Neurological Complications In Adults Research Articles

Insights into Zika Virus Pathogenesis and Potential Therapeutic Strategies.

Zika virus (ZIKV) has emerged as a significant public health threat, reaching pandemic levels in 2016. Human infection with ZIKV can manifest as either asymptomatic or as an acute illness characterized by symptoms such as fever and headache. Moreover, it has been associated with severe neurological complications in adults, including Guillain-Barre syndrome, and devastating fetal abnormalities, like microcephaly. The primary mode of transmission is through Aedes spp. mosquitoes, and with half of the world's population residing in regions where Aedes aegypti, the principal vector, thrives, the reemergence of ZIKV remains a concern. This comprehensive review provides insights into the pathogenesis of ZIKV and highlights the key cellular pathways activated upon ZIKV infection. Additionally, we explore the potential of utilizing microRNAs (miRNAs) and phytocompounds as promising strategies to combat ZIKV infection.

Long-term neurological implications of severe acute respiratory syndrome coronavirus 2 infections in neonates: Innate immune memory and chronic neuroinflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause long-term neurological complications in adults. However, the mechanisms by which early-life SARS-CoV-2 infection increases the risk of abnormal neurodevelopment remain unknown.Recent studies have shown an association with chronic proinflammatory cytokine/chemokine production in the central nervous system (CNS). Therefore, it was hypothesised that innate immune activation and induction of innate immune memory may play a potential role in the neonatal brain. Haematopoietic stem cells in the bone marrow are exposed to SARS-CoV-2, SARS-CoV-2 envelope protein (E protein), lipopolysaccharide (LPS)-bound spike proteins (S1 and S2 proteins), and damage-associated molecular patterns (DAMPs). Myeloid progenitors enter the stroma of the choroid plexus and are further directed to incessantly supply the brain parenchyma with resident innate immune cells. The S proteins-LPS complex can cross the blood–brain barrier and plays an important role in microglial and astrocytic inflammatory responses and innate immune memory. Persistently activated microglia with memory release pro-inflammatory cytokines/chemokines which contribute to abnormal synaptic development in the frontal lobe and cerebellum, potentially leading to long-term neurological complications, similar to those observed in autism spectrum disorder (ASD). In addition, this hypothesis suggests that bacterial and fungal products may act as adjuvants to S proteins and may also explain why S proteins alone are insufficient to induce neuroinflammation in neonates.

Management of neurological complications related to aneurysmal subarachnoid hemorrhage: A comparison of the bedside therapeutic algorithms

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is of the most serious emergencies in neurosurgical practice and continues to be associated with high morbidity and mortality. Beyond securing the ruptured aneurysm to prevent a rebleed, physicians continue to be concerned about potential complications such as cerebral vasospasm-delayed cerebral ischemia (DCI), an area where management remains highly variable. This study aimed at reviewing the most recent literature and assessing any up-to-date schemes for treating the most common aSAH neurological complications in adults that can be applied in daily clinical practice towards optimising outcomes. MethodsA systematic review was performed according to PRISMA guidelines on the management of aSAH neurological complications in adults. The literature surveyed was between 2016 and 2022 inclusive, using the Pubmed search engine. Comparisons between the methods suggested by existing therapeutic algorithms were discussed. ResultsSix stepwise algorithms assisting the decision-making for treating cerebral vasospasm-DCI were recognised and compared. No algorithm was found for the management of any other neurological complications of aSAH. Despite differences in the algorithms, induced hypertension and endovascular therapy were common treatments in all approaches. Controversy in the therapeutic process of these complications surrounds not only the variability of methods but also their optimal application towards clinical outcome optimisation. ConclusionsA universal approach to managing aSAH complications is lacking. Despite advances in the techniques to secure a ruptured aneurysm, there persist a high rate of neurological deficit and mortality, and several unanswered questions. More research is required towards stratification of current treatment algorithms as per the quality of their evidence.

INTEGRATIVE LITERATURE REVIEW

Herpes zoster is a viral disease that can cause neurological complications in adults. In this integrative literature review, 15 scientific articles published in the last five years were analyzed to explore the main topics related to neurological complications of herpes zoster in adults. The topics covered include epidemiology, vaccination, risk factors, treatment, impact on quality of life, and multidisciplinary approach. Herpes zoster has an increased incidence in the elderly and immunocompromised individuals, and is associated with a higher risk of stroke. Vaccination is an effective strategy for preventing the disease and its complications, such as postherpetic neuralgia. Risk factors such as advanced age and severe pain during the acute episode are associated with the development of postherpetic neuralgia. Corticosteroids are an effective treatment option for reducing the risk of this complication. Herpes zoster and postherpetic neuralgia can have a significant impact on patients’ quality of life, especially in the physical and emotional aspects. A multidisciplinary approach involving healthcare professionals from different fields is essential for comprehensive and effective care.

Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (VSV-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSVΔM-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSVΔM-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSVΔM control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSVΔM-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSVΔM-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSVΔM-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSVΔM-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.

Immune Recognition versus Immune Evasion Systems in Zika Virus Infection

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host-viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection.

A method for mapping the linear epitopes targeted by the natural antibody response to Zika virus infection using a VLP platform technology

Zika virus (ZIKV), a mosquito-borne pathogen, is associated with neurological complications in adults and congenital abnormalities in newborns. There are no vaccines or treatments for ZIKV infection. Understanding the specificity of natural antibody responses to ZIKV could help inform vaccine efforts. Here, we used a technology called Deep Sequence-Coupled Biopanning to map the targets of the human antibody responses to ZIKV infection. A bacteriophage virus-like particle (VLP) library displaying overlapping linear peptides derived from the ZIKV polyprotein was generated. The library was panned using IgG from 23 ZIKV-infected patients from Panama and deep sequencing identified common targets of anti-ZIKV antibodies within the ZIKV envelope glycoprotein. These included epitopes within the fusion loop within domain II and four epitopes within domain III. Additionally, we showed that VLPs displaying selected epitopes elicited antibodies that bound to native ZIKV envelope protein but failed to prevent infection in a mouse challenge model.

CD8+ T Cells Trigger Auricular Dermatitis and Blepharitis in Mice after Zika Virus Infection in the Absence of CD4+ T Cells

Zika virus (ZIKV) became a public health concern when it re-emerged in 2015 owing to its ability to cause congenital deformities in the fetus and neurological complications in adults. Despite extensive data on protection, the interplay of protective and pathogenic adaptive immune responses toward ZIKV infection remains poorly understood. In this study, using a T-cell‒deficient mouse model that retains persistent ZIKV viral titers in the blood and organs, we show that the adoptive transfer of CD8+ T cells led to a significant reduction in viral load. This mouse model reveals that ZIKV can induce grossly visible auricular dermatitis and blepharitis, mediated by ZIKV-specific CD8+ T cells. Single-cell RNA sequencing of these causative CD8+ T cells from the ears shows an overactivated and elevated cytotoxic signature in mice with severe symptoms. Our results strongly suggest a role for CD8+ T-cell‒associated pathologies after ZIKV infection in CD4+ T-cell‒immunodeficient patients.

The Epidemiology of Neurological Complications in Adults With Sickle Cell Disease: A Retrospective Cohort Study.

Introduction: Risk factors for neurological complications in sickle cell disease differ in the adult and pediatric populations. Here, we focused on neurological complications in adults with sickle cell disease.Methods: Patients were selected using the audit data from the St George's Hospital Red Cell Database. The genotyping, demographics, clinical data, and investigation findings were collected.Results: A total of 303 patients were enrolled in the study: hemoglobin S homozygosity (HbSS) genotype 56%, hemoglobin S and C coinheritance (HbSC) genotype 35%, and hemoglobin S and β-thalassemia coinheritance (HbSβ) thalassemia genotype 9%; the mean age was 38.8 years (±13.5 SD) with 46% males. The most common neurological complication was cerebrovascular disease (n = 37, 12%) including those with ischemic stroke (10%), cerebral vasculopathy (3%), and intracranial hemorrhage (1%). Ischemic stroke was common among the HbSS genotype compared with other genotypes (8 vs. 1.6%, p = 0.001). Comparing the patients with sickle cell disease who had suffered a stroke to those who had not, there was a higher proportion of intracranial vasculopathy (p = 0.001, in particular, Moyamoya) and cognitive dysfunction (p < 0.0001).Conclusion: Our cohort supports previous reports that the most common neurological complication in adult sickle cell patients is cerebrovascular disease. Strategies to prevent cerebral vasculopathy and cognitive impairment should be explored.

Neonatal Chikungunya Presented as Apnea

Neonatal Chikungunya virus (CHIKV) infection is sporadic, and the prevalence of the entity has been described only recently. Neurological complications in adults have been reported, but there is a lack of data in this regard in neonates. In this retrospective case series done during the outbreak of Chikungunya, we observed 7 neonates who presented with fever, irritability, excessive cry, and rash, which was confirmed by polymerase chain reaction. Out of 7, 5 neonates presented with encephalopathy with apnea and seizures (80%), which were the most common presenting symptoms. Identifying this entity based on clinical and epidemiological background helps in management and aids in prognostication of the affected neonate.

Narrative Review of Neurologic Complications in Adults on ECMO: Prevalence, Risks, Outcomes, and Prevention Strategies.

Extracorporeal membrane oxygenation (ECMO), a life-saving technique for patients with severe respiratory and cardiac diseases, is being increasingly utilized worldwide, particularly during the coronavirus disease 2019(COVID-19) pandemic, and there has been a sharp increase in the implementation of ECMO. However, due to the presence of various complications, the survival rate of patients undergoing ECMO remains low. Among the complications, the neurologic morbidity significantly associated with venoarterial and venovenous ECMO has received increasing attention. Generally, failure to recognize neurologic injury in time is reportedly associated with poor outcomes in patients on ECMO. Currently, multimodal monitoring is increasingly utilized in patients with devastating neurologic injuries and has been advocated as an important approach for early diagnosis. Here, we highlight the prevalence and outcomes, risk factors, current monitoring technologies, prevention, and treatment of neurologic complications in adult patients on ECMO. We believe that an improved understanding of neurologic complications presumably offers promising therapeutic solutions to prevent and treat neurologic morbidity.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Descriptive analysis of surveillance data for Zika virus disease and Zika virus-associated neurological complications in Colombia, 2015–2017

Zika virus (ZIKV) is a mosquito-borne pathogen that recently caused a major epidemic in the Americas. Although the majority of ZIKV infections are asymptomatic, the virus has been associated with birth defects in fetuses and newborns of infected mothers as well as neurological complications in adults. We performed a descriptive analysis on approximately 106,000 suspected and laboratory-confirmed cases of Zika virus disease (ZVD) that were reported during the 2015-2017 epidemic in Colombia. We also analyzed a dataset containing patients with neurological complications and recent febrile illness compatible with ZVD. Females had higher cumulative incidence of ZVD than males. Compared to the general population, cases were more likely to be reported in young adults (20 to 39 years of age). We estimated the cumulative incidence of ZVD in pregnant females at 3,120 reported cases per 100,000 population (95% CI: 3,077-3,164), which was considerably higher than the incidence in both males and non-pregnant females. ZVD cases were reported in all 32 departments. Four-hundred and eighteen patients suffered from ZIKV-associated neurological complications, of which 85% were diagnosed with Guillain-Barré syndrome. The median age of ZIKV cases with neurological complications was 12 years older than that of ZVD cases. ZIKV-associated neurological complications increased with age, and the highest incidence was reported among individuals aged 75 and older. Even though neurological complications and deaths due to ZIKV were rare in this epidemic, better risk communication is needed for people living in or traveling to ZIKV-affected areas.

The Epidemiology of Neurological Complications in Adults with Sickle Cell Disease: A Retrospective Cohort Study (2733)

The Epidemiology of Neurological Complications in Adults with Sickle Cell Disease: A Retrospective Cohort Study (2733)

Zika virus exposure affects neuron-glia communication in the hippocampal slices of adult rats

Zika virus (ZIKV) infection during pregnancy was associated with microcephaly in neonates, but clinical and experimental evidence indicate that ZIKV also causes neurological complications in adults. However, the changes in neuron-glial communication, which is essential for brain homeostasis, are still unknown. Here, we report that hippocampal slices from adult rats exposed acutely to ZIKV showed significant cellular alterations regarding to redox homeostasis, inflammatory process, neurotrophic functions and molecular signalling pathways associated with neurons and glial cells. Our findings support the hypothesis that ZIKV is highly neurotropic and its infection readily induces an inflammatory response, characterized by an increased expression and/or release of pro-inflammatory cytokines. We also observed changes in neural parameters, such as adenosine receptor A2a expression, as well as in the release of brain-derived neurotrophic factor and neuron-specific enolase, indicating plasticity synaptic impairment/neuronal damage. In addition, ZIKV induced a glial commitment, with alterations in specific and functional parameters such as aquaporin 4 expression, S100B secretion and glutathione synthesis. ZIKV also induced p21 senescence-associated gene expression, indicating that ZIKV may induce early senescence. Taken together, our results indicate that ZIKV-induced neuroinflammation, involving nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NFκB) pathways, affects important aspects of neuron-glia communication. Therefore, although ZIKV infection is transient, long-term consequences might be associated with neurological and/or neurodegenerative diseases.

Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling.

Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.

Neurological complications in adults with Zika and chikungunya virus infection

In the past decade, many tropical regions have had arboviruses epidemics, including of Zika, dengue, and chikungunya viruses. Factors related to arboviral infection epidemics include population growth, unplanned urbanisation, increased travel, climate change, and decline of vector control programmes. The geographical distribution of Zika, dengue, and chikungunya viruses overlap and co-circulation became a serious concern in regions where Aedes spp mosquito vectors are endemic. Particularly, the Americas suffered from simultaneous outbreaks and co-circulation of these arthropod-borne viruses.

In Vitro Inhibition of Zika Virus Replication with Poly(Sodium 4-Styrenesulfonate).

Zika virus (ZIKV) is an emerging mosquito-borne pathogen associated with microcephaly and other congenital abnormalities in newborns as well as neurologic complications in adults. The explosive transmission of the virus in the last ten years put it in the limelight and improved our understanding of its biology and pathology. Currently, no vaccine or drugs are available to prevent or treat ZIKV infections. Knowing the potential of flaviviruses to broaden their geographic distribution, as observed for the West Nile virus, it is of importance to develop novel antiviral strategies. In this work, we identified poly(sodium 4-styrenesulfonate) (PSSNa) as a new polymeric ZIKV inhibitor. We demonstrated that PSSNa inhibits ZIKV replication in vitro both in animal and human cells, while no cytotoxicity is observed. Our mechanistic studies indicated that PSSNa acts mostly through direct binding to ZIKV particle and blocking its attachment to the host cells.

Systematic Analysis of Structure Similarity between Zika Virus and Other Flaviviruses

Zika virus (ZIKV) infection has caused global concern because of its association with fetal microcephaly and serious neurological complications in adults since 2016. Currently, no specific anti-ZIKV therapy is available to control ZIKV infection. During the last couple of years, the intensive investigation of ZIKV structure has provided significant information for structure-based vaccine and drug design. In this review, we summarized the research progress on the structures of ZIKV and its component proteins. We analyzed the structure identity and the differences between ZIKV and other flaviviruses. This information is crucial to guiding structure-based anti-ZIKV inhibitors and vaccine discovery.

History of arthropod-borne virus infections in French Polynesia.

In French Polynesia, arthropod-borne diseases are major public health problems. From the mid-1940s, the four serotypes of dengue virus (DENV-1 to -4) have caused 15 epidemics of variable severity. In 2013, for the first time, a sustained co-circulation of two different DENV serotypes (DENV-1 and -3) was reported. The same year, Zika virus (ZIKV) caused the largest outbreak ever recorded at that time. Severe neurologic complications in adults, including Guillain-Barré syndrome and central nervous system malformations in newborns and foeteuses, such as microcephaly, were reported, and a causal link with ZIKV infection was established. In addition to mosquito-borne transmission, the potential for perinatal, sexual and blood-transfusion transmission of ZIKV was demonstrated. In 2014, chikungunya virus (CHIKV) caused an explosive outbreak. Series of Guillain-Barré syndrome temporally associated with the CHIKV epidemic were reported. Except for DENV, ZIKV and CHIKV, no other arboviruses have been detected so far, but serologic evidence suggested the past silent circulation of Ross River virus. From May 2015 DENV-1 has been the only arbovirus transmitted in French Polynesia, but the reemergence of DENV-2 is highly expected since the detection of two autochthonous cases of DENV-2 infection in June 2018.