Academic literature on the topic 'Encephalitis'

Abstract Background Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies. Objective This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis. Methods We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-d-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed. Discussion The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.

Anti-NMDA receptor encephalitis is a well-recognised immunotherapy-responsive condition which often occurs as a paraneoplastic phenomenon. A typical presentation is in a young individual with a viral-like prodrome followed by the development of severe psychiatric symptoms, memory loss, seizures, reduced consciousness and sometimes orofacial dyskinesias, and progression to autonomic and respiratory instability. Fulminant meningitis is a very rare presenting feature of anti-NMDA receptor encephalitis with our literature search only revealing one other reported case.We present a case of a 33-year old Caucasian woman who initially presented with lymphocytic meningitis but subsequently developed clinical and investigative features consistent with anti-NMDA receptor encephalitis. Through this case, we aim to present and discuss possible mechanisms1–3underlying this atypical presentation and to highlight frank meningitis as an atypical presenting feature of anti-NMDA-receptor encephalitis. Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative micro-organism and there is rapid development of an encephalitic phenotype. A multidisciplinary approach is required to address the neurological, gynaecological, oncological, and neuropsychiatric aspects of this challenging and incompletely understood disorder.ReferencesBektaş Ö, et al.Neuropediatrics2014;45(6):396–401Irani SR, et al.Brain2010;133(Pt 6):1655–67Dalmau J, et al.Lancet Neurol2008;7(12):1091–8

Encephalitis is an inflammation of the brain, often caused by an autoimmune reaction, or in most cases because of a direct viral, bacterial, or parasitic infection. Viral encephalitides (VE) presents a significant public health concern globally, especially in West Africa. There are more than five hundred known arthropod-borne viruses (arboviruses), with over a hundred of them identified to cause encephalitic diseases in humans and animals, giving rise to a tremendous burden of the diseases and socioeconomic strains in tropical and subtropical regions worldwide. Despite their importance, few effective preventive and control measures in the form of vaccines and therapies are available, and when they are, their use is limited. These limitations are largely hinged on the paucity of information about the molecular epidemiology and transmission patterns of VE in West Africa. Here, we reviewed the transmission dynamics, molecular epidemiology, and the ecological drivers of VE in West Africa. Collectively, timely and accurate interventions are essential for encephalitic viral disease control. Moreover, the integrated health system approach, combining surveillance, vaccination, vector control, and community engagement, could be effective in preventing viral encephalitis globally.

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitic illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.

AbstractThe understanding of the manifestations, mechanisms, and management of autoimmune encephalitis has expanded dramatically in recent decades. Immune-mediated encephalitides are comparable in incidence and prevalence to infectious etiologies, and are associated with significant morbidity, especially when there is a delay in recognition and treatment. As such, clinicians from many specialties must develop a functional understanding of these disorders. Herein we provide an overview of the autoimmune and paraneoplastic encephalitides, including those associated with either intracellular or cell surface/synaptic neuronal autoantibodies. After briefly reviewing the current understanding of the pathobiology of autoimmune encephalitis, we combine a neuroanatomical approach with specific antibody syndromes to provide the reader with a clinically relevant review of these disorders. The clinical manifestations, diagnosis, and management of autoimmune encephalitis are reviewed, with an emphasis on clinical relevance. We also introduce updates in the field, including autoimmune encephalitis associated with novel cancer immunotherapies, infectious triggers of autoimmune encephalitis, and autoimmune encephalitis with demyelinating overlap syndromes.

‘Query encephalitis’ is a common neurological consultation in hospitalised patients. Identifying the syndrome is only part of the puzzle. Although historically encephalitis has been almost synonymous with infection, we increasingly recognise parainfectious or postinfectious as well as other immune-mediated causes. We must also distinguish encephalitis from other causes of encephalopathy, including systemic infection, metabolic derangements, toxins, inherited metabolic disorders, hypoxia, trauma and vasculopathies. Here, we review the most important differential diagnoses (mimics) of patients presenting with an encephalitic syndrome and highlight some unusual presentations (chameleons) of infectious encephalitis.

Rift Valley fever (RVF) is an arboviral disease of humans and livestock responsible for severe economic and human health impacts. In humans, RVF spans a variety of clinical manifestations, ranging from an acute flu-like illness to severe forms of disease, including late-onset encephalitis. The large variations in human RVF disease are inadequately represented by current murine models, which overwhelmingly die of early-onset hepatitis. Existing mouse models of RVF encephalitis are either immunosuppressed, display an inconsistent phenotype, or develop encephalitis only when challenged via intranasal or aerosol exposure. In this study, the genetically defined recombinant inbred mouse resource known as the Collaborative Cross (CC) was used to identify mice with additional RVF disease phenotypes when challenged via a peripheral foot-pad route to mimic mosquito-bite exposure. Wild-type Rift Valley fever virus (RVFV) challenge of 20 CC strains revealed three distinct disease phenotypes: early-onset hepatitis, mixed phenotype, and late-onset encephalitis. Strain CC057/Unc, with the most divergent phenotype, which died of late-onset encephalitis at a median of 11 days post-infection, is the first mouse strain to develop consistent encephalitis following peripheral challenge. CC057/Unc mice were directly compared to C57BL/6 mice, which uniformly succumb to hepatitis within 2–4 days of infection. Encephalitic disease in CC057/Unc mice was characterized by high viral RNA loads in brain tissue, accompanied by clearance of viral RNA from the periphery, low ALT levels, lymphopenia, and neutrophilia. In contrast, C57BL/6 mice succumbed from hepatitis at 3 days post-infection with high viral RNA loads in the liver, viremia, high ALT levels, lymphopenia, and thrombocytopenia. The identification of a strain of CC mice as an RVFV encephalitis model will allow for future investigation into the pathogenesis and treatment of RVF encephalitic disease and indicates that genetic background makes a major contribution to RVF disease variation.

ABSTRACT West Nile virus (WNV) has re‐emerged with a much wider geographic distribution and a higher incidence than ever. In spite of some recent reports on the neurological manifestations and EEG changes caused by WNV encephalitis, there are few data on the incidence of seizures, status epilepticus or post‐encephalitic epilepsy. There is also no systematic review of EEG changes caused by WNV encephalitis that is based on a large series of patients. Here, we review the pertinent literature, and report the electroclinical evolution and therapeutic complexity of a patient with WNV encephalitis who developed refractory, non‐convulsive status epilepticus.

BackgroundNeuroimaging findings in autoimmune encephalitis may include normal MRI as well as limbic and extra-limbic involvement. Prompt recognition allows early immunosuppression and improved outcomes.MethodsRetrospective review of patients with Autoimmune encephalitis over the last 5 years.ResultsWe identified N-methyl-d-aspartate receptor (NMDAR) n=8, voltage gated potassium channel (VGKC) n=11, and leucine-rich glioma inactivated 1 (LGI1) n=11 encephalitis patients. 1/8 NMDAR encephalitis patients had abnormal MRI findings of T2 hyper intense signal in right anterior temporal and bilateral frontal and left insular lobe. DWI sequence showed restricted diffusion. 4/11 with VGKC encephalitis had positive MRI findings. Two patients had limbic involvement while one also had involvement of basal ganglia. Two patients had modest cerebral atrophy. Four patients had normal MRI findings. MRI scan was not available for three patients. 5/11 LGI1 encephalitis patients had bilateral mesial temporal lobe changes. In one patient, MRI could not be done due to permanent pacemaker. Five patients had normal MRI findings.ConclusionsIn our series, 33% patients had abnormal MRI findings consistent with a diagnosis of autoimmune encephalitis, which is lower than reported in literature. High clinical suspicion should lead to prompt diagnosis even in the absence of typical encephalitic changes on MRI.

AbstractBackground/ObjectiveHerpes simplex encephalitis usually has a progressive cause. Sudden neurological deficits are unusual.MethodCase study.ResultsA 17-year-old girl presented with an acute onset focal neurological deficit followed one week later by the more classical feature of altered level of consciousness, fever and focal seizures. The diagnosis of hepetic encephalitis was made by magnetic resonance imaging (MRI) and by the significant increase in cerebrospinal fluid titres of antibodies against herpes simplex type I.ConclusionHerpetic encephalitis should be considered in the differential diagnosis of acute stroke in young patients even in the absence of encephalitic features, if common etiological factors such as embolization and intracerebral bleed are excluded.

This thesis was completed by Della Nicolle for the degree of Doctor of Clinical Psychology at Cardiff University. The thesis is a systematic review and an interpretative phenomenological analysis investigating the impact of anti-NMDAR on cognitive functioning and identity respectively. This thesis was submitted on the 26th May 2017 and is comprised of a thesis abstract followed by three papers. Paper one has been prepared for submission to Archives of Clinical Neuropsychology and paper two for submission to Psychology & Health. Paper one presents a systematic review of current published neuropsychological case studies and series with people with a diagnosis of anti-NMDAR encephalitis. The review was conducted to investigate the emerging cognitive profile for people diagnosed with anti- NMDAR encephalitis. It assessed the quality of these studies using a quality assessment tool created for the purpose of the study. The neuropsychological results were synthesised and the results discussed narratively. A review revealed difficulties with memory, particularly verbal memory, executive functioning and attention/processing speed. Paper two is an interpretative phenomenological analysis of women with a diagnosis of anti-NMDAR encephalitis. The aim of this study was to explore the experience of women diagnosed with anti-NMDAR encephalitis and the phenomenon of identity change. Using a semi-structured interview the women were interviewed about their experience of having the illness, with a focus on impact on identity. These interviews were analysed for themes using the IPA method and four superordinate themes were discussed with direct quotes. Four superordinate themes were revealed ‘Re-finding the ‘normal’ self; ‘A ‘special’ identity’; ‘Evolving from the illness’ and ‘Revised roles. Analysis revealed themes common to many ! 2! severe physical illnesses such as, not feeling oneself and post-traumatic growth. However, themes emerged specific to anti-NMDAR such as feeling abnormal due to the rarity of the disease and its psychiatric symptoms, feeling viewed as special and concerns around fertility and motherhood. Paper three is a Commentary on the former two studies. This paper offers critical appraisal and reflection on the research process, the strengths and limitations of the papers and line of enquiry, as well as implications for further research, clinical practice and personal/professional development, and finally proposals for dissemination. The term ‘patients’ will be used within the systematic review because of its common usage in the target journals, however, it is recognised that its origins are from the medical perspective and other terms that are more person-centred could also be chosen.

N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is a recently described autoimmune encephalopathy defined by the presence of serum antibodies that bind NMDARs (NMDAR-Abs). NMDAR-Ab encephalitis is a severe, but treatmentresponsive encephalitis with subacute onset. It can be associated with tumours and affects mainly young adults. Patients present with cognitive dysfunction, seizures, psychiatric and sleep disorders and most develop dyskinesias, autonomic instability and reduced consciousness. To explore further the NMDAR-Abs and their potential pathogenicity, a series of in vitro investigations were performed and preliminary attempts at passive transfer of disease. Human embryonic kidney (HEK) cells transfected with the NR1 and NR2B subunits, and live cultured neurons, were used first to detect NMDAR-Ab binding. Immunocytochemistry and ow cytometry demonstrated that binding to transfected HEK cells could be improved when NMDAR were presented in clusters by cotransfection with the postsynaptic density protein PSD-95. The NR1 subunit was identified as the target of NMDAR-Abs, and a novel quantitative assay based on immunoprecipitation of NR1 tagged by fusion with green uorescent protein was developed. Measurement of NMDAR-Ab levels showed that antibody levels corresponded to the clinical disease score within individual patients. Although the purification of full length NR1 was not successful, a secreted N-terminal construct was created and expressed in HEK cells. The binding of NMDAR-Abs was confirmed and this construct will be used for active immunisation in future. To explore pathogenic mechanisms in vitro, the main antibody subclasses were shown to be IgG1 and IgG3. Moreover the patients' autoantibodies, but not healthy control antibodies, were able to activate the complement cascade in vitro in cell lines and primary cultures. Finally, the NMDAR-Abs were shown to bind to primary microglial cultures and to cause morphological changes corresponding to early activation processes after prolonged exposure. The research has developed new assays that could be used for diagnosis and serial studies and revealed new potential mechanisms in NMDAR-Ab encephalitis.

BACKGROUND: The autoimmune encephalitis represents a new category of immune- mediated diseases of the brain that are mediated by antibodies against neurotransmitter receptors, ion channels or neuronal cell-surface proteins. Among the many encephalitis considered idiopathic, there are subtypes that are probably immune-mediated and are pending to be discovered. In the last 11 years, 16 subtypes of idiopathic encephalitis have been found to be immune mediated. The recognition of these disorders is important because despite being potentially lethal, they are curable if promptly recognized and treated. On a more basic level, the study of these diseases has uncovered novel antibody-mediated mechanisms of synaptic dysfunction that lead to changes in memory and behavior, epilepsy, abnormal movements, or decreased level of consciousness. OBJECTIVES: 1) Identify patients with encephalitis of unclear etiology but whose clinical features and initial investigations strongly suggest an antibody-mediated cause; 2) characterize the new autoantibodies associated with these disorders along with the neuronal target antigens, and develop unambiguous diagnostic tests, and 3) determine in animal models how autoantibodies alter the level and function of neuronal synaptic antigens (NMDAR and LGI1) potentially resulting in an impairment of memory and behavior. METHODS: Rat brain sections and primary cultures of dissociated rat hippocampal neurons served to identify patients whose serum and CSF samples contained novel neuronal antibodies. Techniques of tissue immunohistochemistry, neuronal immunocytochemistry and cell-based assays were used to identify the antibodies. Cell- surface neuronal protein immunoprecipitation with patients’ antibodies was used to isolate the target antigen, which was subsequently characterized by mass spectrometry. Cerebroventricular transfer of patients’ antibodies to mice through subcutaneously implanted mini-osmotic pumps was used to determine the pathogenic effect of patients’ antibodies on the corresponding synaptic targets and how these changes altered memory and behavior. An extensive combination of techniques was used for these studies, including quantitative confocal microscopy analysis of the levels of synaptic targets, immunoprecipitation of brain-bound antibodies, immunoblot of precipitated proteins, electrophysiology on acute sections of mice hippocampus, and a comprehensive panel of standard behavioral tests. All studies were conducted with sets of mice at different time points during the antibody infusion (disease phase) and after the infusion was stopped (recovery phase). RESULTS: (1) Two novel autoimmune encephalitis were identified: anti-GABAaR encephalitis and anti-neurexin-3α encephalitis. Anti-GABAaR encephalitis can affect children and adults, associates with prominent seizures and highly suggestive MRI abnormalities, and is treatable with immunotherapy. In some patients the immune response is triggered by the presence of a tumor. Anti-neurexin-3α encephalitis manifests with a less distinctive syndrome, often associates with seizures and is also treatable with immunotherapy. No tumor association has been identified. (2) Immunoprecipitation of the target antigen of anti-GABAaR encephalitis demonstrated that the epitopes are mainly located in the alpha1 and beta3 subunits, and less frequently in the γ2 subunit. Whereas the antibodies against alpha1 and beta3 subunits are disease relevant, the presence of additional antibodies to γ2 does not modify the disease phenotype. Patients’ GABAaR antibodies cause a decrease in the total and synaptic levels of GABAaR clusters, supporting their pathogenicity. (3) Immunoprecipitation of the target antigen of patients with anti-neurexin-3α encephalitis demonstrated that the epitopes are specifically located in neurexin-3α, but not in its postsynaptic ligand LRRTM2. Patients’ antibodies cause a reduction of the total number of synapses as well as the levels of the presynaptic protein Bassoon and the post-synaptic protein Homer1, supporting the pathogenicity of the antibodies. (4) Recombinant expression of the indicated subunits of the GABAaR and neurexin-3α in HEK293 cells can be used as a test to diagnose patients with these autoimmune encephalitis. (5) The infusion of patients’ NMDAR antibodies into the cerebroventricular system of mice, cause memory deficits, anhedonia, and depressive-like behavior. The infused antibodies specifically bind to brain NMDAR resulting in a highly specific reduction of the density of these receptors at synaptic and extrasynaptic levels. The behavioral and molecular effects caused by patients’ antibodies are reversible upon stopping the infusion of antibodies. (6) The administration of ephrin-B2 antagonizes the pathogenic effects of patients’ NMDAR antibodies in all the investigated paradigms, including memory, depressive-like behavior, density of cell-surface and synaptic NMDAR and EphB2, and long-term synaptic plasticity. These findings reveal a strategy beyond immunotherapy to antagonize patients’ antibody effects. (7) The antibodies of patients with anti-LGI1 encephalitis abrogate the binding of the neuronal secreted LGI1 with the presynaptic ADAM23 and with the postsynaptic ADAM22. (8) The infusion of patients’ LGI1 antibodies into the cerebroventricular system of mice cause protracted memory deficits, together with a decrease of presynaptic Kv1.1 potassium channels and post- synaptic AMPAR. These structural effects associate with impairment of synaptic plasticity and increase of neuronal excitability, which are in line with the models of genetic depletion of LGI1. CONCLUSIONS: (1) Anti-GABAaR and anti-neurexin-3α encephalitis are two new forms of antibody-mediated encephalitis for which there is evidence of antibody-mediated pathogenicity. These findings support the concept that among the many types of encephalitis of unclear etiology, there are some that are immune mediated but are still pending to characterize. (2) Direct neuronal antigen precipitation using patients’ antibodies is an excellent strategy to isolate and characterize disease-relevant antigens, and subsequently develop diagnostic screening tests. (3) My studies have contributed to develop two animal models of antibody-mediated symptoms (NMDAR, LGI1) and uncover the underlying antibody-mediated changes in synaptic function and plasticity. Both models fulfill the Witebsky’s criteria for antibody-mediated disease, and provide the basis for modeling other antibody-mediated neurological disorders.
INTRODUCCIÓN: La encefalitis autoimmune representa una nueva categoria de enfermedades immunomediadas del cerebro que estan mediadas por anticuerpos dirigidos contra receptores sinápticos, canales iónicos o proteinas neuronales de superfície. De entre todas las encefalitis consideradas idiopaticas, hay un subgrupo, probablemente immunomedidos, pendientes de ser identificadas. En los ultimos 11 años, 16 subtipos de encefalitis idiopaticas han sido identificadas como immunomediadas. La identificación de estas enfermedades es importante porque, aunque son potencialmente letales, son curables si se identifican rapid de nuevas en amente y se tratan. El estudio de estas enfermedades ha permitido el descubrimiento de nuevos mecanismos de alteración de la sinapsi medidados por anticuerpos que dan lugar a alteraciones de comportamiento y de memoria, epilepsia, movimientos anormales, o bajo nivel de consciencia. OBJETIVOS: 1) Identificar pacientes con encefalitis de etiologia desconocida, pero con caracteristicas clinicas y paraclinicas que sugieren una causa immunomedidada; 2) Caracterizar nuevos autoanticuerpos asociados a estos trastornos asi como las dianas antigenicas, y desarrollar pruebas diagnosticas inequivocas, y 3) determinar en modelos animales como los autoanticuerpos alteran el nivel y funcion de de los antigenos neuronales sinápticos (NMDAR y LGI1). MÉTODOS: Se usaron secciones de cerebro de rata y cultivos primarios de neuronas hipocampales de rata para la identificación de nuevos anticuerpos contra proteinas neuronales en muestras de suero y liquido cefaloraquideo (LCR) de pacientes. Para la detección de los anticuerpos se usó immunohistoquimica, immunocitoquimica de neuronas y en células HEK293 transfectadas. El aislamiento de nuevos antigeno diana se hizo mediante la immunoprecipitacion de proteinas de superficie neuronal con anticuerpos de los pacientes, y posterior caracterización por espectometria de masas. Para determinar el efecto patogenico de los anticuerpos de los pacientes, durante 14 dias los ratones fueron expuestos de manera cerebroventricular a los anticuerpos mediante la implantación subcutanea de bombas osmoticas, y posteriormente se analizó el efecto sobre las dianas antigenicas asi como alteraciones de comportamiento y memoria. Para ello, se usaron tecnicas de microscopia confocal cuantitativa de los niveles de antigenos sinápticos, immunoprecipitación de los anticuerpos unidos al tejido cerebral, immunoblot de las proteinas precipitadas, electrofisiologia en secciones de cerebro de raton, y una bateria de pruebas de comportamiento estandarizadas. Todos los estudios se realizaron en dias determinados de exposición a los anticuerpos (fase de la enfermedad), asi como después de la infusión (fase de recuperación). RESULTADOS: (1) Se identificaron dos nuevas encefalitis autoimmunes: encefalitis anti-GABAaR y encefalitis anti-neurexin-3α. La encefalitis anti-GABAaR puede afectar niños y adultos, esta asociada con crisis epilepticas y anormalidades en la resonancia magnetica del cerebro, y es tratable con immunoterapia. En algunos pacientes la respuesta immune se desencadena por la presencia de un tumor. La encefalitis anti-neurexin-3α manifiesta con un sindrome menos distintivo, a menudo se asocia con crisis epilepticas y tambien es tratable con immunoterapia. No se ha identificado asociacion tumoral. (2) La diana antigenica de los anticuerpos de la encefalitis anti-GABAaR se encuentra principalmente en las subunidades alfa1 y β3, y menos frecuentemente en la subunidad γ2. Mientras que las subunidades alfa1 y β3 son relevantes para la enfermedad, la presencia de anticuerpos adicionales contra γ2 no modifica el fenotipo de la enfermedad. Los anticuerpos anti-GABAaR producen una disminución de los niveles de GABAaR totales y sinapticos, apoyando su patogenicidad. (3) La immunoprecipitación de la diana antigenica de pacientes con encefalitis anti-neurexin-3α demostró que los epitopos estan localizados en la subunidad 3alfa, y no en su ligando postsinaptico LRRTM2. Estos autoanticuerpos causan una reducción del numero total de sinapsis asi como de la proteina presinaptica Bassoon, y de la postsinaptica Homer1, apoyando su patogenicidad. (4) La expresion recombinante de las subunidades antigenicas en celulas HEK293, pueden ser usadas como prueba diagnostica para identificar pacientes con estas encefalitis autoimmunes. (5) La infusión de anticuerpos NMDAR en el sistema cerebroventricular de ratones causa problemas de memoria, anhedonia, y comportamientos depresivos. Los anticuerpos infusionados se unen especificamente a los receptores NMDA del cerebro y provocan la disminución de la densidad de dichos receptores a nivel sinaptico y extrasinaptico. Estos efectos son reversibles despues de la suspension de la infusion de anticuerpos. (6) La administracion de ephrin-B2 antagoniza el efecto patogenico de los anticuerpos contra NMDAR de los pacientes, incluyendo los efectos de memoria, depresion, densidad de receptores NMDA y EphB2, y plasticidad sinaptica a largo plazo, pudiendo ser usado como estrategia terapeutica. (7) Los anticuerpos de los pacientes con encefalitis anti-LGI1 impiden la unión entre la proteina neuronal secretada LGI1 y la proteina presinaptica ADAM23 y la postsinaptica ADAM22. (8) La infusión de anticuerpos de los pacientes contra LGI1 en el sistema cerebroventricular de los ratones causa problemas de memoria, asi como disminución de los niveles de canales de potasio Kv1.1 presinapticos y de receptores AMPA postsinapticos. Estos efectos se asocian a una alteración de la plasticidad sinaptica e incremento de excitabilidad neuronal, de manera similar a los modelos de depleción genetica de LGI1. CONCLUSIONES: (1) Las encefalitis Anti-GABAaR y anti-neurexin-3α encephalitis son dos nuevas formas de encefalitis mediadas por anticuerpos. Hay evidencia que sostiene que estos anticuerpos son patogenicos, apoyando el concepto de que hay encefalitis sin caracterizar dentro de las muchas formas de encefalitis de causa desconocida. (2) La precipitación del antigeno neuronal es una estrategia excelente para aislar y caracterizar antigenos relevantes para la enfermedad, y poder desarrollar pruebas de detección. (3) Estos estudios han contribuido a desarrollar dos modelos animales de infusión de anticuerpos de encefalitis autoimmunes (NMDAR, LGI1) y a descubrir los cambios subyacentes mediados por anticuerpos en la función sináptica y la plasticidad. Los dos modelos cumplen con los criterios de Witebsky para enfermedades immunomediadas, y proporcionan la base para modelar otros trastornos neurológicos mediados por anticuerpos.

Background: Autoimmune encephalitis (AIE) is the main cause of non-infectious encephalitis and results from the peripheral immune response against cell surface antigens in the central nervous system. The clinical presentations are varied and known triggers are tumors and herpetic infections. Arboviruses Zika (ZIKV), Dengue (DENGV) and Chikungunya (CHIKV) are neurotropic infections that present neurological manifestations whose mechanism is unknown. Objective: Verify the frequency of arboviruses antibodies in patients with autoimmune encephalitis in a Brazilian cohort Design and setting: It is a transversal study performed by Hospital Israelita Albert Einstein in Brazil Methods: Patients who met the criteria for probable AIE (Graus 2016) evaluated at the 18 centers of the BrAIN network were included. Clinical, epidemiological and laboratory data were compiled. Antineuronal antibodies were detected using TBA, CBA and immunoblot in serum and CSF; antibodies against ZIKV, DENGV and CHIKV were detected by ELISA. The cohort was divided into two groups: seropositive encephalitic (SPE) and non-encephalitic (NE) and the frequencies of viral serologies were compared. Results: Among 619 patients included in the BrAIN cohort, serology for arboviruses was performed in 482 patients, being 79 SPE and 99 NE. The SPEgroup showed the following frequency of antibodies: 58.2% anti-NMDA, 7.6% antiLGI1, 6.3% anti-Caspr2, 2.5% anti-GABA B, 1.3% anti-GABA A, 3.8% anti-AMPAr, 1.3% anti-AQ4, 8.9% anti-MOG, 1.3% anti-IgLON5, 7.6% anti-GlyR and 5.1% others. The frequency of serology was IgG DENG (SPE 42.3% X NP 43.4%, p = 0.82); IgG CHIK (SPE 16.5% X 3.1% NP, p = 0.001); IgG ZIKV (SPE31.6% X NP 28.3%, p = 0.62). The frequency of triple positive serology (IgG DENG, ZIKV, CHIK) was 11.39% (SPE X 2.02% NP, p = 0.009). Conclusions: Patients with SPE have IgG CHIKV antibodies most commonly. In addition, they present a higher frequency of positivity for IgG CHIKV, ZIKV, DENGV simultaneously. Future studies should assess the association between arboviruses as a trigger for AIE or as a marker of susceptibility to immunological alteration.

Background: Autoimmune encephalitis (AIE) is the main differential diagnosis of infectious encephalitis. Brain MRI is normal in up to 50% of cases and studies indicate that changes in FDG-PET/CT are more frequent and early. Objectives: To describe FDG-PET/CT findings in patients with AIE of Hospital Israelita Albert Einstein (HIAE) from 2015-2020. Design and setting: Retrospective cross-sectional study at HIAE. Methods: Medical records of patients with suspected AIE were reviewed. Laboratory results were compiled, and images were reassessed. Results: Amongst 250 records, we found 7.6% (n=19) of AIE, being 8 seropositive (5 anti-NMDA, 1 anti-CASPR2, 1 anti-MOG, 1 anti-VGKC and 1 anti-LGI1), 5 seronegative and 4 limbic encephalitis. The mean age was 48-22 years, 52% male. In encephalitic patients, the most common manifestations were epilepsy (78%), cognitive changes (63%), and behavioral changes (63%). Only 57% had abnormal MRI. We evaluated 23 PET/CTs at different stages of treatment; of the 9 FDG-PET/CTs performed at initial presentation, 88% were abnormal and 30% had normal MRI. Most frequent patterns found were hypometabolism in frontal (59.1%), temporal (39.1%) and left parietal (39.1%) regions. In follow-up, only 2 patients normalized FDG-PET/CT, with clinical improvement. Conclusions:FDG-PET/CT was altered in 88% of patients. In this series, no typical PET/CT pattern was demonstrated for AIE; the most frequent findings were hypometabolism in cortical areas, which also occur in degenerative diseases. We did not find hypermetabolism, or mixed areas of hypo- and hypermetabolism. The specificity of PET/CT for AIE diagnosis should be evaluated in future studies.