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NCT06019975
The goal of this retrospective observational study is to compare brain fluorodeoxyglucose-positron emission tomography (FDG-PET) of patients with autoimmune encephalitis, normal controls and patients with Alzheimer's disease (AD). The main question it aims to answer is: •is there a specific pattern of brain metabolism in patients with autoimmune encephalitis Participants data and images will be retrospectively collected from hospital records, and FDG-PET images will be analyzed by means of statistical parametric mapping (SPM). Controls will be selected from validated public databases.
NCT07477015
Autoimmune encephalitis is a debilitating neurological disorder that usually appears as a rapidly progressive form of brain dysfunction, typically developing in less than six weeks, caused by inflammation in the brain. These conditions show a wide range of clinical and immunological presentations and are generally divided into two main types. The first type includes what are called paraneoplastic syndromes. In these cases, the immune system produces antibodies in response to a tumor that mistakenly target parts of the nervous system. The antibodies are not directly harmful themselves, but they are a sign that the immune system has launched a T-cell-driven attack on brain tissue because it recognizes a protein that's found both in the tumor and in the nervous system. These forms usually follow a single, non-repeating course and tend to respond poorly to treatment, which mostly focuses on removing or treating the underlying tumor and using immunotherapy to reduce the immune response. The second type includes what we more properly call autoimmune encephalitis, where the immune system produces antibodies that directly attack proteins on the surface of neurons or on synaptic receptors in the brain. Unlike in paraneoplastic syndromes, these antibodies are directly responsible for the disease, and they don't usually indicate the presence of a tumor. Most people with this type of autoimmune encephalitis-around 70% to 80%-respond well to treatment with immunotherapy and can make a good or even full recovery. However, in about 20% of cases, the disease can come back or lead to long hospital stays, with a slower or only partial recovery. There is also a third group of autoimmune encephalitides where the antibodies target synaptic proteins. These may or may not be linked to cancer, and the proteins they target are usually found inside the cells rather than on their surface. A fourth group includes what are called seronegative autoimmune encephalitides. These are cases that meet the clinical criteria for autoimmune encephalitis, but no specific antibodies have been identified so far. Among the autoimmune neurological disorders without known antibodies is Susac syndrome, a rare condition that affects the brain, the retina, and the inner ear. It's especially interesting because its features suggest the involvement of antibodies, even though no disease-causing antibodies have yet been found. The diagnosis of autoimmune encephalitis is based on clinical signs and symptoms, the detection of specific antibodies in blood or spinal fluid, and, in paraneoplastic cases, identifying the underlying tumor. To detect autoantibodies, doctors use various lab techniques, including immunoblotting and different types of immunofluorescence tests-some based on cultured cells, others on brain tissue from rodents. Despite important progress in recent years, many cases of autoimmune encephalitis remain undiagnosed. One reason is that the disease can begin with vague or incomplete symptoms, making it difficult to recognize. Another issue is that current testing methods might not be sensitive enough to detect all possible antibodies. This means that the group of patients diagnosed with seronegative autoimmune encephalitis might actually include people who have antibodies we just haven't discovered yet. In many cases, especially in the seronegative forms, the exact cause of the disease is still not fully understood. The main goal of this study is to better understand how autoimmune encephalitis develops, especially in cases involving antibodies that target proteins on the surface of brain cells-such as NMDAR, GABABR, AMPAR, LGI1, and DNER-as well as in seronegative autoimmune encephalitis and in Susac syndrome. A second goal is to try to discover new autoantibodies that could explain the disease in patients who currently test negative.
NCT07158229
NMDA receptor antibody encephalitis is a rare autoimmune neurological disease of the central nervous system with an estimated incidence of 1.5 people per million per year. Patients with anti-NMDAR encephalitis experience an acute phase of the disease characterized by psychosis, memory loss, seizures, autonomic nervous system instability, or coma. Since the discovery of this disease 14 years ago by Prof. Dalmau, the clinical presentation of the acute phase has been well characterized, while the psychosocial impact of the disease remains largely unexplored. Currently, there are few cohort studies of patients that have identified persistent cognitive impairment as a factor impacting remission after the acute phase. Given the scarcity of information concerning the post-acute phase, it is therefore essential to determine the long-term social and psychological outcomes and their daily effects on the social and functional life of this severe disease. This is especially important as the patients are young, with a median age of 21 years, and may face lasting limitations potentially detrimental to their success in professional, educational, or social environments.
NCT06575153
The study is a Phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of ART5803 compared with placebo in healthy adult participants
NCT04806620
The unhide® Project is a non-interventional, longitudinal research study designed to establish a secure data repository of demographic, health, and lifestyle information from individuals with brain inflammation and related neuroinflammatory conditions. Participants in the United States aged 2 years and older will provide self-reported health data, biometrics, and symptom diaries through the MyDataHelps™ app (branded as unhide® for this study). The goal is to create comprehensive longitudinal profiles to facilitate research into disease subtypes, causes, diagnostics, and potential treatments, as well as to identify potential participants for future optional studies. "Healthy" individuals without brain inflammation are also eligible to participate. The digital health research platform used in this study was originally developed and designed by Solve M.E and was called SolveTogether. The Brain Inflammation Collaborative (BIC) expanded upon Solve M.E.'s work to include related diagnoses, pediatric participants, enhance symptom tracking, and more. BIC and Solve M.E. combined Solve Together and unhide®, to create The unhide® Solve Together Unified Platform in 2025.
NCT06753955
This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of ART5803 following IVIG administration in healthy participants to investigate the potential interactions between ART5803 and IVIG
NCT03993262
Autoimmune Encephalitis is a disorder of the central nervous system caused by bodily substances, called antibodies. Antibodies normally help the body to prevent infections. However, in this disorder, the antibodies turn against the body itself and especially against cells in the brain and disturb the normal brain function. They are therefore called autoantibodies. There is no specific therapy for patients with autoimmune encephalitis so far. At the moment, the symptoms are treated with approved medications such as cortisone and immunotherapies also used in oncology. These therapies are unspecified and aim to reduce the number of autoantibodies and to contain the autoimmune process. In this trial we aim to test a new therapy option: in this therapy the body cells producing autoantibodies will be specifically targeted by a substance called bortezomib. The trial addresses patients with severe autoimmune encephalitis. The aim of the trial is to evaluate the efficacy and safety of bortezomib in patients with severe autoimmune encephalitis.
NCT06079294
Prospective cohort study evaluating FDG PET in 56 patients with confirmed autoimmune encephalitis - based on 2016 Graus criteria, and 2021 paraneoplastic neurological syndromes criteria - at the acute phase, before immunomodulating treatment, or within 10 days of treatment initiation.
NCT07133113
Autoimmune encephalitides are severe neurological disorders requiring urgent treatment, even though there is no standard guideline by lack of empirical evidence. Commonly used treatments are divided into so-called first-line (steroids, intravenous immunoglobulins, plasma exchanges) and second-line (rituximab, cyclophosphamide, tocilizumab, others), and may be used in association or sequentially. There is no standard practice, and initial treatment protocol may consist in first-line alone, first-line with rituximab, or first-line with dual immunosuppression (rituximab and cyclophosphamide). Absence of clear response to initial treatment in the first 4 to 6 weeks may indicate undertreatment and is generally followed by treatment escalation, mostly to dual immunosuppression. However, as the frequency of non-responders to initial treatment is unknown, it is still unclear whether dual immunosuppression should be offered to all patients from inception.
NCT03872284
Autoimmune encephalitis represents a group of rare and heterogeneous neurological disorders. Pathophysiological mechanisms in these diseases are still unknown. Recently, oculomotor and neurovisual disorders have been described. Cerebral areas and neuronal networks associated with these abnormalities are well described. The investigator proposes to study and describe such neuro-ophthalmological disorders in a prospective cohort of patients with a autoimmune encephalitis, to better understand the pathophysiological basis of this neurological condition.
NCT06760091
This study aims to establish an autoimmune encephalitis cohort and observe the prognosis of patients with different subtypes and subgroups (e.g. epilepsy subgroup and teratoma subgroup ). Clinical characteristics, biological samples, and imaging data will be collected to discover blood and imaging biomarkers for providing support for the treatment, early warning, and outcome prediction.
NCT06697678
A prospective study aims to establish a multicenter clinical diagnosis and treatment database for patients with autoimmune encephalitis (AE). The study will analyze the characteristics of disease progression, changes in immune-inflammatory markers, immunotherapy regimens, and patient outcomes. It seeks to identify clinical indicators for the early recognition of severe AE patients, develop and validate a predictive model for severe AE, and explore effective treatment strategies to rapidly control disease progression during the acute phase of severe AE.
NCT06502015
Neurological autoimmune diseases are a group of disorders characterized by the abnormal immune response attacking the nervous system, including the brain, spinal cord and peripheral nerves. These diseases exhibit high heterogeneity, diverse clinical presentations, and are challenging to diagnose and manage due to a lack of effective treatments. In this study, the investigators will recruit eight kinds of autoimmune diseases of nervous system including Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathy (IIM), and multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD). Through this study, the investigators aim to discover biomarkers with high sensitivity, specificity, and stability, which can support early diagnosis, disease monitoring, and personalized treatment for neurological autoimmune diseases, thereby improving the quality of life and prognosis for patients.
NCT04561557
Antibody-mediated inflammatory diseases of the nervous system (also known as autoimmune diseases of the nervous system) are autoimmune diseases in which autoimmune cells and immune molecules attack the nervous system as the main pathogenic mechanism. In the immune response, pathogenic antibodies acting on autoantigens of the nervous system are collectively referred to as autoantibodies of the nervous system, and antibody-mediated inflammatory diseases of the nervous system can occur in the central nervous system, peripheral nervous system, and neuromuscular junctions, and muscles. In this study, we will recruit eight kinds of autoimmune diseases of nervous system including Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathyand (IIM), multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) and POEMS Syndrome. B-cell maturation antigen (BCMA) is expressed on the surface of plasma cells, thus making it an ideal target for targeted therapies. Chimeric antigen receptor (CAR) T cells against BCMA offers another potential therapeutic option to eliminate plasma cells in patients with neurological autoimmune diseases driven by abnormal antibody who still suffer recurrent attacks from conventional treatments. In the current study, the safety and efficacy of a novel CAR-T cell therapy using CT103A cells, are evaluated in patients with relapsed/refractory antibody-mediated idiopathic inflammatory diseases.
NCT06432803
Autoimmune encephalitis (AE) is a rare neurological disorder mediated by autoimmune antibody response against neuronal cell surface and intraneuronal proteins associated with specific brain areas, resulting in severe inflammation and damage in the associated brain regions, all most frequently manifesting diverse cognition and memory impairment symptoms at follow-up. However, these symptoms may co-exist or mimic other CNS autoimmune and neurodegenerative disorders. The most common guideline for diagnosing autoimmune encephalitis relies on cerebrospinal fluid (CSF) antibody testing which might take several weeks to obtain, making it not optimal for the early diagnosis of AE. As for magnetic resonance imaging (MRI), which is the most common imaging tool utilized for aiding in the diagnosis of AE, can possess several limitations as some patients, like anti-NMDAr AE patients, can present memory and behavioral deficits even in the presence of normal brain MRI. Positron emission tomography (PET) with 2-deoxy-2-\[fluorine-18\] fluoro-D-glucose (18F-FDG) have been addressed by several studies as an important examination for the early diagnosis of AE . One study demonstrated that the fraction of having an abnormal MRI in AE patients is lower than having an abnormal PET, by which certain PET patterns were associated with autoantibody types of AE. Moreover, one report demonstrated that even with autoantibody negative test and normal brain MRI, FDG-PET examination showed abnormal hypometabolism and hypermetabolism patterns. More specifically, these distinct patterns include medial temporal and striatal hypermetabolism with cortical diffuse hypometabolism. Leiris et al. revealed that the methadology used for the analysis of these PET images is highly variable, especially intensity normalization methods, where most possess some limitations (e.g., proportional scaling) as they can impede the accurate differential diagnosis of autoimmune encephalitis (AE) by potentially indicating false hypermetabolism in otherwise preserved brain regions. Absolute quantification is not possible since the disease presents both diffuse hypometabolism and hypermetabolism on PET images. So, they suggested that it's best to parametrize the brain's activity by dividing it by that of the striatum. Their voxel-based analysis, comparing individuals with AE to both healthy subjects and those with mild cognitive impairment (MCI), demonstrated that a decrease in the cortex/striatal metabolic ratio is a robust biomarker for the early diagnosis of AE.
NCT06245447
Anti-CASPR2 limbic encephalitis (CASPR2-LE) is a rare neurological disorder primarily affecting males over the age of 50. It is mediated by an autoimmune antibody response in the central nervous system (CNS) against the cellular adhesion molecule contactin-associated protein-like 2 (CASPR2). This protein plays an important role in the trafficking of KV1 channels under the myelin sheath in the juxtaparanodal region of myelinated axons. It is mostly present in the neurons of the limbic system, basal ganglia, and other motor related and sensation areas (Qin, Yang, Zhu, Wang, \& Shan, 2021). This distribution explains the diverse clinical manifestations of the disease, primarily characterized by cognitive impairment. Other manifestations include cerebellar ataxia, hyperkinetic movement disorders (HMDs), seizures, and neuropathic pain, which all typically develop around 10.4 months after onset. At last visit, memory impairment is seen in 69% of the patients, cerebellar ataxia in 42% of the patients, and functional dependency in 25% of the patients. Even though most patients' symptoms improve with immune-active treatments, up to 69% of them have long-term memory impairments due to damage to hippocampal structures (Benoit et al., 2023). Research has primarily focused on understanding the disease's clinical features, underlying mechanisms, and potential treatment options. On the other hand, it is shown that MRIs performed at baseline show signal changes in the hippocampus in 62-71% of the patients, and these changes are subject to variations in subsequent follow-up scans, that differ widely among patients as mentioned before (Bien et al., 2017). And since the dynamics of hippocampal volume changes and its association with the development of hippocampal atrophy and long-term cognitive impairment are not well studied yet in CASPR2-LE, we primarily aim to examine the longitudinal changes of hippocampal volume in anti-CASPR2 Limbic Encephalitis (CASPR2-LE) patients to examine whether it correlates to the development of anterograde amnesia and hippocampal atrophy on follow-up.
NCT05741619
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.
NCT05645185
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.
NCT02905136
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.
NCT04175522
The purpose of this study is to evaluate the safety and efficacy of IGIV 10% in patients with autoimmune encephalitis