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3.
Neurol India ; 68(3): 560-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32643664

RESUMO

COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.


Assuntos
Ageusia/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/imunologia , Encefalite/fisiopatologia , Síndrome de Guillain-Barré/fisiopatologia , Cefaleia/fisiopatologia , Transtornos do Olfato/fisiopatologia , Pneumonia Viral/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Ageusia/etiologia , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Barreira Hematoencefálica , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Coma/etiologia , Coma/fisiopatologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Delírio/etiologia , Delírio/fisiopatologia , Encefalite/etiologia , Encefalite/imunologia , Encefalomielite Aguda Disseminada/etiologia , Encefalomielite Aguda Disseminada/imunologia , Encefalomielite Aguda Disseminada/fisiopatologia , Fadiga/etiologia , Fadiga/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Cefaleia/etiologia , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/imunologia , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Mialgia/etiologia , Mialgia/fisiopatologia , Transtornos do Olfato/etiologia , Pandemias , Equipamento de Proteção Individual/efeitos adversos , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia
5.
PLoS One ; 15(7): e0236162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697807

RESUMO

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a 'model' of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point.


Assuntos
Encefalite/etiologia , Infecções por HIV/complicações , HIV-1/isolamento & purificação , Herpes Zoster/etiologia , Leucocitose/etiologia , RNA Viral/líquido cefalorraquidiano , Adulto , Estudos Transversais , Encefalite/líquido cefalorraquidiano , Encefalite/patologia , Feminino , Infecções por HIV/virologia , Herpes Zoster/líquido cefalorraquidiano , Herpes Zoster/patologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Leucocitose/líquido cefalorraquidiano , Leucocitose/patologia , Estudos Longitudinais , Masculino , Estudos Retrospectivos
6.
Ann Neurol ; 88(1): 1-11, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506549

RESUMO

In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Infecções por Coronavirus/complicações , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Encefalite/etiologia , Encefalite/fisiopatologia , Encefalomielite Aguda Disseminada/etiologia , Encefalomielite Aguda Disseminada/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Inflamação , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Meningite Viral/etiologia , Meningite Viral/fisiopatologia , Doenças do Sistema Nervoso/etiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Trombofilia/etiologia , Trombofilia/fisiopatologia
7.
Mol Immunol ; 123: 74-87, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438202

RESUMO

BACKGROUND: Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R. METHODS: I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed. RESULTS: We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume. INTERPRETATION: Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.


Assuntos
Isquemia Encefálica , Encefalite/prevenção & controle , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroproteção/efeitos dos fármacos , Traumatismo por Reperfusão , Ubiquinona/análogos & derivados , Animais , Animais Recém-Nascidos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Células Cultivadas , Encefalite/etiologia , Inflamassomos/metabolismo , Inflamassomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
9.
Am J Emerg Med ; 38(7): 1549.e3-1549.e7, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32425321

RESUMO

BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barré syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Infecções por Coronavirus/complicações , Encefalite/etiologia , Encefalite/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Pandemias , Pneumonia Viral/complicações
10.
Mult Scler Relat Disord ; 43: 102216, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464585

RESUMO

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.


Assuntos
Transtornos da Consciência/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Encefalite/fisiopatologia , Glucocorticoides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/fisiopatologia , Convulsões/fisiopatologia , Adulto , Antibacterianos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Betacoronavirus , Encéfalo/diagnóstico por imagem , Transtornos da Consciência/diagnóstico por imagem , Transtornos da Consciência/etiologia , Transtornos da Consciência/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/terapia , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Encefalite/diagnóstico por imagem , Encefalite/etiologia , Encefalite/terapia , Feminino , Inibidores da Protease de HIV/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Levetiracetam/uso terapêutico , Pulmão/diagnóstico por imagem , Imagem por Ressonância Magnética , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Ponte/diagnóstico por imagem , Respiração Artificial , Convulsões/tratamento farmacológico , Convulsões/etiologia , Lobo Temporal/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tomografia Computadorizada por Raios X
11.
BMC Neurol ; 20(1): 179, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32397957

RESUMO

BACKGROUND: Diverse mechanisms including infections, autoimmune inflammatory reactions, neoplasms, and degeneration are involved in the central nervous system in cases of acquired immune deficiency syndrome. In such cases, it is difficult to determine the precise pathogenesis by radiological examination and laboratory testing. CASE PRESENTATION: We report a 37-year-old Japanese woman who had untreated hypertension and gender identity disorder and had been taking testosterone injections since she was 19 years old. She developed a headache and visual field deficits together with elevated blood pressure. According to radiological findings, she was initially suspected as having posterior reversible encephalopathy syndrome in the right parieto-occipital lobe with reversible cerebral vasoconstriction syndrome. Human immunodeficiency virus antibody was positive and the CD4+ T-lymphocyte count was 140 cells/µl. Therefore, antiretroviral therapy was started. Antiretroviral therapy suppressed the activity of acquired immune deficiency syndrome but worsened her visual symptoms and expanding radiological lesions. Brain biopsy led to the diagnosis of CD8+ encephalitis, and she also fulfilled the diagnosis of paradoxical immune reconstitution inflammatory syndrome. Corticosteroid therapy alleviated her symptoms. CONCLUSIONS: This is a rare case of CD8+ encephalitis, with an exacerbation owing to paradoxical immune reconstitution inflammatory syndrome after antiretroviral therapy, which radiologically mimicked posterior reversible encephalopathy syndrome. Corticosteroid therapy was effective; thus, it is important to provide a pathological diagnosis in such cases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Encefalite/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Adulto , Fármacos Anti-HIV/efeitos adversos , Diagnóstico Diferencial , Encefalite/etiologia , Encefalite/imunologia , Feminino , Disforia de Gênero , Infecções por HIV/imunologia , Humanos , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamente
12.
Brain Behav Immun ; 87: 18-22, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32240762

RESUMO

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.


Assuntos
Infecções por Coronavirus/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Coronavirus Humano 229E , Infecções por Coronavirus/complicações , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Disgeusia/etiologia , Disgeusia/fisiopatologia , Encefalite/etiologia , Encefalite/fisiopatologia , Encefalite Viral/etiologia , Encefalite Viral/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio , Doenças do Sistema Nervoso/etiologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/virologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Polineuropatias/etiologia , Polineuropatias/fisiopatologia , Vírus da SARS , Convulsões/etiologia , Convulsões/fisiopatologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
15.
Proc Natl Acad Sci U S A ; 117(12): 6708-6716, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32161123

RESUMO

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/patologia
16.
Brain Behav Immun ; 87: 645-659, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32097763

RESUMO

Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1ß, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.


Assuntos
Antivirais/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Encefalite/etiologia , Encefalite/prevenção & controle , Glioma/complicações , Glioma/psicologia , Nanopartículas/uso terapêutico , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Disfunção Cognitiva/psicologia , Citocinas/biossíntese , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Transplante de Neoplasias , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
17.
Epilepsia ; 61(2): 203-215, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31943156

RESUMO

Owing to the complexity of the pathophysiological mechanisms driving epileptogenesis following traumatic brain injury (TBI), effective preventive treatment approaches are not yet available for posttraumatic epilepsy (PTE). Neuroinflammation appears to play a critical role in the pathogenesis of the acquired epilepsies, including PTE, but despite a large preclinical literature demonstrating the ability of anti-inflammatory treatments to suppress epileptogenesis and chronic seizures, no anti-inflammatory treatment approaches have been clinically proven to date. TBI triggers robust inflammatory cascades, suggesting that they may be relevant for the pathogenesis of PTE. A major cell type involved in such cascades is the microglial cells-brain-resident immune cells that become activated after brain injury. When activated, these cells can oscillate between different phenotypes, and such polarization states are associated with the release of various pro- and anti-inflammatory mediators that may influence brain repair processes, and also differentially contribute to the development of PTE. As the molecular mechanisms and key signaling molecules associated with microglial polarization in brain are discovered, strategies are now emerging that can modulate this polarization, promoting this as a potential therapeutic strategy for PTE. In this review, we discuss the relevant literature regarding the polarization of brain-resident immune cells following TBI and attempt to put into perspective a role in epilepsy pathogenesis. Finally, we explore potential strategies that could polarize microglia/macrophages toward a neuroprotective phenotype to mitigate PTE development.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Epilepsia Pós-Traumática/etiologia , Epilepsia Pós-Traumática/patologia , Microglia/patologia , Animais , Polaridade Celular , Encefalite/tratamento farmacológico , Encefalite/etiologia , Encefalite/patologia , Epilepsia Pós-Traumática/terapia , Humanos
18.
Lancet Infect Dis ; 20(4): 467-477, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31924550

RESUMO

BACKGROUND: In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis. METHODS: All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999-2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed. FINDINGS: BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir. INTERPRETATION: BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions. FUNDING: German Federal Ministry of Education and Research.


Assuntos
Doença de Borna/complicações , Doença de Borna/epidemiologia , Vírus da Doença de Borna/genética , Encefalite/etiologia , Encefalite/patologia , Zoonoses , Animais , Anticorpos Antivirais/sangue , Doença de Borna/virologia , Encefalite/mortalidade , Alemanha/epidemiologia , Cavalos/genética , Humanos , RNA Viral/genética , Ovinos/genética , Replicação Viral
19.
Hematology ; 25(1): 43-47, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31906810

RESUMO

Background: Cytomegalovirus (CMV) infection of the central nervous system (CNS) is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Cases presentation: Two patients with drug-resistant CMV encephalitis after allo-HSCT were successfully treated with donor CMV-specific cytotoxic T lymphocytes (CTLs). In the first case, a 27-year-old male who received haploidentical transplantation to treat T-cell acute lymphoblastic leukemia (T-ALL), developed CMV encephalitis during the time of the ganciclovir maintenance treatment. After intravenous foscarnet and donor CMV-specific CTLs, CMV-DNA of CSF became undetectable and the abnormal signs of brain magnetic resonance imaging (MRI) were limited. Another case, a 57-year-old female with acute myeloid leukemia (AML) who underwent haploidentical transplantation, also developed CMV encephalitis during the maintenance treatment of the ganciclovir. After administering donor CMV-specific CTLs intrathecally, the CMV load of the CSF decreased.Conclusions: The intravenous/intratheca administration of donor CMV-specific CTLs may be a safe and effective treatment for CMV encephalitis, especially for patients who suffered from drug-resistant CMV infection.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Encefalite/etiologia , Encefalite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T Citotóxicos/transplante , Adulto , Antivirais/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/tratamento farmacológico , Farmacorresistência Viral , Encefalite/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Doadores de Tecidos , Transplante Homólogo/efeitos adversos
20.
Clin Microbiol Infect ; 26(3): 281-290, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31760115

RESUMO

BACKGROUND: The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption. OBJECTIVES: The aim was to evaluate the ME panel in a diagnostic test accuracy review. DATA SOURCES: The PubMed and EMBASE databases were systematically searched through May 2019. STUDY ELIGIBILITY CRITERIA: Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately. PARTICIPANTS: Patients with suspected ME for whom a panel was ordered were included. METHODS: The ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel. RESULTS: Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86-93%) and 97% (95% CI 94-99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease. CONCLUSIONS: The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.


Assuntos
Encefalite/diagnóstico , Meningite/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Multiplex/normas , Kit de Reagentes para Diagnóstico , Encefalite/etiologia , Humanos , Meningite/etiologia , Viés de Publicação , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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