Treatment Of Autoimmune Neurological Disorders Research Articles

Autoimmune Movement Disorders in Children

Over the last decade, there have been significant advances in the identification, characterization, and treatment of autoimmune neurologic disorders in children. Many of these diseases include a typical movement disorder that can be a powerful aid to diagnosis. Frequently, movement disorders in autoimmune conditions are the sole or among a few presenting symptoms, allowing for earlier diagnosis of an underlying malignancy or systemic autoimmune disease. Given that early detection and treatment with immunotherapy may confer improved outcomes, recognizing these patterns of abnormal movements is essential for child neurologists. The purpose of this review is to summarize the clinical characteristics, diagnosis, and treatment of movement disorders that occur in pediatric autoimmune disorders.

Chapter 27 - Current and future immunotherapy targets in autoimmune neurology

Randomized controlled treatment trials of autoimmune neurologic disorders are generally lacking and data pertaining to treatment are mostly derived from expert opinion, large case series, and anecdotal reports. The treatment of autoimmune neurologic disorders comprises oncologic therapy (where appropriate) and immunotherapy. In this chapter, we first describe the standard acute and chronic immunotherapies and provide a practical overview of their use in the clinic (mechanisms of action, dosing, monitoring, and side effects). Novel approaches to treatment of autoimmune neurologic disorders, through new drug discovery or repurposing, are dependent on improved mechanistic understanding of immunopathology. Such approaches, with emphasis on monoclonal antibodies, are discussed using the paradigm of three autoimmune neurologic disorders whose immunopathogenesis is better understood, specifically myasthenia gravis, neuromyelitis optica, and chronic inflammatory demyelinating polyradiculoneuropathy. It is important to realize that the treatment strategy and management plan must be individualized for each patient. In general these are influenced by the following: clinical severity, antibody type, presence or absence of cancer, and prior treatment response, if known.

Therapieoptionen bei immunvermittelten Enzephalomyelitiden

Autoantibodies to neuronal tissue are becoming increasingly more important in the evaluation and classification of several neurological diseases, e.g. neuromyelitis optica, paraneoplastic syndromes of the central nervous system (CNS), stiff person syndrome or autoimmune epilepsy. As these disorders are rare, no evidence-based recommendations for therapy are available. Currently, immunomodulating or immunosuppressive drugs are administered in most cases. In paraneoplastic syndromes treatment of the underlying cancer is of considerable importance. This overview summarizes current experiences and recommendations in the treatment of autoimmune neurological disorders.

Editorial [Hot Topic:Autoimmune Neurologic Disorders (Guest Editor: Sasa zivkovic)

Autoimmune disorders affect 5-10% of the general population, [1] and often involve central and peripheral nervous system. In this special issue of Current Neuropharmacology experts discuss pathophysiology, clinical features and treatment of various neurologic autoimmune disorders. In the last decade we have witnessed remarkable scientific advances which have greatly improved our understanding of pathophysiology of the autoimmune disorders leading to an increasing number of treatment options with many of new therapies already being used in the treatment of neurologic disorders as their role continues to evolve [2]. The first article summarizes pathophysiology, diagnosis and treatment of neuromuscular autoimmune conditions including Guillain Barre syndrome, myasthenia gravis and polymyositis. This is followed by a comprehensive review of treatment of multiple sclerosis by Drs. Loma and Heyman describing standard treatment protocols as well as newly approved treatments. The next article by Drs. Awad and Stuve highlights clinical features and pathophysiology of idiopathic transverse myelitis and neuromyelitis optica which often result in significant disability. Dr. David Lacomis discusses clinical features and treatment of neurosarcoidosis which may affect central and/or peripheral nervous system, usually in combination with multisystemic disease. Dr. Maria Cid and her colleagues provide a detailed review of systemic and primary CNS vasculitides and their pathophysiology and treatment. Neuropsychiatric lupus is often called a “great mimicker” due to its wide spectrum of clinical manifestations, and Drs. Kao and Popescu review its pathophysiology and treatment. Over the last few years, autoimmune channelopathies have become one of the hot topics of basic and clinical research, and Dr. Kleopa reviews paraneoplastic and non-paraneoplastic autoimmune channelopathies. The issue concludes with a comprehensive review of toxicities of immunosuppressive treatment by Drs. Fadul and Lallana. Authors discuss potential risks of various therapies used in the treatment of autoimmune neurologic disorders. I would like to thank the authors of this Current Neuropharmacology issue for all their time and effort in preparing their articles to create a comprehensive and up-to-date collection of articles on the wide spectrum of autoimmune neurologic disorders.

Neurogenesis and Neuroprotection in the CNS — Fundamental Elements in the Effect of Glatiramer Acetate on Treatment of Autoimmune Neurological Disorders

Multiple sclerosis (MS) is no longer considered to be simply an autoimmune disease. In addition to inflammation and demyelination, axonal injury and neuronal loss underlie the accumulation of disability and the disease progression. Specific treatment strategies should thus aim to act within the central nervous system (CNS) by interfering with both neuroinflammation and neurodegeneration. Specific treatment strategies to autoimmune neurological disorders should aim to act within the CNS by interfering with both neuroinflammation and neurodegeneration. The cumulative effect of Glatiramer acetate (GA; Copaxone(R), Copolymer 1), an approved drug for the treatment of MS, reviewed herewith, draws a direct linkage between anti-inflammatory immunomodulation, neuroprotection, neurogenesis, and therapeutic activity in the CNS. GA treatment augmented the three processes characteristic of neurogenesis, namely, neuronal progenitor cell proliferation, migration, and differentiation. The newborn neurons manifested massive migration through exciting and dormant migratory pathways, into injury sites in brain regions, which do not normally undergo neurogenesis, and differentiated to mature neuronal phenotype, thus, counteracting the neurodegenerative course of disease. The plausible mechanism underlying this multifactorial effect is the induction of GA-reactive T cells in the periphery and their infiltration into the CNS, where they release immunomodulatory cytokines and neurotrophic factors in the injury site.

Antibody-mediated Remyelination: Relevance to Multiple Sclerosis

Intravenous immunoglobulin (IVIG) is widely used for treatment of autoimmune neurological disorders and is currently in clinical trials as a therapy for multiple sclerosis. We have previously demonstrated that certain mouse monoclonal antibodies of the IgM isotype, promote significant remyelination when administered to mice with chronic Theiler's murine encephalomyelitis virus-induced demyelinating disease. These IgM antibodies bind to antigens expressed on oligodendrocytes. We now demonstrate that polyclonal human IgG (IVIG) and polyclonal human IgM also promote remyelination in this system. Although both polyclonal human IgG and IgM promote remyelination, IgM is more potent. Polyclonal human IgM also differs from human IgG in its ability to bind strongly to antigens expressed in the CNS and by oligodendrocytes. We propose that polyclonal IgG and polyclonal IgM may function to promote remyelination by different mechanisms. IVIG may function based on its immunomodulatory activity, while the activity of IgM is critically dependent upon its reactivity with CNS antigens. This possibility has clear relevance to the use of antibodies as a therapy for multiple sclerosis, suggesting that combined treatment with antibodies exerting immunomodulatory activity, in concert with antibodies that function through direct binding to CNS antigens, may synergize to enhance the efficacy of the therapy.