapid onset of the effect, the lack of long-term toxicity, and the possibility to reduce the required doses of immunosuppressive drugs. IVIg appears to have a role as an acute treatment in rapidly progressive myasthenia gravis weakness, particularly in situations when therapeutic apheresis is not feasible. In addition, IVIg is safer than plasma exchange (PE) in patients with hypotension or autonomic instability, in children, in patients of older age (>65 years), and in those suffering from sepsis. For these reasons, at present, IVIg are recommended during crises of myasthenia gravis in older patients when PE is contraindicated or not feasible IVIg can be also used as a chronic maintenance therapy when other immunosuppressive treatments have failed or cannot be used. Periodic administration of IVIg on a bimonthly or monthly basis may be able to stabilize chronic, nonresponding patients.     

Treatment of myasthenia gravis with high-dose intravenous immunoglobulin

We treated 37 patients affected by autoimmune generalized myasthenia gravis (MG) with high-dose intravenous gammaglobulin (HDIVIg), 400 mg/kg per day on 5 consecutive days. A one-degree improvement of Oosterhuis global clinical classification of myasthenic severity (OGCCMS), the disappearance of bulbar involvement or both were recorded 12 days after the beginning of the treatment in 70.3% of the patients and persisted up to 60 days in 58.7%. A two-degree improvement of OGCCMS was recorded in 54.1% of the patients and it was maintained up to 60 days in 37.8%. The percentage of improvement did not significantly differ between patients entering the treatment in a long-standing, drug-refractory stationary phase of the illness (n = 26) and patients who received HDIVIg in an acute phase of MG (n = 11). None of the patients experienced side effects. Our data indicates that HDIVIg is an interesting, virtually riskless therapeutic choice for MG patients, and allows the planning of a controlled trial versus plasma-exchange.