scholarly journals The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations

2021 ◽  
Vol 15 (8) ◽  
pp. e0009575
Author(s):  
Igor Salerno Filgueiras ◽  
Amanda Torrentes de Carvalho ◽  
Daniela Prado Cunha ◽  
Dennyson Leandro Mathias da Fonseca ◽  
Nadia El Khawanky ◽  
...  

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain–Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection–associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.


2016 ◽  
Vol 141 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Maria Gabriela Alvarado ◽  
David A. Schwartz

Context.—The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. Objectives.—To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. Data Sources.—Comprehensive review of published scientific literature. Conclusions.—Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.


2017 ◽  
Vol 8 ◽  
pp. 1178122X1770899 ◽  
Author(s):  
Mohammad Zare Mehrjardi

Zika virus (ZIKV) is a mosquito-borne arbovirus from the family Flaviviridae, which had caused some epidemics since its discovery in 1947 without any significant impacts on public health. In 2015, however, a 20-fold increase in congenital microcephaly cases in northeastern Brazil was attributed to prenatally acquired ZIKV infection. Traditionally, TORCH agents have 4 common characteristics including causing a mild illness in infected mother, vertical transmission to fetus, developing several anomalies in the affected fetus, and in some instances, maternal therapy may not ameliorate fetal prognosis. Prenatal ZIKV infection has shown the aforementioned characteristics during the recent epidemics in South America and the Caribbean region; therefore, it should be considered as an emerging TORCH agent that may seriously threaten public health. Fetal ultrasound can be used as a safe, inexpensive, and easy-to-access imaging modality for detecting suspicious cases of congenital Zika syndrome in utero and suggesting confirmatory diagnostic examinations to these patients.


Author(s):  
R. M. Manapova ◽  
Alaudin M. Aliskandiev ◽  
M. I. Izrailov

It is generally accepted the risk factors for the development of the gastrointestinal tract (GIT) diseases to have a hereditary predisposition, unfavorable environmental conditions, eating disorders, emotional stress, excessive body weight, and inactivity. Also in a number of studies, it was convincingly shown the perinatal central nervous system (CNS) damage to be a risk factor for the development of GIT diseases; in the history of children with perinatal CNS lesions, chronic gastrointestinal diseases develop 3-4 times more often than in children without it in the history. Perinatal CNS damage leading to the development of a number of disorders of the nervous system is revealed in the history of the majority of children with gastrointestinal diseases, while the severity of neurological manifestations is directly related to the duration and severity of gastroenterological diseases.


2019 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Dimitrios Panagopoulos

Background: Meningeal melanocytoma is a rare benign tumor, most frequently located in the posterior fossa and spinal canal. Our objective is to illustrate a case of this tumor that originated in the thoracolumbar area of the spine and had an uneventful clinical course after total resection. Case description: We present the case of a 59 years old woman who presented with a medical history of ongoing neurological deterioration due to spastic paresis of the lower extremities. MRI of the thoracolumbar region identified a melanocytic melanoma as the underlying cause. Conclusions: Melanocytic tumors of the central nervous system have a typical appearance on MRI scans, varying with the content and distribution of melanin. However, the differential diagnosis between malignant melanoma and melanocytoma still depends on pathological criteria. Spinal meningeal melanocytoma has a benign course, and it is amenable for gross total resection. The outcome is favorable following complete resection.


2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.


2016 ◽  
Vol 49 (1) ◽  
pp. 125-129 ◽  
Author(s):  
Danilo Bretas de Oliveira ◽  
Guilherme Machado ◽  
Gabriel Magno de Freitas Almeida ◽  
Paulo César Peregrino Ferreira ◽  
Cláudio Antônio Bonjardim ◽  
...  

1995 ◽  
Vol 32 (3) ◽  
pp. 309-311 ◽  
Author(s):  
G. L. Foley ◽  
J. F. Zachary

A 1-year-old mixed breed heifer was presented to the Veterinary Medical Teaching Hospital at the University of Illinois with a 3-day history of abnormal mentation and aggressive behavior. Based on the history and clinical examination, euthanasia and necropsy were recommended. The differential diagnoses included rabies, pseudorabies, and a brain abscess. The brain was removed within 60 minutes of death, and the section submitted for fluorescent antibody testing was positive for rabies virus antigen. Residual brain tissue was immersion fixed in 10% neutral buffered formalin. Histologic examination revealed a marked perivascular and meningeal lymphocytic meningoencephalitis and locally extensive spongiform change of the gray matter affecting the neuropil and neuron cell bodies. The most severely affected regions with spongiform change were the thalamus and cerebral cortex. No Negri bodies were found in any sections. Since the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom, there has been an increased surveillance of bovine neurologic cases in an effort to assess if BSE has occurred in the USA. In areas where rabies virus is endemic, rabies should be included as a possible differential diagnosis in cases of spongiform changes of the central nervous system.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098265 ◽  
Author(s):  
Liming Cao ◽  
Yanwei Lin ◽  
Hongliang Jiang ◽  
Jiehong Wei

Neurolisteriosis is a foodborne infection of the central nervous system that is easily misdiagnosed, especially in healthy adults with atypical symptoms. A 50-year-old man presented with a 3-day history of distortion of the oral commissure. Facial neuritis was diagnosed and treated with intravenous dexamethasone. His condition deteriorated rapidly, and he presented with a slow pharyngeal reflex, stiff neck, and signs of peripheral facial paralysis. Brain magnetic resonance imaging revealed multiple ring-enhanced foci in the brainstem. Routine and biochemical cerebrospinal fluid (CSF) analyses showed increased white blood cells and microproteins. Blood culture and high-throughput genome sequencing revealed Listeria monocytogenes DNA in the CSF. Ampicillin, amikacin, and meropenem were administered, and the patient was transferred from the intensive care unit to a standard medical ward after 2 months. The patient could walk and eat normally; however, he required intermittent mechanical ventilation at 11 months after discharge. Although L. monocytogenes meningitis is rare in healthy immunocompetent adults, it must be considered as a differential diagnosis, especially in adults whose conditions do not improve with cephalosporin antibiotic administration. L. monocytogenes rhombencephalitis mimics facial neuritis and develops quickly. Prompt diagnosis is essential for rapid initiation of antibiotic therapy to achieve the best outcome.


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