Astrocyte Control of Zika Infection Is Independent of Interferon Type I and Type III Expression

Zika virus (ZIKV) is a pathogenic neurotropic virus that infects the central nervous system (CNS) and results in various neurological complications. Astrocytes are the dominant CNS cell producer of the antiviral cytokine IFN-β, however little is known about the factors involved in their ability to mediate viral infection control. Recent studies have displayed differential responses in astrocytes to ZIKV infection, and this study sought to elucidate astrocyte cell-specific responses to ZIKV using a variety of cell models infected with either the African (MR766) or Asian (PRVABC59) ZIKV strains. Expression levels of pro-inflammatory (TNF-α and IL-1β) and inflammatory (IL-8) cytokines following viral infection were low and mostly comparable within the ZIKV-resistant and ZIKV-susceptible astrocyte models, with better control of proinflammatory cytokines displayed in resistant astrocyte cells, synchronising with the viral infection level at specific timepoints. Astrocyte cell lines displaying ZIKV-resistance also demonstrated early upregulation of multiple antiviral genes compared with susceptible astrocytes. Interestingly, pre-stimulation of ZIKV-susceptible astrocytes with either poly(I:C) or poly(dA:dT) showed efficient protection against ZIKV compared with pre-stimulation with either recombinant IFN-β or IFN-λ, perhaps indicating that a more diverse antiviral gene expression is necessary for astrocyte control of ZIKV, and this is driven in part through interferon-independent mechanisms.

Neurological Complications of Biological Treatment of Psoriasis

In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis. The use of biological drugs in psoriasis, although it yields positive therapeutic results, is not without numerous side effects. Serious neurological side effects of the therapy are most often visible with the use of anti-TNF-alpha, which is why patients should be monitored for their potential occurrence. Early detection of complications and rapid discontinuation of treatment with the drug may potentially increase the patient’s chances of a full recovery or improvement of his/her neurological condition. It also seems reasonable that, in the case of complications occurring during anti-TNF-alpha therapy, some of the drugs from other groups should be included in the therapy.

Is Diffusion Tensor Imaging-Guided Radiotherapy the New State-of-the-Art? A Review of the Current Literature and Technical Insights

Despite the increasing precision of radiotherapy delivery, it is still frequently associated with neurological complications. This is in part due to damage to eloquent white matter (WM) tracts, which is made more likely by the fact they cannot be visualised on standard structural imaging. WM is additionally more vulnerable than grey matter to radiation damage. Primary brain malignancies also are known to spread along the WM. Diffusion tensor imaging (DTI) is the only in vivo method of delineating WM tracts. DTI is an imaging technique that models the direction of diffusion and therefore can infer the orientation of WM fibres. This review article evaluates the current evidence for using DTI to guide intracranial radiotherapy and whether it constitutes a new state-of-the-art technique. We provide a basic overview of DTI and its known applications in radiotherapy, which include using tractography to reduce the radiation dose to eloquent WM tracts and using DTI to detect or predict tumoural spread. We evaluate the evidence for DTI-guided radiotherapy in gliomas, metastatic disease, and benign conditions, finding that the strongest evidence is for its use in arteriovenous malformations. However, the evidence is weak in other conditions due to a lack of case-controlled trials.

The Efficacy of Adjuvant Corticosteroids in Surgical Management of Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis

Objective: This systematic review aimed to assess the efficacy of adjuvant corticosteroids in managing patients with chronic subdural hematoma (CSDH) undergoing surgical intervention.Methods: We searched for eligible studies electronically on the databases of PubMed, Embase, and Google Scholar. The last date of the search was 15th Jun 2021. Outcomes were pooled to calculate risk ratios (RR) with 95% confidence intervals (CI).Results: Eleven studies were included. Four of them were randomized controlled trials (RCTs). Six studies reported data on good neurological outcomes but with variable definitions. Combining all studies, we noted no statistically significant difference in good neurological outcome with the use of adjuvant corticosteroids (RR: 0.91 95% CI: 0.74, 1.12 I2 = 92% p = 0.39). Similar results were obtained on subgroup analysis based on definition and study type. However, the use of adjuvant corticosteroids was associated with a significantly reduced risk of recurrence (RR: 0.51 95% CI: 0.40, 0.64 I2 = 0% p < 0.0001). The meta-analysis also demonstrated no statistically significant difference in mortality rates with the use of adjuvant corticosteroids (RR: 1.01 95% CI: 0.47, 2.21 I2 = 76% p = 0.97). The results did not differ between RCTs and non-RCTs. Limited studies reported data on complications, and pooled analysis indicated no significant increase in infectious, gastrointestinal, and neurological complications with the use of adjuvant corticosteroids.Conclusion: The use of corticosteroids with surgery for CSDH might be associated with a reduction in recurrence rate. However, corticosteroids do not improve functional outcomes or mortality rates. Future studies should assess the impact of different corticosteroid regimens on patient outcomes, and should use standardized reporting of neurological outcomes with uniform follow-up duration.

Posterior Reversible Encephalopathy Syndrome (PRES) Associated With COVID-19 Infection—A Case Report and Review

Coronavirus disease 2019 (COVID-19) has caused a large number of systemic complications including a variety of neurological complications. Some of the neurological complications are not known. Posterior reversible encephalopathy syndrome (PRES) is a known acute neurotoxic syndrome causing a wide range of neurological symptoms. If remains untreated, it can potentially become a life-threatening condition. However, it is not a known neurological complication of COVID-19. We describe a presentation of PRES in a patient with positive COVID-19 and presented with altered mental status. A 78-year-old male with history of idiopathic epilepsy was initially admitted with respiratory illness with negative COVID-19 test. Later during his hospitalization, his respiratory condition got worse and his repeat COVID-19 test came back positive. He had continued encephalopathy and was found to have status epilepticus afterward. Magnetic Resonance Imaging brain showed extensive PRES-related changes. His blood pressure remained overall within control without significant fluctuations. No other apparent etiology was identified for PRES except for possible correlation with COVID-19. Clinicians should consider PRES early in their differential diagnoses in patients with severe COVID-19 with continued encephalopathy.

Trajectories of chemosensory and cognitive functions up to 1.5 years after acute COVID-19

There is an increasing recognition of neurological manifestations from SARS-CoV-2 infection. Quantifications of such manifestations and their long-term dynamics in the general infected population are of essence in understanding the health and socioeconomic burden of neurological complications of COVID-19. Through rigorous empirical testing of over 800 volunteers, we present here repeated cross-sectional and longitudinal data that depict the trajectories of chemosensory functions, cognitive performances and depressive symptoms up to 1.5 years after acute COVID-19 in discharged patients with respect to non-infected controls. Overall, deficits in smell, taste and chemesthesis slowly resolved within about a year of discharge. Concerningly, cognitive impairments –– independent of elevated depressive symptoms and evident even in those with nonsevere disease –– showed no sign of improvement over time. In people over 50 years, COVID-19 was associated with a substantially increased risk for mild cognitive impairment. Our findings urge for cognitive and emotional interventions targeting COVID-19 convalescents.

COVID-19–Associated Acute Asymmetric Hemorrhagic Necrotizing Encephalopathy: A Case Report

Background: Coronavirus disease 2019 (COVID-19) has been associated with many neurological complications affecting the central nervous system. Purpose: Our aim was to describe a case of COVID-19 associated with a probable variant of acute necrotizing encephalopathy (ANE). Results: A 60-year-old man who presented with a 3-day history of dyspnea, fever, and cough tested positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Five days following his admission, the patient was intubated secondary to respiratory failure. Following his extubation 16 days later, he was found to have a left-sided weakness. Magnetic resonance imaging (MRI) of the brain showed hemorrhagic rim-enhancing lesions involving the right thalamus, left hippocampus, and left parahippocampal gyrus. These lesions showed decreased relative cerebral blood flow on MR perfusion and restricted on diffusion-weighted imaging. These neuroimaging findings were consistent with ANE. The left-sided weakness gradually improved over the subsequent weeks. Conclusions: We concluded that COVID-19 can be associated with ANE, a condition believed to be the result of an immune-mediated process with activation of the innate immune system. Future studies must address whether biological drugs targeting the pro-inflammatory cytokines could prevent the development of this condition.

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.

Antidepressant Sertraline Is a Broad-Spectrum Inhibitor of Enteroviruses Targeting Viral Entry through Neutralization of Endolysosomal Acidification

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs as of yet to treat EV71 infections. In this study, we conducted antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be greatly relieved by exposing virus-infected cells to extracellular low-pH culture media. Ultimately, we have identified a use for an FDA-approved antidepressant in broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

Is there a rendezvous for SARS-CoV-2 and Agmatine?

The catastrophe of the ongoing COVID-19 pandemic is caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). The respiratory system appears to be ground zero in the majority of the patients. However, many other organs can get infected by cytokines, chemokines and other mediators released in response to the presence of the virus. The neurotropism by the SARS-CoV-2 is established beyond doubt. In addition to non-specific symptoms, the symptoms specific to central and/or peripheral nervous system diseases as well as neuromuscular diseases have been observed in numerous clinical cases. These observations and the experiences with other coronavirus infections earlier and flu pandemics raise concerns not only about the neurological effects in active disease but also about the long-term effects generated by the infection, immune and inflammatory functions. The knowledge of biological actions of agmatine in the backdrop of physiological events instigated by invading SARS-CoV-2 and host’s response, especially in neural events, focuses on the possible overlaps of biomolecular pathways at a number of instances. This is not surprising since the factors stimulated during SARS-CoV-2 infection are the disease-generating neuroinflammatory components altered by agmatine. Hence, we hypothesize the possible beneficial role of agmatine in SARS-CoV-2 infection. Based on a narrative review of the literature, agmatine can be proposed as a plausible beneficial candidate for supporting treatment of SARS-CoV-2 infection and for addressing post-infection neurological complications.