Anti-GABAB receptor encephalitis: clinical and laboratory characteristics, imaging, treatments and prognosis.

Introduction: Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis.

Methods: Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years.

Anti-GAD65 autoantibody levels measured by ELISA and alternative types of immunoassays in relation to neuropsychiatric diseases versus diabetes mellitus type 1.

Background: Anti-GAD65 autoantibodies (GAD65-Abs) may occur in patients with epilepsy and other neurological disorders, but the clinical significance is not clear-cut. Whereas high levels of GAD65-Abs are considered pathogenic in neuropsychiatric disorders, low or moderate levels are only considered as mere bystanders in, e.g.

Novel treatment strategies for acetylcholine receptor antibody-positive myasthenia gravis and related disorders.

The presence of autoantibodies directed against the muscle nicotinic acetylcholine receptor (AChR) is the most common cause of myasthenia gravis (MG). These antibodies damage the postsynaptic membrane of the neuromuscular junction and cause muscle weakness by depleting AChRs and thus impairing synaptic transmission. As one of the best-characterized antibody-mediated autoimmune diseases, AChR-MG has often served as a reference model for other autoimmune disorders.

The search for an autoimmune origin of psychotic disorders: Prevalence of autoantibodies against hippocampus antigens, glutamic acid decarboxylase and nuclear antigens.

The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused by an autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novel hippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls were first tested for reactivity on neuropil of rat brain sections.

Novel neuronal surface autoantibodies in plasma of patients with depression and anxiety.

Neuronal surface autoantibodies (NSAbs) against various antigens cause autoimmune encephalitis. Some of these antigens are also involved in the pathology of depression and anxiety. To study whether NSAbs are more common in plasma of individuals with depression and anxiety than in controls, and to investigate if NSAbs correlate with disease status, plasma samples of 819 individuals with a current diagnosis of depression and/or anxiety, 920 in remission and 492 individuals without these disorders were included in this study.

Unidentified Neuronal Surface IgG Autoantibodies in a Case of Hashimoto's Encephalopathy.

Hashimoto's encephalopathy is an encephalitis of presumed autoimmune origin characterized by the presence of autoantibodies against thyroid proteins. We present a case of a young patient with pre-existing Hashimoto's thyroiditis and progressive cognitive complaints, absence-like episodes, and sporadic bilateral epileptiform frontal and frontotemporal activity. No abnormalities were observed during the neurological examination and on MRI.

Absence of Autoantibodies Against Neuronal Surface Antigens in Sera of Patients With Psychotic Disorders.

This study examines the prevalence of autoantibodies against neuronal surface antigens in the sera of individuals with psychotic disorders compared with control participants.

Autoimmunity in psychotic disorders. Where we stand, challenges and opportunities.

Psychotic disorders are debilitating mental illnesses associated with abnormalities in various neurotransmitter systems. The development of disease-modifing therapies has been hampered by the mostly unknown etiologies and pathophysiologies. Autoantibodies against several neuronal antigens are responsible for autoimmune encephalitis.

Characterization of the thymus in Lrp4 myasthenia gravis: Four cases.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen.

Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient.

We report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the γ-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines.

Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.

Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target.

IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients.

Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown.

Real-time visual feedback of COM and COP motion properties differentially modifies postural control structures.

The experiment was setup to investigate the control of human quiet standing through the manipulation of augmented visual information feedback of selective properties of the motion of two primary variables in postural control: center of pressure (COP) and center of mass (COM). Five properties of feedback information were contrasted to a no feedback dual-task (watching a movie) control condition to determine the impact of visual real-time feedback on the coordination of the joint motions in postural control in both static and dynamic one-leg standing postures. The feedback information included 2D COP or COM position and macro variables derived from the COP and COM motions, namely virtual time-to-contact (VTC) and the COP-COM coupling.

Some Behaviorial Science Measurement Concerns and Proposals.

Primarily from a measurement standpoint, we question some basic beliefs and procedures characterizing the scientific study of human behavior. The relations between observed and unobserved variables are key to an empirical approach to building explanatory theories and we are especially concerned about how the former are used as proxies for the latter. We believe that behavioral science can profitably reconsider the prevailing version of this arrangement because of its vulnerability to limiting idiosyncratic aspects of observed/unobserved variable relations.

A Rejoinder.

Three commentaries on the Nesselroade and Molenaar target article in this issue are responded to in the interest of elaborating and defending the points of view expressed in our article. The commentaries feature philosophy of science, general structural modeling, and broad behavioral research perspectives. Responding to the commentaries afforded us the opportunity to clarify further matters that we deem critical to the fundamental matter of measurement in behavioral science, especially as it emphasizes (properly, we believe) the individual as the primary unit of analysis.

Bridging the Nomothetic and Idiographic Approaches to the Analysis of Clinical Data.

The nomothetic approach (i.e., the study of interindividual variation) dominates analyses of clinical data, even though its assumption of homogeneity across people and time is often violated.

Dealing with Multiple Solutions in Structural Vector Autoregressive Models.

Structural vector autoregressive models (VARs) hold great potential for psychological science, particularly for time series data analysis. They capture the magnitude, direction of influence, and temporal (lagged and contemporaneous) nature of relations among variables. Unified structural equation modeling (uSEM) is an optimal structural VAR instantiation, according to large-scale simulation studies, and it is implemented within an SEM framework.

Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis.

Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life.

A posteriori model validation for the temporal order of directed functional connectivity maps.

A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.

A voxelwise approach to determine consensus regions-of-interest for the study of brain network plasticity.

Despite exciting advances in the functional imaging of the brain, it remains a challenge to define regions of interest (ROIs) that do not require investigator supervision and permit examination of change in networks over time (or plasticity). Plasticity is most readily examined by maintaining ROIs constant via seed-based and anatomical-atlas based techniques, but these approaches are not data-driven, requiring definition based on prior experience (e.g.

Models of Postural Control: Shared Variance in Joint and COM Motions.

This paper investigated the organization of the postural control system in human upright stance. To this aim the shared variance between joint and 3D total body center of mass (COM) motions was analyzed using multivariate canonical correlation analysis (CCA). The CCA was performed as a function of established models of postural control that varied in their joint degrees of freedom (DOF), namely, an inverted pendulum ankle model (2DOF), ankle-hip model (4DOF), ankle-knee-hip model (5DOF), and ankle-knee-hip-neck model (7DOF).

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors--Recommendations for methods and experimental designs.

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses.

An alternative framework to investigating and understanding intraindividual processes in substance abuse recovery: an idiographic approach and demonstration.

Background: Sustained recovery from substance abuse is a dynamic intraindividual-level process.

Objectives: We argue that research on recovery process will benefit from a theoretical approach that captures both the dynamic and the idiographic nature of substance abuse recovery. In addition to setting out why we believe that research on recovery can benefit from such an approach, we provide a demonstration of idiographic within-individual analyses of between- and within-day associations among negative affect, substance use craving, and positive social experiences.

Glycine receptor antibodies in PERM: a new channelopathy.

This scientific commentary refers to ‘Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes', by Carvajal-González et al. (doi:10.1093/brain/awu142).

Proteasome inhibition with bortezomib depletes plasma cells and specific autoantibody production in primary thymic cell cultures from early-onset myasthenia gravis patients.

Bortezomib is a potent inhibitor of proteasomes currently used to eliminate malignant plasma cells in multiple myeloma patients. It is also effective in depleting both alloreactive plasma cells in acute Ab-mediated transplant rejection and their autoreactive counterparts in animal models of lupus and myasthenia gravis (MG). In this study, we demonstrate that bortezomib at 10 nM or higher concentrations killed long-lived plasma cells in cultured thymus cells from nine early-onset MG patients and consistently halted their spontaneous production not only of autoantibodies against the acetylcholine receptor but also of total IgG.