RESUMO
Autoimmune encephalitis (AE) is a group of inflammatory conditions that can associate with the presence of antibodies directed to neuronal intracellular, or cell surface antigens. These disorders are increasingly recognized as an important differential diagnosis of infectious encephalitis and of other common neuropsychiatric conditions. Autoantibody diagnostics plays a pivotal role for accurate diagnosis of AE, which is of utmost importance for the prompt recognition and early treatment. Several AE subgroups can be identified, either according to the prominent clinical phenotype, presence of a concomitant tumor, or type of neuronal autoantibody, and recent diagnostic criteria have provided important insights into AE classification. Antibodies to neuronal intracellular antigens typically associate with paraneoplastic neurological syndromes and poor prognosis, whereas antibodies to synaptic/neuronal cell surface antigens characterize many AE subtypes that associate with tumors less frequently, and that are often immunotherapy-responsive. In addition to the general features of AE, we review current knowledge on the pathogenic mechanisms underlying these disorders, focusing mainly on the potential role of neuronal antibodies in the most frequent conditions, and highlight current theories and controversies. Then, we dissect the crucial aspects of the laboratory diagnostics of neuronal antibodies, which represents an actual challenge for both pathologists and neurologists. Indeed, this diagnostics entails technical difficulties, along with particularly interesting novel features and pitfalls. The novelties especially apply to the wide range of assays used, including specific tissue-based and cell-based assays. These assays can be developed in-house, usually in specialized laboratories, or are commercially available. They are widely used in clinical immunology and in clinical chemistry laboratories, with relevant differences in analytic performance. Indeed, several data indicate that in-house assays could perform better than commercial kits, notwithstanding that the former are based on non-standardized protocols. Moreover, they need expertise and laboratory facilities usually unavailable in clinical chemistry laboratories. Together with the data of the literature, we critically evaluate the analytical performance of the in-house vs commercial kit-based approach. Finally, we propose an algorithm aimed at integrating the present strategies of the laboratory diagnostics in AE for the best clinical management of patients with these disorders.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Neoplasias , Humanos , Encefalite/diagnóstico , Encefalite/etiologia , Autoanticorpos , Antígenos de Superfície , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/complicaçõesRESUMO
Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABAA-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABAA-R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABAA-R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABAA-R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABAA-R and LMO5 is frequent in GABAA-R encephalitis and supports the hypothesis of a paraneoplastic etiology.
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Antígenos de Neoplasias/imunologia , Autoanticorpos/imunologia , Reações Cruzadas/imunologia , Suscetibilidade a Doenças , Encefalite/etiologia , Receptores de GABA-A/imunologia , Autoantígenos/imunologia , Doenças Autoimunes do Sistema Nervoso/etiologia , Doenças Autoimunes do Sistema Nervoso/metabolismo , Autoimunidade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Suscetibilidade a Doenças/imunologia , Encefalite/metabolismo , Encefalite/patologia , Humanos , Células Piramidais/imunologia , Células Piramidais/metabolismoRESUMO
BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.
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Encefalite , Infecções por HIV , Encefalite Infecciosa , Humanos , Encefalite/diagnóstico , Encefalite/epidemiologia , Encefalite/etiologia , Herpesvirus Humano 3 , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Encefalite Infecciosa/complicações , Estudos Prospectivos , Pessoa de Meia-Idade , IdosoRESUMO
Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.
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Encefalite , Transplante de Rim , Meningite , Humanos , Estudos Retrospectivos , Estudos de Coortes , Transplante de Rim/efeitos adversos , Meningite/complicações , Meningite/diagnóstico , Encefalite/diagnóstico , Encefalite/epidemiologia , Encefalite/etiologiaRESUMO
INTRODUCTION: Various neurologic manifestations have already been described in children during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The central nervous system disorders reported in children are mainly encephalopathies during multisystem inflammatory syndrome. We present here an acute meningoencephalitis with cerebral vasculitis associated to a coronavirus disease 2019 (COVID-19) infection in a 13-year-old girl with a 1-year clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) follow-up. CASE REPORT: A 13-year-old girl presented acute symptoms of consciousness impairment, frontal headache, hyperthermia, and aphasia, with moderate lymphopenia (900/mm3), elevated C-reactive protein (17 mg/L), cerebrospinal fluid (CSF) pleocytosis (15 cells/mm3), slow background with frontal focalization on EEG, a left frontal ischemic lesion, leptomeningeal enhancement, and bilateral limbic fluid-attenuated inversion recovery hyperintensity on cerebral MRI. Reverse transcription-polymerase chain reaction for SARS-CoV-2 was positive in nasopharyngeal swab and COVID serology was positive for immunoglobulin (Ig) M and G, whereas extensive autoimmune antibody investigation was negative except for a positive low titer of anti-myelin oligodendrocyte glycoprotein in CSF and blood. The diagnosis of probable encephalitis associated to cerebral vasculitis after COVID infection was suggested and steroids pulse were started. She recovered within a few days. Six months later, she had moderate clinical sequels including persistent intermittent headaches, an isolated spatial deficit, and focal spikes on the EEG without argument for epilepsia. CONCLUSION: A teenager without previous medical history presented with acute encephalitis with leptomeningitis and vasculitis after a recent COVID-19 infection. Steroids pulse therapy allowed clinical improvement. Cerebral MRI and EEG helped diagnosis, follow-up of the encephalitis, and evolution after treatment.
Assuntos
COVID-19 , Encefalite , Meningoencefalite , Vasculite do Sistema Nervoso Central , Feminino , Humanos , COVID-19/complicações , SARS-CoV-2 , Meningoencefalite/complicações , Meningoencefalite/tratamento farmacológico , Encefalite/tratamento farmacológico , Encefalite/etiologia , Corticosteroides , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/tratamento farmacológicoRESUMO
PURPOSE: Autoimmune encephalitis is a neurological emergency of new-onset altered mental status, caused by an exaggerated immune-mediated response that targets the central nervous system. Autoimmune encephalitis has become an emerging differential diagnosis, when a classical infection cannot explain neurological symptoms. Displaying overlapping clinical presentations, ranging from the insidious onset of cognitive deficiency to more severe forms of encephalopathy with refractory seizures, autoimmune encephalitis can be challenging for clinicians. When evidence of malignancy is absent and pathogenic autoantibodies are undetected, with typical clinical and imaging features of autoimmune encephalitis, seronegative autoimmune encephalitis may be considered. Recently, vaccination-related autoimmune encephalitis and acute encephalitis after COVID-19 vaccination have attracted attention. METHODS AND RESULTS: We report a case series consisting of three patients with autoimmune encephalitis occurring shortly after COVID-19 vaccination and a current review of all previous reported autoimmune encephalitis related to COVID-19 vaccines. CONCLUSION: We emphasise on the prompt diagnosis of autoimmune encephalitis induced by Covid-19 vaccines and its timely treatment to improve the clinical outcome of this severe neurological condition. Post-licencing vaccine safety surveillance for potential adverse events is essential for vaccine safety and public confidence.
Assuntos
Doenças Autoimunes do Sistema Nervoso , COVID-19 , Encefalite , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Encefalite/diagnóstico , Encefalite/etiologia , Teste para COVID-19Assuntos
Pessoal Administrativo , COVID-19/complicações , Pessoas com Deficiência/legislação & jurisprudência , Política de Saúde , Direitos Humanos , Formulação de Políticas , Adulto , COVID-19/economia , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/psicologia , Direitos Civis , Eficiência , Encefalite/etiologia , Encefalite/virologia , Feminino , Herpesvirus Humano 4/patogenicidade , Hospitalização/estatística & dados numéricos , Direitos Humanos/normas , Humanos , Influenza Pandêmica, 1918-1919/estatística & dados numéricos , Esclerose Múltipla/etiologia , Esclerose Múltipla/virologia , Doença de Parkinson Pós-Encefalítica/etiologia , Doença de Parkinson Pós-Encefalítica/virologia , Direito à Saúde , Estigma Social , Síndrome de COVID-19 Pós-AgudaRESUMO
It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.
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Autoanticorpos , Encefalite , Feminino , Humanos , Encefalite/tratamento farmacológico , Encefalite/etiologia , Terapia de Imunossupressão/efeitos adversos , FígadoRESUMO
Monkeypox is a global health issue caused by the monkeypox virus. It can spread from person to person through respiratory secretions, direct exposure to dermatological lesions of infected patients, or exposure to contaminated objects. It is more common in homosexual men, and most patients are asymptomatic. The gold standard for diagnosis is a real-time polymerase chain reaction. In the absence of testing facilities, clinicians rely upon detailed history to exclude other causes of fever with rashes. Initially, there is a prodrome phase of a few days, which is followed by the appearance of rashes. The dermatological manifestations are in the form of an exanthematous rash, which transforms through a macular, papular, and vesicular phase and disappears after crusting in approximately 3 weeks. There can be associated lymphadenopathy in these patients. Respiratory manifestations include nasal congestion and shortness of breath that may result in secondary bacterial infections. Additionally, patients can have neurological involvement in the form of encephalitis. Furthermore, ocular involvement can occur in the form of conjunctivitis, keratitis, and corneal ulceration. Other symptoms can include diarrhea, vomiting, myalgia, and backache. Since most patients do not require hospitalization, the approach to treatment is mainly vigilant monitoring, antiviral therapy, and management of associated complications.
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Mpox , Mpox/complicações , Mpox/diagnóstico , Mpox/fisiopatologia , Mpox/terapia , Humanos , Monkeypox virus/genética , Monkeypox virus/isolamento & purificação , Monkeypox virus/patogenicidade , Exantema/etiologia , Exantema/virologia , Linfadenopatia/etiologia , Linfadenopatia/virologia , Dispneia/etiologia , Dispneia/virologia , Encefalite/etiologia , Encefalite/virologia , Conjuntivite/etiologia , Conjuntivite/virologia , Ceratite/etiologia , Ceratite/virologia , Úlcera da Córnea/etiologia , Úlcera da Córnea/virologiaRESUMO
Antibodies against neuronal receptors and synaptic proteins are associated with a group of ill-defined central nervous system (CNS) autoimmune diseases termed autoimmune encephalitides (AE), which are characterized by abrupt onset of seizures and/or movement and psychiatric symptoms. Basal ganglia encephalitis (BGE), representing a subset of AE syndromes, is triggered in children by repeated group A Streptococcus (GAS) infections that lead to neuropsychiatric symptoms. We have previously shown that multiple GAS infections of mice induce migration of Th17 lymphocytes from the nose into the brain, causing blood-brain barrier (BBB) breakdown, extravasation of autoantibodies into the CNS, and loss of excitatory synapses within the olfactory bulb (OB). Whether these pathologies induce functional olfactory deficits, and the mechanistic role of Th17 lymphocytes, is unknown. Here, we demonstrate that, whereas loss of excitatory synapses in the OB is transient after multiple GAS infections, functional deficits in odor processing persist. Moreover, mice lacking Th17 lymphocytes have reduced BBB leakage, microglial activation, and antibody infiltration into the CNS, and have their olfactory function partially restored. Th17 lymphocytes are therefore critical for selective CNS entry of autoantibodies, microglial activation, and neural circuit impairment during postinfectious BGE.
Assuntos
Encéfalo/patologia , Modelos Animais de Doenças , Encefalite/etiologia , Encefalomielite Autoimune Experimental/etiologia , Doença de Hashimoto/etiologia , Transtornos do Olfato/etiologia , Infecções Estreptocócicas/complicações , Células Th17/imunologia , Animais , Autoanticorpos/imunologia , Gânglios da Base/imunologia , Gânglios da Base/patologia , Barreira Hematoencefálica , Encéfalo/imunologia , Encefalite/metabolismo , Encefalite/patologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Doença de Hashimoto/metabolismo , Doença de Hashimoto/patologia , Camundongos , Microglia/imunologia , Microglia/patologia , Neurônios/imunologia , Neurônios/patologia , Transtornos do Olfato/metabolismo , Transtornos do Olfato/patologia , Percepção Olfatória , Streptococcus pyogenes/fisiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/patologiaRESUMO
Since few years, a new etiology of epilepsy emerges with the labelling of new autoantibodies against the central nervous system. In 2017, the International League Against Epilepsy (ILAE) concluded that autoimmunity is one of six etiologies contributing to epilepsy and that autoimmune epilepsy is directly caused by immune disorders in which seizures constitute a core symptom. Epileptic disorders of immune origin are now distinguished in two different entities: acute symptomatic seizures secondary to autoimmune (ASS) and autoimmune-associated epilepsy (AAE) with different expected clinical outcome under immunotherapy. If acute encephalitis is usually related to ASS with a classic good control of the disease under immunotherapy, clinical phenotype characterized by isolated seizures (new onset seizures and chronic focal epilepsy patients) may be due to either ASS or to AAE. Decision of Abs testing and early immunotherapy initiation needs the development of clinical scores able to select patients with high risk of positive Abs testings. If this selection is now included in the usual medical care of encephalitic patients, specifically with NORSE, the actual bigger challenge is in patients with non or only mild encephalitic symptoms followed for new onset seizures or chronic focal epilepsy patients of unknown origin. The emergence of this new entity provides new therapeutic strategies with specific etiologic and probably anti epileptogenic medication rather than the usual and nonspecific ASM. In the world of the epileptology, this new autoimmune entity appears as a big challenge with an exciting chance to improve or even definitely cure patients of their epilepsy. However, the detection of these patients has to be done in the early phase of the disease to offer the best outcome.
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Encefalite , Epilepsias Parciais , Epilepsia , Autoanticorpos , Autoimunidade , Encefalite/diagnóstico , Encefalite/etiologia , Encefalite/terapia , Epilepsias Parciais/complicações , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/terapia , Convulsões/diagnóstico , HumanosRESUMO
Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing ('metatranscriptomics') to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.
Assuntos
Encefalite , Vírus , Austrália , Criança , Encefalite/diagnóstico , Encefalite/etiologia , Humanos , Metagenômica , Reação em Cadeia da PolimeraseRESUMO
PURPOSE OF REVIEW: Autoimmune encephalitis (AE) refers to immune-mediated neurological syndromes often characterised by the detection of pathogenic autoantibodies in serum and/or cerebrospinal fluid which target extracellular epitopes of neuroglial antigens. There is increasing evidence these autoantibodies directly modulate function of their antigens in vivo. Early treatment with immunotherapy improves outcomes. Yet, these patients commonly exhibit chronic disability. Importantly, optimal therapeutic strategies at onset and during escalation remain poorly understood. In this review of a rapidly emerging field, we evaluate recent studies on larger cohorts, registries, and meta-analyses to highlight existing evidence for contemporary therapeutic approaches in AE. RECENT FINDINGS: We highlight acute and long-term treatments used in specific AE syndromes, exemplify how understanding disease pathogenesis can inform precision therapy and outline challenges of defining disability outcomes in AE. SUMMARY: Early first-line immunotherapies, including corticosteroids and plasma exchange, improve outcomes, with emerging evidence showing second-line immunotherapies (especially rituximab) reduce relapse rates. Optimal timing of immunotherapy escalation remains unclear. Routine reporting of outcome measures which incorporate cognitive impairment, fatigue, pain, and mental health will permit more accurate quantification of residual disability and comprehensive comparisons between international multicentre cohorts, and enable future meta-analyses with the aim of developing evidence-based therapeutic guidelines.
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Encefalite , Doença de Hashimoto , Autoanticorpos , Encefalite/diagnóstico , Encefalite/etiologia , Encefalite/terapia , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , SíndromeRESUMO
BACKGROUND: Vaccination is an important public health strategy; however, many neurological adverse effects are associated with COVID-19 vaccination, being encephalitis a rare manifestation. CASE PRESENTATION: We present the case of a 33-year-old woman who received the first dose of the BBIBP-CorV vaccine against COVID-19 on April 4 and the second dose on April 28, 2021. Three days after receiving the second dose, she experienced a subacute episode of headache, fever, insomnia, and transient episodes of environment disconnection. We obtained negative results for infectious, systemic, and oncological causes. Brain magnetic resonance imaging showed lesions in the bilateral caudate nucleus and nonspecific demyelinating lesions at the supratentorial and infratentorial compartments. The results of the neuronal autoantibodies panel were negative. She had an adequate response to immunoglobulin and methylprednisolone; however, she experienced an early clinical relapse and received a new cycle of immunosuppressive treatment followed by a satisfactory clinical evolution. CONCLUSIONS: We report the first case of severe encephalitis associated with BBIBP-CorV (Sinopharm) vaccination in Latin America. The patient had atypical imaging patterns, with early clinical relapse and a favorable response to corticosteroid therapy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Encefalite , Adulto , Feminino , Humanos , Vacinas contra COVID-19/efeitos adversos , Encefalite/tratamento farmacológico , Encefalite/etiologia , Encefalite/patologia , Recidiva , VacinaçãoRESUMO
Rasmussen's encephalitis (RE) is a rare condition of unknown etiology that causes a severe chronically neurological disorder with mostly affecting children. The main clinical feature of RE includes frequent seizures with drug-resistant, unilateral hemispheric atrophy, and progressive neurological deficits. In this review, we summarized five pathogenesis on the basis of the current research including virus infection, antibody-mediated degeneration, cell-mediated immunity, microglia-induced degeneration, and genetic mutations. So far, no exact virus in RE brain tissue or definite antigen in humoral immune system was confirmed as the determined etiology. The importance of cytotoxic CD8+ T lymphocytes and activated microglial and the role of their immune mechanism in RE development are gradually emerging with the deep study. Genetic researches support the notion that the pathogenesis of RE is probably associated with single nucleotide polymorphisms on immune-related genes, which is driven by affecting inherent antiretroviral innate immunity. Recent advances in treatment suggest immunotherapy could partially slows down the progression of RE according to the histopathology and clinical presentation, which aimed at the initial damage to the brain by T cells and microglia in the early stage. However, the cerebral hemispherectomy is an effective means to controlling the intractable seizure, which is accompanied by neurological complications inevitably. So, the optimal timing for surgical intervention is still a challenge for RE patient. On the contrary, exploration on other aspects of pathogenesis such as dysfunction of adenosine system may offer a new therapeutic option for the treatment of RE in future.
Assuntos
Encefalite , Hemisferectomia , Criança , Humanos , Encefalite/etiologia , Encefalite/terapia , Encéfalo , Convulsões , Atrofia/patologiaRESUMO
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.
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Lesões Encefálicas Traumáticas/patologia , Neurônios/patologia , Sinapses/patologia , Animais , Astrócitos/patologia , Axônios/patologia , Lesões Encefálicas Traumáticas/complicações , Encefalite/etiologia , Encefalite/patologia , Humanos , Estresse OxidativoRESUMO
PURPOSE: The BioFire FilmArray® Meningitis/Encephalitis Panel (FAMEP) is designed to rapidly and accurately detect common multiple pathogens that cause central nervous system (CNS) infection, including viruses, bacteria, and yeast. The FAMEP's usefulness in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully evaluated. This retrospective study evaluated the usefulness of the FAMEP in the screening for CNS infection after allogeneic HSCT. METHODS: Cerebrospinal fluid (CSF) was obtained from 12 patients to evaluate the causes of CNS disorders after allogeneic HSCT, and the FAMEP was applied. RESULTS: The median day of the FAMEP evaluations was 27 days post-transplant (range, 0-390). Human herpesvirus 6 (HHV-6) was detected in three patients and cytomegalovirus was detected in one patient, leading to the diagnosis of encephalitis/myelitis. In three patients (HHV-6, n = 2; CMV, n = 1), the presence of the viruses was confirmed by conventional real-time polymerase chain reaction (PCR). However, in the remaining patient with HHV-6 detected by the AMEP, HHV-6 was not detected by real-time PCR at the onset but was detected 7 days later. The treatments for the detected viruses improved the clinical conditions in the four patients. CONCLUSIONS: Our results suggest that the FAMEP can be a useful sensitive assay in the screening and diagnosis of CNS viral infections after allogeneic HSCT.
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Infecções do Sistema Nervoso Central , Encefalite , Transplante de Células-Tronco Hematopoéticas , Meningite , Infecções por Roseolovirus , Encefalite/diagnóstico , Encefalite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos RetrospectivosRESUMO
INTRODUCTION: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease, is a rare benign self-limiting inflammatory disease often seen in young adults. The main clinical features are fever with cervical lymphadenopathy. Neurological complications of Kikuchi-Fujimoto disease were occasionally reported although the specific pathogenesis was not clear. The condition could be severe when encephalitis coexists. METHODS: Here we reported a young case of Kikuchi-Fujimoto disease with subsequent severe autoimmune encephalitis. RESULTS: The symmetric striatal and limbic MRI lesions combined with psycho-cognitive, epileptic symptoms supported encephalitis. Tissue-based immunofluorescence revealed widely cytoplasmic fluorescence in rat cerebellar and hippocampal neurons, which provide evidence for immune-mediated encephalitis. The clinical outcome was satisfactory after immunosuppressive therapy with MRI lesions largely disappeared. CONCLUSION: The encephalitis complication of Kikuchi disease may be autoimmune and mediated by cytotoxic T cells.
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Encefalite , Doença de Hashimoto , Linfadenite Histiocítica Necrosante , Linfadenopatia , Encefalite/complicações , Encefalite/etiologia , Febre/complicações , Doença de Hashimoto/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/diagnóstico por imagem , Humanos , Linfadenopatia/complicações , Linfadenopatia/diagnóstico , Adulto JovemRESUMO
INTRODUCTION: Post-ChAdOx1 vaccine (AZD1222) adverse events following immunization (AEFI) are uncommon. Recently described neurological events include thrombocytopenia with thrombosis syndrome (TTS) with cerebral venous thrombosis and Guillain-Barré syndrome. There are very few AEFI reports following COVID vaccination from India, because of underreporting or other factors. A few cases of acute transverse myelitis (ATM) and post-vaccinal encephalitis have also been reported. MATERIALS AND METHODS: Over 11 months, in 2 districts of Kerala, India, 8.19 million people were vaccinated with the ChAdOx1 vaccine. RESULTS: During this period, we encountered five cases of autoimmune central nervous system (CNS) AEFI following ChAdOX1 (Oxford/AstraZeneca, Covishield™) vaccination. These included three cases of acute disseminated encephalomyelitis (ADEM), one case of opsoclonus myoclonus ataxia syndrome (OMAS), and one case of limbic encephalitis. The calculated crude incidence of post-ChAdOX1 autoimmune CNS AEFI was approximately 0.24 cases per million for encephalitis and 0.36 per million for ADEM. This was compared to the crude annual incidence of community-acquired ADEM worldwide (3.2-4 per million) and the crude annual incidence of community-acquired encephalitis in India (8.35-10 per million). CONCLUSION: There was no increase in the incidence of post-vaccination CNS AEFI (ADEM or encephalitis) as compared to the community incidence of ADEM or encephalitis. While this emphasizes the safety of ChAdOX1 nCoV-19 vaccination for COVID-19, it is important to recognize these post-vaccination autoimmune syndromes early to initiate immunosuppressive therapy.
Assuntos
COVID-19 , Encefalite , Encefalomielite Aguda Disseminada , Síndrome de Opsoclonia-Mioclonia , Vacinas , Vacinas contra COVID-19/efeitos adversos , Sistema Nervoso Central , ChAdOx1 nCoV-19 , Encefalite/etiologia , Humanos , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS) tend to suffer from several central nervous system (CNS) infections due to hypoimmunity. However, CNS aspergillosis (CNSAG) is extremely rare and difficult to diagnose. Thus, it is easily misdiagnosed. CASE PRESENTATION: We reported a 47-year-old male AIDS patient with ghosting vision and anhidrosis on the left head and face. He was accordingly diagnosed with Toxoplasma gondii encephalitis (TE) at other hospitals, for which he received regular anti-Toxoplasma gondii and anti-human immunodeficiency virus (anti-HIV) treatment. Then, the patient was transferred to our hospital due to a lack of any improvement with the prescribed treatment. The patient's neurological examination revealed no abnormalities at admission, only a slight change in the cerebrospinal fluid. His cranial magnetic resonance imaging (MRI) revealed multiple abnormal signals in the brain parenchyma, and his blood was positive for Toxoplasma gondii IgG antibody. The initial diagnosis at our hospital was also TE. Considering the poor efficacy of anti-TE treatment, cerebrospinal fluid metagenomics next-generation sequencing (mNGS) was performed, but no pathogenic bacteria were detected. However, Aspergillus fumigatus was detected in the cerebrospinal fluid via targeted next-generation sequencing (tNGS) and bronchoalveolar alveolar lavage fluid via mNGS. The diagnosis was accordingly revised to CNSAG combined with his other clinical manifestations. After administering voriconazole antifungal therapy, the patient's symptoms were relieved, with improved absorption of the intracranial lesions. CONCLUSIONS: The present case experience indicates the need for clinicians to strengthen their understanding of CNSAG. Moreover, for patients with diagnostic difficulties, early mNGS and tNGS (using biological samples with only a few pathogens) are helpful for early diagnosis and treatment, potentially allowing patients to achieve favorable outcomes.