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1.
Signal Transduct Target Ther ; 8(1): 24, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609561

RESUMO

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.


Assuntos
COVID-19 , Encefalite , Humanos , Monócitos , COVID-19/genética , Autopsia , Proteômica , Fator A de Crescimento do Endotélio Vascular
2.
J Int Med Res ; 51(1): 3000605221149879, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36694984

RESUMO

We herein report two cases involving children who died of influenza A (H3N2) virus infection-associated encephalopathy/encephalitis (IAE). Both children developed convulsions and impaired consciousness within a relatively short period and eventually died of brainstem failure. Patient 1 presented with high fever, vomiting, and diarrhea. Laboratory tests indicated persistently high lactate, alanine aminotransferase, and urea nitrogen concentrations in the blood as well as a high protein concentration in the cerebrospinal fluid. Patient 2 presented with persistent hyperthermia and progressive disturbance of consciousness, but the cerebrospinal fluid remained normal during the disease course. Both patients were actively given oseltamivir antiviral treatment after diagnosis of influenza virus infection. However, the disease progressed and invasive mechanical ventilation was performed. Both children's condition quickly progressed to IAE, and they eventually died. IAE is a rare complication of influenza virus infection with high mortality, and its pathogenesis remains unclear. The purpose of this report is to draw attention to the serious central nervous system complications of influenza infection and raise awareness of the fatal consequences of this disease among pediatricians.


Assuntos
Encefalopatias , Encefalite , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Criança , Influenza Humana/diagnóstico , Vírus da Influenza A Subtipo H3N2 , Encefalopatias/complicações , Encefalopatias/diagnóstico , Oseltamivir/uso terapêutico
3.
Viruses ; 15(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36680228

RESUMO

More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study ("BoDV-1 after solid-organ transplantation") to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.


Assuntos
Doença de Borna , Vírus da Doença de Borna , Encefalite Transmitida por Carrapatos , Encefalite Viral , Encefalite , Infecções por Flavivirus , Animais , Humanos , Vírus da Doença de Borna/genética , Doença de Borna/epidemiologia , Doença de Borna/genética , Encefalite Viral/epidemiologia , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Alemanha/epidemiologia
4.
J Clin Virol ; 159: 105356, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608619

RESUMO

BACKGROUND: Mpox (formerly monkeypox) is an emerging zoonotic disease of public health concern that presents as a rash mimicking other common viral exanthems. Unlike traditional testing algorithms relying on several assays, the BioFire FilmArray meningitis/encephalitis (ME) panel simultaneously detects common viruses causing rashes; however, Biofire ME is only licensed for testing on cerebral spinal fluid. OBJECTIVES: This study evaluated use of the Biofire ME panel for detection and discrimination of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human herpesviruses type 6 (HHV-6), enteroviruses (EVs), and human paraechoviruses (HPeVs) from a dermal or mucocutaneous swabs collected in universal transport media (UTM). STUDY DESIGN: Results of the BioFire ME panel were compared against methods used during clinical testing. Ten-fold serial dilutions in UTM of cultured viruses were used to compare analytical sensitivity, and analytical specificity was assessed using panels of microorganisms in UTM. Clinical sensitivity and specificity were assessed using 20 positive specimens each for HHV-1, HHV-2, HHV-6, VZV, EVs, and HPeV, as well as 35 known negative specimens that included 15 mpox-positive specimens. RESULTS: Biofire ME was as sensitive as comparator methods, and correctly discriminated all HSV-1, HSV-2, VZV, HHV-6, EVs, and HPeVs from mpox and mpox-mimickers. Cross-reaction between EV and rhinoviruses A, B, and C were noted in the specificity panel. CONCLUSIONS: Swabs in UTM collected for mpox testing are suitable for use on the Biofire ME panel, allowing more streamlined diagnostic testing for viral exanthems in patients under investigation for mpox infection.


Assuntos
Encefalite , Herpesvirus Humano 1 , Herpesvirus Humano 6 , Meningite , Varíola dos Macacos , Viroses , Vírus , Humanos , Caça , Viroses/diagnóstico , Herpesvirus Humano 3 , Herpesvirus Humano 2 , Encefalite/etiologia
5.
Cells ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36672216

RESUMO

Autoimmune encephalitis (AE) associated with autoantibodies against leucine-rich glioma-inactivated protein-1 (LGI1) can present with faciobrachial dystonic seizures (FBDS) and/or limbic encephalitis (LE). The reasons for this heterogeneity in phenotypes are unclear. We performed autoantibody (abs) characterization per patient, two patients suffering from LE and two from FBDS, using isolated antibodies specified with single amino acid epitope mapping. Electrophysiological slice recordings were conducted alongside spine density measurements, postsynaptic Alpha-amino-3-hydoxy-5-methyl-4-isoaxole-proprionate-receptors (AMPA-R) and N-methyl-D-aspartate-receptors receptor (NMDA-R) cluster counting. These results were correlated with the symptoms of each patient. While LGI1 abs from LE patients mainly interacted with the Leucine-rich repeat section of LGI1, abs from both FBDS patients also recognized the Epitempin section as well. Six-hour incubation of mouse hippocampal slices with LE patients autoantibodies but not from the FBDS patients resulted in a significant decline in long-term potentiation (p = 0.0015) or short-term plasticity at CA3-CA1 neurons and in decreased hippocampal synaptic density. Cluster differentiation showed no decrease in postsynaptic AMPA-R and NMDA-R. LGI1 autoantibodies selected by phenotype show an almost distinct epitope pattern, elicit disparate functional effects on hippocampal neurons, and cause divergent effects on spine density. This data illuminates potential pathomechanisms for disease heterogeneity in LGI1 AE.


Assuntos
Encefalite , Encefalite Límbica , Animais , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular , Leucina , N-Metilaspartato , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Autoanticorpos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico , Convulsões/complicações , Fenótipo
6.
J Psychiatr Pract ; 29(1): 82-89, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649557

RESUMO

Catatonia can be associated with multiple physical and mental illnesses, and idiopathic catatonia is a well-recognized clinical entity. Here we report a case of recurrent idiopathic catatonia with underlying immunologic abnormalities, with an emphasis on etiological hypotheses. An 18-year-old female with mild learning disability, dyspraxia, autoimmune hypothyroidism, and nonceliac gluten intolerance was referred to mental health services after developing an episode of catatonia following tonsillitis. She had experienced 2 previous episodes suggestive of catatonia, one of which developed after a snakebite and the other after a viral infection. Samples of cerebrospinal fluid and whole blood tested positive for human herpesvirus (HHV) on DNA-polymerase chain reaction testing during her third episode, but the patient had no signs of encephalitis. She responded well to lorazepam but developed significant side effects with low-dose olanzapine and aripiprazole. She returned to her usual baseline with medical management. Very little is known about possible etiologies of recurrent idiopathic catatonia. An atypical response to an HHV infection is a likely cause of one of the episodes in this case. There is substantial evidence connecting immune dysregulation to mental illnesses. Proinflammatory effects of latent HHV, proinflammatory genetic polymorphisms related to learning disability, and autoimmune dysfunction are likely factors that may have contributed to the development of recurrent catatonia following external antigen exposure in this case. Future research should focus on immune-mediated etiologies of catatonia, the role of immunotherapy in the treatment of idiopathic catatonia, and systems research to improve multidisciplinary management of neuropsychiatric disorders.


Assuntos
Catatonia , Encefalite , Transtornos Mentais , Feminino , Humanos , Adolescente , Catatonia/diagnóstico , Lorazepam/uso terapêutico , Olanzapina/uso terapêutico
7.
Viruses ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36680234

RESUMO

More than 40 human infections with the zoonotic Borna disease virus 1 (BoDV-1) have been reported to German health authorities from endemic regions in southern and eastern Germany. Diagnosis of a confirmed case is based on the detection of BoDV-1 RNA or BoDV-1 antigen. In parallel, serological assays such as ELISA, immunoblots, and indirect immunofluorescence are in use to detect the seroconversion of Borna virus-reactive IgG in serum or cerebrospinal fluid (CSF). As immunopathogenesis in BoDV-1 encephalitis appears to be driven by T cells, we addressed the question of whether an IFN-γ-based ELISpot may further corroborate the diagnosis. For three of seven BoDV-1-infected patients, peripheral blood mononuclear cells (PBMC) with sufficient quantity and viability were retrieved. For all three patients, counts in the range from 12 to 20 spot forming units (SFU) per 250,000 cells were detected upon the stimulation of PBMC with a peptide pool covering the nucleocapsid protein of BoDV-1. Additionally, individual patients had elevated SFU upon stimulation with a peptide pool covering X or phosphoprotein. Healthy blood donors (n = 30) and transplant recipients (n = 27) were used as a control and validation cohort, respectively. In this pilot study, the BoDV-1 ELISpot detected cellular immune responses in human patients with BoDV-1 infection. Its role as a helpful diagnostic tool needs further investigation in patients with BoDV-1 encephalitis.


Assuntos
Doença de Borna , Vírus da Doença de Borna , Encefalite , Animais , Humanos , Vírus da Doença de Borna/genética , Projetos Piloto , Leucócitos Mononucleares/metabolismo , Doença de Borna/epidemiologia , Doença de Borna/patologia , Interferon gama
8.
BMC Infect Dis ; 23(1): 55, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703115

RESUMO

BACKGROUND: Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. OBJECTIVE: To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. METHODS: This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. RESULTS: Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2-62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30-55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2-14.6). The included studies presented regular quality and substantial heterogeneity. CONCLUSION: Even with antiviral therapy, half of patients will develop some type of disability.


Assuntos
Encefalite por Herpes Simples , Encefalite Viral , Encefalite , Herpes Simples , Humanos , Criança , Simplexvirus , Herpes Simples/complicações , Progressão da Doença , Encefalite/complicações , Encefalite por Herpes Simples/complicações
9.
Mol Brain ; 16(1): 14, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36694204

RESUMO

Status epilepticus (SE) in humans is characterized by prolonged convulsive seizures that are generalized and often difficult to control. The current antiseizure drugs (ASDs) aim to stop seizures quickly enough to prevent the SE-induced brain inflammation, injury, and long-term sequelae. However, sole reliance on acute therapies is imprudent because prompt treatment may not always be possible under certain circumstances. The pathophysiological mechanisms underlying the devastating consequences of SE are presumably associated with neuroinflammatory reactions, where prostaglandin E2 (PGE2) plays a pivotal role. As the terminal synthase for pathogenic PGE2, the microsomal prostaglandin E synthase-1 (mPGES-1) is rapidly and robustly induced by prolonged seizures. Congenital deletion of mPGES-1 in mice is neuroprotective and blunts gliosis following chemoconvulsant seizures, suggesting the feasibility of mPGES-1 as a potential antiepileptic target. Herein, we investigated the effects of a dual species mPGES-1 inhibitor in a mouse pilocarpine model of SE. Treatment with the mPGES-1 inhibitor in mice after SE that was terminated by diazepam, a fast-acting benzodiazepine, time-dependently abolished the SE-induced PGE2 within the brain. Its negligible effects on cyclooxygenases, the enzymes responsible for the initial step of PGE2 biosynthesis, validated its specificity to mPGES-1. Post-SE inhibition of mPGES-1 also blunted proinflammatory cytokines and reactive gliosis in the hippocampus and broadly prevented neuronal damage in a number of brain areas. Thus, pharmacological inhibition of mPGES-1 by small-molecule inhibitors might provide an adjunctive strategy that can be implemented hours after SE, together with first-line ASDs, to reduce SE-provoked brain inflammation and injury.


Assuntos
Encefalite , Estado Epiléptico , Animais , Camundongos , Dinoprostona , Modelos Animais de Doenças , Encefalite/genética , Encefalite/metabolismo , Encefalite/prevenção & controle , Gliose/complicações , Gliose/tratamento farmacológico , Prostaglandina-E Sintases , Convulsões/tratamento farmacológico , Convulsões/genética , Convulsões/metabolismo , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/genética , Estado Epiléptico/metabolismo
10.
J Formos Med Assoc ; 122(2): 182-186, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610889

RESUMO

We present the case of a 6-year-old Taiwanese boy with a fulminant course of COVID-19 manifesting as high fever, acute consciousness changes, and status epilepticus. Brain MRI showed restricted diffusion in the bilateral hemisphere. Electroencephalogram showed diffuse slow waves with few spikes. CSF study was clear without evidence of common pathogens. He received treatment with antiviral agents, corticosteroids, intravenous immunoglobulins, and anti-IL-6 monoclonal antibodies. However, progressive fulminant hepatitis, hyperammonaemia, and disseminated intravascular coagulopathy developed. Rescue therapy with hybrid continuous renal replacement therapy and plasma exchange were performed in the first 11 days. The patient improved and was extubated on the 11th day. After physical therapy, his neurological function improved significantly. The patient was discharged under rehabilitation after 1 month of hospitalization. Viral sequencing confirmed infection with the Omicron BA.2.3 variant, one of the dominant strains in Taiwan and Hong Kong. Whole-exome sequencing revealed heterozygous uncertain significance variants in TICAM-1, RNF 31, and mitochondrial MT-RNR1, which provide additional support for the fulminant course. To the best of our knowledge, this is the first reported case of COVID-19 in a child with a fulminant course of acute encephalitis and hepatitis who successfully recovered by hybrid continuous renal replacement therapy and plasma exchange.


Assuntos
COVID-19 , Encefalite , Hepatite , Masculino , Humanos , Criança , COVID-19/terapia , Antivirais/uso terapêutico , Encefalite/terapia , Troca Plasmática
11.
BMC Neurol ; 23(1): 43, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707826

RESUMO

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.


Assuntos
Varicela , Encefalite , Paralisia Facial , Herpes Zoster da Orelha Externa , Herpes Zoster , Meningite Viral , Zumbido , Adulto Jovem , Humanos , Masculino , Herpes Zoster da Orelha Externa/complicações , Herpes Zoster da Orelha Externa/diagnóstico , Herpes Zoster da Orelha Externa/tratamento farmacológico , Varicela/complicações , Paralisia Facial/tratamento farmacológico , Paralisia Facial/etiologia , Tontura/complicações , Zumbido/complicações , Herpesvirus Humano 3 , Vertigem/complicações , Encefalite/complicações , Meningite Viral/complicações , Meningite Viral/diagnóstico , Herpes Zoster/complicações
12.
Brain Dev ; 45(1): 16-25, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36511273

RESUMO

OBJECTIVE: Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan. METHODS: We sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis. RESULTS: Five-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year. CONCLUSION: The prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange.


Assuntos
Encefalite , Síndrome de Guillain-Barré , Síndrome de Miller Fisher , Oftalmoplegia , Criança , Humanos , Masculino , Feminino , Adolescente , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/epidemiologia , Síndrome de Miller Fisher/terapia , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/terapia , Tronco Encefálico , Encefalite/diagnóstico , Encefalite/epidemiologia , Encefalite/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-36446612

RESUMO

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease characterized by infiltration of immune cells in multifocal areas of the CNS. The specific molecular processes allowing autoreactive immune cells to enter the CNS compartment through the blood-brain barrier remain elusive. METHODS: Using endothelial cell (EC) enrichment and single-cell RNA sequencing, we characterized the cells implicated in the neuroinflammatory processes in experimental autoimmune encephalomyelitis, an animal model of MS. Validations on human MS brain sections of the most differentially expressed genes in venous ECs were performed using immunohistochemistry and confocal microscopy. RESULTS: We found an upregulation of genes associated with antigen presentation and interferon in most populations of CNS-resident cells, including ECs. Interestingly, instead of transcriptionally distinct profiles, a continuous gradient of gene expression separated the arteriovenous zonation of the brain vasculature. However, differential gene expression analysis presented more transcriptomic alterations on the venous side of the axis, suggesting a prominent role of venous ECs in neuroinflammation. Furthermore, analysis of ligand-receptor interactions identified important potential molecular communications between venous ECs and infiltrated immune populations. To confirm the relevance of our observation in the context of human disease, we validated the protein expression of the most upregulated genes (Ackr1 and Lcn2) in MS lesions. DISCUSSION: In this study, we provide a landscape of the cellular heterogeneity associated with neuroinflammation. We also present important molecular insights for further exploration of specific cell processes that promote infiltration of immune cells inside the brain of experimental autoimmune encephalomyelitis mice.


Assuntos
Encefalite , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Animais , Camundongos , Encefalomielite Autoimune Experimental/genética , Transcriptoma , Esclerose Múltipla/genética , Encéfalo , Endotélio
14.
J Clin Neurosci ; 107: 172-177, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36494269

RESUMO

We conducted a retrospective study to determine the incidence and frequency of different subtypes of encephalitis in patients aged 15 and older in the Auckland and Northland regions of New Zealand between 2009 and 2018. Residents in Auckland and Northland presenting with encephalitis between 2009 and 2018 were identified from three overlapping databases: positive cerebrospinal fluid (CSF) viral polymerase chain reaction (PCR) tests, CSF neuronal antibody requests, and CSF neuronal antibody tests sent overseas. A diagnosis of autoimmune encephalitis required fulfilment of diagnostic criteria published by Graus and colleagues (2016). One hundred and thirty-six (69, 50.7% female) patients met study inclusion criteria. The median age was 59 (range 15-92). The annual incidence was 1.10 cases per 100,000 person-years. Of these 136 patients, 56 (41.2%) had an infectious aetiology, with varicella zoster (26, 46.4%) and herpes simplex (23, 41.1%) being the most common agents. Autoimmune encephalitis was diagnosed in 32 patients (23.5%). LGI-1 antibody was the most commonly identified neuronal autoantibody (10 patients, 13.2%). Forty-eight patients (35.3%) had encephalitis of unknown cause. In-hospital mortality for infectious encephalitis was 12.5%, autoimmune encephalitis 6.3%, and encephalitis of unknown cause 10.4%. Compared to a previous analysis of encephalitis in adults in Auckland, the incidence of encephalitis and autoimmune encephalitis had increased. The proportion of patients with an unknown cause for encephalitis had decreased.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Nova Zelândia/epidemiologia , Encefalite/epidemiologia , Autoanticorpos , Doenças Autoimunes do Sistema Nervoso/complicações
15.
Vet Microbiol ; 277: 109633, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36543092

RESUMO

Equine herpesvirus type 1 (EHV-1) is a devastating pathogen of horses, their natural hosts, and causes fatal encephalitis in non-natural hosts. We previously demonstrated that acylation of the tegument protein UL11 is required for viral replication in cultured cells. We created a mutant virus (EHV-1 UL12 trunc UL11 G2AC7AC9A), in which glycyl and cysteinyl residues at positions 2, 7 and 9 of UL11 that are normally acylated were replaced with alanyl residues. This virus, designated the 2/7/9 mutant, has a limited-replication cycle (LRC), in which replication stops after just a few cycles. Here, we tested whether the 2/7/9 mutant could be used as a vaccine against fatal encephalitis in a mouse model. A virulence test showed that the 2/7/9 mutant was not pathogenic in mice and elicited an antibody response. We also attempted to use the 2/7/9 mutant to immunize mice against a zebra-borne EHV-1, 94-137. Two trials were conducted, each with five immunized mice, five non-immunized and five control mice. In both trials, clinical signs and fatalities were much lower in the immunized mice than in the non-immunized mice. In addition, none of the mice in either trial developed neutralizing antibodies, indicating that the immunity induced by the 2/7/9 mutant was not due to neutralizing activity. The results indicate that the 2/7/9 LRC mutant has promise as a vaccine against EHV-1 infection non-natural hosts.


Assuntos
Encefalite , Infecções por Herpesviridae , Herpesvirus Equídeo 1 , Doenças dos Cavalos , Doenças dos Roedores , Cavalos , Animais , Camundongos , Herpesvirus Equídeo 1/genética , Vacinação/veterinária , Imunização/veterinária , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Encefalite/veterinária , Replicação Viral , Doenças dos Cavalos/prevenção & controle , Anticorpos Antivirais
16.
Mult Scler Relat Disord ; 69: 104442, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521387

RESUMO

BACKGROUND: Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease (MOGAD) is an emerging disorder recognized as a clinical entity distinct from Multiple Sclerosis and Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorders (NMOSD-AQP4+), and its phenotypic spectrum continues to expand. Most information about its clinical course has emerged from retrospective studies, and treatment response both in acute and chronic-relapsing disease is still limited. We aimed to describe the clinical and paraclinical characteristics of monophasic and relapsing, paediatric and adult patients with MOGAD under regular clinical care in Chile, highlighting some challenging cases that are far from being considered benign. METHODS: Observational, retrospective, and prospective longitudinal multicentre study including patients with positive serum MOG-IgG assessed by cell-based assay. RESULTS: We include 35 patients, 71% women, median age at onset 30 years (range 1-68), 23% had paediatric onset, with a median disease-duration 24 months (range 12-348). In the whole cohort, the most frequent symptoms at onset were isolated optic neuritis (ON) (34%) and myelitis (22%). Encephalitis with seizures or encephalomyelitis was the most common presentation in paediatric-onset patients 75% (n = 6), compared to 11% (n = 3) of the adult-onset patients (p < 0.001). A relapsing course was observed in 34%, these patients were younger (25 vs. 34 years, p = 0.004) and with a longer disease duration (64 vs. 6 months, p = 0.004) compared to monophasic patients. Two patients developed encephalitis with seizures/status epilepticus, with concomitant positive CSF anti-NMDAR-IgG. Chronic immunotherapy was ever prescribed in 77%, the most frequent was rituximab (35%). Relapses under chronic immunotherapy occurred in 5/27 patients (18.5%), two of them under rituximab, one paediatric patient who started combined therapy with monthly IVIG and one adult patient that switched to satralizumab plus mycophenolate. The median EDSS at the last follow-up was 1.5 (range 0-6.0). CONCLUSION: In Chile, patients with MOGAD exhibit a wide spectrum of clinical presentations at disease onset and during relapses. Close monitoring is needed, particularly in younger patients with short follow-up periods.


Assuntos
Encefalite , Neuromielite Óptica , Feminino , Masculino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Rituximab , Chile/epidemiologia , Glicoproteína Mielina-Oligodendrócito , Aquaporina 4 , Convulsões , Autoanticorpos , Imunoglobulina G , Oligodendroglia
17.
Toxicol Lett ; 375: 48-58, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586703

RESUMO

Lead (Pb) is a developmental neurotoxin that can disrupt brain development and damage the brain regions responsible for executive function, behavioral regulation and fine motor control. Sodium para-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that can cross the blood-brain barrier. The purpose of this study was to examine the effects of juvenile rat Pb exposure on behavioral changes and brain inflammation, and the efficacy of PAS-Na in ameliorating these effects. The results showed that Pb exposure during the juvenile period (from weaning to adult period) delayed rats' growth development and impaired their motor learning. Pb exposure not only increased Pb concentrations in several brain regions (including hippocampus, striatum and substantia nigra), but also disrupted metal-homeostasis in the brain, as higher levels of iron (Fe) and calcium (Ca) were observed in the substantia nigra. Moreover, Pb activated the MAPK pathway and increased levels of inflammatory factors such as IL-1ß, TNF-α and IL-6 in the hippocampus, striatum and substantia nigra. Furthermore, Pb increased the levels of alpha-synuclein (α-syn) in these brain sites. PAS-Na improved the motor deficits and brain inflammation in the Pb-exposed rats. Moreover, the elevated Pb, Fe and Ca concentrations in the brain were significantly reduced by PAS-Na, which contains amino, carboxyl and hydroxyl functional groups, suggesting that it may act as a chelator of brain metals. In addition, PAS-Na inhibited the Pb-induced MAPK pathway activation and α-syn accumulation in the same brain regions. Taken together, our novel study suggest that PAS-Na shows efficacy in improving the Pb-induced behavioral changes in rats by inhibiting MAPK-dependent inflammatory pathways and reducing α-syn accumulation.


Assuntos
Ácido Aminossalicílico , Encefalite , Ratos , Animais , Ácido Aminossalicílico/farmacologia , Ácido Aminossalicílico/uso terapêutico , alfa-Sinucleína , Chumbo/toxicidade , Doenças Neuroinflamatórias , Sódio , Encéfalo , Encefalite/induzido quimicamente , Encefalite/tratamento farmacológico , Sistema de Sinalização das MAP Quinases
18.
J Neuroimmunol ; 374: 578007, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481703

RESUMO

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely.


Assuntos
COVID-19 , Encefalite , Humanos , COVID-19/complicações , SARS-CoV-2 , Encefalite/etiologia , Imunoglobulina G , Anticorpos Antivirais , Tronco Encefálico/diagnóstico por imagem
19.
Pediatr Neurol ; 139: 65-69, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529001

RESUMO

BACKGROUND: Acute necrotizing encephalopathy of childhood (ANEC) is a rare parainfectious neurological disorder. ANEC is associated with a high mortality rate and poor neurological outcomes. ANEC is postulated to arise from immune-mediated or metabolic processes driven by viral infections. Although there have been some case reports of acute necrotizing encephalopathy with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection in adults, paediatric cases are rare. METHODS: A single case report of SARS-CoV-2-related ANEC in an 11-year-old boy is presented through retrospective chart review. Literature search was performed using PubMed, Embase, Cochrane database, and Google Scholar to compare and analyze similar cases of parainfectious immune-mediated encephalopathies related to SARS-CoV-2 in children. RESULTS: An 11-year-old boy with acute SARS-CoV-2 infection presented with ophthalmoplegia, ataxia, and aphasia. Neuroimaging findings demonstrated significant swelling and signal changes in bilateral thalami, brainstem, and cerebellar hemispheres, consistent with ANEC. His high ANEC Severity Score indicated poor neurological prognosis. Treatment with a combination of early steroid therapy, intravenous immunoglobulin therapy, and targeted interleukin 6 (IL-6) blockade yielded good neurological improvements. Literature search identified 19 parainfectious immune-mediated neurological disorders related to SARS-CoV-2 in children. The only other pediatric ANEC case identified was postinfectious and thus not included. CONCLUSIONS: This is the first report of a pediatric case of SARS-CoV-2-related ANEC, which responded well to early immunotherapy, including IL-6 blockade. Early immunotherapy with IL-6 blockade can be considered as an adjunct in managing severe ANEC.


Assuntos
COVID-19 , Encefalite , Doenças do Sistema Nervoso , Criança , Humanos , Masculino , COVID-19/complicações , Encefalite/complicações , Interleucina-6 , Doenças do Sistema Nervoso/etiologia , Estudos Retrospectivos , SARS-CoV-2
20.
Pediatr Neurol ; 139: 35-42, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36508881

RESUMO

BACKGROUND: Our study aimed to characterize seizure incidence and seizure outcome of pediatric autoimmune encephalitis (AE) focusing on subgroup analysis based on antibody (Ab). METHODS: Among 110 pediatric patients with AE, we compared seizure characteristics and outcomes in 68 patients with seizure, who satisfied the proposed criteria of pediatric AE. Accordingly, patients were classified into three groups, anti-myelin oligodendrocyte glycoprotein (anti-MOG) AE, anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) AE, and Ab-negative AE. Univariate and multivariate analyses were performed to evaluate the risk factors for postencephalitic seizures, defined as persisting seizures six months after onset. RESULTS: Seizure incidence in the anti-NMDAR (88.9%) and Ab-negative (71.1%) groups differed from anti-MOG group (37.8%). Median seizure frequency within six months was higher in the Ab-negative group (6.0, interquartile range [IQR] 3.0 to 13.0) than in the anti-NMDAR group (3.0, IQR 2.0 to 4.5) and anti-MOG group (2.0, IQR 1.0 to 5.0). Patients in the Ab-negative group tended to develop postencephalitic seizures more frequently and have a lower seizure freedom rate than those in the anti-NMDAR and anti-MOG groups. Ab-negative status, high seizure frequency within six months, and the presence of status epilepticus were associated with the development of postencephalitic seizures on univariate analysis. On multivariate analysis, Ab-negative status remained the only significant variable linked with postencephalitic seizure (odds ratio, 4.17; 95% confidence interval, 1.02 to 18.05). CONCLUSIONS: We delineated the seizure incidence, evolution, and outcome of pediatric patients with Ab-positive and Ab-negative AE. Ab-negative status is predictive of higher seizure burden, more frequent development of postencephalitic seizures, and less favorable seizure outcome than anti-NMDAR and anti-MOG Ab-positive status.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Doenças Autoimunes do Sistema Nervoso , Encefalite , Doença de Hashimoto , Humanos , Convulsões/etiologia , Convulsões/complicações , Encefalite/complicações , Encefalite/epidemiologia , Doença de Hashimoto/complicações , Doença de Hashimoto/epidemiologia , Glicoproteína Mielina-Oligodendrócito , Doenças Autoimunes do Sistema Nervoso/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/epidemiologia , Autoanticorpos
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