Autoimmune-mediated Encephalitis Research Articles

Functional changes in neuronal circuits due to antibody-driven autoimmune response

Autoimmune-mediated encephalitis syndromes are increasingly being recognized as important clinical entities. They need to be thought of as differential diagnosis in any patient presenting with fast-onset psychosis or psychiatric problems, memory deficits or other cognitive problems, including aphasias, as well as seizures or motor automatisms, but also rigidity, paresis, ataxia or dystonic / parkinsonian symptoms. Diagnosis including imaging and CSF search for antibodies needs to be fast, as progression of these inflammatory processes is often causing scarring of brain tissue, with hypergliosis and atrophy.As these symptoms show, the autoantibodies present in these cases appear to act within the CNS. Several of such antibodies have by now been identified such as IgG directed against NMDA-receptors, AMPA receptors, GABAA and GABAB receptors, and voltage gated potassium channels and proteins of the potassium channel complex (i.e. LGI1 and CASPR2). These are neuropil / surface antigens where antibody interaction can well be envisaged to cause dysfunction of the target protein, including internalization. Others, such as antibodies directed against GAD65 (an intracellular enzyme responsible for GABA-synthesis from glutamate), are discussed to constitute epiphenomena, but not causal agents in disease progression.This review will focus on the current knowledge of antibody interaction mechanisms, especially discussing cellular excitability changes and synaptic interactions in hippocampal and other brain networks. One challenge in this context is to find viable hypotheses for the emergence of both, hyperexcitability and seizures, and presumably reduced synaptic plasticity and underlying cognitive dysfunction.

Autoimmune-mediated encephalitis and mimics: A neuroimaging review.

Autoimmune encephalitis is a category of autoantibody-mediated neurological disorders that often presents a diagnostic challenge due to its variable clinical and imaging findings. The purpose of this image-based review is to provide an overview of the major subtypes of autoimmune encephalitis and their associated autoantibodies, discuss their characteristic clinical and imaging features, and highlight several disease processes that may mimic imaging findings of autoimmune encephalitis. A literature search on autoimmune encephalitis was performed and publications from neuroradiology, neurology, and nuclear medicine literature were included. Cases from our institutional database that best exemplify major imaging features were presented.

小児期発症自己免疫性介在性脳炎後てんかんにおける抗てんかん薬の有用性の検討

小児期発症自己免疫性介在性脳炎後てんかんにおける抗てんかん薬の有用性の検討

Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders.

Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.

Pediatric Autoimmune Encephalitis Following COVID-19 Infection.

Similar to the pathogenesis of autoimmune disease, SARS-CoV-2 (COVID-19) infection has been shown to be associated with dysregulated and persistent inflammatory reactions and production of some antibodies. We report 3 pediatric patients found to have serum SARS-CoV-2 antibodies who presented with neurologic findings suggestive of postinfectious autoimmune-mediated encephalitis. All 3 cases showed lymphocytic pleocytosis on cerebrospinal fluid studies and marked improvement in neurologic symptoms after high-dose intravenous corticosteroids. The manifestations of SARS-CoV-2 infection in the pediatric population are still an evolving area of study, and these cases suggest autoimmune-mediated encephalitis as yet another SARS-CoV-2 related complication.

Neuroimmunological antibody-mediated encephalitis and implications for diagnosis and therapy in neuropsychiatry.

The past decade has seen a surge of reports and investigations into cases of autoimmune-mediated encephalitis. The increasing recognition of these disorders is especially of relevance to the fields of neurology and psychiatry. Autoimmune encephalitis involves antibodies against synaptic receptors, neuronal cell surface proteins and intracellular targets. These disorders feature prominent symptoms of cognitive impairment and behavioural changes, often associated with the presence of seizures. Early in the clinical course, autoimmune encephalitis may manifest as psychiatric symptoms of psychosis and involve psychiatry as an initial point of contact. Although commonly associated with malignancy, these disorders can present in the absence of an inciting neoplasm. The identification of autoimmune encephalitis is of clinical importance as a large proportion of individuals experience a response to immunotherapy. This review focuses on the current state of knowledge on n-methyl-d-aspartate (NMDA) receptor-associated encephalitis and limbic encephalitis, the latter predominantly involving antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, the γ-aminobutyric acid (GABA)B receptor and leucine-rich glioma-inactivated 1 (LGI1) protein. In addition, we briefly describe anti-dopamine D2 receptor encephalitis. A summary of the literature will focus on common clinical presentations and course, diagnostic approaches and response to treatment. Since a substantial proportion of patients with autoimmune encephalitis exhibit symptoms of psychosis, the relevance of this disorder to theories of psychosis and schizophrenia will also be discussed.

Autoimmune-Mediated Encephalitis: Main Clinical Syndromes and Antibody Effects

Autoimmune-Mediated Encephalitis: Main Clinical Syndromes and Antibody Effects

84. Case Report: Bilateral Teratomas with Immature Focus in a Patient Presenting with Immune Mediated Encephalitis

About 30-40% of patients with anti-NMDA receptor encephalitis, an autoimmune mediated encephalitis, have an underlying neoplasm. We present a unique case of a 16 year old with bilateral ovarian teratomas, one that was immature.

Biomarkers of Neurodegeneration in Autoimmune-Mediated Encephalitis.

Progranulin (PGRN), Total-Tau (t-tau), and Neurofilament light chain (NfL) are well known biomarkers of neurodegeneration. The objective of the present study was to investigate whether these parameters represent also biomarkers in autoimmune-mediated Encephalitis (AE) and may give us insights into the pathomechanisms of AE. We retrospectively examined the concentration of PGRN in the cerebrospinal fluid (CSF) and serum of 38 patients suffering from AE in acute phase and/or under treatment. This AE cohort comprises patients with autoantibodies against: NMDAR (n = 18 patients), Caspr2 (n = 8), Lgi-1 (n = 10), GABAB(R) (n = 1), and AMPAR (n = 1). Additionally, the concentrations of NfL (n = 25) and t-tau (n = 13) in CSF were measured when possible. Follow up data including MRI were available in 13 patients. Several age-matched cohorts with neurological diseases besides neuroinflammation or neurodegeneration served as control groups. We observed that PGRN was significantly elevated in the CSF of patients with NMDAR-AE in the acute phase, but normalized at follow up under treatment (p < 0.01). In the CSF of other patients with AE PGRN was in the range of the CSF levels of control groups. T-tau was highly elevated in the CSF of patients with temporal FLAIR-signal in the MRI and in patients developing a hippocampal sclerosis. NfL was exceptionally high initially in Patients with AE with a paraneoplastic or parainfectious cause and also normalized under treatment. The normalizations of all biomarkers were mirrored in an improvement on the modified Rankin scale. The data suggest that the concentration of PGRN in CSF might be a biomarker for acute NMDAR-AE. Pathological high t-tau levels may indicate a risk for hippocampal sclerosis. The biomarker properties of NfL remain unclear since the levels decrease under treatment, but it could not predict severity of disease in this small cohort. According to our results, we recommend to measure in clinical practice PGRN and t-tau in the CSF of patients with AE.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Review and Neuropsychological Case Study

Objective: Anti-N-Methyl-d-Aspartate Receptor (NMDAR) Encephalitis is an autoimmune-mediated encephalitis, which may be associated with a tumor, which occurs when antibodies bind central NMDA receptors. Although typically diagnosed in women, approximately 20% of cases have been males. Due to the challenges with identification, imaging, and diverse symptom presentation, this syndrome is often misdiagnosed. Accurate diagnosis may provide an opportunity for introduction of disease-modifying therapies, which may alter disease trajectory. Moreover, neuropsychology has yet to fully clarify the pattern of impairments expected with this disorder. Methods: This manuscript reviews a single case study of a 42-year-old male diagnosed with NMDAR encephalitis. Neuropsychological evaluation was completed subsequent to diagnosis, treatment, and rehabilitation. Ongoing patient complaints, approximately six months post diagnosis, included reduced sustained attention, poor word retrieval, and daily forgetfulness. Adaptive skills were improved following rehabilitation. Results: Direct testing revealed mildly impaired sustained attention, processing speed, oral word fluency, and executive functioning. All other cognitive domains were within estimated premorbid range, low average to average. Conclusions: Neuropsychological deficits were consistent with mild frontal brain dysfunction and continued recovery. This case illustrates the need for medical and psychological practitioners to understand NMDAR encephalitis, its symptom presentation, and related neuropsychological impact; particularly with the potential for misdiagnosis.

Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders.

Limbic encephalitis is far more common than previously thought. It is not always associated with cancer, and it is potentially treatable. Autoantibodies against various neuronal cell antigens may arise independently or in association with cancer and cause autoimmune damage to the limbic system. Neuroimaging plays a key role in the management of patients with suspected limbic encephalitis by supporting diagnosis and excluding differential possibilities. This article describes the main types of autoimmune limbic encephalitis and its mimic disorders, and emphasizes their major imaging features.

Parents who wish no further treatment for their child

BackgroundIn the ethical and clinical literature, cases of parents who want treatment for their child to be withdrawn against the views of the medical team have not received much attention....

FLAIR fornix hyperintensity in VGKC-related autoimmune encephalitis

A 52-year-old man presented with progressive fatigue, drowsiness, weight loss, and memory impairment associated with left-sided temporal lobe seizures. Brain MRI revealed increased bilateral FLAIR signal in the hippocampus, amygdala, mammillary bodies, hypothalamus and fornix (Figs. 1, 2). Blood analysis showed normal CRP, TSH, vitamin B1 and B12 levels. Routine immunological screening, and HIV and syphilis serology were negative. Anti-voltage-gated potassium channel (VGKC) antibodies were positive (463 pmol/l; normal range 0–100 pmol/l), in the absence of antiganglioside antibodies, NMDA/TPO/ GAD antibodies and other paraneoplastic antibodies. CSF analysis showed oligoclonal bands in the absence of other abnormalities. Brain FDG-PET revealed bilateral frontal, parietal and temporal hypometabolism (all equally involved). Whole-body FDG-PET, thoraco-abdominal– pelvic CT and testicular echography were normal. Oral antiepileptic treatment (valproic acid 500 mg bid) led to seizure freedom. Important clinical improvement after corticosteroid treatment (60 mg od for 1 month, followed by tapering during 3 months) was seen, in the presence of persistent MRI abnormalities (although increased signal became less severe) 4 months later. After 1 year of followup, no clinical relapse occurred, and thoraco-abdominal– pelvic CT and whole-body FDG-PET remained normal. A diagnosis of VGKC-related autoimmune, probably nonparaneoplastic, encephalitis was made. Autoimmune-mediated encephalitis can involve several brain areas with notably frequent involvement of limbic system structures (referred to as limbic encephalitis) including the hippocampus, amygdala and the mammillary bodies [1, 2]. MRI (together with FDG-PET) is probably the most adequate imaging technique to reveal abnormalities in these structures. MRI abnormalities due to autoimmune-mediated encephalitis are best seen on FLAIR sequences as an increased signal. To the best of our knowledge, despite radiological involvement of other limbic substructures and associated brain areas (e.g., the hypothalamus), fornix signal changes have never been reported in autoimmune encephalitis. The fornix is an important fiber bundle or projection bundle within the limbic system explaining probably its involvement in our patient. The limbic system includes territories of the diencephalon (the epithalamus, hypothalamus, subthalamic zona incerta), telencephalon (the septal and preoptic regions, hippocampus and some adjacent cortical areas, amygdala, the bed nucleus of the stria terminalis), and mesencephalon. Fornix involvement has been described in multitude other diseases [3]. The fornix is a compact fiber bundle connecting the hippocampus with the hypothalamus and various other structures. Its anterior–posterior orientation makes coronal MRI views particularly interesting. Because of the close proximity of the fornix to structures containing CSF, FLAIR imaging is of special interest to visualize fornix signal abnormalities. Neuropathological findings in autoimmune limbic encephalitis are non-specific, including gliosis, perivascular lymphocyte infiltration and microglial activation. In our patient, it is unclear if signal changes of the fornix were secondary (e.g., due to edema or Wallerian degeneration) D. Renard (&) D. Ratiu Department of Neurology, CHU Nimes, Hopital Caremeau, Place du Pr Debre, 30029 Nimes Cedex 4, France e-mail: dimitrirenard@hotmail.com

Late Delirious Behavior With 2009 H1N1 Influenza: Mild Autoimmune-Mediated Encephalitis?

Delirious behavior associated with influenza usually has an onset within a few days after fever and lasts <24 hours. As we encountered several patients with 2009 H1N1 influenza who presented with late-onset and long-standing delirious behavior, we retrospectively evaluated the clinical, radiologic, and laboratory features to elucidate the possible pathophysiology. This information was collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years) with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate drowsiness between the episodes of delirious behavior. Electroencephalography was normal except for 1 patient with high voltage and slow activity bilaterally in the occipital regions. Brain MRI was normal. The outcome was excellent with no neurologic sequel in 4 of the 5 patients. In all 5 patients, autoantibodies against N-methyl-D-aspartate type glutamate receptor were elevated or positive in cerebrospinal fluid or serum; the autoantibody levels normalized in the 3 patients who had follow-up studies. This study indicates that 2009 H1N1 influenza has a tendency to cause late-onset and long-standing delirious behavior, at least in Japanese children. Mild autoimmune-mediated encephalitis should be considered as an underlying cause.

Autoimmune-mediated encephalitis

Autoimmune-mediated encephalitis may occur as a paraneoplastic or as a non-paraneoplastic condition. The role of neuroimaging in autoimmune-mediated encephalitis has changed in the last decade partly due to improvements in sequence optimisation and higher field strength and partly due to the discovery of an increasing number of antibodies to neuronal cell and cell membrane antigens. Imaging is important since it can support the clinical diagnosis particularly in the absence of antibodies. Structural imaging findings can be subtle and are usually best seen on FLAIR images. A progressive as well as a relapsing-remitting course can be observed. Autoimmune-mediated encephalitis is classically linked to involvement of the hippocampus and amygdala, but extensive changes in the temporal cortex, basal ganglia, hypothalamus, brain stem, frontal and parietal cortex are not unusual. This report is based on a review of the literature (except the literature in Japanese) and own findings in patients with autoimmune-mediated encephalitis.

A medical overview of encephalitis

Encephalitis is uncommon but is a neurological emergency which must be considered in a patient presenting with altered consciousness. Encephalitis is a diffuse inflammatory process of the brain parenchyma associated with evidence of brain dysfunction. The presentation of encephalitis can be acute or chronic. The aetiology of encephalitis can be broadly divided into two major subtypes. (1) Infection-related encephalitis which is a direct consequence of pathogenic viral, bacterial or parasitic agents. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are the most common cause of acute infectious encephalitis. (2) Autoimmune-mediated encephalitis which is mediated by an aberrant immune response. This can be triggered by a recent viral infection or vaccination. An example of this would be acute disseminated encephalitis (ADEM). This article will focus on the medical management of acute encephalitis. This will involve an extensive overview of the literature reviewing the diagnosis, investigation and treatment of acute viral encephalitis, ADEM and acute haemorrhagic leukoencephalopathy (AHLE). Encephalitis can also present chronically, and some of the different types of chronic encephalitis will be discussed.