Search

Introduction: Variations in muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIg to SCIg)., Methods: In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40-MWT)., Results: The coefficient of variance of cIKS during the IVIg and SCIg treatment periods was unchanged (mean ± SD: 6.97 ± 4.83% vs. 5.50 ± 3.13%, P = 0.21). The variations in the 9-HPT and 40-MWT were significantly lower in the SCIg group (P = 0.01 and P = 0.005, respectively)., Discussion: When therapy was changed from IVIg to SCIg, fluctuation of muscle strength was unchanged, but performance fluctuations were diminished. Muscle Nerve 57: 610-614, 2018., (© 2017 Wiley Periodicals, Inc.)

This review focuses on recent developments in the treatment of inflammatory neuropathies arising from immune dysregulation, rather than from infectious causes. The dysimmune inflammatory neuropathies are diseases of the peripheral nerves that have varying etiologies and may respond to immunomodulatory therapies. They are characterized by inflammatory changes in the nerve with associated destruction of myelin and axons. The underlying immune mechanisms are better understood in some of these conditions than others. Correct diagnosis and treatment is important to prevent clinical progression. Randomized controlled trials of some treatments in the more common inflammatory neuropathies have clarified their effectiveness; however, there are still groups of patients who are resistant to currently available treatments and for whom little effective treatment is available. Newer, targeted biologics and larger controlled trials of existing and novel therapies in these conditions offer promise of improved morbidity and mortality in this group of diseases.

The IgG molecule is the main component of IVIg. Commercial preparations of IVIg are derived from a pool of donors and subsequently, IVIg products contain smaller amounts of IgA and IgM antibodies as well as Th2 cytokines and cytokine antagonists that may also contribute to therapeutic effects. Numerous targets for IVIg include: T-cells, cytokines, immune cell trafficking, B-cells, complement and Fc-receptors. IVIg has been demonstrated to inactivate auto-reactive T-cells by competing for and interrupting their interaction with antigen presenting cells. The balance of cytokines also appears to be restored by IVIg, with studies showing that IVIg contains antibodies and antagonists to pro-inflammatory cytokines. In addition, IVIg is thought to interfere with and prevent the passage of auto-immune T-cells into the blood-nerve barrier. The effects of exogenous antibodies on B-cells have been well studied; IVIg is thought to down-regulate antibody production by B-cells, interfere with B-cell proliferation via a blockade of cell surface receptors and prevent the activation of certain subtypes of B-cell. In addition, IVIg can affect innate immunity by interrupting the steps in the complement activation cascade and blocking Fc-receptor mediated activity, which results in down-regulation of macrophage activity. In conclusion, IVIg has numerous modes of action, which culminate in the down-regulation of the immune response; many of which may be relevant to neuromuscular disorders and immune neuropathies.

A number of autoimmune disorders have been identified in which IVIg treatment may be beneficial. Evidence for the use of IVIg in inflammatory myopathies comes from controlled trials in dermatomyositis (DM) and sporadic-inclusion body myositis (s-IBM). In DM, muscle strength was increased and neuromuscular scores and skin rashes improved. Results for s-IBM have not been as encouraging as those observed for DM. Subsequently, IVIg should be recommended as a second-line therapy in DM and used for life-threatening dysphagia in s-IBM. Using an animal model of experimental autoimmune myasthenia gravis (MG), studies also indicate that IVIg can significantly improve clinical symptoms and affect pathogenic idiotypic antibodies. In human MG, studies indicate that IVIg exhibited equal efficacy compared to plasmapheresis. IVIg can therefore be recommended for use in an MG crisis or in lieu of plasmapheresis. The role of IVIg in the chronic management of MG has not been studied. IVIg has also been investigated in autoimmune CNS disorders. In a controlled study in patients with stiff person syndrome IVIg was effective, with improvements in the distribution of stiffness index and heightened sensitivity scores. For neurodegenerative diseases such as Alzheimer's disease, post-polio syndrome, pain, fibrosis, and autoimmune sleep disorders, some early promising results for the use of IVIg are emerging, but remain to be fully investigated. In conclusion, IVIg appears to be an effective treatment for a number of autoimmune disorders, however, optimal dosing and pharmacogenetic studies are necessary.

Intravenous Immunoglobulin (IVIg) are therapeutic preparations of normal human IgG that are obtained from pools of plasma from healthy blood donors. IVIg can be used at high dose as an immunomodulatory agent in a large number of autoimmune and/or systemic inflammatory diseases, particularly in hematologic or neurologic diseases. Mechanisms of action of IVIg are multiple and intricate. The development of new therapeutic trials in association with analyses of mechanisms of action should help to define new indications of IVIg therapy.

Autoimmune neurological disorders are very common. Health-related quality-of-life measures, obtained through a patient-oriented tool (a self-administered questionnaire), are now considered essential in the evaluation of therapies, especially for pathologies that may affect patients' general status. We reviewed the most common autoimmune neurological disorders and their treatment, and we report on our experience on intravenous immunoglobulin (IVIG) administration and the relationship between IVIG and health-related quality of life. Generally, IVIG administration is effective in the most common autoimmune neurological diseases. Concerning the relationship between IVIG treatment and health-related quality of life, our results reveal an improvement of physical aspects of patients' health-related quality of life after IVIG administration. Conversely, the comparison of mental scores between the evaluation at baseline and the evaluation at follow-up exhibited no difference. Although the use of IVIG is effective for autoimmune neurological disorders, there are no commonly accepted protocols for the use of IVIG treatment. Further controlled studies on IVIG, including quality-of-life assessments, are necessary to develop needed evidence on the use of IVIG in clinical practice.

Introduction and Aims: Chronic immune-mediated neuropathies are characterised by their being predominantly demyelinating, by being associated to specific antibodies and by their response to immunotherapy. We evaluated the clinical, electrophysiological and immunological responses following treatment with intravenous immunoglobulins (IVIg) in different clinical forms., Case Reports: We report on three patients with: 1. Multifocal motor neuropathy, 2. Multifocal sensory-motor neuropathy, and 3. Hypertrophic brachial plexopathy, who were evaluated before and 14 days after treatment with IVIg by means of clinical scales (MRC, Rankin), electrophysiological studies (ENG-EMG), and antibody (antiganglioside) determination. The three patients showed clinical improvement (> 20% MRC, > 1 Rankin) between the 4th and 7th day after the infusion, and this was maintained for 4-16 weeks. The ENG in cases 1 and 2 revealed conduction block (CB) in some nerves, lowered amplitude in others, and signs of demyelination. Following treatment, the CB disappeared in some nerves, while in others there was an improvement in the distal amplitude (distal block), but with no correlative improvement in the proximal amplitude, revealing new CBs that had previously gone undetected. The sum of post-treatment amplitudes improved in cases 1 and 2. In case 3, we were unable to demonstrate the existence of CBs, although we believe that they did exist proximally, and we found indirect signs of CB in EMG. The three cases had increased antiganglioside IgM antibodies levels, which did not undergo any significant variations., Conclusions: A 'consistent' clinical improvement was observed following treatment with IVIg. There was no correlation between the electrophysiological response (although apparent) and the degree of clinical response. CBs exist at different levels in the same nerve, which can be revealed after treatment. Following therapy, antiganglioside antibody levels remain high.

An 11-year-old boy presented with acute dysautonomia manifesting as severe orthostatic hypotension following fever. Serial orthostatic tests with measurement of the coefficient of variation in the R-R intervals showed improvement after one course and complete recovery after two courses of intravenous high-dose immunoglobulin therapy (IVIg). Repeated courses of IVIg should be considered to treat this disorder if spontaneous remission does not occur.

The use of intravenous immune globulin (IVIg) has increased significantly in the past decade, benefiting a wide variety of immune diseases. Seven different formulations of IVIg are now licensed in the United States. Although all contain pooled IgG, there are differences in their production and composition that affect their efficacy, tolerability, and side-effect profile. Important variables include concentration, volume, osmolality, sodium, and sugar content. This article reviews what is known about the composition and properties of the various IVIg formulations that might affect the therapeutic outcome.