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Torque teno virus (TTV) is a ssDNA orphan virus belonging to the Anelloviridae family, but some recent studies suggested its possible involvement in central nervous system (CNS) pathology. We analyzed serum and cerebrospinal fluid samples (CSF) from 109 patients with encephalitis for TTV infection using serological and molecular testing, virus quantitative measurement, and next-generation sequencing-based (NGS) phylogenetic analysis. TTV noncoding region (UTR) and/or open reading frame 1 (ORF-1) sequences were detected in serum of 86 (79%) patients and in nine (8%) patients in CSF. Five of the latter patients were coinfected with various entero- and herpesviruses. Anti-TTV-IgG were detected in 80 (73.4%) sera and in two (1.8%) CSF samples, while anti-TTV-IgM were present in three (2.8%) sera and in none of the CSFs. Phylogenic analysis of CSF-derived TTV ORF-1 sequences revealed the presence of three unique variants in one patient. TTV was quantified in five CSF-serum pairs: in two patients viral loads were similar, and in three serum TTV loads were approximately one log higher. Our results suggest at least an occasional replication of TTV in CNS. However, whether TTV could be the cause of encephalitis requires further studies. [ABSTRACT FROM AUTHOR]

Background Toxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid β plaques. We aimed to determine if there is a brain regional difference in amyloid β reduction in the brains of T. gondii- infected compared to control mice. Method Three-month-old 5xFAD (AD model) mice were injected with T. gondii or with phosphate-buffered saline as a control. Intact brains were harvested at 6 weeks postinfection, optically cleared using iDISCO+, and brain-wide amyloid burden was visualized using volumetric light-sheet imaging. Amyloid signal was quantified across each brain and computationally mapped to the Allen Institute Brain Reference Atlas to determine amyloid density in each region. Results A brain-wide analysis of amyloid in control and T. gondii- infected 5xFAD mice revealed that T. gondii infection decreased amyloid burden in the brain globally as well as in the cortex and hippocampus, and many daughter regions. Daughter regions that showed reduced amyloid burden included the prelimbic cortex, visual cortex, and retrosplenial cortex. The olfactory tubercle, a region known to have increased monocytes following T. gondii infection, also showed reduced amyloid after infection. Conclusions T. gondii infection of AD mice reduces amyloid burden in a brain region-specific manner that overlaps with known regions of T. gondii infection and peripheral immune cell infiltration. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. Methods: 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. Results: Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. Conclusions: Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE. [ABSTRACT FROM AUTHOR]

Background: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear. Methods: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers. Results: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P <.05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P <.0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P >.05). Conclusion: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour's clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features. [ABSTRACT FROM AUTHOR]

Background. According to some authors, neuroinfection agents play a role in the development of several neurological disorders, including epilepsy. For many years, it was believed that acute infectious diseases, such as tick-borne encephalitis virus and meningococcus played a leading role in the emerging epileptic process of postinfectious etiology. Regarding a role for chronically persistent infections, it has not been fully explored.Objective: to identify clinical, diagnostic, and morphological features of locally induced postinfectious epilepsy, both at disease onset upon emergence of the first epileptic seizures during acute infectious process and during their recurrence in a chronically persistent infection.Material and methods. The study included observations of 1500 patients with locally induced epilepsy admitted and treated from 2007 to 2017 in various medical inpatient and outpatient institutions. Post-infection locally induced epilepsy with clear causality link between previous neuroinfection and onset of epileptic seizure was found in 127 patients (Group 1). During initial visits, infectious agents in a cohort of patients with recurrent epileptic seizures manifested as chronic persistent infection were suspected in more than 1/3 of the 1373 subjects who sought medical aid comprising 550 people (Group 2). In addition to the clinical evaluation of patients, instrumental studies were performed, including routine electroencephalography (EEG), sleep video-EEG monitoring, magnetic resonance imaging (MRI), and some patients underwent pathomorphological examination using electron microscopy and histological techniques.Results. Gross and marked diffuse disturbances in brain bioelectrical activity were most often detected (58% and 31%, respectively) during video-EEG monitoring in Group 1, whereas moderate alterations were recorded less frequently (11% of observations). In Group 2, the majority of diffuse disturbances in brain bioelectrical activity were of moderate level (79%) followed by mild and irritative changes recorded less frequently (in 21% of cases). MRI data showed that disorders of the amygdala-hippocampal system were observed in 41 (32%) and 211 (38%) patients in Groups 1 and 2, respectively. Histological and electron microscopic data revealed a number of morphological disorders in patients with locally induced postinfectious epilepsy common with earlier described mitochondrial encephalomyopathies (mitochondrial megaconia and pleioconia) as well as a set of specific manifestations typical to such pathology.Conclusion. The conducted clinical, neurophysiological, neuroimaging, and pathomorphological studies of postinfectious epilepsy revealed specific features underlying its development at different stages, from its onset in acute infectious process to chronization in persistent infection. It was found that a comprehensive analysis of the presence and impact of infectious agents in patients with epileptic seizures is important for course and prognosis of postinfectious epilepsy, which is relevant for timely diagnosis and development of specific pharmacotherapy.

To this day, there are cases of neuro infections that cannot be etiologically specified and are cured empirically. Clinics are difficult, and the healing process is prolonged with risks of complications. It is not uncommon for diseases to remain unrecognized for a long time due to an atypical clinical picture. This leads to prolonged exposure of the patient to the harmful effects of infection and prolongation of the disease process. The result is many costly studies without results. It is necessary to revise the current course of neuro infections and their classification, as well as to share information in specially created platforms for searching for coincidence and exchange of experience. In this regard, we present one of our cases, which remained undiagnosed and we find it interesting. The presented clinical case is atypical and etiologically unproven. An example of a challenge in diagnosis and treatment, that bears no resemblance to the relatively rare neuro infections in our region. We have studied the current changes and course of some of the most common encephalitis and summarized them with an aim to do the differential diagnosis. We need a revision of the current course of neuroinfections and a new classification based on the clinical picture.

ABSTRACT The highly prevalent herpes simplex virus type 1 (HSV-1) causes a range of diseases, including cold sores, blinding keratitis, and life-threatening encephalitis. HSV-1 initially replicates in epithelial cells, enters the peripheral nervous system via neurites, and establishes lifelong infection in the neuronal cell bodies. Neurites are highly dynamic structures that grow or retract in response to attractive or repulsive cues, respectively. Here, we show that infection with HSV-1, but not with a mutant virus lacking glycoprotein G (gG), reduced the repulsive effect of epithelial cells on neurite outgrowth and facilitated HSV-1 invasion of neurons. HSV-1 gG was required and sufficient to induce neurite outgrowth by modifying the protein composition of extracellular vesicles, increasing the amount of neurotrophic and neuroprotective proteins, including galectin-1. Antibodies directed against galectin-1 neutralized the capacity of extracellular vesicles released from HSV-1-infected cells to promote neurite outgrowth. Our study provides new insights into the neurotropism of HSV-1 and identifies a viral protein that modifies the protein composition of extracellular vesicles to stimulate neurite outgrowth and invasion of the nervous system.IMPORTANCEHerpes simplex virus type 1 (HSV-1) must infect neurites (or nerve endings) to establish a chronic infection in neurons. Neurites are highly dynamic structures that retract or grow in the presence of repulsive or attractive proteins. Some of these proteins are released by epithelial cells in extracellular vesicles and act upon interaction with their receptor present on neurites. We show here that HSV-1 infection of epithelial cells modulated their effect on neurites, increasing neurite growth. Mechanistically, HSV-1 glycoprotein G (gG) modifies the protein composition of extracellular vesicles released by epithelial cells, increasing the amount of attractive proteins that enhance neurite outgrowth and facilitate neuronal infection. These results could inform of therapeutic strategies to block HSV-1 induction of neurite outgrowth and, thereby, neuronal infection.

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To this day, there are cases of neuro infections that cannot be etiologically specified and are cured empirically. Clinics are difficult, and the healing process is prolonged with risks of complications. It is not uncommon for diseases to remain unrecognized for a long time due to an atypical clinical picture. This leads to prolonged exposure of the patient to the harmful effects of infection and prolongation of the disease process. The result is many costly studies without results. It is necessary to revise the current course of neuro infections and their classification, as well as to share information in specially created platforms for searching for coincidence and exchange of experience. In this regard, we present one of our cases, which remained undiagnosed and we find it interesting. The presented clinical case is atypical and etiologically unproven. An example of a challenge in diagnosis and treatment, that bears no resemblance to the relatively rare neuro infections in our region. We have studied the current changes and course of some of the most common encephalitis and summarized them with an aim to do the differential diagnosis. We need a revision of the current course of neuroinfections and a new classification based on the clinical picture. [ABSTRACT FROM AUTHOR]

Abstract Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.

Abstract Background Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. Methods In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. Results Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. Conclusions These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. [ABSTRACT FROM AUTHOR]

Neuroinfections of the central nervous system (CNS) can be triggered by various pathogens. Viruses are the most widespread and have the potential to induce long-term neurologic symptoms with potentially lethal outcomes. In addition to directly affecting their host cells and inducing immediate changes in a plethora of cellular processes, viral infections of the CNS also trigger an intense immune response. Regulation of the innate immune response in the CNS depends not only on microglia, which are fundamental immune cells of the CNS, but also on astrocytes. These cells align blood vessels and ventricle cavities, and consequently, they are one of the first cell types to become infected after the virus breaches the CNS. Moreover, astrocytes are increasingly recognized as a potential viral reservoir in the CNS; therefore, the immune response initiated by the presence of intracellular virus particles may have a profound effect on cellular and tissue physiology and morphology. These changes should be addressed in terms of persisting infections because they may contribute to recurring neurologic sequelae. To date, infections of astrocytes with different viruses originating from genetically distinct families, including Flaviviridae, Coronaviridae, Retroviridae, Togaviridae, Paramyxoviridae, Picomaviridae, Rhabdoviridae, and Herpesviridae, have been confirmed. Astrocytes express a plethora of receptors that detect viral particles and trigger signaling cascades, leading to an innate immune response. In this review, we summarize the current knowledge on virus receptors that initiate the release of inflammatory cytokines from astrocytes and depict the involvement of astrocytes in immune functions of the CNS. [ABSTRACT FROM AUTHOR]

There are multiple lines of evidence for the existence of communication between the central nervous system (CNS), gut, and intestinal microbiome. Despite extensive analysis conducted on various neurological disorders, the gut microbiome was not yet analyzed in neuroinfections. In the current study, we analyzed the gut microbiome in 47 consecutive patients hospitalized with neuroinfection (26 patients had viral encephalitis/meningitis; 8 patients had bacterial meningitis) and in 20 matched for age and gender health controls. Using the QIIME pipeline, 16S rRNA sequencing and classification into operational taxonomic units (OTUs) were performed on the earliest stool sample available. Bacterial taxa such as Clostridium, Anaerostipes, Lachnobacterium, Lachnospira, and Roseburia were decreased in patients with neuroinfection when compared to controls. Alpha diversity metrics showed lower within-sample diversity in patients with neuroinfections, though there were no differences in beta diversity. Furthermore, there was no significant change by short-term (1–3 days) antibiotic treatment on the gut microbiota, although alpha diversity metrics, such as Chao1 and Shannon’s index, were close to being statistically significant. The cause of differences between patients with neuroinfections and controls is unclear and could be due to inflammation accompanying the disease; however, the effect of diet modification and/or hospitalization cannot be excluded.

Encephalitis caused by Borrelia burgdorferi sensu lato is a rare clinical manifestation of Lyme neuroborreliosis and only in few cases have brain parenchymal inflammation been documented. Here, we present a case of Lyme neuroborreliosis with encephalitis with significant parenchymal inflammation on magnetic resonance imaging (MRI) in an immunosuppressed patient.

Background: Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. Methods: In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. Results: Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. Conclusions: These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis. [ABSTRACT FROM AUTHOR]

Neuroinfections caused by herpesviruses, mainly by HHV-1, represent a significant problem for modern medicine due to the small number of therapeutic substances available in the pharmaceutical sector. Furthermore, HHV-1 infection has been linked to neurodegenerative processes such as Alzheimer's disease, which justifies the search for new effective therapies. The development of nanotechnology opens up new possibilities for the treatment of neuroinflammation. Gold and silver nanoparticles are gaining popularity, and the number of clinical trials involving metallic nanoparticles is constantly increasing. This paper reviews the research on gold and silver nanoparticles and their potential use in the treatment of herpesvirus neuroinfection. [ABSTRACT FROM AUTHOR]

The increasing number of cases of tick-borne encephalitis (TBE) reported in recent years in Europe and, more recently, in Poland is a consequence of factors related to climate and environmental change leading to increasing tick populations and human behavior favoring exposure. In Poland, there is considerable regional variation in the incidence of TBE, resulting, among other factors, from underreporting of all cases and limited access to laboratory diagnostics. The consequence is low public awareness of the disease and insufficient use of vaccination as optimal prevention. The current system of surveillance for TBE in Poland needs to be improved: the introduction of standardised standards of clinical practice and wider access to laboratory. Med Pr Work Health Saf. 2024;75(6)., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

The identification of central nervous system inflammation etiology leads to adjusted therapy. We analyzed the potential inflammatory and neuro-axonal damage markers in children. Our target was to correlate the findings with a disease's course or a sequalae risk and assess their clinical usefulness. The study included 96 children with symptoms of central nervous system inflammation who underwent diagnostics. The research group involved 24 children with autoimmune disorders and 31 with neuroinfection. The control group included patients with both etiologies excluded. We analyzed the results of routine laboratory tests together with chosen serum (neopterin, interleukin [IL]-1ß, IL-6) and CSF (metalloproteinase [MMP]-9, S100B protein) markers. In the whole cohort, CSF MMP-9 correlated with CSF cytosis and serum IL-6 and CRP. In the undivided neuroinflammatory group, CSF S100B correlated with serum IL-6 and IgM concentrations. CSF cytosis was associated with CSF MMP-9 and serum neopterin levels. Among the infective patients, IL-6 was linked with increased CSF MMP-9. We conclude that astroglial protein S100B, neopterin, and cytokine concentrations may enable predicting long-term consequences, whereas CSF MMP-9 concentration may reflect the actual central nervous system injury regardless of etiology. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), has been a global epidemic in our healthcare system. SARS-CoV-2 primarily affects the respiratory system, but neurological involvement has also been reported, including Guillain-Barré syndrome (GBS) development. Case Presentation: A 58-year-old male with known co-morbid hypertension and type 2 diabetes mellitus presented to the emergency room with complaints of worsening shortness of breath, dry cough, and fever for the past 10 days. On day 20 of hospitalization, he developed neurological symptoms after being tested positive for COVID-19. A neuroelectrophysiology study was conducted to evaluate neurological symptoms and suggested that the patient suffers from acute motor-sensory axonal polyneuropathy (AMSAN). CSF analysis showed elevated protein levels that confirmed the diagnosis of GBS. He was subsequently treated with oral prednisolone and IVIG, which improved neurological symptoms. Conclusion: Ever since the emergence of COVID-19, GBS has surfaced as to its potentially dangerous outcome. Healthcare professionals should be mindful of GBS and should rule it out in anyone having sensory symptoms or weakness during or after a COVID-19 infection. Its early detection and treatment can result in improved clinical outcomes. [ABSTRACT FROM AUTHOR]

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease- 2019 (COVID-19), has been a global epidemic in our healthcare system. SARS-CoV-2 primarily affects the respiratory system, but neurological involvement has also been reported, including Guillain–Barré syndrome (GBS) development.Case PresentationA 58-year-old male with known co-morbid hypertension and type 2 diabetes mellitus presented to the emergency room with complaints of worsening shortness of breath, dry cough, and fever for the past 10 days. On day 20 of hospitalization, he developed neurological symptoms after being tested positive for COVID-19. A neuroelectrophysiology study was conducted to evaluate neurological symptoms and suggested that the patient suffers from acute motor-sensory axonal polyneuropathy (AMSAN). CSF analysis showed elevated protein levels that confirmed the diagnosis of GBS. He was subsequently treated with oral prednisolone and IVIG, which improved neurological symptoms.ConclusionEver since the emergence of COVID-19, GBS has surfaced as to its potentially dangerous outcome. Healthcare professionals should be mindful of GBS and should rule it out in anyone having sensory symptoms or weakness during or after a COVID-19 infection. Its early detection and treatment can result in improved clinical outcomes.

In patients with coronavirus infection, the nervous system involvement is very diverse. It undeniably directly affects the function of genitourinary system and other body systems. This can be most prominently manifested in urination, the complex and complicated process of bladder emptying. These symptoms are well-known and can be identified from the very first minutes of doctor-patient communication under the condition of knowledge about the symptoms and willingness for focused identification. Conscious control of urination requires complex interactions between the autonomic (sympathetic and parasympathetic) and the somatic nervous system. Medical history is important for diagnosis. On the one hand, the information obtained is twice as subjective, being the physician’s subjective assessment of the patient’s subjective perceptions. However, one should not forget about the need for individual approach to diagnosis taking into account each patient’s characteristics. Drug therapy should be accomplished only through the joint effort of urologist and neurologist during both therapy and rehabilitation.

Introduction and objective The article focuses mainly on SARS-CoV-2 neurotropism and its consequences for hearing and otolaryngological disorders. The leading hypotheses regarding the mechanisms of the virus internalisation as well as its influence on the nervous system in extenso are presented, as well as the latest available knowledge, after a selective choice of articles relating to the subject. Brief description of the state of knowledge Dizziness, tinnitus and sudden hearing loss are the main symptoms in the organ of hearing and balance, but it is often not possibile to objectively investigate their etiology and make a proper diagnosis. Among the most common causes of hearing disorders, such as vestibular neuritis, sudden sensorineural hearing loss and tinnitus, there are infections, injuries, and diseases that predispose to the occurrence of symptoms of hearing disorders. Despite the numerous possible causes, a high percentage of clinical symptoms still remain without diagnosis. Conclusions The global health crisis has provoked a change in the perspective of thinking about infections and the consequences of viral infections; it haalso given rise to a new perception and conceptualisation of the impact of infections on other human systems. The challenge faced by scientists due to this virus is multi-dimensional, and it requires explication and reinterpretation of the knowledge to-date. It even forces us to retrospect the existing explanations of the known disorders, as well as to conduct prospective correlative studies that will help in understand the mechanisms of SARS-CoV-2 pathogenesis, and consequentl, to be able to establish a management pattern in order to prevent the spread of the virus causing the pandemic.

Introduction: Epilepsy affects about 50 million people worldwide, 80% of whom live in low- and middle-income countries. In Brazil, epidemiological studies are outdated and restricted to specific regions, mostly due to the continental size of country. Objective: We aimed to present the first evidence-based study on the epidemiological aspects of individuals with epilepsy, mapping the characteristics of this disease in a referral center in a region of Southeast Brazil. Methods: A retrospective study was carried out from January 2010 to March 2021. Patients were selected according to the International League Against Epilepsy Criteria. Results: From a total of 618 selected patients, 317 (51.3%) were men and 301 (48.7%) were women with an average age of 34.03 ± 20.66 years. The average age at the first seizure was 15.16 ± 17.61 years. The prevalence ratio was 1.30 cases/1,000 habitants. Childhood febrile seizure was present in 44 patients (7.9%) and family history of epilepsy in 231 (37.4%) patients. The predominant type of seizure was focal in 401 (64.9%) patients. The most frequent etiologies were structural in 254 (41.1%) patients and unknown in 238 (38.5%) patients. Most of the patients' treatments were based on anti-seizure drugs in monotherapy [389 (62.9%)] with 398 (64.4%) drug-responsive patients. Conclusions: Our epilepsy prevalence rate was lower than other studies in the Southeast Region of Brazil. In addition, the structural epilepsy type was predominant in our study compared with unknown causes, which is more frequent in other Brazilian regions and worldwide studies. The differences may be attributed to our region, which presents a high prevalence of neuroinfection, specially neurocysticercosis, and a referral center for traumatic brain injury. Moreover, the contrasting results reinforce the need for an adequate epidemiological assessment of epilepsy incidence in a region of Southeast Brazil. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. Medline, Embase, Scopus, Cochrane library. There was no discrimination on study type, time of publication or language. Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis. Review : Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died. This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi -endemic areas should be considered. [ABSTRACT FROM AUTHOR]

Despite the success of vaccine prophylaxis and therapy, neuroinfections remain a serious problem due to the epidemic threat, high mortality and residual disabling and maladaptive neurological deficits in half of the cases.The aim of the literature review was to study modern publications concerning the dynamics of the infectious process in the central nervous system, the nature and predictors of its outcome in children.The results confirmed the effectiveness of social modification with the help of vaccination, guidelines and increased availability of medical care, leading to a decrease in mortality and morbidity of vaccine-controlled neuroinfections. At the same time, the general morbidity and due to the severity of complications and structural acute phase defect post-infectious neurological deficit in the form of epilepsy, motor, cognitive and behavioral disorders remain the same.The study of the outcomes of neuroinfections, their clinic and treatment at all stages, including the remote one, is necessary to develop an optimal protocol for the treatment and rehabilitation of children who have undergone meningitis and encephalitis in order to improve their quality of life.

IntroductionEpilepsy affects about 50 million people worldwide, 80% of whom live in low- and middle-income countries. In Brazil, epidemiological studies are outdated and restricted to specific regions, mostly due to the continental size of country.ObjectiveWe aimed to present the first evidence-based study on the epidemiological aspects of individuals with epilepsy, mapping the characteristics of this disease in a referral center in a region of Southeast Brazil.MethodsA retrospective study was carried out from January 2010 to March 2021. Patients were selected according to the International League Against Epilepsy Criteria.ResultsFrom a total of 618 selected patients, 317 (51.3%) were men and 301 (48.7%) were women with an average age of 34.03 ± 20.66 years. The average age at the first seizure was 15.16 ± 17.61 years. The prevalence ratio was 1.30 cases/1,000 habitants. Childhood febrile seizure was present in 44 patients (7.9%) and family history of epilepsy in 231 (37.4%) patients. The predominant type of seizure was focal in 401 (64.9%) patients. The most frequent etiologies were structural in 254 (41.1%) patients and unknown in 238 (38.5%) patients. Most of the patients' treatments were based on anti-seizure drugs in monotherapy [389 (62.9%)] with 398 (64.4%) drug-responsive patients.ConclusionsOur epilepsy prevalence rate was lower than other studies in the Southeast Region of Brazil. In addition, the structural epilepsy type was predominant in our study compared with unknown causes, which is more frequent in other Brazilian regions and worldwide studies. The differences may be attributed to our region, which presents a high prevalence of neuroinfection, specially neurocysticercosis, and a referral center for traumatic brain injury. Moreover, the contrasting results reinforce the need for an adequate epidemiological assessment of epilepsy incidence in a region of Southeast Brazil.

Summary: Background: Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined as lasting symptoms several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses and neurodegenerative processes may occur in absence of overt neuroinvasion. Methods: Here we determined whether intranasal SARS-CoV-2 infection in male and female syrian golden hamsters results in persistent brain pathology. Brains 3 (symptomatic) or 14 days (viral clearance) post infection versus mock (n = 10 each) were immunohistochemically analyzed for viral protein, neuroinflammatory response and accumulation of tau, hyperphosphorylated tau and alpha-synuclein protein. Findings: Viral protein in the nasal cavity led to pronounced microglia activation in the olfactory bulb beyond viral clearance. Cortical but not hippocampal neurons accumulated hyperphosphorylated tau and alpha-synuclein, in the absence of overt inflammation and neurodegeneration. Importantly, not all brain regions were affected, which is in line with selective vulnerability. Interpretation: Thus, despite the absence of virus in brain, neurons develop signatures of proteinopathies that may contribute to progressive neuronal dysfunction. Further in depth analysis of this important mechanism is required. Funding: Federal Ministry of Health (BMG; ZMV I 1-2520COR501), Federal Ministry of Education and Research (BMBF 01KI1723G), Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20), German Research Foundation (DFG; 398066876/GRK 2485/1), Luxemburgish National Research Fund (FNR, Project Reference: 15686728, EU SC1-PHE-CORONAVIRUS-2020 MANCO, no > 101003651).

Background: Histoplasmosis is a fungal disease endemic in some regions of the United States of America, Canada, and Latin America. The geographic characteristics, humidity, soil, and climate are responsible for such distribution. In Brazil, there are case reports of histoplasmosis throughout its territory, being considered an endemic region. It is considered an opportunistic disease, affecting mostly immunocompromised patients. To the present date, scientific publications dealing with pediatric cases of histoplasmosis are restricted to case series. Spinal cord injuries caused by histoplasmosis are rare, even in the adult population, being described in few studies. Case Description: The present report deals with a 4-year-old patient, from the southeast region of Brazil, who started a condition of fever, weight loss, cervicobrachialgia, and symmetrical tetraparesis, with evolution over 2 months. In the diagnostic investigation, she was found to have primary immunodeficiency and neuroimaging examinations showed a cervical spinal cord lesion at the level of C4-C6. The anatomopathological diagnosis of histoplasmosis was possible after surgery for decompression and biopsy of the lesion. Conclusion: According to our research, there are no reports in the literature that address the situation of spinal cord compression syndrome due to histoplasmosis in the pediatric population. [ABSTRACT FROM AUTHOR]

Ocular infection with Toxoplasma gondii causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in hippocampal-dependent tasks, and their relationship with the morphology and number of microglia, is less well understood. Here, in 6-month-old, female BALB/c mice, 5 μl of a suspension containing 48.5 × 106 tachyzoites/ml was introduced into the conjunctival sac; control received an equal volume of saline. Before and after instillation, all mice were subject to an olfactory discrimination (OD) test, using predator (cat) feces, and to an open-field (OF) task. After the behavioral tests, the animals were culled at either 22 or 44 days post-instillation (dpi), and the brains and retinas were dissected and processed for immunohistochemistry. The total number of Iba-1-immunolabeled microglia in the molecular layer of the dentate gyrus was estimated, and three-dimensional reconstructions of the cells were evaluated. Immobility was increased in the infected group at 12, 22, and 43 dpi, but the greatest immobility was observed at 22 dpi and was associated with reduced line crossing in the OF and distance traveled. In the OD test, infected animals spent more time in the compartment with feline fecal material at 14 and at 43 dpi. No OD changes were observed in the control group. The number of microglia was increased at 22 dpi but returned to control levels by 44 dpi. These changes were associated with the differentiation of T. gondii tachyzoites into bradyzoite-enclosed cysts within the brain and retina. Thus, infection of mice with T. gondii alters exploratory behavior, gives rise to a loss in predator's odor avoidance from 2 weeks after infection, increased microglia number, and altered their morphology in the molecular layer of the dentate gyrus. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is an inflammation of the meninges associated with the invasion of bacteria. The etiologic agents vary by age group. Bacterial meningitis due to group B streptococcus (GBS) is common for the neonatal period but is deemed to be rare in adult patients. Since 2000, more than two-thirds of all cases occur in adults, which is becoming a growing problem worldwide. We present a rare case of GBS meningitis presented with cerebral infarction in an adult patient and briefly review the etiology and incidence of GBS infections in adults. There is an increasing incidence of cases in elderly patients, particularly in those with more medical comorbidities. Cerebral infarction as an adverse effect in bacterial meningitis is both a sign of severity and a predictor of a poor clinical outcome with a high mortality rate. Early recognition of the infection, a search for deep-seated infection, and early antimicrobial therapy are vital moments for successful management of the GBS disease. [ABSTRACT FROM AUTHOR]

Neurological disorders related to neuroinfections are highly prevalent in Sub-Saharan Africa (SSA), constituting a major cause of disability and economic burden for patients and society. These include epilepsy, dementia, motor neuron diseases, headache disorders, sleep disorders, and peripheral neuropathy. The highest prevalence of human immunodeficiency virus (HIV) is in SSA. Consequently, there is a high prevalence of neurological disorders associated with HIV infection such as HIV-associated neurocognitive disorders, motor disorders, chronic headaches, and peripheral neuropathy in the region. The pathogenesis of these neurological disorders involves the direct role of the virus, some antiretroviral treatments, and the dysregulated immune system. Furthermore, the high prevalence of epilepsy in SSA (mainly due to perinatal causes) is exacerbated by infections such as toxoplasmosis, neurocysticercosis, onchocerciasis, malaria, bacterial meningitis, tuberculosis, and the immune reactions they elicit. Sleep disorders are another common problem in the region and have been associated with infectious diseases such as human African trypanosomiasis and HIV and involve the activation of the immune system. While most headache disorders are due to benign primary headaches, some secondary headaches are caused by infections (meningitis, encephalitis, brain abscess). HIV and neurosyphilis, both common in SSA, can trigger long-standing immune activation in the central nervous system (CNS) potentially resulting in dementia. Despite the progress achieved in preventing diseases from the poliovirus and retroviruses, these microbes may cause motor neuron diseases in SSA. The immune mechanisms involved in these neurological disorders include increased cytokine levels, immune cells infiltration into the CNS, and autoantibodies. This review focuses on the major neurological disorders relevant to Africa and neuroinfections highly prevalent in SSA, describes the interplay between neuroinfections, immune system, neuroinflammation, and neurological disorders, and how understanding this can be exploited for the development of novel diagnostics and therapeutics for improved patient care. [ABSTRACT FROM AUTHOR]

Ocular infection with Toxoplasma gondii causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in hippocampal-dependent tasks, and their relationship with the morphology and number of microglia, is less well understood. Here, in 6-month-old, female BALB/c mice, 5 μl of a suspension containing 48.5 × 106 tachyzoites/ml was introduced into the conjunctival sac; control received an equal volume of saline. Before and after instillation, all mice were subject to an olfactory discrimination (OD) test, using predator (cat) feces, and to an open-field (OF) task. After the behavioral tests, the animals were culled at either 22 or 44 days post-instillation (dpi), and the brains and retinas were dissected and processed for immunohistochemistry. The total number of Iba-1-immunolabeled microglia in the molecular layer of the dentate gyrus was estimated, and three-dimensional reconstructions of the cells were evaluated. Immobility was increased in the infected group at 12, 22, and 43 dpi, but the greatest immobility was observed at 22 dpi and was associated with reduced line crossing in the OF and distance traveled. In the OD test, infected animals spent more time in the compartment with feline fecal material at 14 and at 43 dpi. No OD changes were observed in the control group. The number of microglia was increased at 22 dpi but returned to control levels by 44 dpi. These changes were associated with the differentiation of T. gondii tachyzoites into bradyzoite-enclosed cysts within the brain and retina. Thus, infection of mice with T. gondii alters exploratory behavior, gives rise to a loss in predator’s odor avoidance from 2 weeks after infection, increased microglia number, and altered their morphology in the molecular layer of the dentate gyrus.

Neurological disorders related to neuroinfections are highly prevalent in Sub-Saharan Africa (SSA), constituting a major cause of disability and economic burden for patients and society. These include epilepsy, dementia, motor neuron diseases, headache disorders, sleep disorders, and peripheral neuropathy. The highest prevalence of human immunodeficiency virus (HIV) is in SSA. Consequently, there is a high prevalence of neurological disorders associated with HIV infection such as HIV-associated neurocognitive disorders, motor disorders, chronic headaches, and peripheral neuropathy in the region. The pathogenesis of these neurological disorders involves the direct role of the virus, some antiretroviral treatments, and the dysregulated immune system. Furthermore, the high prevalence of epilepsy in SSA (mainly due to perinatal causes) is exacerbated by infections such as toxoplasmosis, neurocysticercosis, onchocerciasis, malaria, bacterial meningitis, tuberculosis, and the immune reactions they elicit. Sleep disorders are another common problem in the region and have been associated with infectious diseases such as human African trypanosomiasis and HIV and involve the activation of the immune system. While most headache disorders are due to benign primary headaches, some secondary headaches are caused by infections (meningitis, encephalitis, brain abscess). HIV and neurosyphilis, both common in SSA, can trigger long-standing immune activation in the central nervous system (CNS) potentially resulting in dementia. Despite the progress achieved in preventing diseases from the poliovirus and retroviruses, these microbes may cause motor neuron diseases in SSA. The immune mechanisms involved in these neurological disorders include increased cytokine levels, immune cells infiltration into the CNS, and autoantibodies. This review focuses on the major neurological disorders relevant to Africa and neuroinfections highly prevalent in SSA, describes the interplay between neuroinfections, immune system, neuroinflammation, and neurological disorders, and how understanding this can be exploited for the development of novel diagnostics and therapeutics for improved patient care.

Pott's puffy tumors are assumed to be infrequent concomitant intra- and extracranial abscesses, mainly secondary to complicated frontal sinusitis during infancy. Due to the close proximity to the superior sagittal sinus, there is a risk of developing venous infections, thrombosis, and morbidity. In this case report, we present a case of an 11-year-old girl who presented with headache and face edema. After recognizing the Pott's puffy tumor pattern on the CT scan and brain MRI, the neurosurgical approach involved pus evacuation and frontal sinus blockage, and the patient received antibiotic therapy and was evaluated for total recovery. To our knowledge, the prompt diagnosis and treatment of such conditions are paramount to avoid complications, and differential diagnosis should be encouraged in medical practice., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ferreira Furtado et al.)

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain. [ABSTRACT FROM AUTHOR]

Background and purpose: An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID‐19) have been reported. Methods: A systematic review was performed of cases of ATM described in the context of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection by screening both articles published and in preprint. Results: Twenty cases were identified. There was a slight male predominance (60.0%) and the median age was 56 years. Neurological symptoms first manifested after a mean of 10.3 days from the first onset of classical, mostly respiratory symptoms of COVID‐19. Overall, COVID‐19 severity was relatively mild. Polymerase chain reaction of cerebrospinal fluid for SARS‐CoV‐2 was negative in all 14 cases examined. Cerebrospinal fluid findings reflected an inflammatory process in most instances (77.8%). Aquaporin‐4 and myelin oligodendrocyte protein antibodies in serum (tested in 10 and nine cases, respectively) were negative. On magnetic resonance imaging, the spinal cord lesions spanned a mean of 9.8 vertebral segments, necrotic‐hemorrhagic transformation was present in three cases and two individuals had additional acute motor axonal neuropathy. More than half of the patients received a second immunotherapy regimen. Over a limited follow‐up period of several weeks, 90% of individuals recovered either partially or near fully. Conclusion: Although causality cannot readily be inferred, it is possible that cases of ATM occur para‐ or post‐infectiously in COVID‐19. All identified reports are anecdotal and case descriptions are heterogeneous. Whether the condition and the observed radiological characteristics are specific to SARS‐CoV‐2 infection needs to be clarified. [ABSTRACT FROM AUTHOR]

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.

Neuroinfections caused by herpesviruses, mainly by HHV-1, represent a significant problem for modern medicine due to the small number of therapeutic substances available in the pharmaceutical sector. Furthermore, HHV-1 infection has been linked to neurodegenerative processes such as Alzheimer’s disease, which justifies the search for new effective therapies. The development of nanotechnology opens up new possibilities for the treatment of neuroinflammation. Gold and silver nanoparticles are gaining popularity, and the number of clinical trials involving metallic nanoparticles is constantly increasing. This paper reviews the research on gold and silver nanoparticles and their potential use in the treatment of herpesvirus neuroinfection.

Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in December 2019. SARS-CoV-2 has infected several millions of people, resulting in a huge socioeconomic cost and over 2.5 million deaths worldwide. Though the pathogenesis of COVID-19 is not fully understood, data have consistently shown that SARS-CoV-2 mainly affects the respiratory and gastrointestinal tracts. Nevertheless, accumulating evidence has implicated the central nervous system in the pathogenesis of SARS-CoV-2 infection. Unfortunately, however, the mechanisms of SARS-CoV-2 induced impairment of the central nervous system are not completely known. Here, we review the literature on possible neuropathogenic mechanisms of SARS-CoV-2 induced cerebral damage. The results suggest that downregulation of angiotensin converting enzyme 2 (ACE2) with increased activity of the transmembrane protease serine 2 (TMPRSS2) and cathepsin L in SARS-CoV-2 neuroinvasion may result in upregulation of proinflammatory mediators and reactive species that trigger neuroinflammatory response and blood brain barrier disruption. Furthermore, dysregulation of hormone and neurotransmitter signalling may constitute a fundamental mechanism involved in the neuropathogenic sequelae of SARS-CoV-2 infection. The viral RNA or antigenic peptides also activate or interact with molecular signalling pathways mediated by pattern recognition receptors (e.g., toll-like receptors), nuclear factor kappa B, Janus kinase/signal transducer and activator of transcription, complement cascades, and cell suicide molecules. Potential molecular targets and therapeutics of SARS-CoV-2 induced neurologic damage are also discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Neurotoxocarosis (NT) is induced by larvae of the dog or cat roundworm (Toxocara canis or T. cati) migrating and persisting in the central nervous system of paratenic hosts, including humans, and may be accompanied by severe neurological symptoms. Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis, but detailed data on pathogenic mechanisms and involvement of signalling molecules during cerebral Toxocara species infections are scarce. Methods To elucidate alterations in immunomodulatory mediator pattern, comprehensive multiplex bead array assays profiling comprising 23 different cytokines and chemokines were performed during the course of T. canis- and T. cati-induced NT. To this end, cerebra and cerebella of experimentally infected C57Bl/6 J mice serving as paratenic host models were analysed at six different time points (days 7, 14, 28, 42, 70 and 98) post infectionem (pi). Results Brain-body mass ratios of T. canis and T. cati-infected mice were significantly lower than those of the uninfected control group at day 14 pi, and also at day 28 pi for T. canis-infected mice. Both infection groups showed a continuous decrease of pro-inflammatory cytokine concentrations, including TNF-α, IFN-γ, GM-CSF and IL-6, in the cerebrum over the course of infection. Additionally, T. canis but not T. cati-induced neurotoxocarosis was characterised by significantly elevated levels of anti-inflammatory IL-4 and IL-5 in the cerebrum in the acute and subacute phase of the disease. The higher neuroaffinity of T. canis led to a prominent increase of eotaxin and MIP-1α in both the cerebrum and cerebellum, while in T. cati-infected mice, these chemokines were significantly elevated only in the cerebellum. Conclusions The direct comparison of T. canis- and T. cati-induced NT provides valuable insights into key regulatory mechanisms of Toxocara species in paratenic hosts. The cerebral cyto-/chemokine milieu is shifted to a predominantly anti-inflammatory immune response during NT, possibly enabling both survival of the parasite and the neuroinfected paratenic host. Alteration of eotaxin and MIP-1α concentrations are congruent with the higher neuroaffinity of T. canis and species-specific tropism of T. canis to the cerebrum and T. cati to the cerebellum.

Abstract Background The chemokine CXCL13 is an intensively investigated biomarker in Lyme neuroborreliosis (LNB). Its role in other neuroinfections is increasingly recognized but less clear. Objective To determine the significance of CXCL13 in established central nervous system (CNS) infections other than LNB by matching cerebrospinal fluid (CSF) CXCL13 elevations with severity of the disease course. Methods We investigated 26 patients with bacterial (n = 10) and viral (n = 16; tick-borne encephalitis, n = 6; varicella zoster infection, n = 10) neuroinfections of whom CSF CXCL13 levels were available twice, from lumbar punctures (LP) performed at admission and follow-up. As outcome classification, we dichotomized disease courses into “uncomplicated” (meningitis, monoradiculitis) and “complicated” (signs of CNS parenchymal involvement such as encephalitis, myelitis, abscesses, or vasculitis). CXCL13 elevations above 250 pg/ml were classified as highly elevated. Results Eight of 26 patients (31%) with both bacterial (n = 4) and viral (n = 4) neuroinfections had a complicated disease course. All of them but only 3/18 patients (17%) with an uncomplicated disease course had CSF CXCL13 elevations > 250 pg/ml at the follow-up LP (p 250 pg/ml. All four patients with a complicated disease course but only one with an uncomplicated disease course had sustained CXCL13 elevations at follow-up. Patient groups did not differ with regard to age, time since symptom onset, LP intervals, type of infections, and anti-pathogen treatments. Conclusion Our study revealed pronounced CXCL13 elevations in CSF of patients with severe disease courses of bacterial and viral neuroinfections. This observation indicates a role of CXCL13 in the CNS immune defense and points at an additional diagnostic value as biomarker for unresolved immune processes leading to or associated with complications.

The spectrum of health complications instigated by coronavirus disease 2019 (COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) pandemic has been diverse and complex. Besides the evident pulmonary and cardiovascular threats, accumulating clinical data points to several neurological complications, which are more common in elderly COVID-19 patients. Recent pieces of evidence have marked events of neuro infection and neuroinvasion, producing several neurological complications in COVID-19 patients; however, a systematic understanding of neuro-pathophysiology and manifested neurological complications, more specifically in elderly COVID-19 patients is largely elusive. Since the elderly population gradually develops neurological disorders with aging, COVID-19 inevitably poses a higher risk of neurological manifestations to the aged patients. In this report, we reviewed SARS-CoV-2 infection and its role in neurological manifestations with an emphasis on the elderly population. We reviewed neuropathological events including neuroinfection, neuroinvasion, and their underlying mechanisms affecting neuromuscular, central- and peripheral- nervous systems. We further assessed the imminent neurological challenges in the COVID-19 exposed population, post-SARS-CoV-2-infection. Given the present state of clinical preparedness, the emerging role of AI and machine learning was also discussed concerning COVID-19 diagnostics and its management. Taken together, the present review summarizes neurological outcomes of SARS-CoV-2 infection and associated complications, specifically in elderly patients, and underlines the need for their clinical management in advance.

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in China, causing a new coronavirus disease, termed COVID-19 by the WHO on February 11, 2020. At the time of this paper (January 31, 2021), more than 100 million cases have been recorded, which have claimed over 2 million lives worldwide. The most important clinical presentation of COVID-19 is severe pneumonia; however, many patients present various neurological symptoms, ranging from loss of olfaction, nausea, dizziness, and headache to encephalopathy and stroke, with a high prevalence of inflammatory central nervous system (CNS) syndromes. SARS-CoV-2 may also target the respiratory center in the brainstem and cause silent hypoxemia. However, the neurotropic mechanism(s) by which SARS-CoV-2 affects the CNS remain(s) unclear. In this paper, we first address the involvement of astrocytes in COVID-19 and then elucidate the present knowledge on SARS-CoV-2 as a neurotropic virus as well as several other neurotropic flaviviruses (with a particular emphasis on the West Nile virus, tick-borne encephalitis virus, and Zika virus) to highlight the neurotropic mechanisms that target astroglial cells in the CNS. These key homeostasis-providing cells in the CNS exhibit many functions that act as a favorable milieu for virus replication and possibly a favorable environment for SARS-CoV-2 as well. The role of astrocytes in COVID-19 pathology, related to aging and neurodegenerative disorders, and environmental factors, is discussed. Understanding these mechanisms is key to better understanding the pathophysiology of COVID-19 and for developing new strategies to mitigate the neurotropic manifestations of COVID-19.

The spectrum of health complications instigated by coronavirus disease 2019 (COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) pandemic has been diverse and complex. Besides the evident pulmonary and cardiovascular threats, accumulating clinical data points to several neurological complications, which are more common in elderly COVID-19 patients. Recent pieces of evidence have marked events of neuro infection and neuroinvasion, producing several neurological complications in COVID-19 patients; however, a systematic understanding of neuro-pathophysiology and manifested neurological complications, more specifically in elderly COVID-19 patients is largely elusive. Since the elderly population gradually develops neurological disorders with aging, COVID-19 inevitably poses a higher risk of neurological manifestations to the aged patients. In this report, we reviewed SARS-CoV-2 infection and its role in neurological manifestations with an emphasis on the elderly population. We reviewed neuropathological events including neuroinfection, neuroinvasion, and their underlying mechanisms affecting neuromuscular, central- and peripheral- nervous systems. We further assessed the imminent neurological challenges in the COVID-19 exposed population, post-SARS-CoV-2-infection. Given the present state of clinical preparedness, the emerging role of AI and machine learning was also discussed concerning COVID-19 diagnostics and its management. Taken together, the present review summarizes neurological outcomes of SARS-CoV-2 infection and associated complications, specifically in elderly patients, and underlines the need for their clinical management in advance. [ABSTRACT FROM AUTHOR]