Infectious Diseases Of Central Nervous System Research Articles

Revolutionizing Medicine: Advances in Polymeric Drug Delivery Systems

Polymeric drug delivery systems have emerged as a transformative force in modern medicine, reshaping the landscape of drug delivery and patient care. This review article comprehensively explores the advancements and innovations that have propelled polymeric drug delivery systems to the forefront of medical research and practice. Beginning with a historical perspective, we trace the evolution of drug delivery systems, highlighting the pivotal role played by polymers in this journey. We delve into the diverse array of polymeric drug delivery systems, ranging from nanoparticles and hydrogels to implantable devices and polymer-drug conjugates, elucidating their unique characteristics and applications. A critical focus of this review lies in the criteria governing polymer selection, including biocompatibility, biodegradability, and drug-loading capabilities. We illuminate the remarkable impact of polymeric drug delivery systems across various medical domains, including oncology, central nervous system disorders, cardiovascular diseases, infectious diseases, and chronic conditions. Furthermore, we explore recent breakthroughs, such as smart polymers for responsive drug release and nanotechnology-driven precision medicine, which are revolutionizing patient care. Clinical success stories and FDA-approved polymeric drug delivery systems underscore the tangible benefits these innovations bring to patients. Despite these remarkable achievements, challenges and future directions are also examined, addressing regulatory considerations, scalability issues, and the integration of emerging technologies. We conclude by emphasizing the transformative potential of polymeric drug delivery systems and call for sustained research and development efforts to harness their full capabilities. This review illuminates the dynamic and promising future of polymeric drug delivery systems in revolutionizing medicine and advancing the frontiers of patient-centric care.

Evaluation of seegene anyplex MTB/NTM real-time detection assay for diagnosis of tuberculous meningitis

BackgroundTuberculous meningitis (TBM) is a common central nervous system infectious disease. Polymerase chain reaction (PCR) assay is a useful method for the rapid diagnosis of TBM. The Seegene Anyplex MTB/NTM real-time detection assay has good sensitivity and specificity for detection of tuberculosis in respiratory specimens, though, data regarding other specimens are lacking. This study aims to define the diagnostic role of Seegene Anyplex MTB/NTM real-time detection assay in TBM in adults.MethodsThis was a retrospective study of 367 adults with symptomatic community acquired meningitis between December 2013 and December 2019. Cerebrospinal fluid (CSF) had been sent for conventional diagnosis, including culture to identify Mycobacterium tuberculosis, and Seegene Anyplex MTB/NTM real-time detection assay. Other diagnostic examinations were performed as necessary.ResultsOf the 367 patients in the study, 37 were diagnosed with TBM (14 with definite TBM and 23 with probable TBM). Between the total TBM cases (n = 37) and non-TBM cases (n = 330), clinical sensitivity was 32.4% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 93.0%. Between the definite TBM cases (n = 14) and non-TBM cases (n = 330), clinical sensitivity was 50.0% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 97.9%.ConclusionDue to lack of sensitivity, we suggest Seegeen Anyplex MTB/NTM real-time detection assay should not be used to rule out TBM but is useful for definite diagnosis.

Findings Related to Cerebrospinal Fluid and Central Nervous System Disorders in Small Ruminants-A Retrospective Study on Sheep and Goats.

Small ruminants often suffer from central nervous system (CNS) disorders, and cerebrospinal fluid (CSF) analysis can be used as a diagnostic tool in this regard. In small animals and cattle, specific CSF patterns have been defined for specific disease categories. No data exist regarding CSF results obtained from small ruminants and their association with certain CNS diseases. The objective of this study was to retrospectively investigate CSF findings obtained from sheep and goats and to identify possible CSF patterns associated with disease categories. CSF samples and medical records from 44 sheep and 27 goats were included in this study. All animals were presented to the Veterinary Teaching Hospital Zurich of the Veterinary Teaching Hospital Zurich of the Vetsuisse Faculty of the University of Zurich between 2003 and 2016 and had either a confirmed CNS diagnosis or showed CSF changes without a specific CNS diagnosis. Mixed mononuclear pleocytosis was the most common CSF pattern in sheep (25%), followed by monocytic pleocytosis (21%). Lymphocytic pleocytosis was most frequently found in goats (37%). In 75% of sheep and 56% of goats, infectious CNS diseases were diagnosed, with listeriosis being the most common infectious disease in both species, followed by parasitic disorders (nematodiasis and coenurosis). The cytologic CSF patterns in small ruminants are mainly based on the increased presence of monocytic and lymphocytic cells with variable quantitative expression, whereas neutrophilic pleocytosis and cytoalbuminologic dissociation were rare findings. Infectious diseases of bacterial origin were the most common underlying causes for CSF alterations in sheep and goats, followed by parasitic disorders. The pleocytosis type is not helpful for differentiating disease types.

Application of VirCapSeq-VERT and BacCapSeq in the diagnosis of presumed and definitive neuroinfectious diseases.

Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.

The clinical utility of metagenomic next-generation sequencing for the diagnosis of central nervous system infectious diseases.

To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system infections (CNSI). Cerebrospinal fluid (CSF) from 54 patients who were high-level clinical suspicion of CNSI was collected and sent for mNGS and conventional tests from January 2019 to March 2022. Twenty out of 54 patients were diagnosed with CNSI and 34 non-CNSI. Among the 34 non-CNSI, one was false positive by mNGS. Among the 20 CNSI, 11 had presumed viral encephalitis and/or meningitis, 5 had presumed bacterial meningitis, 2 had presumed TMB, 1 had Crytococcus meningitis and 1 had neurosyphilis. The sensitivity of viral encephalitis and/or meningitis was 0.73 (8/11); 10 virus were detected; 9/10 was dsDNA; 1/10 was ssRNA. SSRN ranged from 1 to 13. The accuracy rate was 0.4, the accuracy rate was positively correlated with SSRN (r = 0.738, P = 0.015), SSRN ≥ 1, the accuracy rate was 0.4; SSRN ≥ 3, the accuracy rate was 0.66; SSRN ≥ 4, the accuracy rate was 0.75; SSRN ≥ 6, the accuracy rate was 1. The sensitivity of bacterial meningitis was 1. Seven kinds of bacteria were detected, among which 3/7 were gram positive, 3/7 were gram negative, and 1/7 was infected NTM (nontuberculous mycobacteria). The accuracy rate was 0.43 (3/7). The sensitivity of TBM was 0.66 (2/3), the accuracy rate was 1. The sensitivity of Crytococcus meningitis was 1, the accuracy rate was 0.5. PPV (positive predictive value) of mNGS was 0.94, NPV (negative predictive value) of mNGS was 0.89, specificity was 0.97 and sensitivity was 0.8. The AUG for CSF mNGS diagnosis of CNSI was 0.89 (95% CI = 0.78-0.99) Headache, meningeal irritation sign and image of meninges abnormal were correlated with the sensitivity of mNGS (r = 0.451, 0.313, 0.446; p = 0.001, 0.021, 0.001); CSF Glucose and CSF Chloride were negatively correlated with sensitivity of mNGS (r = -0.395, -0.462; p = 0.003, ＜ 0.001). mNGS is a detection means with high sensitivity, wide coverage and strong timeliness, which can help clinicians to identify the pathogen diagnosis quickly, conduct targeted anti-infection treatment early and reduce antibiotic abuse. The pathogen which causing low CSF Glucose, low CSF Chloride or meninges infections was more likely to be detected by mNGS. It may be related to growth and structural characteristics of the pathogen and blood-brain barrier damage.

Lymphoma of Nervous System or the Great Imitator in Neurology

Background: Lymphoma of the central nervous system (CNS), both primary and secondary, represents a very rare part of patients with non-Hodgkin lymphoma. Methods: Exams included a neurological exam, laboratory blood tests, МRI, biopsy, and electromyography. Results: Three different clinical cases of patients with lymphoma of the nervous system are presented. The first patient is a 44-year-old male admitted to the emergency room because of neck stiffness, with MRI data for a tumour in the left cavernous sinus area. Biopsy was performed 3 months prior to hospitalisation, showing connective tissue, partially hyalinised. Lumbar tap was performed to exclude CNS infection. Cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis, atypical cells in different phases of mitosis, and the result did not confirm lymphocytic choriomeningitis. Flow cytometric measurement (FCM) of CSF led to the diagnosis of T-lymphoblastic lymphoma of CNS. The second patient is a 50-year-old female hospitalised in the authors’ neurological department because of lower limb weakness and decreased sensation, dysphagia, and facial nerve palsy. Brain MRI showed no abnormal lesions. Guillain–Barré syndrome was considered after performing electromyography and electroneurography. CSF showed lymphocytic pleocytosis and 47% of them were atypical. FCM of CSF helped the authors diagnose the patient with B-lymphoblastic lymphoma. The third case presents a 63-year-old male with right sided hemiparesis and progressive cognitive impairment. Previously performed CTs and MRIs of the brain showed both hemispheres and left cerebellar peduncle diffuse lesions. Ischaemic stroke, tumour, and CNS infectious disease were considered. Most of these were excluded because CSF showed no pathological findings. Brain tissue biopsy of one of the lesions was performed, and the patient was diagnosed with diffuse large B cell lymphoma. Conclusion: Lymphoma of the CNS is rare disease. Differential diagnoses include different conditions. FCM of CSF and biopsy could be useful in complicated patients and unknown diagnosis affecting the CNS.

Common infectious and parasitic diseases as a cause of seizures: geographic distribution and contribution to the burden of epilepsy

This educational review article aims to provide information on the central nervous system (CNS) infectious and parasitic diseases that frequently cause seizures and acquired epilepsy in the developing world. We explain the difficulties in defining acute symptomatic seizures, which are common in patients with meningitis, viral encephalitis, malaria, and neurocysticercosis, most of which are associated with increased mortality and morbidity, including subsequent epilepsy. Geographic location determines the common causes of infectious and parasitic diseases in a particular region. Management issues encompass prompt treatment of acute symptomatic seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiseizure therapy. Although healthcare provider education, to recognize and diagnose seizures and epilepsy related to these diseases, is a feasible objective to save lives, prevention of CNS infections and infestations is the only definitive way forward to reduce the burden of epilepsy in developing countries.

Severe courses of meningitis and encephalitis in children and adolescents

Die bakterielle Meningitis und die virale Enzephalitis sind die infektiösen Erkrankungen des Zentralnervensystems (ZNS), die meist mit schwerwiegenden Folgeerscheinungen bis hin zum Tod einhergehen. Trotz Fortschritten in der Prävention durch Impfungen ist die globale Krankheitslast der bakteriellen Meningitis enorm. Die Inzidenz der viralen Enzephalitis im Kindesalter war vor der durch die „coronavirus disease 2019“ (COVID-19) ausgelösten Pandemie zunehmend. Dies hängt mit der wachsenden Verbreitung von „emerging pathogens“ wie dem Enterovirus-A71 und dem West-Nil-Virus in den hiesigen Breitengraden zusammen, aber auch mit der häufigeren Anwendung von Immunsuppressiva und der häufigeren Durchführung von Stammzelltransplantationen im Kindesalter.In der vorliegenden Übersichtsarbeit werden Häufigkeit und klinische Zeichen von infektiösen ZNS-Erkrankungen zusammengefasst und die aktuellen Therapieempfehlungen dargestellt.

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment.

BACKGROUNDThe diagnostic value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infectious diseases after empirical treatment has not been reported.AIMTo investigate the diagnostic value of mNGS of cerebrospinal fluid (CSF) in the empirically treated CNS infectious diseases.METHODSA total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021. Both mNGS and conventional methods were used for testing. The conventional methods included microbial culture, smear, polymerase chain reaction, etc.RESULTSAmong 262 suspected cases, 183 cases (69.84%) were diagnosed as CNS infection, including 86 cases of virus infection (47.00%), 70 cases of bacterial infection (38.25%) and 27 cases of fungal infection (14.76%). The sensitivity and specificity of mNGS were 65.6% (95%CI: 58.2%-72.3%) and 89.6% (95%CI: 79.1%-95.3%), respectively. The PPV of mNGS was 94.5% (95%CI: 88.6%-97.6%), and the NPV was 48.8% (95%CI: 39.7%–57.9%). The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods (Sensitivity: 65.6% vs 37.2%; P < 0.001; Accuracy: 72.0% vs 50%, P < 0.001). The results showed that compared with conventional methods, mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment.CONCLUSIONmNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.

Cerebrospinal fluid analysis: current diagnostic methods in central nervous system infectious diseases.

Cerebrospinal fluid (CSF) analysis is an important diagnostic tool for many conditions affecting the central nervous system (CNS), especially CNS infectious diseases. Despite its low specificity, CSF white blood cell counts, CSF protein levels, CSF serum glucose ratio and CSF lactate measurement are useful in differentiating infections caused by distinct groups of pathogens. CSF direct examination and cultures can identify causative organisms and antibiotic sensitivities as well. Adjunctive tests such as latex agglutination, different immunological assays and molecular reactions have great specificities and increasing sensitivities. In this article, some recent diagnostic methods applied to CSF analysis for frequent CNS infections are presented.

A Case of Japanese Encephalitis Misdiagnosed as Tuberculous Meningoencephalitis

Backgroud Japanese encephalitis is a kind of central nervous system infectious disease caused by Japanese encephalitis virus transmitted through mosquito [1]. Most patients with JE occured acute onset and critically ill, with high fever, disturbance of consciousness, epilepsy, abnormal mental behavior, cognitive impairment, and positive meningeal irritation. Case Presentation A 15-year-old boy was admitted to the hospital with acute febrile illness,headache,jet vomiting,disorder of consciousness,diagnosed as central nervous system(CNS) infection.According to the characteristics of blood and cerebrospinal fluid(CSF),the patient was initially diagnosed with tuberculous meningoencephalitis and took antituberculosis treatment.However,subsequent magnetic resonance images(MRI) did not match the performance of typical tuberculous meningoencephalitis.Further laboratory testing for infections was conducted.JE was confirmed by the center for disease control and prevention of Lanzhou City through the detection of Japanese encephalitis IgM antibodies in both blood and CSF of the patients.After diagnosis of JE,the patient was provided the treatment of Human immunoglobulin and methylprednisolone therapy.After 3 weeks,the patient was transferred to the department of rehabilitation medicine to continue treatment. After 3 months and 6 months of follow-up, the patient recovered and the FIM score were 126, which were completely independent. Conclusion Given the similar clinical manifestations of Japanese encephalitis and other types of encephalitis, it is essential to enhance the awareness of Japanese encephalitis.

Role and Relevance of Cerebrospinal Fluid Cells in Diagnostics and Research: State-of-the-Art and Underutilized Opportunities.

Cerebrospinal fluid (CSF) has recently experienced a revival in diagnostics and research. However, little progress has been made regarding CSF cell analysis. For almost a century, CSF cell count and cytomorphological examination have been central diagnostic parameters, with CSF pleocytosis as a hallmark finding of neuroinflammation and cytology offering valuable clues regarding infectious, autoimmune, and malignant aetiologies. A great deal of information, however, remains unattended as modern immune phenotyping technologies have not yet been broadly incorporated into routine CSF analysis. This is a serious deficit considering the central role of CSF cells as effectors in central nervous system (CNS) immune defence and autoimmune CNS processes, and the diagnostic challenges posed by clinically overlapping infectious and immune-mediated CNS diseases. Here, we summarize historical, specimen-intrinsic, methodological, and technical issues determining the state-of-the-art diagnostics of CSF cells and outline future perspectives for this underutilized window into meningeal and CNS immunity.

Preparation, characterization, and antibacterial activity of tigecycline-loaded, ultrasound-activated microbubbles

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm2 and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections.

Anti-inflammatory effects of kaempferol-3-O-rhamnoside on HSV-1 encephalitis in vivo and in vitro

BackgroundHerpes simplex virus encephalitis (HSE) is an acute central nervous system infectious disease caused by herpes simplex virus (HSV). Currently, there is no effective treatment for HSE infection, which produces many pro-inflammatory factors. Kaempferol-3-O-rhamnoside (K-3-rh) is a plant flavonoid. This study was investigated the anti-inflammatory effect of K-3-rh on encephalitis induced by HSV-1. MethodsHSV-1 was co-cultured with VERO cells. Cells were divided into four groups, including the control group, virus group, K-3-rh group, Astragalus polysaccharide (APS) group and dexamethasone group. Flow cytometry were utilized to determine cell apoptosis, respectively. Proteins and mRNAs were estimated by western blot and qRT-PCR, respectively. ResultsAfter viral infection, the cytokines were significantly increased. After K-3-rh intervention, the expression of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and nitric oxide (NO) in microglia were reduced contrast with those in the virus group, and the expression of interleukin-10 (IL-10) did not change. After viral infection, the apoptotic rate increased significantly, and K-3-rh could inhibit viral-induced apoptosis in the microglial cell line. The induction of microglia apoptosis was achieved by cytochrome c and caspase-9-mediated mitochondrial pathway. Also, the pathological changes of brain tissue in mice of each drug intervention group were alleviated. ConclusionsIn conclusion, K-3-rh had the potential to reduce HSV-1-induced brain injury by reducing the secretion of microglial pro-inflammatory factors, inducing apoptosis of microglia cells, and through cytochrome C and caspase-3 pathway.

A novel yeast-based high-throughput method for the identification of protein palmitoylation inhibitors.

Protein S-acylation or palmitoylation is a widespread post-translational modification that consists of the addition of a lipid molecule to cysteine residues of proteins through a thioester bond. Palmitoylation and palmitoyltransferases (PATs) have been linked to several types of cancers, diseases of the central nervous system and many infectious diseases where pathogens use the host cell machinery to palmitoylate their effectors. Despite the central importance of palmitoylation in cell physiology and disease, progress in the field has been hampered by the lack of potent-specific inhibitors of palmitoylation in general, and of individual PATs in particular. Herein, we present a yeast-based method for the high-throughput identification of small molecules that inhibit protein palmitoylation. The system is based on a reporter gene that responds to the acylation status of a palmitoylation substrate fused to a transcription factor. The method can be applied to heterologous PATs such as human DHHC20, mouse DHHC21 and also a PAT from the parasite Giardia lamblia. As a proof-of-principle, we screened for molecules that inhibit the palmitoylation of Yck2, a substrate of the yeast PAT Akr1. We tested 3200 compounds and were able to identify a candidate molecule, supporting the validity of our method.

Volatile Organic Compounds to Identify Infectious (Bacteria/Viruses) Diseases of the Central Nervous System: A Pilot Study

Background: Central nervous system (CNS) infectious diseases are common diseases in emergency rooms and neurology departments. CNS pathogen identification methods are time consuming and expensive and have low sensitivity and poor specificity. Some studies have shown that bacteria and viruses can produce specific volatile organic compounds (VOCs). The aim of this study is to find potential biomarkers by VOC analysis of cerebrospinal fluid (CSF) in patients with bacterial and viral meningitis/encephalitis (ME). Methods: CSF samples from 16 patients with bacterial ME and 42 patients with viral ME were collected, and solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the metabolites in the CSF. Results: There are 2 substances (ethylene oxide and phenol) that were found to be different between the 2 groups. Ethylene oxide was significantly greater in the group of bacterial ME patients than in the viral ME group of patients (p < 0.05). In addition, phenol was remarkably increased in the group of ME patients compared with the bacterial ME patients (p < 0.05). Conclusions: Ethylene oxide and phenol may be potential biomarkers to distinguish bacterial ME and viral ME. VOC analysis of CSF may be used as a supporting tool for clinical diagnosis.

Double-edged effects of tamoxifen-in-oil-gavage on an infectious murine model for multiple sclerosis.

Tamoxifen gavage is a commonly used method to induce genetic modifications in cre‐loxP systems. As a selective estrogen receptor modulator (SERM), the compound is known to have immunomodulatory and neuroprotective properties in non‐infectious central nervous system (CNS) disorders. It can even cause complete prevention of lesion development as seen in experimental autoimmune encephalitis (EAE). The effect on infectious brain disorders is scarcely investigated. In this study, susceptible SJL mice were infected intracerebrally with Theiler's murine encephalomyelitis virus (TMEV) and treated three times with a tamoxifen‐in‐oil‐gavage (TOG), resembling an application scheme for genetically modified mice, starting at 0, 18, or 38 days post infection (dpi). All mice developed ‘TMEV‐induced demyelinating disease’ (TMEV‐IDD) resulting in inflammation, axonal loss, and demyelination of the spinal cord. TOG had a positive effect on the numbers of oligodendrocytes and oligodendrocyte progenitor cells, irrespective of the time point of application, whereas late application (starting 38 dpi) was associated with increased demyelination of the spinal cord white matter 85 dpi. Furthermore, TOG had differential effects on the CD4+ and CD8+ T cell infiltration into the CNS, especially a long lasting increase of CD8+ cells was detected in the inflamed spinal cord, depending of the time point of TOG application. Number of TMEV‐positive cells, astrogliosis, astrocyte phenotype, apoptosis, clinical score, and motor function were not measurably affected. These data indicate that tamoxifen gavage has a double‐edged effect on TMEV‐IDD with the promotion of oligodendrocyte differentiation and proliferation, but also increased demyelination, depending on the time point of application. The data of this study suggest that tamoxifen has also partially protective functions in infectious CNS disease. These effects should be considered in experimental studies using the cre‐loxP system, especially in models investigating neuropathologies.

Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing.

Cerebrospinal fluid (CSF) is a clear and paucicellular fluid that circulates within the ventricular system and the subarachnoid space of the central nervous system (CNS), and diverse CNS disorders can impact its composition, volume, and flow. As conventional CSF testing suffers from suboptimal sensitivity, this review aimed to evaluate the role of next-generation sequencing (NGS) in the work-up of infectious, neoplastic, neuroimmunological, and neurodegenerative CNS diseases. Metagenomic NGS showed improved sensitivity—compared to traditional methods—to detect bacterial, viral, parasitic, and fungal infections, while the overall performance was maximized in some studies when all diagnostic modalities were used. In patients with primary CNS cancer, NGS findings in the CSF were largely concordant with the molecular signatures derived from tissue-based molecular analysis; of interest, additional mutations were identified in the CSF in some glioma studies, reflecting intratumoral heterogeneity. In patients with metastasis to the CNS, NGS facilitated diagnosis, prognosis, therapeutic management, and monitoring, exhibiting higher sensitivity than neuroimaging, cytology, and plasma-based molecular analysis. Although evidence is still rudimentary, NGS could enhance the diagnosis and pathogenetic understanding of multiple sclerosis in addition to Alzheimer and Parkinson disease. To conclude, NGS has shown potential to aid the research, facilitate the diagnostic approach, and improve the management outcomes of all the aforementioned CNS diseases. However, to establish its role in clinical practice, the clinical validity and utility of each NGS protocol should be determined. Lastly, as most evidence has been derived from small and retrospective studies, results from randomized control trials could be of significant value.

RARE-43. PRIMARY CENTRAL NERVOUS SYSTEM EWING SARCOMA: A SINGLE INSTITUTION EXPERIENCE

Abstract INTRODUCTION Ewing Sarcoma (ES) is defined by molecular markers, being t(11,22) the most frequent. Intracranial ES/pPNET usually represent metastases from extracranial sites. Primary Central Nervous System (CNS) lesions are extremely rare. MATERIAL AND METHODS Retrospective review of clinical records from patients with primary CNS ES/pPNET assessed at a neurological center in Argentina between 2007–2019. All confirmed with molecular marker. Clinical characteristics, imaging, histopathology, and treatment response were evaluated. Extensive workup included whole-body CT scan, skeletal-scintigraphy, and positron-emission tomography, excluding extracranial primary lesions in all cases. RESULTS Total 24p. Median age 22yo (2–65); M:F 2:1. Clinical presentation: intracranial hypertension, focal neurological deficit or seizures. In brain MRI 11 supratentorial lesions, 7 infratentorial and 6 diffuse leptomeningeal. Histopathology: diffuse pattern with small round blue cells 13/24p, other patterns were also described. CD99 marked positive in all cases and T(11.22) confirmed as well: 22 PCR and 2 FISH for EWSR1-rearrangement. Misdiagnosis lead to median delay for accuracy of 7,5mo (0–124); including other CNS primary tumors (n= 13), infectious diseases (n= 5) and other diagnoses (n= 4). Most patients (n= 10) were treated with Euro99-protocol (6 cycles plus local radiotherapy (RT)), 4 with Temozolomide, Irinotecan plus RT, 7 with other regimens and 2 received no treatment. Mean overall survival (OS): 58mo (0–132) and progression-free survival 22mo (0–85). Five year OS:41%. CONCLUSION Clinical behavior in primary CNS ES deferred from extraosseous ES, being necessary to apply a specific regimen for this pathology as there is no standard regime for intracranial ES/pPNET. Results showed two different groups of patients with long and very short survival. Presentation, histology, and outcomes are so uneven that we propose if a more specific molecular classification should be necessary. This is, to our knowledge, the largest case series reported describing a heterogeneous group despite the presence of accurate molecular diagnosis.

MRI-etiology parallels study of medial and lateral temporal lobe epilepsy in Uzbekistan

MRI-etiology dedicated study on Temporal lobe epilepsy (TLE) has not previously conducted in Uzbekistan. We study MRI etiology factors and structural pathology in lateral and medial temporal epilepsy (LTLE and MTLE). The results based on of examination of 48 patients with MTLE and LTLE, who were on a stationary examination in the department of neurology of the first clinic of Tashkent Medical Academy from 2016 to 2018 years. The study was performed on an MRI-tomography with a magnetic field induction of 1.5 T. All patients underwent standard protocol programs. The most common etiologic factor in the group of patients with MTLE was sclerosis of the hippocampus (78.2%, p = .02), while in the group of patients with LTLE with the same frequency, the main etiological factor was tumors and craniocerebral traumas of 36.4% and 31.6% respectively, p = .02. The tumor factor in the MTLE group was only 8.4%, p = .02. Malformation of the cortex and infectious diseases of central nervous system (CNS) were found to be the same in both groups at 8.4% accordingly, p = .02%. To sum up, pathological findings of damage in the medial temporal lobe, resulting from not only the hippocampus and the amygdala, but also the tumor factors and infectious diseases of CNS. In most cases craniocerebral trauma and tumors of temporal lobe results in LTLE.