View clinical trials related to Autoimmune Encephalitis.
Filter by:The term "autoimmune encephalitis" denotes an heterogenous group of diseases commonly associated with autoantibodies targeting neural or glial antigens. Patients harboring antibodies against the leucine-rich glioma-inactivated protein 1 (LGI1) usually respond well to immunotherapy, but a significant percentage develop cognitive sequelae and disability nonetheless. These patients would likely benefit for more aggressive and prolonged immunotherapy, aiming to prevent permanent neurological deficits. Identifying features predicting poor outcome would be crucial to guide treatment decisions. Brain magnetic resonance imaging is a key diagnostic tool in the acute phase, but radiological changes may also appear in follow-up studies, including global brain atrophy, hippocampal atrophy and mesial temporal sclerosis. We hypothesize that specific changes identifiable in the acute and chronic phase underlie a higher risk of poor outcome and persistent neurological deficits.
Detection of autoantibodies targeting neuronal surface or intracellular antigens is a keystone for the diagnosis and the treatment of auto-immune encephalitis and paraneoplastic neurological syndromes. A strategy commonly used for their detection is to perform a screening with a tissue-based immunofluorescence assay or immunohistochemistry assay and a second line test to confirm and identify the autoantibody. Since several years, commercial kits are used by a growing number of laboratories to screen the presence of these autoantibodies. However, the diagnostic performance of these commercial kits is highly variable and several studies reported a high prevalence of false-positive and false-negative results with commercial immunodots and cell-based assays. It is therefore essential to explore commercial kits limitations in order to avoid false-positive and false-negative results that could lead to misdiagnosis and/or to delay the treatments. To assess the diagnostic performance of commercial kits, the investigators performed a prospective study in which the investigators screened patients neuronal autoantibodies in cerebrospinal fluid and sera using commercial tissue-based indirect immunofluorescence assay and CBAs in comparison with an in-house tissue-based indirect immunofluorescence assay.
First described in 2010, GABA-B-receptor antibodies-associated encephalitis is a disease with a severe vital and functional prognosis. Indeed, functional status is mostly altered by encephalitis and it induced consequences while vital status is mostly engaged by cancer very often associated in the course of the disease, mostly small-cell lung cancer (SCLC). While knowledge is growing on clinical features at each stage of the disease, long-term outcome data is still lacking even if known to be pejorative. In this study, we aimed to describe long-term follow up of all patients who were diagnosed a GABAb-receptor antibodies-associated encephalitis in the French Paraneoplastic Neurological Syndrome Reference Center until now.
Paraneoplastic neurological syndromes (PNS) are rare complications of cancer occurring in 0.01% of cases. Their clinical, biological and radiological presentation is heterogeneous and may constitute a diagnostic challenge. Anti-Ma2 PNS are rare diseases with a guarded prognosis. They are most often associated with a seminoma-like testicular tumor but can also be associated with lung cancer. Classically, they present as limbic, diencephalic and/or brainstem encephalitis. Anti-Ma2 antibodies target intracellular receptors and are characteristic of a particular form of encephalitis. Atypical manifestations including narcolepsy-cataplexy, weight gain, sexual dysfunction and motor neuron syndrome have been described and explain the difficulty in diagnosing anti-Ma2 associated PNS. It seems interesting to better characterize the phenotypes of Ma2 patients in order to optimize the diagnosis and follow-up.
Autoimmune encephalitis and paraneoplastic neurological syndromes are rare diseases caused by an abnormal immune response toward the nervous system. This can lead to life-threatening symptoms, but is in many cases treatable if a swift and correct diagnosis is made. Antibodies targeting neuronal proteins (i.e. "neuronal antibodies") can be detected in serum or cerebrospinal fluid (CSF) in about half of the patients suffering from these conditions. Although an important part of the diagnostical process of these conditions, diagnosis cannot be made only based on a positive antibody test, but the clinical findings have to be compatible as well. As these conditions are so rare, clinicians might struggle to interpret antibody test results. In this study the investigators aim to estimate the incidence rate of autoimmune encephalitides and paraneoplastic neurological syndromes in the Uppsala-Örebro health care region in Sweden between the years 2015 and 2019. Medical records from patients belonging to the Uppsala-Örebro health care region (a region in the middle of Sweden with a population of approximately 2.1 million), that tested positive for any neuronal antibody in serum or CSF will be studied to obtain clinical, laboratory and radiological data. This data will be used to ascertain if diagnostic criteria are fulfilled as well as to describe clinical characteristics and identifying possible comorbidities.
The purpose of this study is to evaluate the safety and efficacy of IGIV 10% in patients with autoimmune encephalitis
Most of patients with autoimmune encephalitis are left with permanent cognitive deficits of varying severity. The patients' life and career would be affected definitely by cognitive deficits. Recently, more and more clinical physician have begun to focus on cognitive impairment of patients with autoimmune encephalitis. Generally, the outcome was measured by the modified Rankin Scale (mRS). However, the mRS are commonly used to evaluate the degree of disability or dependence in the daily activities of the patients suffering from a stroke and cognition function were minimally evaluated in this scale. It is crucial to adopt detailed cognition tools to study the long-term cognitive outcomes and as an indicator of overall curative effect judgment in autoimmune encephalitis. Currently, only early immunotherapy is uniformly and consistently considered to produce favorable cognitive outcomes. However, studies concerning the association of second-line immunotherapy with cognitive outcomes have been scarce and have shown conflicting results regarding autoimmune encephalitis. Hence, the goal of this study was to explore cognitive neural mechanism of autoimmune encephalitis by using neuropsychological tests and multi-mode MRIs.
Neurological and psychiatric diseases are one of the major health problems worldwide. Decades of fundamental and clinical research have led to the model that these disorders results from synaptic imbalance between excitatory, inhibitory and modulatory systems in key brain structures. Although the network and neurotransmitter systems involved have been delineated, the mechanisms leading to improper neurotransmissions remain poorly understood. One major limitation lays in the difficulty to transpose the identified dysregulation in humans to relevant animal models in which molecular and cellular targets can be manipulated. The amino-acid glutamate mediates the vast majority of excitatory neurotransmission in the mammalian brain. We know that the glutamatergic synapses can change their strength by regulating surface expression and dynamics of their postsynaptic receptors, through changes in receptor recycling and/or lateral diffusion. This synaptic plasticity underlies higher cognitive functions such as learning and memory and is likely compromised in several disease states. Regulating glutamate receptor number and function is thus of primary importance. New subcellular imaging technique rendered possible the study of receptor trafficking and receptor regulation in various conditions including pathological models opening new fundamental questions. Moreover, recent breakthroughs on glutamate receptor structure offer unprecedented clues on the molecular and structural mechanisms underpinning receptor dysfunction at the atomic level. Recently, description of encephalitis associated with specific autoantibodies (Abs) directed against neuronal synaptic receptors or proteins (NSA-Abs) opens new lights in the pathophysiological mechanisms of some human brain disorders. The best example and the most frequent syndrome is the synaptic autoimmune encephalitis associated with autoantibodies against extracellular domains of the glutamatergic NMDA receptor (NMDAR-Abs). Classically, patients first present psychiatric symptoms with hallucinations and bizarre behavior before development of neurological symptoms such as seizures, dyskinesia, and autonomic instability. Despite the severity of neuropsychiatric symptoms, more than 80% of patients fully recover after immunomodulatory treatments and many arguments suggest a direct role of NMDAR-Abs in the symptoms. The investigators recently demonstrated that NMDAR-Abs directly modify, at the synaptic level, NMDAR lateral diffusion by disruption of the interaction between NMDAR and EphrinB2 receptor, a synaptic protein anchoring NMDAR at the synapse (Mikasova et al, Brain 2012; Dupuis et al, EMBOJ 2014). These data suggest that NMDAR-Abs could directly participate in the neuropsychiatric disorders observed in patients and that NMDAR dysfunctions could be directly responsible for the observed symptoms. Furthermore, these data suggest that other NSA-Abs directed against other synaptic proteins could explain specific neurological symptoms in patients with encephalitis that are not associated with NMDAR-Abs. The aim of MECANO is to combine multidisciplinary approaches (clinical, immunological, and neurobiological ones) to identify new NSA-Abs, to characterize their specific pathological roles and to decipher acute and chronic NMDAR-Abs effects on biophysical and structural properties of the NMDA receptor, synaptic plasticity, neuronal morphology, and cognitive performance. This project should provide key insights onto the effects of patients' NSA-Abs on the cellular dynamic and regulation of synaptic proteins or receptors and on the molecular cascades activated during synapse dysfunction. The investigators will investigate how NSA-Abs binding alter receptor activity, modify surface receptor mobility and dynamically regulate the maturation of synapses and circuitries. For that purpose, The investigators will use a unique combination of high-resolution imaging (single nanoparticle tracking), receptor engineering, cellular electrophysiology, computational (structural modeling) and cellular and molecular biology approaches and finally behaviour assays. Based on both cutting-edge neurobiology and clinical expertise of autoimmune disorders, and strengthened by promising preliminary experiments, the MECANO project will likely open new avenues of fundamental research in the understanding of synaptic dysfunction and clinical research for the treatment of neuropsychiatric disorders.