Current evidence of neurological features, diagnosis, and neuropathogenesis associated with COVID-19

Abstract Recent reports indicate that besides respiratory and systemic symptoms among coronavirus disease (COVID-19) patients, the disease has a wide spectrum of neurological manifestations (encephalitis, meningitis, myelitis, acute disseminated encephalomyelitis, metabolic and acute hemorrhagic necrotizing encephalopathy, cerebrovascular diseases, Guillain-Barré syndrome, polyneuritis cranialis, dysautonomia, and myopathies). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from the respiratory system to the central nervous system, using transneuronal and hematogenous mechanisms. Although not every COVID-19 patient will test positive for the virus in the cerebrospinal fluid exam, the appearance of neurological symptoms associated with SARS-CoV-2 infection reveals the importance of understanding the neurologic manifestations and capacity for neural invasion associated with the pathogen. These aspects are relevant for correct diagnosis and treatment, and for the potential development of vaccines. This review highlights the latest evidence of SARS-CoV-2 infection with a focus on neurological involvement and potential neuropathogenesis mechanisms.

Advances and new insights in the neuropathogenesis of dengue infection / Avanços e novos aspectos na neuropatogênese da dengue

Dengue virus (DENV) infects approximately 390 million persons every year in more than 100 countries. Reports of neurological complications are more frequently. The objective of this narrative review is to bring up the advances in the dengue neuropathogenesis. DENV can access the nervous system through blood-brain barrier disturbance mediated by cytokine. The blood-cerebrospinal fluid (CSF) barrier seems to be also involved, considering the presence of the virus in the CSF of patients with neurological manifestations. As for neurotropism, several studies showed the presence of RNA and viral antigens in brain tissue and CSF in humans. In murine model, different virus mutations were associated to neurovirulence. Despite the advances in the dengue neuropathogenesis, it is still necessary to determine a more appropriate animal model and increase the number of cases of autopsy. The detection of neurovirulence markers may contribute to establish a prognosis, the disease control and vaccine development.

O vírus da dengue (DENV) infecta anualmente cerca de 390 milhões de indivíduos em mais de 100 países. Complicações neurológicas estão se tornando frequentes. O objetivo desta revisão narrativa é abordar os avanços sobre neuropatogênese na dengue. O DENV invade o sistema nervoso central através do distúrbio da barreira hemato-encefálica, mediado por citocina. A barreira hemato-liquórica (LCR) parece também estar envolvida, considerando a presença do vírus no LCR. Estudos demonstraram RNA e antígenos virais no tecido cerebral e LCR de indivíduos infectados pelo DENV, confirmando o neurotropismo viral. Em modelo murino, diferentes mutações virais foram associadas a neurovirulência. Apesar dos avanços no conhecimento da neuropatogênese da dengue, ainda são necessários a determinação de um modelo animal mais adequado e aumento do número de casos de autopsia. A determinação de marcadores de neurovirulência pode contribuir para o estabelecimento de prognóstico, controle da doença e no desenvolvimento de vacina.

Manifestaciones neurológicas durante la infección por el virus del dengue / Neurological manifestations during dengue virus infection

El dengue es la enfermedad viral transmitida por mosquitos más importante en el mundo. Alrededor del 10% de los pacientes con dengue, pueden presentar alteraciones neurológicas durante o después de la infección, asociadas a la replicación viral en el tejido, a la respuesta inmunológica local, a la disfunción endotelial y a signos hemorrágicos en el tejido. En muchos de estos casos se ha detectado virus o anticuerpos en el tejido, sugiriendo la invasión del virus al encéfalo, sin embargo, no siempre es posible hacer esta relación, dando origen a una gran pregunta: ¿son los daños del tejido nervioso producto de una encefalopatía asociada a disfunción extraneural o son debidos a la infección misma del tejido? Como sigue siendo controversial la interpretación de los signos neurológicos durante el dengue, a continuación presentamos algunas generalidades del virus, sus forma clínicas y algunas evidencias clínicas y experimentales que intentan explicar y asociar la neuroinfección y la neuropatogenia por DENV.

Dengue is the most important viral infection transmitted by arthropods in the world. Some studies report that about 10% of dengue or severe dengue patients present neurological symptoms and these signs could be related with nervous system viral replication, immune response and endothelial or metabolic dysfunction in neural or extraneural tissues. These nervous system signs are more frequent in endemic zones and in some patients, viruses or specific antibodies can be detected in the brain, suggesting a direct neural invasion. However, in other cases we cannot establish a direct relationship, begging the question: are the neurological signs and nervous tissue damage secondary to extraneural organ dysfunction or are these changes related to viral replication in the brain? Given the controversy, this review is intended to present some general information on the dengue virus, the clinical characteristics of the disease and current evidence on the neurological manifestations. In addition, we will present experimental evidence to explain the dengue virus neuroinfection and neuropathogenesis.

Cellular & molecular basis of HIV-associated neuropathogenesis.

Although a plethora of molecules have been implicated in the development of HIV associated dementia (HAD), the identity of the indispensable ones is still elusive. The action of various molecules appears to follow a cascade path with one molecule activating another thereby regulating the expression and modulation of the regulatory machineries. Two pathways have been proposed leading to HIV-induced central nervous system (CNS) injury. First involving neurotoxic effect of viral proteins and second, with immunomodulatory substances secreted by the infected cells playing vital role. The viral transfer from infected cells (for example, cells representing macrophage-microglial lineage) to uninfected cells (such as same cell type or nerve cells) occurring perhaps via virological synapse is also not well documented. While the mechanism underlying transfer of HIV-1 through blood-brain barrier is not clearly understood, macrophage-microglial cell lineages are undisputedly predominant cell types that HIV uses for transmission in CNS. The present review describes existing knowledge of the modus operandi of HIV-induced neuropathogenesis gathered through research evidences. of HIV-induced neuropathogenesis gathered through research Mechanisms by which regulatory molecules exploit such cell types in promoting neuropathogenesis would provide key insights in intersecting pathway(s) for designing intervention strategies.