International review of neurobiology最新文献

Therapies for myasthenia gravis (MG) include symptomatic and immunosuppressive/ immunomodulatory treatment. The application of one or more treatments should be based on known efficacy, particularly for specific disease subtypes, disease activity, adverse effect profile, and patient co-morbidities. Traditional treatments include symptomatic treatment and disease- modifying therapy, such as steroids, immunosuppressants, plasmapheresis, intravenous immunoglobulin and thymectomy. Most patients are started with pyridostigmine and steroids but depending on severity or specific type of MG the immunosuppressant or other therapy are added. There is some variability in current recommendations in different MG management guidelines (e.g. Japanese compared to North American), mainly in the selection of glucocorticoids and the first-line non-steroidal immunosuppressants. In this chapter we carry out a review and comparison of all these treatments and compare the different international and national guidelines and consensus, and regional approaches. Approvals of novel therapeutics in MG should not deter clinicians from looking at older interventions, as these still play a key role in the treatment of MG.

Animal models offer a platform to advance our understanding of myasthenia gravis (MG), an autoimmune disorder characterized by impaired neuromuscular transmission. Experimental autoimmune MG models (EAMG) actively induce autoimmunity through antigen immunization, aiding in understanding the immune response to self. Passive transfer models (PTMG) involve the injection of pathogenic antibodies into animals, providing insights into antibody-mediated mechanisms and complement-driven damage to the neuromuscular junction (NMJ). The pathogenic effect of autoantibodies targeting acetylcholine receptors (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4) results in changes to the NMJ that are mechanistically distinct. These models validate therapeutic interventions preclinically, with methodologies ranging from antibody transfer to genetic modifications. Despite the translational challenges, these models bridge preclinical research and clinical applications, enabling the development of targeted treatments for MG.

Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies attack proteins at the neuromuscular junction, resulting in impaired neuromuscular transmission. Like other autoimmune diseases, MG arises when the immune system fails to distinguish self from non-self, attacking and damaging normal tissues. The pathological response involves not only B cells, responsible for autoantibody production, but also T cells, which provide essential support for B cell pathogenicity. While the precise triggers of this abnormal immune response remain undefined, MG is recognized as a multifactorial disease influenced by immune dysregulation along with genetic and environmental factors. This chapter explores the complex immunopathology of MG, highlighting how these factors collectively contribute to disease development. We examine the physiological development of T and B cell compartments, the tolerance checkpoints designed to prevent autoimmunity, and the consequences of their failure. Finally, we discuss the dysregulation of these cellular compartments in MG, emphasizing their roles in disease progression, the persistence of autoimmunity, and responses to treatment.

The neuromuscular junction (NMJ) connects a motor neuron to a skeletal muscle cell. Cholinergic synaptic transmission enables muscle contraction, which is crucial for survival. Although synaptic communication at the NMJ is robust, with an inherent safety margin, it becomes hampered in the neuro-immunological disorder myasthenia gravis (MG). The synaptic dysfunction underlies the (fatigable) muscle weakness, which hallmarks this disease. In this chapter, we will review normal NMJ physiology and the pathophysiological consequences of autoimmune attacks in MG, focusing on recent insights and developments.

Understanding the neural and cognitive mechanisms underlying hypnosis has been a central focus of investigation over recent decades. Dominant approaches have often aimed to identify a single, distinct neural signature capable of accounting for the emergence of hypnotic phenomena. However, despite robust behavioural evidence supporting the concept of hypnotic responding, findings from neuroimaging and electrophysiological studies have been highly heterogeneous, limiting the establishment of a consistent neurophysiological framework. This chapter provides an up-to-date overview of the neural dynamics associated with hypnotic responses and explores the primary sources of variability in brain-based markers of hypnosis. We propose a componential approach, suggesting that the hypnotic process comprises multiple distinct yet interacting mechanisms. Specifically, we describe how different aspects of hypnotic phenomena correspond to specific neural patterns: large-scale network connectivity changes induced by hypnotic induction, localized modulations driven by suggestion, and individual susceptibility amplifying these neural responses. We further argue that additional variability may stem from individual differences beyond susceptibility, contributing to the lack of convergence across studies. The chapter concludes by advocating for a multi-componential framework as a promising direction for future research that better captures the complexity of the cognitive and neural architecture underlying hypnotic responding.

In this chapter, we propose to discuss the role of hypnosis and the combination of virtual reality and hypnosis (VRH) in emotional regulation as substantiated by clinical and neuroimaging evidence. The hypnotic process is characterised by focused attention, dissociation, and increased responsiveness to suggestions. This technique, related to the modulation of a large-scale neuronal network involved in emotional processing, could be drawn upon for treating psychological disorders in different clinical contexts, such as acute and chronic pain, oncology, anxiety disorders, phobias, and posttraumatic disorders. Neuroimaging studies focused on hypnosis have highlighted the specific modulation of the default mode, executive control, and salience networks, which play key roles in emotional processing and adaptive coping strategies. The chapter summarizes how hypnosis reshapes emotional experience and cognitive patterns by integrating clinical perspectives with neuroimaging data. It also discusses future directions, emphasising how VRH could change therapeutic practices, improving accessibility and outcomes for diverse populations.

To deal with the only constant in life, change, we use a set of top-down processes called cognitive control. Cognitive control enables us to develop new stimulus-response associations appropriate for the task at hand instead of being rigidly bound to our existing repertoire of responses. Given the central role cognitive control has in our lives, it is not a surprise that different methods have been tested for improving it; however, few have shown generalizable, long-term effects. One approach, which has shown great promise in enhancing performance in different tasks requiring cognitive control (e.g., Stroop, Simon, Flanker, Go-NoGo, and tone-monitoring tasks), is using task-relevant direct-verbal suggestions, including posthypnotic and nonhypnotic suggestions. The observed effects of suggestions are both reliable, as they have been replicated by different labs over three decades, and generalizable, as they have proven effective in enhancing different aspects of cognitive control, such as inhibition and working memory updating. In the current review, we discuss recent developments in the understanding of cognitive control and its hierarchies and elucidate the effects of suggestions on cognitive control and their underlying mechanisms. Finally, we argue that besides the applicability of task-relevant suggestions in training regimens for enhancing cognitive control, their effects have theoretical implications for conceptual questions regarding both motivated hierarchical cognitive control and hypnotic phenomena.

The diagnosis of myasthenia gravis (MG) is strongly considered in a patient complaining of fatigable weakness and in whom muscle fatigability is demonstrated during bedside examination. This chapter will be dedicated to the history-taking and clinical examination of patients with MG and we will also touch upon other myasthenic syndromes and mimics. Most patients first experience fatigable ocular symptoms. The symptoms may remain isolated to the eyes (ocular MG) or later involve the limb, bulbar or respiratory muscles (generalized MG). The examination of the myasthenic patient serves to demonstrate fatigability and distinguish this from non-specific central fatigue or lack of energy. This chapter presents a focused discussion by a neuro-ophthalmologist and neurologists, largely based on their clinical experience.

Autoimmune Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness and autoantibodies. It can be divided by the presence of serum autoantibodies into two major categories where Immunoglobulin G (IgG) against either the acetylcholine receptor (AChR), or muscle specific kinase (MuSK) causes fatigable muscle weakness. The clinical relevance of Low-density lipoprotein-receptor related protein-4 IgG (LRP4) is debated. These antibodies disrupt neuromuscular transmission via different mechanisms: AChR antibodies, mostly of IgG1 and IgG3 subclass, can activate complement leading to a simplification of the NMJ architecture, block acetylcholine binding to its receptor to prevent channel opening, and internalize AChR. By contrast, MuSK antibodies, mostly of the IgG4 subclass, impair MuSK-LRP4 interactions, and LRP4 antibodies may interfere with agrin-induced clustering. Once these antibody targets were identified the development of antibody assays began. Patrick and Lindstrom made the landmark discovery that antibodies against soluble AChR caused acute flaccid paralysis in immunized rabbits which kickstarted test development. The first, and until recently, most useful test was the radioimmunoassay (RIA) where AChR radiolabeled with toxin from venomous snakes allowed quantitative measurement of AChR-IgG. Most recently the clustered AChR cell-based assays (CBA) provide a significant improvement in test sensitivity over all other methods. MuSK assays followed a similar but shorter path. The accurate detection of AChR and MuSK antibodies has a crucial role in supporting the clinical diagnosis and management of MG which includes a diverse population of patients with a wide range of clinical manifestations, disease severity and response to standard and new therapies. In this chapter we highlight how distinct target-specific IgG autoantibodies cause neuromuscular transmission defects, and subsequently shape disease manifestations in the different MG antibody subgroups. We review the evolution of diagnostic assays, from early RIA to modern CBA, and addresses interpretative pitfalls, particularly in borderline or "seronegative" cases. Finally, the authors address the significance of accurate autoantibody detection in the diagnosis and management of patients with one of the antibody MG subtypes, as well as in patients with other autoimmune conditions and thymic malignancies.

Understanding the pathophysiology of Myasthenia Gravis (MG) and developing effective treatments requires using cell models that replicate key features of the disease, particularly those involved in the autoimmune response and neuromuscular dysfunction. This chapter reviews the various cell-based models used in MG research and those with potential for preclinical MG studies, including muscle cells and co-culture models to form neuromuscular junctions (NMJ). We discuss the strengths and limitations of these models, further outline methods for characterizing these, and provide an outlook on the future refinement and abilities of cell models for advancing MG research.