BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value ...BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid(CSF)in the empirically treated CNS infectious diseases.METHODS A 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.RESULTS Among 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.CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.展开更多
Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central n...Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.展开更多
HThe incidence of fungal infections of the central nervous system(CNS) has gradually increased in recent years. Intracranial fungal infection can be classified as diffuse and focal infections. The clinical manifestati...HThe incidence of fungal infections of the central nervous system(CNS) has gradually increased in recent years. Intracranial fungal infection can be classified as diffuse and focal infections. The clinical manifestations of these infections include fever and cranial pressure caused by meningitis or meningoencephalitis, and focal neurological defects caused by lesions in the intracranial space. Diagnosing fungal infections of the CNS requires the comprehensive analysis of the patient's medical history, epidemiology, underlying disease, clinical manifestation, imaging manifestations, and various laboratory test results. The identification of fungal bodies or structures in brain tissue or cerebrospinal fluid specimens is the golden standard of diagnosis. The principles for the treatment of the fungal infections of the CNS are the effective control of pathogenic risk factors, use of effective antifungal drugs, and the active implementation of surgical intervention for fungal abscesses and granuloma. In the meantime, new diagnoses and treatments should be actively explored to improve the prognosis of patients.展开更多
BACKGROUND Prenatal examination is an important measure for the screening and diagnosis of fetal malformations.AIM To investigate the accuracy of ultrasonography in the diagnosis of fetal central nervous system(CNS)ma...BACKGROUND Prenatal examination is an important measure for the screening and diagnosis of fetal malformations.AIM To investigate the accuracy of ultrasonography in the diagnosis of fetal central nervous system(CNS)malformations.METHODS One hundred and thirteen pregnant women suspected of having fetal CNS malformations were examined at our hospital from December 2018 to October 2020 using two-dimensional ultrasonography and three-dimensional ultrasonography,respectively.RESULTS According to the pathological results,there were 79 cases of CNS malformations and 34 cases of non-CNS malformations among the 113 pregnant women suspected of having fetal CNS malformation.Fifty-one cases of CNS malformation and 26 cases of non-CNS malformation were detected by two-dimensional ultrasonography,and 73 cases of CNS malformation and 30 cases of non-CNS malformation were detected by three-dimensional ultrasonography.The diagnostic sensitivity(92.41%)and accuracy(91.15%)of three-dimensional ultrasonography were higher than those of two-dimensional ultrasonography(64.56% and 68.14%,respectively)(P=0.000).The specificity of three-dimensional ultrasonography(88.24%)was higher than that of two-dimensional ultrasonography(76.47%);however,the difference was not significant(P=0.203).CONCLUSION Three-dimensional ultrasonography has high application value in the diagnosis of fetal CNS malformations.In addition,the image quality is clear,and the diagnostic sensitivity and accuracy are high.展开更多
Recognition and characterization of central nervous system infections poses a formidable challenge to the neuro-radiologist.Imaging plays a vital role,the lesions typically being relatively inaccessible to tisue sampl...Recognition and characterization of central nervous system infections poses a formidable challenge to the neuro-radiologist.Imaging plays a vital role,the lesions typically being relatively inaccessible to tisue sampling.The results of an accurate diagnosis are endlessly re-warding,given the availability of excellent pharmaco-logical regimen.The availability of numerous magnetic resonance(MR)sequences which provide functional and molecular information is a powerful tool in the hands of the radiologist.However,the plethora of se-quences and the possibilities on each sequence is also intimidating,and often confusing as well as time con-suming.While a large number of reviews have already described in detail the possible imaging findings in each infection,we intend to classify infections based on their imaging characteristics.In this review we describe an algorithm for first classifying the imaging findings into patterns based on basic MR sequences(T1,T2 and enhancement pattern with Gadolinium),and then sub-classify them based on more advanced molecular and functional sequences(Diffusion,Perfusion,Susceptibili-ty imaging,MR Spectroscopy).This patterned approachis intended as a guide to radiologists in-training and in-practice for quickly narrowing their list of differentials when faced with a clinical challenge.The entire content of the article has also been summarised in the form of flow-charts for the purpose of quick reference.展开更多
Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the ...Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3%(677/785), 9.4%(74/785) and 4.3%(34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1%(15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7%(39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5%(98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8%(93/785) and 7.6%(60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/ sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics.展开更多
BACKGROUND Central nervous system graft-vs-host disease(CNS-GVHD)is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation.Currently,establishing a diagnosis of CNS-GVHD is challenging ...BACKGROUND Central nervous system graft-vs-host disease(CNS-GVHD)is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation.Currently,establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out.CASE SUMMARY Here,we present two patients with CNS-GVHD.Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes,and had abnormal cerebrospinal fluid(CSF)studies as determined by CSF and blood immune biomarker examinations,suggestive of suspected CNS-GVHD.Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients,we did not attempt to perform a brain biopsy,but prompted the initiation of empirical immunosuppressive therapy.In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings,a final diagnosis of CNS-GVHD was made.CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNSGVHD,which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.展开更多
Central nervous system(CNS)infections are urgent conditions with high morbidity and mortality.Bacteria,viruses,parasites or fungi can cause them.Intracranial infections after craniotomies are an important complication...Central nervous system(CNS)infections are urgent conditions with high morbidity and mortality.Bacteria,viruses,parasites or fungi can cause them.Intracranial infections after craniotomies are an important complication of treatment,especially in oncological patients that are already immunologically compromised due to the disease and treatment.The consequence of CNS infections in oncological patients includes longer treatment with antibiotics,additional surgical procedures,higher treatment costs and poorer treatment outcomes.Additionally,the management of primary pathology may be prolonged or postponed as a result of the active infection.By introducing new and improved protocols,tightening controls on their implementation,constantly educating the entire team involved in patient treatment and educating both patients and relatives,the incidence of infections can be reduced effectively.展开更多
West Nile virus(WNV) is an emerging neurotropic flavivirus that has recently spread to America and Southern Europe via an enzootic/epizootic bird-mosquito-bird transmission cycle. The virus can occasionally infect hum...West Nile virus(WNV) is an emerging neurotropic flavivirus that has recently spread to America and Southern Europe via an enzootic/epizootic bird-mosquito-bird transmission cycle. The virus can occasionally infect humans through mosquito bites, and man-to-man transmission has also been reported via infected blood or organ donation. In the human host, WNV causes asymptomatic infection in about 70%-80% of cases, while < 1% of clinical cases progress to severe neuroinvasive disease; long-term neurological sequelae are common in more than 50% of these severe cases. Thepathogenesis of the neuroinvasive form of WNV infection remains incompletely understood, and risk factors for developing severe clinical illness are largely unknown. The innate immune response plays a major role in the control of WNV replication, which is supported by the fact that the virus has developed numerous mechanisms to escape the control of antiviral interferons. However, exaggerated inflammatory responses lead to pathology, mainly involving the central nervous system. This brief review presents the salient features of innate host responses, WNV immunoevasion strategies, and WNV-induced immunopathology.展开更多
BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,c...BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,clinical features,imaging findings,pathological characteristics,immunohistochemical characteristics,diagnoses,treatments,and risks of postoperative recurrence of IMT in the central nervous system.CASE SUMMARY A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo.Magnetic resonance imaging(MRI)showed a 2.4 cm×1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa,which was closely related to the dura mater.Before surgery,we suspected the mass to be meningioma.The entire mass was successfully removed under neuronavigation and electrophysiological monitoring,and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells.Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence.CONCLUSION From the histological,immunohistochemical,and genetic analyses,the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.展开更多
BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltr...BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.展开更多
<strong>Background:</strong> Sub-Saharan Africa is the region most affected by the Human Immunodeficiency Virus (HIV) with an increasing prevalence of related cognitive impairments. Magnetic Resonance Imag...<strong>Background:</strong> Sub-Saharan Africa is the region most affected by the Human Immunodeficiency Virus (HIV) with an increasing prevalence of related cognitive impairments. Magnetic Resonance Imaging (MRI) plays an important role in the early detection of lesions. This work aimed to describe the MRI aspects of different brain lesions occurred in HIV positive patients in our practice. <strong>Methods:</strong> This was a descriptive cross-sectional study that took place from June 2014 to July 2016 in the medical imaging department of the EL RAPHA private Polyclinic in Libreville, Gabon. It included all patients referred for imaging for the exploration of a Central Nervous System (CNS) lesions at MRI, based on clinical and/or paraclinical arguments. <strong>Results:</strong> Among the 39 patients included, 19 (48.7%) had a previous brain CT scan, 11 of which were normal (28.2%). Thirty-five (89.74%) patients had a pathological MRI. The main etiologies found were toxoplasmosis (37.14%), tuberculosis (17.14%), cerebral atrophy (17.14%) and HIV encephalitis (14.28%). Among the eleven patients with a normal Computer Tomography scan, the MRI found 7 abnormalities including 1 case of toxoplasmosis, 3 cases of HIV encephalitis and 3 cases of Progressive Multifocal Leukoencephalopathy (PML). <strong>Conclusion:</strong> MRI played an important role in the diagnosis of CNS disorders in HIV-infected individuals. It can be used to differentiate and characterize various brain lesions. Improving its accessibility in sub-Saharan Africa should contribute to better care for people living with HIV.展开更多
BACKGROUND Prevotella oris-induced meningitis and Prevotella oris-induced meningitis concomitant with spinal canal infection are extremely rare.To the best of our knowledge,only 1 case of Prevotella oris-induced centr...BACKGROUND Prevotella oris-induced meningitis and Prevotella oris-induced meningitis concomitant with spinal canal infection are extremely rare.To the best of our knowledge,only 1 case of Prevotella oris-induced central system infection has been reported.This is the second report on meningitis combined with spinal canal infection due to Prevotella oris.CASE SUMMARY We report a case of a 9-year-old boy suffering from meningitis and spinal canal infection.The patient presented to the neurosurgery department with lumbosacral pain for 1 mo and headache and vomiting for 1 d.He had been treated with cephalosporin and nonsteroidal anti-inflammatory drugs for fever,otalgia and pharyngalgia in a local hospital 2 mo prior to this admission.During hospitalization,magnetic resonance imaging suggested meningitis and L3-S1 lumbosacral dural sac infection.The cerebrospinal fluid and blood cultures were negative,but the cerebrospinal fluid specimen indicated the presence of Prevotella oris by metagenomic next-generation sequencing.Previous cases of Prevotella oris infection were retrieved from PubMed to characterize the clinicopathological features and identify the prognostic factors and related antimicrobial treatment of infection due to Prevotella oris.CONCLUSION This report shed light on the characteristics of Prevotella oris infection and highlighted the role of metagenomic next-generation sequencing in pathogen detection.展开更多
Fibroblasts are typically described as cells that produce extracellular matrix,contribute to the formation of connective tissue,and maintain the structural framework of tissues.Fibroblasts are the first cell type to b...Fibroblasts are typically described as cells that produce extracellular matrix,contribute to the formation of connective tissue,and maintain the structural framework of tissues.Fibroblasts are the first cell type to be transdifferentiated into inducible pluripotent stem cells(iPSCs),demonstrating their versatility and reprogrammability.Currently,there is relatively extensive characterization of the anatomical,molecular,and functional diversity of fibroblasts in different peripheral organs and tissues.With recent advances in single cell RNA sequencing,heterogeneity and diversity of fibroblasts in the central nervous system(CNS)have also begun to emerge.Based on their distinct anatomical locations in the meninges,perivascular space,and choroid plexus,as well as their molecular diversity,important roles for fibroblasts in the CNS have been proposed.Here,we draw inspirations from what is known about fibroblasts in peripheral tissues,in combination with their currently identified CNS locations and molecular characterizations,to propose potential functions of CNS fibroblasts in health and disease.Future studies,using a combination of technologies,will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS.展开更多
Primary central nervous system lymphoma(PCNSL)is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes.This article aims to present a brief profile of PCNSL diagnosis...Primary central nervous system lymphoma(PCNSL)is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes.This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients.The authors retrieved information from the PubMed database up to September 2019.The annual incidence of PCNSL increased over the last four decades.The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate,which is now the backbone of all first-line treatment polychemotherapy regimens.Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-kB,B cell antigen receptor,and Janus kinases/signal transducer and activator of transcription proteins signal pathways.Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy.In particular,lenalidomide and ibrutinib have demonstrated durable efficiency.Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups,but there is still room to improve outcome by optimizing current chemotherapy and novel agents.展开更多
Background:To explore central nervous system(CNS)involvement in this disease,from the perspectives of diagnosis,treatment,and misdiagnosis Methods:Twenty-eight patients with CNS echinococcosis were included in this re...Background:To explore central nervous system(CNS)involvement in this disease,from the perspectives of diagnosis,treatment,and misdiagnosis Methods:Twenty-eight patients with CNS echinococcosis were included in this retrospective study,including 18 males(64.3%)and 10(35.7%)females.The average age of all the patients were 23.5 years(ranged 4–60 years).Twenty-three(23)patients(82.1%)received the first surgical resection in our hospital.Five(5)patients(17.9%)gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals,and albendazole was applied for a long-term(3–6 months)adjunct therapy for the 5 patients.The average follow-up time was 8 years.Results:For the 28 patients,23 cases received surgical treatments,and the diagnosis was confirmed by pathological examinations.The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed,resulting in a misdiagnosis rate of 21.4%(6/28).For the pathological examination,a total of 17 cases were infected with Echinococcus granulosus(including 2 cases of spinal cord echinococcosis),and 6 cases were infected with Echinococcus alveolaris.Conclusion:The diagnosis should be specifically considered in endemic regions.The clinical features of CNS hydatidosis were intracranial space-occupying lesions.For the treatment,the surgical removal of cysts should be necessary.In addition,the adjuvant therapy with drug and intraoperative prophylaxis is also suggested.The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations,as well as the accuracy of hydatid immunologic test.展开更多
BACKGROUND:Serum uric acid level is associated with some chronic diseases and prognosis of severe infection.This study aimed to investigate the relationship between serum uric acid(SUA)and prognosis of infection in cr...BACKGROUND:Serum uric acid level is associated with some chronic diseases and prognosis of severe infection.This study aimed to investigate the relationship between serum uric acid(SUA)and prognosis of infection in critically ill patients.METHODS:The data from 471 patients with infection admitted from January 2003 to April 2010 were analyzed retrospectively at Huashan Hospital Affiliated to Fudan University,Shanghai,China.The data of SUA,serum creatinine,blood urea nitrogen(BUN) and other relevant examinations within24 hours after admission were recorded and the levels of SUA in those patients were described,then Student's t test was used to evaluate the relationship between SUA and pre-existing disorders.Different levels of SUA were graded for further analysis.The Chi-square test was used to examine the difference in the prognosis of infection.RESULTS:The mean initial level of SUA within 24 hours after admission was 0.232±0.131mmol/L and the median was 0.199 mmol/L.Remarkable variations in the initial levels of SUA were observed in patients with pre-existing hypertension(t=-3.084,P=0.002),diabetes mellitus(t=-2.487,P=0.013),cerebral infarction(t=-3.061,P=0.002),renal insufficiency(t=-4.547,P<0.001),central nervous system infection(f=5.096,P<0.001) and trauma(r=2.875,P=0.004).SUA was linearly correlated with serum creatinine and BUN(F=159.470 and 165.059,respectively,P<0.001).No statistical correlation was found between the initial levels of SUA and prognosis of infection(x^2=60.892,P=0.100).CONCLUSION:The current study found no direct correlation between the initial levels of SUA after admission and prognosis of infection in critically ill patients.展开更多
Aim:The pathogenesis of central nervous system infections(CNSI)has not been fully understood;some studies indicated that reactive oxygen species may induce brain damage.The aim of our study was to investigate serum an...Aim:The pathogenesis of central nervous system infections(CNSI)has not been fully understood;some studies indicated that reactive oxygen species may induce brain damage.The aim of our study was to investigate serum antioxidant status in patients with CNSI.Methods:The serum levels of uric acid(UA),bilirubin and albumin of 548 individuals were enrolled in our study,comprising of 114 healthy controls(HC)and 434 patients with five different kinds of CNSI,which including viral meningitis and/or meningoencephalitis,cysticercosis of brain,tuberculous meningitis and/or meningoencephalitis,cryptococcus meningitis and/or meningoencephalitis,and bacterial meningitis and/or meningoencephalitis.Results:The data suggested that there were reducing levels of oxidation state(serum UA,bilirubin and albumin)in CNSI patients when compared with HC.Likewise,similar results were observed when cohorts were divided into male and female subgroups.Conclusion:The authors demonstrated that serum antioxidant status in patients with CNSI was lower;the reason may be due to exhaustion of antioxidant capacity.Therefore,enhancing antioxidant power and keeping oxidative stress and antioxidants in balance may be beneficial to the patients with CNSI.展开更多
文摘BACKGROUND The diagnostic value of metagenomic next-generation sequencing(mNGS)in central nervous system(CNS)infectious diseases after empirical treatment has not been reported.AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid(CSF)in the empirically treated CNS infectious diseases.METHODS A 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.RESULTS Among 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.CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.
基金financially supported by the Russian Government Program of Competitive Growth of Kazan Federal Universitysupported by state assignment 20.5175.2017/6.7 of the Ministry of Education and Science of Russian Federationthe President of the Russian Federation grant НШ-3076.2018.4
文摘Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.
文摘HThe incidence of fungal infections of the central nervous system(CNS) has gradually increased in recent years. Intracranial fungal infection can be classified as diffuse and focal infections. The clinical manifestations of these infections include fever and cranial pressure caused by meningitis or meningoencephalitis, and focal neurological defects caused by lesions in the intracranial space. Diagnosing fungal infections of the CNS requires the comprehensive analysis of the patient's medical history, epidemiology, underlying disease, clinical manifestation, imaging manifestations, and various laboratory test results. The identification of fungal bodies or structures in brain tissue or cerebrospinal fluid specimens is the golden standard of diagnosis. The principles for the treatment of the fungal infections of the CNS are the effective control of pathogenic risk factors, use of effective antifungal drugs, and the active implementation of surgical intervention for fungal abscesses and granuloma. In the meantime, new diagnoses and treatments should be actively explored to improve the prognosis of patients.
基金Supported by the Research Project on Application of Commonweal Technology in Anhui Province,No.1704f0804048.
文摘BACKGROUND Prenatal examination is an important measure for the screening and diagnosis of fetal malformations.AIM To investigate the accuracy of ultrasonography in the diagnosis of fetal central nervous system(CNS)malformations.METHODS One hundred and thirteen pregnant women suspected of having fetal CNS malformations were examined at our hospital from December 2018 to October 2020 using two-dimensional ultrasonography and three-dimensional ultrasonography,respectively.RESULTS According to the pathological results,there were 79 cases of CNS malformations and 34 cases of non-CNS malformations among the 113 pregnant women suspected of having fetal CNS malformation.Fifty-one cases of CNS malformation and 26 cases of non-CNS malformation were detected by two-dimensional ultrasonography,and 73 cases of CNS malformation and 30 cases of non-CNS malformation were detected by three-dimensional ultrasonography.The diagnostic sensitivity(92.41%)and accuracy(91.15%)of three-dimensional ultrasonography were higher than those of two-dimensional ultrasonography(64.56% and 68.14%,respectively)(P=0.000).The specificity of three-dimensional ultrasonography(88.24%)was higher than that of two-dimensional ultrasonography(76.47%);however,the difference was not significant(P=0.203).CONCLUSION Three-dimensional ultrasonography has high application value in the diagnosis of fetal CNS malformations.In addition,the image quality is clear,and the diagnostic sensitivity and accuracy are high.
文摘Recognition and characterization of central nervous system infections poses a formidable challenge to the neuro-radiologist.Imaging plays a vital role,the lesions typically being relatively inaccessible to tisue sampling.The results of an accurate diagnosis are endlessly re-warding,given the availability of excellent pharmaco-logical regimen.The availability of numerous magnetic resonance(MR)sequences which provide functional and molecular information is a powerful tool in the hands of the radiologist.However,the plethora of se-quences and the possibilities on each sequence is also intimidating,and often confusing as well as time con-suming.While a large number of reviews have already described in detail the possible imaging findings in each infection,we intend to classify infections based on their imaging characteristics.In this review we describe an algorithm for first classifying the imaging findings into patterns based on basic MR sequences(T1,T2 and enhancement pattern with Gadolinium),and then sub-classify them based on more advanced molecular and functional sequences(Diffusion,Perfusion,Susceptibili-ty imaging,MR Spectroscopy).This patterned approachis intended as a guide to radiologists in-training and in-practice for quickly narrowing their list of differentials when faced with a clinical challenge.The entire content of the article has also been summarised in the form of flow-charts for the purpose of quick reference.
文摘Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3%(677/785), 9.4%(74/785) and 4.3%(34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1%(15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7%(39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5%(98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8%(93/785) and 7.6%(60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/ sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics.
基金Supported by National Natural Sciences Foundation of China,No.81970180 , 81800105Natural Science Foundation of Tianjin Municipal Science and Technology Commission,China,No.17JCZDJC35800and Tianjin Health and Family Planning Commission,China,No.16KG110.
文摘BACKGROUND Central nervous system graft-vs-host disease(CNS-GVHD)is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation.Currently,establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out.CASE SUMMARY Here,we present two patients with CNS-GVHD.Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes,and had abnormal cerebrospinal fluid(CSF)studies as determined by CSF and blood immune biomarker examinations,suggestive of suspected CNS-GVHD.Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients,we did not attempt to perform a brain biopsy,but prompted the initiation of empirical immunosuppressive therapy.In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings,a final diagnosis of CNS-GVHD was made.CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNSGVHD,which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.
文摘Central nervous system(CNS)infections are urgent conditions with high morbidity and mortality.Bacteria,viruses,parasites or fungi can cause them.Intracranial infections after craniotomies are an important complication of treatment,especially in oncological patients that are already immunologically compromised due to the disease and treatment.The consequence of CNS infections in oncological patients includes longer treatment with antibiotics,additional surgical procedures,higher treatment costs and poorer treatment outcomes.Additionally,the management of primary pathology may be prolonged or postponed as a result of the active infection.By introducing new and improved protocols,tightening controls on their implementation,constantly educating the entire team involved in patient treatment and educating both patients and relatives,the incidence of infections can be reduced effectively.
基金Supported by RFO of University of Bologna,the grant"Fondi Finalizzati Lab P3"from Regione Emilia-Romagnathe grant"Ricerca Finalizzata RF-2009-1539631"from the Italian Ministry of Health
文摘West Nile virus(WNV) is an emerging neurotropic flavivirus that has recently spread to America and Southern Europe via an enzootic/epizootic bird-mosquito-bird transmission cycle. The virus can occasionally infect humans through mosquito bites, and man-to-man transmission has also been reported via infected blood or organ donation. In the human host, WNV causes asymptomatic infection in about 70%-80% of cases, while < 1% of clinical cases progress to severe neuroinvasive disease; long-term neurological sequelae are common in more than 50% of these severe cases. Thepathogenesis of the neuroinvasive form of WNV infection remains incompletely understood, and risk factors for developing severe clinical illness are largely unknown. The innate immune response plays a major role in the control of WNV replication, which is supported by the fact that the virus has developed numerous mechanisms to escape the control of antiviral interferons. However, exaggerated inflammatory responses lead to pathology, mainly involving the central nervous system. This brief review presents the salient features of innate host responses, WNV immunoevasion strategies, and WNV-induced immunopathology.
文摘BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,clinical features,imaging findings,pathological characteristics,immunohistochemical characteristics,diagnoses,treatments,and risks of postoperative recurrence of IMT in the central nervous system.CASE SUMMARY A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo.Magnetic resonance imaging(MRI)showed a 2.4 cm×1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa,which was closely related to the dura mater.Before surgery,we suspected the mass to be meningioma.The entire mass was successfully removed under neuronavigation and electrophysiological monitoring,and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells.Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence.CONCLUSION From the histological,immunohistochemical,and genetic analyses,the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.
基金Supported by the Science and Technology Plan Guide Project of Fujian Province,No.2019D009.
文摘BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.
文摘<strong>Background:</strong> Sub-Saharan Africa is the region most affected by the Human Immunodeficiency Virus (HIV) with an increasing prevalence of related cognitive impairments. Magnetic Resonance Imaging (MRI) plays an important role in the early detection of lesions. This work aimed to describe the MRI aspects of different brain lesions occurred in HIV positive patients in our practice. <strong>Methods:</strong> This was a descriptive cross-sectional study that took place from June 2014 to July 2016 in the medical imaging department of the EL RAPHA private Polyclinic in Libreville, Gabon. It included all patients referred for imaging for the exploration of a Central Nervous System (CNS) lesions at MRI, based on clinical and/or paraclinical arguments. <strong>Results:</strong> Among the 39 patients included, 19 (48.7%) had a previous brain CT scan, 11 of which were normal (28.2%). Thirty-five (89.74%) patients had a pathological MRI. The main etiologies found were toxoplasmosis (37.14%), tuberculosis (17.14%), cerebral atrophy (17.14%) and HIV encephalitis (14.28%). Among the eleven patients with a normal Computer Tomography scan, the MRI found 7 abnormalities including 1 case of toxoplasmosis, 3 cases of HIV encephalitis and 3 cases of Progressive Multifocal Leukoencephalopathy (PML). <strong>Conclusion:</strong> MRI played an important role in the diagnosis of CNS disorders in HIV-infected individuals. It can be used to differentiate and characterize various brain lesions. Improving its accessibility in sub-Saharan Africa should contribute to better care for people living with HIV.
文摘BACKGROUND Prevotella oris-induced meningitis and Prevotella oris-induced meningitis concomitant with spinal canal infection are extremely rare.To the best of our knowledge,only 1 case of Prevotella oris-induced central system infection has been reported.This is the second report on meningitis combined with spinal canal infection due to Prevotella oris.CASE SUMMARY We report a case of a 9-year-old boy suffering from meningitis and spinal canal infection.The patient presented to the neurosurgery department with lumbosacral pain for 1 mo and headache and vomiting for 1 d.He had been treated with cephalosporin and nonsteroidal anti-inflammatory drugs for fever,otalgia and pharyngalgia in a local hospital 2 mo prior to this admission.During hospitalization,magnetic resonance imaging suggested meningitis and L3-S1 lumbosacral dural sac infection.The cerebrospinal fluid and blood cultures were negative,but the cerebrospinal fluid specimen indicated the presence of Prevotella oris by metagenomic next-generation sequencing.Previous cases of Prevotella oris infection were retrieved from PubMed to characterize the clinicopathological features and identify the prognostic factors and related antimicrobial treatment of infection due to Prevotella oris.CONCLUSION This report shed light on the characteristics of Prevotella oris infection and highlighted the role of metagenomic next-generation sequencing in pathogen detection.
基金supported by grants from the National Natural Science Foundation of China(32030049)the Ministry of Science and Technology of China(2021ZD0202500).
文摘Fibroblasts are typically described as cells that produce extracellular matrix,contribute to the formation of connective tissue,and maintain the structural framework of tissues.Fibroblasts are the first cell type to be transdifferentiated into inducible pluripotent stem cells(iPSCs),demonstrating their versatility and reprogrammability.Currently,there is relatively extensive characterization of the anatomical,molecular,and functional diversity of fibroblasts in different peripheral organs and tissues.With recent advances in single cell RNA sequencing,heterogeneity and diversity of fibroblasts in the central nervous system(CNS)have also begun to emerge.Based on their distinct anatomical locations in the meninges,perivascular space,and choroid plexus,as well as their molecular diversity,important roles for fibroblasts in the CNS have been proposed.Here,we draw inspirations from what is known about fibroblasts in peripheral tissues,in combination with their currently identified CNS locations and molecular characterizations,to propose potential functions of CNS fibroblasts in health and disease.Future studies,using a combination of technologies,will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS.
文摘Primary central nervous system lymphoma(PCNSL)is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes.This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients.The authors retrieved information from the PubMed database up to September 2019.The annual incidence of PCNSL increased over the last four decades.The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate,which is now the backbone of all first-line treatment polychemotherapy regimens.Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-kB,B cell antigen receptor,and Janus kinases/signal transducer and activator of transcription proteins signal pathways.Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy.In particular,lenalidomide and ibrutinib have demonstrated durable efficiency.Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups,but there is still room to improve outcome by optimizing current chemotherapy and novel agents.
文摘Background:To explore central nervous system(CNS)involvement in this disease,from the perspectives of diagnosis,treatment,and misdiagnosis Methods:Twenty-eight patients with CNS echinococcosis were included in this retrospective study,including 18 males(64.3%)and 10(35.7%)females.The average age of all the patients were 23.5 years(ranged 4–60 years).Twenty-three(23)patients(82.1%)received the first surgical resection in our hospital.Five(5)patients(17.9%)gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals,and albendazole was applied for a long-term(3–6 months)adjunct therapy for the 5 patients.The average follow-up time was 8 years.Results:For the 28 patients,23 cases received surgical treatments,and the diagnosis was confirmed by pathological examinations.The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed,resulting in a misdiagnosis rate of 21.4%(6/28).For the pathological examination,a total of 17 cases were infected with Echinococcus granulosus(including 2 cases of spinal cord echinococcosis),and 6 cases were infected with Echinococcus alveolaris.Conclusion:The diagnosis should be specifically considered in endemic regions.The clinical features of CNS hydatidosis were intracranial space-occupying lesions.For the treatment,the surgical removal of cysts should be necessary.In addition,the adjuvant therapy with drug and intraoperative prophylaxis is also suggested.The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations,as well as the accuracy of hydatid immunologic test.
文摘BACKGROUND:Serum uric acid level is associated with some chronic diseases and prognosis of severe infection.This study aimed to investigate the relationship between serum uric acid(SUA)and prognosis of infection in critically ill patients.METHODS:The data from 471 patients with infection admitted from January 2003 to April 2010 were analyzed retrospectively at Huashan Hospital Affiliated to Fudan University,Shanghai,China.The data of SUA,serum creatinine,blood urea nitrogen(BUN) and other relevant examinations within24 hours after admission were recorded and the levels of SUA in those patients were described,then Student's t test was used to evaluate the relationship between SUA and pre-existing disorders.Different levels of SUA were graded for further analysis.The Chi-square test was used to examine the difference in the prognosis of infection.RESULTS:The mean initial level of SUA within 24 hours after admission was 0.232±0.131mmol/L and the median was 0.199 mmol/L.Remarkable variations in the initial levels of SUA were observed in patients with pre-existing hypertension(t=-3.084,P=0.002),diabetes mellitus(t=-2.487,P=0.013),cerebral infarction(t=-3.061,P=0.002),renal insufficiency(t=-4.547,P<0.001),central nervous system infection(f=5.096,P<0.001) and trauma(r=2.875,P=0.004).SUA was linearly correlated with serum creatinine and BUN(F=159.470 and 165.059,respectively,P<0.001).No statistical correlation was found between the initial levels of SUA and prognosis of infection(x^2=60.892,P=0.100).CONCLUSION:The current study found no direct correlation between the initial levels of SUA after admission and prognosis of infection in critically ill patients.
文摘Aim:The pathogenesis of central nervous system infections(CNSI)has not been fully understood;some studies indicated that reactive oxygen species may induce brain damage.The aim of our study was to investigate serum antioxidant status in patients with CNSI.Methods:The serum levels of uric acid(UA),bilirubin and albumin of 548 individuals were enrolled in our study,comprising of 114 healthy controls(HC)and 434 patients with five different kinds of CNSI,which including viral meningitis and/or meningoencephalitis,cysticercosis of brain,tuberculous meningitis and/or meningoencephalitis,cryptococcus meningitis and/or meningoencephalitis,and bacterial meningitis and/or meningoencephalitis.Results:The data suggested that there were reducing levels of oxidation state(serum UA,bilirubin and albumin)in CNSI patients when compared with HC.Likewise,similar results were observed when cohorts were divided into male and female subgroups.Conclusion:The authors demonstrated that serum antioxidant status in patients with CNSI was lower;the reason may be due to exhaustion of antioxidant capacity.Therefore,enhancing antioxidant power and keeping oxidative stress and antioxidants in balance may be beneficial to the patients with CNSI.