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.     

Thromboembolic complications following intravenous immunoglobulin therapy in immune-mediated neurological disorders

BackgroundMinor adverse events of intravenous immunoglobulin (IVIg) include flu-like symptoms, eczematous skin reaction, electrolyte disturbance, and transient leukopenia. On rare occasions, serious complications such as aseptic meningitis, arrhythmia, decrease in blood pressure, and thromboembolic complications (TEC) have been described. The current study aimed to understand the frequency and clinical features of TEC related to IVIg administration in patients with immune-mediated neurological disorders.MethodsWe conducted a retrospective chart review of hospitalized patients with immune-mediated neuromuscular or neuroimmunological disorders treated with IVIg from January 2018 to March 2020 in a single tertiary hospital.ResultsDuring the study period, 61 patients were treated with a total of 364 IVIg infusions over 84 treatment courses. Among them, we identified 3 TEC cases that occurred during or after the completion of IVIg therapy: two patients with myasthenia gravis (F/60 and F/80) and one patient with Guillain-Barré syndrome (F/79) had undergone arterial TEC (two for ischemic stroke and one for pulmonary thromboembolism). The rates of TEC per patient, per treatment course, and per infusion were 4.91% (3/61), 3.57% (3/84), and 0.82% (3/364), respectively.ConclusionThe risk of developing TEC upon receiving IVIg infusions is generally low in patients with immune-mediated neurological disorders; however, IVIg-related TEC should be cautiously monitored for in critically ill elderly patients with vascular risk factors, especially those suffering from myasthenic crisis.     

The role of intravenous immunoglobulin therapy in autoimmune and inflammatory disorders

Neurological Sciences - The first use of immunoglobulin therapy, historically, was in 1890 when Emil von Behring developed effective antiserium against diphtheria toxin, but only in the early 1970s...     

Renal and hematologic side effects of long‐term intravenous immunoglobulin therapy in patients with neurologic disorders

Introduction: For patients receiving intravenous immunoglobulin (IVIg), renal and hemolytic side effects are well recognized. However, there are very few data on the effects of chronic IVIg therapy. Methods: We retrospectively analyzed laboratory data on 166 patients who received IVIg for 12 months with a dose range of 0.441–2.58 g/kg/month, measuring changes in hematocrit and glomerular filtration (GFR) rates at 6 and 12 months. Results: Of the 2,232 infusions, there were no incidents of clinical hemolysis. However, after 12 months of treatment, 21% of patients had a ≥3‐g/dl decline in hematocrit and 10% had a ≥20% decline in GFR. Discussion: No clinically significant hemolysis was observed in patients receiving chronic IVIg therapy. However, a significant number of patients had a decline in hematocrit and/or GFR while on therapy. This emphasizes the need for observation of hematologic and renal function in patients treated with chronic IVIg. Muscle Nerve 56 : 1173–1176, 2017     

On the mechanism of high-dose intravenous immunoglobulin treatment of patients with chronic inflammatory demyelinating polyneuropathy

A proportion of patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) improves after polyvalent intravenous immunoglobulin (IVIg) treatment. When anti-neuroblastoma cell line (NBL) antibodies are present, they decrease or disappear after IVIg treatment. Purified IgM anti-NBL antibodies from a CIDP patient were inhibited by F(ab')2 of IVIg and by F(ab')2 of a patient recovered from Guillain-Barré syndrome (GBS). Inhibition of anti-NBL antibodies was also found among sera from normal individuals. This suggests that the self-limiting character of GBS and the therapeutic effect of IVIg in CIDP are dependent on suppression of auto-antibodies. This suppression may be mediated by anti-idiotypes present in recovered GBS patients and in the normal donor population contributing to IVIg.     

Home monitoring of maintenance intravenous immunoglobulin therapy in patients with chronic inflammatory neuropathy

To evaluate the utility of different outcome measures to monitor dose adjustment of intravenous immunoglobulin (IVIg) therapy in patients with chronic inflammatory neuropathy (CIN). We assessed the adjustment of IVIg maintenance therapy in 20 patients (10 CIDP and 10 MMN) by regularly monitoring grip strength (GS) using a Martin Vigorimeter, RODS, and quality of life using the SF‐36 questionnaire. These measures were regularly performed by the patient at home. We also assessed the extended MRC sumscore (eMRC sumscore) at each outpatient visit for IVIg infusion. We also enrolled 30 healthy controls to measure any possible training effect of GS with time and to analyze random fluctuation of GS. Clinically relevant change was detected by eMRC sumscore in 14 (93%) patients, by RODS in 11 (73%) patients, and by GS in 8 (53%) patients. Early sensitivity was greatest for RODS (73%), followed by GS (53%), and eMRC sumscore (27%). This differed from CIDP, with an early change in RODS in 100% of patients, and MMN with an early change in GS in 75%. None of the outcome measures alone was sufficient to detect clinically significant changes in all patients. Home monitoring of outcome measures objectively assisted clinical decision during individualization of IVIg treatment. We recommend a multimodal approach using different outcome measures to monitor the individual patient with CIN.     

Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin

We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients.     

The use of intravenous immunoglobulin as maintenance therapy in myasthenia gravis

The standard therapy for myasthenia gravis (MG) includes steroids and immunosuppressants, which have delayed onset of action and significant side effects. Plasmapheresis and intravenous immunoglobulin have been used mostly for the treatment of severe exacerbations. In the present study we examined the use of intravenous immunoglobulin as maintenance treatment in MG. We included 11 patients with generalized myasthenia gravis. All had severe bulbar and respiratory involvement that required mechanical ventilation in three patients. Intravenous immunoglobulin treatment was initiated at a dose of 400 mg/kg/d for 5 days and followed by maintenance with 400 mg/kg once monthly. Regular medications were continued as necessary. There was significant improvement in all patients, and none required mechanical ventilation over the treatment period of 20.3 months +/- 8.3 (mean +/- SD, total patient years of treatment = 18.7). Steroid and pyridostigmine doses were reduced significantly and steroids were discontinued in two patients. There were no serious side effects related to intravenous immunoglobulin. These results suggest that intravenous immunoglobulin maintenance therapy is a valid modality in patients with MG.     

Plasma C3c changes in myasthenia gravis patients receiving high-dose intravenous immunoglobulin during crisis

Fast-migrating C3c, a sensitive index of complement activation, was assayed in the plasma of 2 myasthenia gravis (MG) patients in crisis who received high-dose IV immunoglobulin therapy. Dramatic responses were observed in both patients. Clinical improvement paralleled a decrement in C3c levels, suggesting that regulation of complement activation may be one possible mechanism of IV immunoglobulin treatment in MG.     

Role of regulatory b cells in neuroimmunologic disorders

B lymphocytes augment the immune response by producing antibodies and activating T cells by antigen presentation. Recent studies have highlighted a specific and functionally significant B‐cell subset that could downregulate excessive immune and inflammatory responses through a vast array of inhibitory cytokines, such as interleukin (IL)‐10 and transforming growth factor‐β (TGF‐β). This subset of B cells is generally referred to as regulatory B cells (Bregs). In addition, recent studies have shown that IL‐35‐producing Bregs also play a role in downregulation of immunity. Diverse phenotypes of Bregs have been proposed to underlie human disorders and their animal models. Most studies have focused on the role of different subsets of Bregs and Bregs‐associated molecules such as IL‐10, TGF‐β, and IL‐35 in the pathogenesis of neuroimmunologic disorders. Furthermore, Bregs exert regulatory function mainly through suppressing the differentiation of Th1/Th17 cells and promoting regulatory T‐cell expansion. Reduced presence of Bregs is reportedly associated with progression of several neuroimmunologic disorders. This Review summarizes the current knowledge on the role of Bregs in neuroimmunologic disorders, including multiple sclerosis, neuromyelitis optica, and myasthenia gravis. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.     

Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis

Randomized Controlled Trials have not jet established the best pharmacological management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are usually employed with good results, but in a few cases the clinical outcome is poor. In other patients, particularly those affected by the site restricted ADEM variants (myelitis), the disease shows a recurrent course resembling that of Multiple Sclerosis. We present here five patients, 3 of them affected by classic disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed a good response to intravenous immunoglobulin (IVIg) after steroid treatment failure. In our report high dose steroids administration was substantially uneffective in all but one case, who showed a good response only during the first episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked functional improvement in all patients starting within the first five days of drug administration and reaching a maximum within three weeks. One patient experienced a good effect nothwithstanding a steady dysability. In all cases, clinical evidence was supported by MRI controls showing improving posttreatment changes. Received: 11 April 2001, Received in revised form: 10 July 2001, Accepted: 16 July 2001     

High-dose intravenous immunoglobulin therapy in dysimmune neuropathies

Neurological Sciences -