Intravenous immunoglobulin: pharmacological properties and use in polyneuropathies

Introduction: Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases with both licensed and off-label indications. The mechanism of action is complex and not fully understood, involving the neutralization of pathological antibodies, Fc receptor blockade, complement inhibition, immunoregulation of dendritic cells, B cells and T cells and the modulation of apoptosis. Areas covered: First, this review describes the pharmacological properties of IVIg, including the composition, mechanism of action, and adverse events. The second part gives an overview of some of the immune-mediated polyneuropathies, with special focus on the pathomechanism and clinical trials assessing the efficacy of IVIg. A literature search on PubMed was performed using the terms IVIg, IVIg preparations, side effects, mechanism of action, clinical trials, GBS, CIDP. Expert opinion: Challenges associated with IVIg therapy and the treatment possibilities for immune-mediated polyneuropathies are discussed. The availability of IVIg is limited, the expenses are high, and, in several diseases, a chronic therapy is necessary to maintain the immunomodulatory effect. The better understanding of the mechanism of action of IVIg could open the possibility of the development of disease-specific, targeted immune therapies. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Established therapies and novel targets in the treatment of Parkinson’s disease

Parkinson’s disease affects more than 1% of individuals older than 60 years of age. The gold standard of its symptomatic treatment is levodopa therapy, which in time leads to motor fluctuations and dyskinesia due to noncontinuous receptor stimulation. Dopamine agonists and monoamine oxidase-B inhibitors are recommended as initial therapy, but they are less effective in the advanced stages of the disease. Treatment should be individualized for the patient, dependent on the stage, with attention to nonmotor symptoms. No effective neuroprotective therapy for Parkinson’s disease is yet available, and there is currently substantial interest in the development of new nondopaminergic agents. Analogs of kynurenic acid and inhibitors of the enzymes involved in the synthesis of quinolinic acid may exert a neuroprotective effect

Zárványtestes myositis - Egy ritkán felismert betegség [Inclusion body myositis - A rarely recognized disorder]

Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-beta failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well

Left ventricular deformation abnormalities in a patient with calpainopathy-a case from the three-dimensional speckle-tracking echocardiographic magyar-path study

Calpainopathy or limb-girdle muscular dystrophy type 2A (LGMD2A) is the most common type of autosomal recessive limb-girdle muscular dystrophies. The disease is caused by mutations in the CAPN3 gene encoding calpain, a protein involved in muscle membrane remodeling and repair. This paper gives an overview of the genetic background, clinical course, and diagnosis of the disease, and presents the first case of calpainopathy in which cardiac deformation mechanics was investigated. Three-dimensional speckle-tracking echocardiography (3DSTE) demonstrated reduced left ventricular (LV) strains and increased LV apical rotation and twist, suggestive of asymptomatic subclinical LV dysfunction. Cardiac involvement has not been previously reported in calpainopathy. © Quantitative Imaging in Medicine and Surgery. All rights reserved