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This narrative review explores the current landscape of functional neurosurgery in Africa, focusing on the challenges and opportunities facing the field. Drawing upon existing literature and expert insights, the review highlights the scarcity of resources, including trained personnel, infrastructure, and specialized equipment, as major hurdles impeding the widespread adoption of advanced neurosurgical techniques. Despite these challenges, the review identifies a growing recognition of the importance of functional neurosurgery in addressing neurological disorders prevalent across the continent. Efforts to enhance training programs, establish collaborations with international partners, and leverage technology are discussed as promising strategies to overcome logistical barriers. Moreover, the review underscores the significance of addressing cultural beliefs and stigmas surrounding neurological conditions to ensure equitable access to care and promote acceptance of neurosurgical interventions. By navigating these challenges and embracing emerging opportunities, functional neurosurgery in Africa holds the potential to significantly impact neurological health outcomes and enhance overall well-being. [ABSTRACT FROM AUTHOR]

Neuroinfections are difficult and time-consuming to treat. The main bottleneck in therapy is drugs’ inability to enter the central nervous system (CNS) via the blood-brain barrier (BBB). Because the diffusion of conventional antibodies in tissues is limited by their large size (150 kDa), it is necessary to find an antibody fragment that can cross the BBB and treat CNS infections. Camelid heavy chain only antibodies, also known as nanobodies, possess a unique Variable domain of a Heavy chain (VHH). The VHH could be used as an alternative to conventional antibodies and have enormous potential in a wide range of medical and bio-technology fields. The VHH with an average molecular weight of 15 kDa can diffuse nearly four times better in tissues and tumours than common antibodies. A VHH is made up of four framework regions (FR1‒4) and three hypervariable complementarity-determining regions (CDR1‒3), with CDR3 being particularly important in interaction with pathogen epitopes. Experimental results have shown that the CDR3 domain alone can bind to epitopes and may contribute to reduce the size of the antigen-recognizing molecule, allowing it to be used more effectively to diffuse much better in tissues, and as well as to cross the BBB and biodistributed in CNS.

Neuroinfections rank among the top ten leading causes of child mortality globally, even in high-income countries. The crucial determinants for successful treatment lie in the timing and swiftness of diagnosis. Although viruses constitute the majority of infectious neuropathologies, diagnosing and treating viral neuroinfections remains challenging. Despite technological advancements, the etiology of the disease remains undetermined in over half of cases. The identification of the pathogen becomes more difficult when the infection is caused by atypical pathogens or multiple pathogens simultaneously. Furthermore, the modern surge in global passenger traffic has led to an increase in cases of infections caused by pathogens not endemic to local areas. This review aims to systematize and summarize information on neuroinvasive viral pathogens, encompassing their geographic distribution and transmission routes. Emphasis is placed on rare pathogens and cases involving atypical pathogens, aiming to offer a comprehensive and structured catalog of viral agents with neurovirulence potential. [ABSTRACT FROM AUTHOR]

Streptococcus equi subsp. zooepidemicus is a rare etiologic agent of bacterial meningitis in humans. The disease is a zoonotic infection and is transmitted through close contact with domestic animals, mainly horses. Only 37 cases of Streptococcus zooepidemicus meningitis have been reported in the literature until July 2023. The aim of this study is to present a rare clinical case of S. zooepidemicus-related meningitis in a human immunodeficiency virus (HIV)-positive patient and analyze the literature. We present a 23-year-old horse breeder patient with advanced immunosuppression due to acquired immunodeficiency syndrome (AIDS) and S. zooepidemicus meningitis, admitted at the Clinic of Infectious Diseases, St. George University Hospital, Plovdiv. The course of meningitis was severe since the beginning, with significant cerebral edema, disturbances in consciousness, persistent fever, and the development of complications against the background of AIDS-related conditions. S. zooepidemicus was microbiologically detected from cerebrospinal fluid culture. After prolonged treatment and a long hospital stay, the patient’s condition improved, and eventually he was discharged and recovered from the acute neuroinfection. Although extremely rare, S. zooepidemicus should be considered in patients with clinical and laboratory evidence of bacterial meningitis who have contact with animals, especially horses, other domestic animals, and their dairy products, as well as in immunocompromised patients. To the best of our knowledge, the current clinical case is the first report of S. zooepidemicus-related meningitis in a patient with HIV/AIDS.

Abstract Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to serious metabolic consequences and even death. Some of the diseases caused by flaviviruses occur continuously in certain regions, while others occur intermittently or sporadically, causing epidemics. Some of the most common flaviviruses are West Nile virus, dengue virus, tick-borne encephalitis virus, Zika virus and Japanese encephalitis virus. Since all the above-mentioned viruses are capable of penetrating the blood–brain barrier through different mechanisms, their actions also affect the central nervous system (CNS). Like other viruses, flaviviruses, after entering the human body, contribute to redox imbalance and, consequently, to oxidative stress, which promotes inflammation in skin cells, in the blood and in CNS. This review focuses on discussing the effects of oxidative stress and inflammation resulting from pathogen invasion on the metabolic antiviral response of the host, and the ability of viruses to evade the consequences of metabolic changes or exploit them for increased replication and further progression of infection, which affects the development of sequelae and difficulties in therapy.

Streptococcus equi subsp. zooepidemicus is a rare etiologic agent of bacterial meningitis in humans. The disease is a zoonotic infection and is transmitted through close contact with domestic animals, mainly horses. Only 37 cases of Streptococcus zooepidemicus meningitis have been reported in the literature until July 2023. The aim of this study is to present a rare clinical case of S. zooepidemicus-related meningitis in a human immunodeficiency virus (HIV)-positive patient and analyze the literature. We present a 23-year-old horse breeder patient with advanced immunosuppression due to acquired immunodeficiency syndrome (AIDS) and S. zooepidemicus meningitis, admitted at the Clinic of Infectious Diseases, St. George University Hospital, Plovdiv. The course of meningitis was severe since the beginning, with significant cerebral edema, disturbances in consciousness, persistent fever, and the development of complications against the background of AIDS-related conditions. S. zooepidemicus was microbiologically detected from cerebrospinal fluid culture. After prolonged treatment and a long hospital stay, the patient's condition improved, and eventually he was discharged and recovered from the acute neuroinfection. Although extremely rare, S. zooepidemicus should be considered in patients with clinical and laboratory evidence of bacterial meningitis who have contact with animals, especially horses, other domestic animals, and their dairy products, as well as in immunocompromised patients. To the best of our knowledge, the current clinical case is the first report of S. zooepidemicus-related meningitis in a patient with HIV/AIDS. [ABSTRACT FROM AUTHOR]

Neuroinfections rank among the top ten leading causes of child mortality globally, even in high-income countries. The crucial determinants for successful treatment lie in the timing and swiftness of diagnosis. Although viruses constitute the majority of infectious neuropathologies, diagnosing and treating viral neuroinfections remains challenging. Despite technological advancements, the etiology of the disease remains undetermined in over half of cases. The identification of the pathogen becomes more difficult when the infection is caused by atypical pathogens or multiple pathogens simultaneously. Furthermore, the modern surge in global passenger traffic has led to an increase in cases of infections caused by pathogens not endemic to local areas. This review aims to systematize and summarize information on neuroinvasive viral pathogens, encompassing their geographic distribution and transmission routes. Emphasis is placed on rare pathogens and cases involving atypical pathogens, aiming to offer a comprehensive and structured catalog of viral agents with neurovirulence potential.

Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to serious metabolic consequences and even death. Some of the diseases caused by flaviviruses occur continuously in certain regions, while others occur intermittently or sporadically, causing epidemics. Some of the most common flaviviruses are West Nile virus, dengue virus, tick-borne encephalitis virus, Zika virus and Japanese encephalitis virus. Since all the above-mentioned viruses are capable of penetrating the blood–brain barrier through different mechanisms, their actions also affect the central nervous system (CNS). Like other viruses, flaviviruses, after entering the human body, contribute to redox imbalance and, consequently, to oxidative stress, which promotes inflammation in skin cells, in the blood and in CNS. This review focuses on discussing the effects of oxidative stress and inflammation resulting from pathogen invasion on the metabolic antiviral response of the host, and the ability of viruses to evade the consequences of metabolic changes or exploit them for increased replication and further progression of infection, which affects the development of sequelae and difficulties in therapy. [ABSTRACT FROM AUTHOR]

Neuroinfections are seen in both adults and children. These can result in serious morbidity and if left untreated and/or associated with comorbidities can be life threatening. Cross-sectional imaging like computed tomography (CT) and magnetic resonance imaging (MRI) are advised by the clinicians for the diagnosing, confirmation of the diagnosis, assess any complications of the infection, and also for follow up. Though CT is the initial imaging investigation commonly asked by the clinician, due to its lesser soft tissue resolution, early brain changes may not be seen on CT. MRI has better soft tissue resolution with no ionizing radiation to the patient and helps in detecting the early signs of infection. Appropriate MRI, not only helps the radiologist to reduce the number of possibilities of the causative organism but also differentiates tumors from infection. However, CT is useful to assess the bony changes and also easily available and affordable cross-sectional imaging modality worldwide. The review summarizes the approach of the radiologist to central nervous system (CNS) infections and their typical imaging characteristic features.

Infections constitute an important and common category of diseases, particularly in less developed countries. Infections present with a broad spectrum of clinical and radiologic features dictated by the cell and tissue tropism and host response elicited, posing a considerable diagnostic challenge. Early diagnosis and treatment are crucial in preventing mortality and morbidity. Recourse is often made to biopsy for ascertaining the diagnosis, and hence the pathologist plays a vital role in patient management. Therefore, knowledge of the histopathologic changes is necessary to recognize the histological changes and guide the diagnostic workup and management. Each microbial agent elicits a distinctive pattern of inflammatory tissue response, which can serve as a clue to the etiological agent. Based on the causative organism, microbial, and host factors, the inflammatory response may be acute or chronic, necrotic or non-necrotic. The inflammation can be of varied patterns – lymphohistiocytic, granulomatous, inflammatory demyelinating, fibrosing, or showing minimal inflammation. The pattern of necrosis also differs based on the causative organism. Typically, pyogenic bacteria are associated with suppurative inflammation, tuberculosis with caseous granulomatous, and fungi with suppurative granulomatous inflammation. Viral infections are associated with lymphohistiocytic non-necrotizing inflammation and, based on cell tropism, can cause demyelination (e.g., JCV) and/or viral inclusions. Parasitic infections (protozoal or metazoal) display a broad spectrum of inflammatory changes that overlap with other types of infections. This review briefly describes pathological patterns and associated pathogens and provides an algorithmic approach based on pattern recognition that may be useful for the practicing pathologist.

Objective: With coronavirus disease 2019 (COVID-19) pandemic across the world, there had been an exponential increase in rhino-orbito-cerebral mucormycosis (ROCM). Extension of infection to cavernous sinus leads to cavernous sinus syndrome (CSS). This study aims to describe incidence, clinicoradiological profile, and outcome of CSS positive along with comparative analysis of CSS negative COVID-19-associated ROCM. Material and Method: This was a prospective and observational study conducted from May 1, 2021, to July 31, 2021. Subjects included ROCM with active or recovered COVID-19 (past 6 weeks) and were categorized and staged. CSS was defined as involvement of two or more of third, fourth, fifth, or sixth cranial nerve with one each direct and indirect qualitative neuroradiological features. Clinicoradiological features of CSS-positive and negative COVID-19-associated ROCM groups were compared. Results: Incidence of CSS with COVID-19-associated ROCM was 28%. Mean age of subjects was 44 ± 15 years with 60% being males and 73% were proven ROCM. Significant differences seen across the CSS-positive and negative groups were ocular, nasal, and cerebral findings including eyelid and periocular discoloration, ptosis, proptosis, ophthalmoplegia, nasal discharge, mucosal inflammation, and fever. Oculomotor, trochlear, and abducens nerves were significantly involved more in CSS-positive group. Significant radiological findings across two groups included indirect features in orbit, nose, and paranasal sinuses along with direct features in cavernous sinus. Surgical intervention was more common in CSS-positive group. Mortality in CSS-positive group at 8-24 weeks was 13 and 27%, respectively. Conclusion: Extension of ROCM to CSS was more common in young males in advanced stages of proven ROCM with concurrent COVID-19. CSS-positive group had significant difference in clinicoradiological features involving orbit, nose, paranasal sinuses, and central nervous system as compared to CSS-negative group. This study highlights the need to develop an objective scoring system considering clinical and radiological features for diagnosis of CSS with COVID-19-associated ROCM. [ABSTRACT FROM AUTHOR]

Background: In newly diagnosed neurocysticercosis (NCC) with seizures, the choice of anti-seizure medication (ASM) seems to be arbitrary due to a lack of comparative studies. Although oxcarbazepine (OXC) is often considered efficacious for focal seizures in NCC, due to adverse effects, newer ASMs like levetiracetam (LCM) and lacosamide are also being explored.Methods: This study was performed by case record review of children with newly diagnosed solitary viable parenchymal NCC aged 4-18years who received lacosamide and OXC at least for 12 weeks between August 2019 and April 2021, from a prospective registry of a tertiary care teaching hospital in north India. Seizure control, electroencephalographic abnormalities, resolution of inflammatory granulomas and adverse effects were compared between two arms at 12 and 24 weeks.Results: Total 31 (8.3 ± 4.7 years, 19 boys) and 72 (8.6 ± 4.2 years, 43 boys) completed at least 12 weeks follow-up in LCM and OXC groups, out of which 2 and 51 completed at least 24 weeks follow-up in LCM and OXC groups, respectively. The occurrence of breakthrough seizure was comparable in both arms at 12 and 24 weeks (1/31 and 2/22 in lacosamide group vs. 2/72 and 4/51 in OXC group, p = 0.66 and 0.59, respectively). Patients receiving OXC had more frequent treatment-emergent adverse events (p = 0.0001) and four patients required discontinuation due to severe adverse events (SAEs), while none in the lacosamide group had SAEs.Conclusions: Lacosamide appears to be efficacious and safe for achieving seizure freedom in patients with solitary viable parenchymal neurocysticercosis. [ABSTRACT FROM AUTHOR]

To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been selected throughout evolution for their use of specific mechanisms. They can enter the central nervous system through direct infection of nerves or cerebral barriers or through cell-mediated transport. Indeed, peripheral lymphoid and myeloid immune cells can interact with the blood–brain and the blood–cerebrospinal fluid barriers and allow viral brain access using the “Trojan horse” mechanism. Among immune cells, at the frontier between innate and adaptive immune responses, dendritic cells (DCs) can be pathogen carriers, regulate or exacerbate antiviral responses and neuroinflammation, and therefore be involved in viral transmission and spread. In this review, we highlight an important contribution of DCs in the development and the consequences of viral brain infections.

Neuroinfections cause significant morbidity, mortality, and long-term disability. These infections rarely present with the classic signs and symptoms taught in textbooks. Due to the similarities in presentation between neuroinfections and many other disease processes, delayed diagnosis is common. Thus, it is important that care providers have a high clinical suspicion for potential cases because early diagnosis and treatment can significantly improve outcomes. This article serves as a review of the approach to a patient with suspected neurological infection with an emphasis on clinical presentation, diagnosis, and treatment of the major causes of meningitis and encephalitis. Additionally, patients in an immunocompromised state are vulnerable to a whole host of additional neuroinfections that present atypically and will also be addressed.

The use of cytoflavin solution in complex therapy of patients with neuroinfection was studied. It showed a favourable effect on the disease clinical process, evident from less pronounced intoxication and meningeal signs by the 11th day of the treatment and improvement of the liquorological picture. The cytoflavin efficacy was also confirmed by normalization of the brain bioelectric activity evident from the electroencephalograms and by reduction of the level of antioxidants, such as metalloproteids and superoxidodismutase, that was in favour of the drug antiinflammatory and antioxidant effects. The use of cytoflavin tablets during in early convalescence period promoted earlier recovery of the intellectual and mnestic reactions. On the whole, the use of cytoflavin promoted favourable process and outcomes of neuroinfections and could be recommended for the use during the acute state and re habilitation of the patients.

Maintaining an intact pool of neural progenitor cells (NPCs) is crucial for generating new and functionally active neurons. Methamphetamine (METH) can exacerbate the HIV-induced deficit of adult neurogenesis; however, potential mechanisms of this influence are still poorly understood. In the present study, we present evidence that chronic exposure to METH combined with brain infection by EcoHIV results in enhanced proliferation of NPCs in the subventricular zone (SVZ) in mice. This effect was long-lasting as it was preserved ex vivo in NPCs isolated from the exposed mice over several passages in the absence of additional treatments. Increased proliferation in response to METH plus HIV was associated with dysregulation of cyclin B1 and cyclin D. Transcriptomic studies indicated that 27 out of the top 30 differentially expressed genes in response to METH plus EcoHIV were targets of the forkhead box O transcriptional factor (FOXO) and primarily FOXO3. Additional ex vivo studies and in vitro experiments using human NPCs exposed to METH and infected with HIV revealed upregulation of the CXCL12-CXCR4 axis, leading to activation of downstream pAkt and pErk, the pathways that can phosphorylate FOXO3 and force its exports from the nuclei into the cytoplasm. Indeed, nuclear expulsion of FOXO3 was demonstrated both in mice exposed to METH and infected with EcoHIV and in cell cultures of human NPCs. These results provide novel information that exposure to METH combined with HIV infection can induce aberrant proliferation of SVZ-derived NPCs and identifies CXCL12-CXCR4-Akt-1-mediated phosphorylation of FOXO3 as the mechanism responsible for this effect. [ABSTRACT FROM AUTHOR]

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Enterovirus infections are diseases with a diverse clinical manifestation. The disease mainly affects young children during the summer months. The causative agents are small viruses of the Picornavirus family. Most often the diseases manifest themselves as rash infections, neuroinfections, infections of the upper respiratory tract. They rarely occur with diarrheal syndrome. The transmission of viruses is faecaloral or airborne. They occur sporadically or as small epidemic outbreaks. Enteroviruses are widespread throughout the world and are one of the leading causes of childhood infections. [ABSTRACT FROM AUTHOR]

Neuroinfections are acute inflammatory diseases of the central and peripheral nervous system that can lead to serious consequences, and even death. Recently, viruses have played a leading role in the emergence of neuroinfections. Rapid identification of the etiological agents is an important prerequisite for proper therapy and a good outcome of the disease. The aim of this study is to determine the role of the cytokines IL-6 and IFN-γ in the cerebrospinal fluid and serum of patients with viral and bacterial neuroinfections in relation to their diagnosis and prognosis. Materials and methods: From 2012-2018, 91 patients were included, aged from 2 months to 82 years. They were divided into 3 groups: 57 with viral neuroinfections , 24 - with bacterial and 10 - control group with cerebral edema. Clinical, epidemiological, laboratory, microbiological, serological and molecular tests were performed in all patients, and in some of them imaging techniques (CT and MRI) had been performed. Cytokines IL-6 and IFN-γ in serum and cerebrospinal fluid were determined by immunological tests. Conclusion: Viral neuroinfections are more common than bacterial ones, they had a milder clinical course and a more favorable outcome. Cytokine levels in the cerebrospinal fluid are a better indicator of inflammatory process in terms of severity than those in the serum. IL-6 levels in the cerebrospinal fluid of viral neuroinfections were higher than IFN-γ. A proportional relationship was established between leukocytes and IL-6 in the cerebrospinal fluid of patients with aseptic meningitis.

Introduction. The increased attention from the state to the organization of rehabilitation measures, especially among children, requires evaluation and development of measures to improve the effectiveness of all areas of rehabilitation – medical, social and professional rehabilitation. The development of measures increasing efficiency is especially important among children, since children are the main potential of the country. The objective of the study was to evaluate the medical and social effectiveness of the rehabilitation measures carried out for children after neuroinfections. Material and methods. During the study, parents of children after neuroinfections were interviewed, as well as the examination of changes in large motor functions and functional state was carried out by doctors of the Clinic of “Scientific and Research Institution of Children’s Infections”. Medical experts used special evaluation scales in order to objectify the research.Results. The overwhelming majority of parents (90.4 %) note an improvement in the condition of their children in terms of medical and social adaptation. More than one third of parents (35.9 %) note the improvement of their children’s condition, according to all seven criteria proposed for the answer (formation of independent walking skills, stabilization of emotional-volitional activity, acquisition of new social household skills, ability to sit, decrease of muscle tone, speech development and improvement of manipulative functions of the hand). According to the expert opinion of the doctors of the Clinic, 78.8 % of children suffered from the disruption of large motor functions, and children of the first level, i.e. the lightest, according to the classification scale for large motor functions (GMFCS), was only 17 %. After four courses of rehabilitation in the Clinic, the proportion of children of the first level increased significantly and amounted to 48.2 %. Improvements in the opinion of medical experts, based on the results of the questioning, were also observed in functional status, in such positions as communication, everyday life skills, socialization and motor skills.Сonclusion. Thus, the effectiveness of rehabilitation measures for children after neuroinfections has been proved. Moreover, with the increase in the number of rehabilitation courses, the state of children improves both by the medical and social criteria.

The aim of the study was to determine the serum level of homocysteine in children with neuroinfections.Mаterials and methods: A blood serum assay of 60 children with viral and bacterial neuroinfections was performed using the enzyme immunoassay to evaluate homocysteinemia as a marker of endothelial dysfunction.Results: In interpreting the results, the average level of hyperhomocysteinemia in patients with bacterial and viral neuroinfections was established. The highest homocysteine levels in serum were observed in bacterial neuroinfections, especially in the presence of signs of meningoencephalitis and pneumococcal etiology of the disease. Dependence of changes in the level of homocysteinemia from the sex of sick children was not revealed.Conclusion: Neuroinfections in children, regardless of the cause, are accompanied by hyperhomocysteinemia, indicating the presence of endothelial activation in this pathology, more pronounced in the case of a bacterial etiology of the infectious process and the combined lesion of the soft dura mater and the brain substance.

The aim is to study the features of the adaptation process in children of different ages with acute neuroinfections depending on the etiology, severity of the disease and the period of the disease using indicators of the pituitary-thyroid system. Material and Methods. A comprehensive clinical and laboratorial checkup of 237 children with different noso-logical forms of neuroinfections was carried out: meningitis: viral, enteroviral, purulent and cerebromeningitis. Control board group was composed of 15 healthy children of the identical age. All the patients underwent the thyroid-stimulating hormone and thyroid hormones blood serum level, IFA technique being used, during acuity and reconvalesence. Re-sults. The neuroinfections status of the pituitary-thyroid system depends on the period and severity of the disease and does not depend on the etiology, age and sex of the child. Conclusion. According to the indices of the pituitary-thyroid system revealed that different adaptive responses develop in neuroinfections depending on the reactivity of child's organism and severity of the disease.

• Purinergic signaling is involved in the pathogenesis of neuroinfectious disease. • P2 receptors have pro-inflammatory and deleterious effects in viral Neuroinfections. • ATP-P2X7 receptor signaling contributes to sepsis-associated encephalopathy. • Adenosine favors brain parasite persistence in cerebral toxoplasmosis. The incidence of infectious diseases affecting the central nervous system (CNS) has been increasing over the last several years. Among the reasons for the expansion of these diseases and the appearance of new neuropathogens are globalization, global warming, and the increased proximity between humans and wild animals due to human activities such as deforestation. Neurotropism affecting normal brain function is shared by organisms such as viruses, bacteria, fungi, and parasites. Neuroinfections caused by these agents activate immune responses, inducing neuroinflammation, excitotoxicity, and neurodegeneration. Purinergic signaling is an evolutionarily conserved signaling pathway associated with these neuropathologies. During neuroinfections, host cells release ATP as an extracellular danger signal with pro-inflammatory activities. ATP is metabolized to its derivatives by ectonucleotidases such as CD39 and CD73; ATP and its metabolites modulate neuronal and immune mechanisms through P1 and P2 purinergic receptors that are involved in pathophysiological mechanisms of neuroinfections. In this review we discuss the beneficial or deleterious effects of various components of the purinergic signaling pathway in infectious diseases that affect the CNS, including human immunodeficiency virus (HIV-1) infection, herpes simplex virus type 1 (HSV-1) infection, bacterial meningitis, sepsis, cryptococcosis, toxoplasmosis, and malaria. We also provide a description of this signaling pathway in emerging viral infections with neurological implications such as Zika and SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The article describes some topical problems of neuroinfections in children and the ways of their solutions on the basis of the experience of a leading institution — Pediatric Research and Clinical Center for Infectious Diseases. There are introduced some innovation approaches of diagnostics and therapy of bacterial purulent meningitis tested at the institution. There are described diagnostic markers of meningitis in children, method of ultrasound evaluation monitoring of the condition of kidneys, renal blood flow, adrenal glands in the patients with a fulminant course of generalized form of meningococcal infection, and innovation therapeutic approach by recombinant interleukin-2 — roncoleukin introduction to the complex therapy. There is reflected an innovation method of differential diagnostics by the determination of acute-phase protein haptoglobin in cerebrospinal fluid. There are presented the tested methods to diagnose sensorineural deafness in children with bacterial purulent meningitis, critical condition polyneuropathy, and inflammatory polyneuropathy by the technique of rehabilitation potential evaluation.

Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.

This study aims to conduct a literature review to describe the main opportunistic infections with CNS involvement in the AIDS context. We performed a narrative literature review on the incidence of major opportunistic infections with central nervous system (CNS) involvement in patients with the diagnosis of AIDS. The articles were searched through the Scientific Electronic Library Online (SCIELO) and US National Library of Medicine National Institutes of Health (PUBMED) databases. The technique used was the descriptors AIDS + Neurotoxoplasmosis, AIDS + Neurotuberculosis, AIDS + Neurocryptococcosis in the aforementioned databases. As partial results there was an increase of these neurological disorders in individuals immunosuppressed by the HIV virus due to the return of the AIDS epidemic in the last decade, with Neurotoxoplasmosis, Neurocriptococcosis and Neurotuberculosis being the most prevalent diseases. Opportunistic neurological diseases are of great relevance due to the important morbidity and mortality in immunocompromised patients. Thus, an adequate approach to clinical, laboratory and imaging tests is necessary to improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Neuroinfections are a significant medical problem and can have serious health consequences for patients. Their outcome, if not fatal, can be associated with permanent residual deficits. Cerebrospinal fluid (CSF) examination is commonly used for meningitis confirmation. Fatty acids (FA) are precursors of lipid mediators with pharmacological activity. They actively modulate inflammation as well as contribute to its resolution. Therefore the aim of this study was to determine the FA and selected endocannabinoids (ECB) content in the CSF obtained from patients with bacterial (BM) and viral meningitis (VM) using chromatographic techniques. A significantly lower level of saturated FA was found in patients with BM and VM as compared to controls. There was a significantly higher concentration of long-chain monounsaturated FA and polyunsaturated n-6 FA in the CSF obtained from patients with neuroinfection. Moreover, a significant reduction of n-3 FA in CSF obtained from patients with BM and VM was demonstrated. The highest amount of ECB was detected in the CSF of patients with VM: eicosapentaenoyl ethanolamide (1.65 pg/mL), docosahexaenoyl ethanolamide (655.5 pg/mL) and nervonoyl ethanolamide (3.09 ng/mL). Results indicate the participation of long-chain monounsaturated and polyunsaturated FA and their derivatives in the inflammatory process and likely in the process of resolution of inflammation during neuroinfection. It seems that the determination of the FA and ECB profile in CSF may be a valuable biomarker of health and may allow the development of new pharmacological strategies, therapeutic goals and fatty acids supplementation necessary in the fight against inflammation of the central nervous system. [ABSTRACT FROM AUTHOR]

Bacterial infections of the central nervous system (CNS) continue to be an important cause of morbidity and mortality in children. The spectrum of bacterial infection of CNS includes; focal or multifocal infections like brain abscesses or subdural empyema; or more generalized or diffuse infections like pyogenic meningitis or ventriculitis. Focal and generalized infections may co-exist in an individual patient. Prompt and adequate antibiotic therapy and occasionally neurosurgical interventions are the cornerstone of effective management. The recent emergence of several multidrug-resistant bacteria poses a threat to the effective management of bacterial CNS infections. Several adjunctive anti-inflammatory and neuroprotective therapies are being tried, however; none has made a remarkable impact on the outcome. Consequently, bacterial CNS infections in children still remain a challenge to manage. In this review, authors discuss the current updates on the diagnostic and therapeutic aspects of bacterial infections of the CNS in children (post-neonatal age group). [ABSTRACT FROM AUTHOR]

We have analyzed the structure, course and clinical picture of 65 cases of acute neuroinfections in children, who were treated in the clinical hospital of pediatric infections of Kyiv in 2014.

In our review we present data on sleep disturbances in neuroinfections (encephalitis and meningitis), their clinical signs, neurochemistry and neurophysiology. These signs include lethargy, narcolepsy, sleep apnoe, sleep structure disruptions and may appear in acute period and as a sequelae of the disease. Reticular formation involvement seems to be the main reason for such sleep disorders. GABA and orexin systems disruption may play the key role in them. Neurophysiology evaluation of such disorders includes polysomnography, EEG-monitoring, brainstem acoustic evoked potentials and H-reflex investigation.

In the article presented results of the examination of acute phase proteins in cerebrospinal liquid in 237 children with meningitis and encephalitis viral and bacterial etiology. The dependence between the level of acute phase proteins in cerebrospinal liquid and etiology of neuroinfectional process, the severity of brain damage and the process stage was determined. Diagnostic and prognostic efficiency of the acute phase proteins (C-reactive protein, albumin, alpha-1-antitripsin, alpha-2-macroglobulin, gaptoglobin) examination in children with neuroinfections was specified. Developed method of express diagnostics of the severity of inflammatory damage of the brain in bacterial meningitis in children by determination in cerebrospinal liquid alpha-2-macroglobulin is described.

Since the first reports of Human Immunodeficiency Virus (HIV) infection, the field of infectology has changed in a vertiginous way resulting in the appearance of two new subspecialties: HIV infectology and neuroHIV the latter focused in the nervous system complications caused by the virus or its treatment. About 50-70% of patients with HIV infection have or will develop any syptom or neurologic síndrome at any point during the course of the illness either caused by the virus, an opportunistic infection or as a complication of the drugs. Among the most common Neurological issues are peripheric neuropathies, neuropsychiatric manifestations and aseptic meningitis, however by far the most challenging and complex aspect is the approach of a patient with a suspected neuroinfection in the context of HIV infection, because immune system has been compromised and its response might not be the expected in an immunocompetent patient. That's why a special algorith must be designed for the diagnosis and management of this population. [ABSTRACT FROM AUTHOR]

Background. Lyme disease (LD) is a vector-borne infection. It is transferred by the tick Ixodes ricinus and caused by the spirochete Borrelia. The Baltic countries have one of the highest rates of LD in Europe. In recent decades, LD morbidity increased due to climate change in Europe. Nervous system involvement occurs in up to 15% of LD. Lymphocytic meningitis, cranial neuropathy (particularly n.facialis) and radiculoneuritis constitute the classic triad of acute Lyme neuroborreliosis (LNB). Materials and methods. We performed a retrospective study and anatyzed medtcal records of patients who were treated in VUH SK in the period from 4 September 2005 to 4 September 2015. Medical records with ICD-10 codes A69.2, G00-G09 were included. We setected 91 patients' medtcal records which fulfilled definite or possible LNB criteria. Results. In the period of 2005-2015, 91 patients were diagnosed with LNB in VUH SK. The average age of the patients was 49±17 years; 48 were men, 43 women. 35.2% of them had a history of a tick bite and 9.9% of erythema migrans. The annualrate of LNB was 4-17 cases, the highest rate was observed in 2009, 2010, 2012 and 2014. We did not find any growth of the annual rate of LNB. 6.6% of all the cases occurred in winter, 8.8% in spring. The most common symptoms/signs were headache (57.1%), radicular pain (54.9%) and meningeal symptoms (59.3%). The most common clinical forms were Garin- Bujadoux-Bannwarth syndrome (47.3%), meningoencephalitis (24.2%) and meningitis (20.9%). The average celebrospinal fluid (CSF) cell count was 173.9±215.1 cells/mm3; the average protein concentration in CSF was 1.2 g/l. Positive serological tests against Borrelia antigens were documented in 91.2% of all the cases. 19.3% of them were positive for intrathecal anti-Borrelia antibody synthesis, 95.2% - for blood serology. 12.1% of all the patients diagnosed with LNB had positive serological test for TBEV, but 61.5% of all the patients were not tested for TBEV se- rol ogy. Conclusions. LNB is a highly seasonal disease, but there are cases of it all around the year. The most common clinical manifestation was Bannwarth syndrome and meningoencephalitis. One of ten of the patients with LNB was co-infected with TBEV and one-third of the patients with LNB meningoencephalitis had a double infection with TBEV. [ABSTRACT FROM AUTHOR]

The aim of our study was to detect differentially regulated proteins and specific signaling pathways in Mongolian gerbil brains during chronic Toxoplasma gondii ( T.gondii ) PRU strain infection. We use a iTRAQ-based strategy to detecte 4935 proteins, out of which 110 proteins were differentially expressed (>/=2.0-fold, p value < 0.05) when the brain of gerbils infected with T.gondii was compared to control brain tissues. We confirmed the authenticity and the accuracy of iTRAQ results through quantitative real-time PCR and western blot (WB), which was consistent with mass spectrometry analysis. Pathway analysis and GO (Gene Ontology) annotations indicated the deregulation of several pathways related to immune response, metabolism and neurological processes, like neuronal growth and neurotransmitter transport. Through the iTRAQ-based strategy, we obtained a comparative proteome profile of brain tissues from Mongolian gerbils with chronic infection of T.gondii . Several differentially expressed proteins involved in neurological pathways, like Parvalbumin, Drebrin or Synaptotagmin, can be further investigated to enhance our understanding of central nervous system (CNS) injury caused by T.gondii . Biological significance T.gondii can infect almost all nucleated cells with a preference for the CNS, which can induce Toxoplasma encephalitis (TE). However, the pathogenesis and mechanisms between the parasite and host associated with TE are largely unexplored. Around 30% of the world population is considered to have latent infection with T.gondii and > 90% patients died of TE, while the proportion of secondary paralysis is also high. Patients of TE may have highly varied neurological symptoms with both focal and diffuse neurological lesions, while mental symptoms and behavior disorders are frequently accompanied, like the Alzheimer's disease (AD). We present a comparative proteomics analysis to explore the differences of protein expression caused by chronic T.gondii infection. The results of this analysis can be helpful for identifying key proteins involved in the pathogenesis of TE. In addition, the study can contribute to a better understanding of molecular mechanisms underlying the host–parasite relationship in chronic infection of T.gondii and facilitate further development of new therapies for TE. [ABSTRACT FROM AUTHOR]

The field of neuro-infectology is an ever changing area due to the advances in microbiology, cerebrospinal fluid (CSF) analysis and the implementation of new techniques of polymerase chain reaction (PCR) detection. In spite of the new diagnostic tools neuroinfectious still represent a challenge for the first approach physician and the involved specialties such as neurology, infectious diseases specialist, and emergency medicine, because to identify etiologic agent at the moment of arrival is not a simple task and the clinical presentations of a disease can be very heterogeneous. Since the first appearance of human immunodeficiency virus (HIV) and induced immunodeficiency as in the cases of solid organ transplant. Clinicians have been observing a broad range of manifestations ranging from poorly symptomatic presentations such as a mild headache to immunologic reconstitution syndrome accompanied by motor focal symptoms, cranial nerve palsies, and seizures which are commonly seen in the context of HIV patients under management with anti-retroviral therapy. Currently is of prime importance to the clinician to be aware of the most common manifestations, etiologic agents as well as the diagnostic and therapeutic approaches followed by the advanced management of these entities. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis affects millions of people worldwide and is especially prevalent in regions with a high burden of HIV/AIDS. The study of the pathophysiology of this often fatal disease has been significantly hindered by the lack of reliable experimental models, especially at the level of the brain, which is the main organ of injury. Here we outline our novel protocol for the use of hippocampal organotypic brain slice cultures (HOCs) to study the host-fungal interactions during cryptococcal infections of the brain. HOCs are a powerful platform for investigating neuroimmune interactions as they allow for the preservation of all innate neuroglial cells including microglia, astrocytes, and neurons, all of which maintain their three-dimensional architecture and functional connectivity. We made HOCs from neonatal mice and infected these with a fluorescent strain of Cryptococcus neoformans for 24 h. Using immunofluorescent staining, we confirmed the presence and morphology of microglia, astrocytes, and neurons in HOCs prior to infection. Using fluorescent and light microscopy, we also confirmed that Cryptococcus neoformans encapsulates and buds in vitro, as it would in a host. Finally, we demonstrate that infection of HOCs with Cryptococcus neoformans results in close association of the fungal cells with host microglial cells. Our results demonstrate the utility of HOCs as a model to study the pathophysiology and host neuroimmune responses in neurocryptococcosis, which may assist in improving our collective understanding of the pathogenesis of this disease., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non- Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non- Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non- Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB. [ABSTRACT FROM AUTHOR]

We present here results obtained from the use of Cytoflavin in the complex treatment of bacterial purulent meningitis and viral encephalitis in 60 children aged from one month to 18 years. Cytoflavin was shown to be clinically effective, decreasing the incidence of residual signs and shortening recovery periods. Cytoflavin was also found to have influences on endothelial dysfunction, the rheological properties of the blood, the clotting system, and vascular tone. The use of Cytoflavin in the complex pathogenetic treatment of neuroinfections in children is recommended. [ABSTRACT FROM AUTHOR]

Objectives – DNA proof is the only widely available direct diagnostic tool in Lyme borreliosis. Sensitive PCR detecting of spirochetal DNA was prepared and a prospective study in neuroborreliosis was performed. Materials and methods – 57 hospitalised patients with active neuroborreliosis and proved CSF antibodies synthesis were examined. Nested-PCR (utilizing three targets) was used for the detection of specific DNA in plasma, CSF and urine. Results – Before treatment 36 positive patients (63.1%) were found in all tested specimens in parallel, 28 patients (49.1%) were positive in urine, 20 in CSF (35.0%) and 16 in plasma 28.0%). Later only urine was tested and the following results were obtained: 17 positive patients (30.0%) immediately after treatment, 8 (14.0%) after 3 months and one patient persisted positivity after 6 months. Conclusions – The highest sensitivity of PCR was achieved in the acute period of neuroborreliosis - 63.1% in three body fluids comparing with CSF antibody synthesis. [ABSTRACT FROM AUTHOR]

Background: Dementia due to potentially reversible etiologies is an important group of dementias to be identified not only because of the number of such Patients encountered but also due to the potential for substantial improvement with treatment.Aims: To prospectively investigate the frequency and causes of dementias with potentially reversible etiologies; to examine the clinical features of this subgroup with a view to identifying a signature profile and to determine if this potential reversibility translates into actual reversibility with appropriate treatment.Setting and Design: A prospective longitudinal study of patients with dementia presenting to the outpatient services of a tertiary referral hospital.Methods: All Patients above 40 years referred for evaluation of cognitive complaints were serially enrolled and underwent clinical examination, various laboratory tests and neuroimaging. Patients were followed-up for one year.Statistical Analysis: One way analysis of variance for continuous variables followed by post hoc comparisons using Scheffe's procedure.Results: A total of 129 patients met Diagnostic and Statistical Manual of Mental Disorders edition 4 (DSM IV) criteria for dementia and qualified for inclusion into the study. Twenty-four patients (18%), all with moderately severe cognitive [mean mini mental state examination (MMSE) score +/- SD = 17.9 +/- 4.8] and neuropsychiatric [mean neuropsychiatric inventory (NPI) score +/- SD = 30.7 +/- 8.7] dysfunction were diagnosed to have reversible causes - neuroinfections in 11 patients, normal pressure hydrocephalus in 8 patients and vitamin B12 deficiency in 5 patients. The majority of these patients had gait and urinary dysfunction reminiscent of subcortical dementias. These reversible causes were clinically suspected in only 58% of patients. In 20/24 patients in whom follow up was possible mean MMSE score had improved to 22.2 and mean NPI score had improved to 8.0, following 6 months of treatment.Conclusions: Reversible causes, especially neuroinfections and vitamin B12 deficiency accounted for 18% all dementias in this study. The majority of these conditions was not clinically suspected though resulting in moderate to severe cognitive and psychiatric dysfunction. Most of these patients had a subcortical pattern of dementia and showed substantial improvement with treatment. [ABSTRACT FROM AUTHOR]

Introduction: The etiologies of acute symptomatic seizures (ASS) differ across the globe. We aimed to evaluate the etiological spectrum of acute seizures and to observe the pattern of seizure types among study participants., Methodology: We conducted this prospective study from 2016 to 18. We included all patients aged 20 years or older, presenting with ASS. We excluded those with pseudoseizures. We performed appropriate descriptive analyses to describe the demographic details, etiology of ASS, and pattern of ASS., Results: One hundred and thirty-eight patients were enrolled, constituting about 0.8% of total hospital admissions. The mean age at presentation was 44.33 ± 17.73 years. The most common etiologies for ASS were cerebrovascular accidents (CVA - 32.6%), neuroinfections (26.8%), metabolic derangements (13%), alcohol withdrawal (10.9%), and intracranial tumors (4.3%). 71% of the patients presented with only a single episode of ASS. The predominant type of seizure was generalized tonic-clonic seizures, seen in 70.2% of all patients, followed by focal with the bilateral tonic-clonic type (15.9%) and focal seizures (10.1%). New-onset seizures presenting as status epilepticus were observed in 3.6%., Discussion: CVA and neuroinfections were the most common causes of ASS in our study, highlighting the need for community awareness of these conditions and the need to seek rapid care. The majority of our patients had only a single episode of seizures, with generalized seizures being the most common type, followed by focal onset seizures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Vemulapalli et al.)

Neuroinfections are seen in both adults and children. These can result in serious morbidity and if left untreated and/or associated with comorbidities can be life threatening. Cross-sectional imaging like computed tomography (CT) and magnetic resonance imaging (MRI) are advised by the clinicians for the diagnosing, confirmation of the diagnosis, assess any complications of the infection, and also for follow up. Though CT is the initial imaging investigation commonly asked by the clinician, due to its lesser soft tissue resolution, early brain changes may not be seen on CT. MRI has better soft tissue resolution with no ionizing radiation to the patient and helps in detecting the early signs of infection. Appropriate MRI, not only helps the radiologist to reduce the number of possibilities of the causative organism but also differentiates tumors from infection. However, CT is useful to assess the bony changes and also easily available and affordable cross-sectional imaging modality worldwide. The review summarizes the approach of the radiologist to central nervous system (CNS) infections and their typical imaging characteristic features., Competing Interests: None