Predictors of cerebrospinal fluid GeneXpert MTB/RIF positivity in patients with tuberculous meningitis:A prospective cohort study

Objective:To identify the clinical,laboratory,and radiological markers that could predict a positive GeneXpert result in patients suspected of tuberculous meningitis.Methods:In this prospective,observational study,patients with tuberculous meningitis were systematically evaluated.Various clinical,laboratory[including cerebrospinal fluid(CSF)microscopy,culture,and GeneXpert],and neuroimaging factors were examined.All participants were administered anti-tuberculous treatment and corticosteroids.A six-month follow-up was done to evaluate the outcome.Results:Of the 116 patients studied,54(46.6%)tested positive for GeneXpert,while 62(53.4%)were negative.Third cranial nerve involvement(OR 3.71,95%CI 1.052-13.09,P=0.04)and the presence of basal exudates on neuroimaging(OR 5.22,95%CI 2.03-13.42,P=0.001)emerged as independent predictive factors for a positive GeneXpert result.A positive CSF GeneXpert result(P=0.002)and drug resistance(P=0.004)were significantly linked to adverse outcomes.Additionally,a high score on the Medical Research Council stageⅢ(OR 5.64,95%CI 1.18-26.87,P=0.03)and elevated CSF cell counts(OR 1.002,95%CI 1.00-1.001,P=0.03)were identified as independent predictors of poor prognosis.Conclusions:Third cranial nerve involvement and the presence of basal exudates were significant indicators of a positive GeneXpert result.MRC stageⅢdisability and elevated CSF cell counts predicted poor outcomes.

Surgical treatment of mixed cervical spondylosis with spontaneous cerebrospinal fluid leakage: A case report

BACKGROUND Spontaneous cerebrospinal fluid(CSF)leaks associated with cervical spondylosis are rare.To our knowledge,only a few cases have been reported in which treatment is challenging and varies from case to case.Here,we review the literature and describe the surgical treatment of a 70-year-old woman who presented with a CSF leak due to a cervical spine spur.CASE SUMMARY A 70-year-old female patient who was treated for a cerebral infarction,presented with complains of weakness in the right lower extremity and a feeling of stepping on cotton.The patient underwent regular neck massage and presented with neck and right shoulder pain radiating to the right upper extremity one-month ago.Magnetic resonance imaging showed a strip of leaking cerebrospinal fluid posterior to the C1-4 vertebrae,and computed tomography showed a“sickleshaped”disc prolapse with calcification in C4/5.We chose to perform an anterior cervical discectomy.When the prolapsed C4/5 disc was scraped,clear fluid leakage was observed,and exploration revealed a 1 mm diameter rupture in the anterior aspect of the dura mater,which was compressed continuously with cotton patties,with no significant cerebrospinal fluid leakage after 1 h.CONCLUSION Three months after surgery,the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

Hydrocephalic cerebrospinal fluid flowing rotationally with pulsatile boundaries:A mathematical simulation of the thermodynamical approach

To study the kinematics of flow rate and ventricular dilatation,an analytical perturbation approach of hydrocephalus has been devised.This research provides a comprehensive investigation of the characteristics of cerebrospinal fluid(CSF)flow and pressure in a hydrocephalic patient.The influence of hydrocephalic CSF,flowing rotationally with realistic dynamical characteristics on pulsatile boundaries of subarachnoid space,was demonstrated using a nonlinear controlling system of CSF.An analytical perturbation method of hydrocephalus has been developed to investigate the biomechanics of fluid flow rate and the ventricular enlargement.In this paper presents a detailed analysis of CSF flow and pressure dynamics in a hydrocephalic patient.It was elaborated with a nonlinear governing model of CSF to show the influence of hydrocephalic CSF,flowing rotationally with realistic dynamical behaviors on pulsatile boundaries of subarachnoid space.In accordance with the suggested model,the elasticity factor changes depending on how much a porous layer,in this case the brain parenchyma,is stretched.It was improved to include the relaxation of internal mechanical stresses for various perturbation orders,modelling the potential plasticity of brain tissue.The initial geometry that was utilised to create the framework of CSF with pathological disease hydrocephalus and indeed the output of simulations using this model were compared to the actual progression of ventricular dimensions and shapes in patients.According to this observation,the non-linear and elastic mechanical phenomena incorporated into the current model are probably true.Further modelling of ventricular dilation at a normal pressure may benefit from the existence of a valid model whose parameters approximate genuine mechanical characteristics of the cerebral cortex.

CfDNA-based liquid biopsy of cerebrospinal fluid in medulloblastoma

Medulloblastoma(MB)is the most common childhood embryonal malignant tumour in the central nervous system.The diagnosis,prognosis and therapeutic targets of MB depend on the molecular characteristics of the tumor,and it is a great challenge to obtain the tissue samples from the patients with brain tumor.Genomic changes found in cell-free DNA(cfDNA)of cerebrospinal fluid(CSF)can predict genomic changes present in tumor tissue,fluid biopsy of CSF can detect the genomic profile of tumor-associated cfDNA and evaluate cfDNA as a marker of measurable residual disease(MRD)in a relatively noninvasive manner,which provides the evidence of"individualized precision therapy"for MB patients.In this paper,we reviewed the recent studies in medulloblastoma based on cfDNA Liquid Biopsy of CSF.

Role of cerebrospinal fluid lactate in diagnosing meningitis in critically ill patients

BACKGROUND Meningitis is a life-threatening clinical condition associated with high mortality and morbidity.Early diagnosis and specific treatment may improve outcomes.Lack of specific clinical signs or tests make the diagnosis challenging.AIM To assess the efficacy of cerebrospinal fluid(CSF)lactate in diagnosing meningitis in critically ill patients.METHODS A prospective,observational cohort study was carried out in a neuro-medical intensive care unit(ICU)over a 22 mo period.Adult patients,with suspected meningitis admitted in ICU,were serially recruited.Patients who refused consent,those with peripheral sensorineural deficit,or with any contraindication to lumber puncture were excluded.CSF cytology,bio-chemistry,lactates,culture and polymerase chain reaction based meningo-encephalitis panel were evaluated.Patients were divided in two groups based on clinical diagnosis of meningitis.The efficacy of CSF lactate in diagnosing meningitis was evaluated and compared with other tests.RESULTS Seventy-one patients were included and 23 were diagnosed with meningitis.The mean values of CSF total leucocyte count(TLC),proteins and lactates were significantly higher in meningitis group.There was a significant correlation of CSF lactate levels with CSF cultures and meningo-encephalitis panel.CSF lactate(>2.72 mmol/L)showed good accuracy in diagnosing meningitis with an area under the curve of 0.81(95% confidence interval:0.69-0.93),sensitivity of 82.6%,and specificity 72.9%.These values were comparable to those of CSF TLC and protein.Twelve patients with bacterial meningitis had significantly higher CSF lactate(8.9±4.7 mmol/L)than those with non-bacterial meningitis(4.2±3.8 mmol/L),P=0.006.CONCLUSION CSF lactate may be used to aid in our diagnosis of meningitis in ICU patients.CSF lactate(>2.72 mmol/L)showed good accuracy,sensitivity,and specificity in diagnosing meningitis and may also help to differentiate between bacterial and non-bacterial meningitis.

Abdominal Cerebrospinal Fluid Pseudocyst—A Rare Complication of Ventriculoperitoneal Shunt

An abdominal cerebrospinal fluid pseudocyst is a rare complication of ventriculoperitoneal shunt. Several theories have been suggested to explain its occurrence. The main symptoms are painful abdominal distension and vomiting, abdominal distension on examination, as abdominal ultrasound and computed tomography confirm its diagnosis. The treatment involves drainage associated with drain relocation and resection of the pseudocyst’s wall. We report two patients diagnosed with this condition who underwent surgical treatment. The first patient had an unremarkable 12-month follow-up, while the second died on the seventh postoperative day due to intravascular disseminated coagulation. In these patients, the cause has not been identified;however, an infection cannot be ruled out.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

A rare complication of measles infection presented with subacute sclerosing panencephalitis: Report of two cases in India

Rationale:Subacute sclerosing panencephalitis(SSPE)is a progressive neurological disorder caused by persistent measles virus infection.SSPE predominantly affects children and adolescents.The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases.Patient concerns:Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks.Diagnosis:Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid,these patients were diagnosed as SSPE.Interventions:Antiepileptics were started for controlling myoclonus along with supportive treatment.Outcomes:Both patients were discharged on antiepileptics and supportive care.Lessons:Whenever there are unusual clinical manifestations with unknown vaccination status,SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies.Our case study also highlights the importance of universal coverage of measles vaccination.To reduce the incidence of measles and associated deaths,it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program.

Clinical characteristics of patients with early-and late-onset optic neuromyelitis optica spectrum disease

Objective:To analyze the different clinical features of patients with early-onset(EO-NMOSDs)and late-onset neuromyelitis optica spectrum diseases(LO-NMOSDs).Methods:A total of 51patients with neuromyelitis optica spectrum disease who were diagnosed in our hospital for the first time from January 2015 to December 2022 were included in the First Affiliated Hospital of Hainan Medical College and divided into 22 cases in the EO-NMOSDs group and 29 cases in the LO-NMOSDs group according to whether the age of onset was 50 years old.The basic data,Extended Disability Status Scale(EDSS)score,blood and cerebrospinal fluid test indicators of the two groups were statistically analyzed.Results:There were no significant differences in demographic characteristics,clinical features and serum AQP-4 antibody positivity rate between the two groups(all P>0.05),and there were significant differences in triglycerides(TG),low-density lipoprotein(LDL),apolipoprotein A(APOA),apolipoprotein B(APOB)and lipoprotein a(P=0.010,P=0.048,P=0.014,P=0.061,P=0.001,respectively),and cerebrospinal fluid LDH,There were significant differences between microprotein quantification and EDSS score(P=0.018,P=0.034,P=0.025,respectively),and the level of microprotein quantification in cerebrospinal fluid of LO-NMOSDs had a certain correlation with the degree of disability(r=0.52,P<0.03).Conclusion:LO-NMOSDs and EO-NMOSDs group patients have similar demographic characteristics,serum AQP-4 antibody positive rate and clinical features,but compared with EO-NMOSDs,patients in LO-NMOSDs group are prone to abnormal lipid metabolism,higher trace proteins in cerebrospinal fluid and more likely to be disabled,and among LO-NMOSDs,the higher the trace protein in the cerebrospinal fluid,the more severe the disability status of patients.

Treatment of spinal cord injury by transplantation of cells via cerebrospinal fluid

It is very important to probe into the axonal regeneration and functional recovery of central nervous system （CNS） after implantation of cells into cerebrospinal fluid （CSF） for spinal cord injury （SCI）. Transplantation of cells via CSF poses great potentials for SCI in clinic. Studies on administration of cells via CSF indicate that the method is safe and convenient. The method is more suitable to treating multiple lesions of the CNS since it does not produce open lesions. However, there are disputes over its promotion effects on axonal regeneration and functional recovery of spinal cord after injury; and some questions, such as the mechanisms of functional recovery of spinal cord, the proper time window of cell transplantation, and cell types of transplantation, still need to be handled. This review summarized the method of cell transplantation via CSF for treatment of SCI.

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

Objective: This study aims to explore the differences in cerebrospinal fluid oligoclonal band (CSF-OCB) expression among different age groups in viral encephalitis and its reference value for diagnosis. Methods: Forty-two patients with viral encephalitis were divided into two groups: 25 adults and 17 children. The presence of oligoclonal bands in the cerebrospinal fluid (CSF) was detected using polyacrylamide gel electrophoresis, and CSF routine analysis was conducted for comparative analysis. Results: The CSF-OCB positivity rate was higher in the adult group (48%) compared with the pediatric group (11.76%), with a statistically significant difference (P Conclusion: 1) The expression of CSF-OCB positivity in patients with viral encephalitis is age-related, with higher positivity rates observed in adults compared to children. 2) Although CSF oligoclonal band detection is not a specific diagnostic marker for viral encephalitis in adults, it still holds certain reference value.

Correlation of Cerebrospinal Fluid Sialic Acid with Various Enzymes in Patients with Meningitis

Meningitis is often associated with cerebral compromise which may be responsible for neurological squeal in nearly half of the survivors. Little is known about the mechanisms of Central Nervous System （CNS） involvement in bacterial meningitis. The present study was undertaken to assess the changes in biochemical parameters including glucose, protein, Sialic Acid （SA） and various enzymes like Aspartate Aminotransferase （AST）, Alanine Aminotransferase （ALT）, Creatine Kinase （CK）, Gamma Glutamyltranspeptidase 7 （GGTP） and Lactate Dehydrogenase （LDH） have been determined in the Cerebrospinal Fluid （CSF） of the meningitis patients （n = 26） and compared with control subjects （n = 26）. Total Protein, CK, SA （P 〈 0.02）, AST （P 〈 0.001） and ALT （P 〈 0.0001） of meningitis patients were significantly higher, whereas, glucose （P 〈 0.05） and Gamma Glutamyltranspeptidase （GGT） （P 〈 0.01 and P 〈 0.05, respectively） were significantly lower than those of the controls. This study suggests that loss of integrity of brain-CSF barriers, sialic acid and enzyme profiles may contribute to the severity and neurological complications of meningitis.

Changes in HIF-1α, VEGF, NGF and BDNF Levels in Cerebrospinal Fluid and TheirRelationship with Cognitive Impairment in Patients with Cerebral Infarction

Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography （CT） were recruited as the ischemic cerebrovascular diseases （ICVD） group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA） was employed to detect the levels of hypoxia-inducible factor 1-alpha （HIF-1α）, vascular endothelial growth factor （VEGF）, nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination （MMSE） score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group （P=-0.037 and P=0.000; P=0.023 and P=-0.005）. In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid （r=-0.327, P=0.021; r=-0.585, P=0.046）. In VCI group, HIF-1α level was correlated with NGF level （r=0.589, P=0.044）. HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.

MANAGEMENT OF CEREBROSPINAL FLUID LEAKAGE FOLLOWING CERVICAL SPINE SURGERY

Objective To investigate the management and outcome of cerebrospinal fluid leakage(CSFL)after cervical surgery.Methods Medical records of 642 patients who underwent cervical surgery between December 1999 and December 2005 at our hospital were retrospectively reviewed.Five patients complicated by CSFL after surgery were enrolled,of which 4 cases were complicated after ossified posterior longitudinal ligament or posterior vertebral osteophyte resection directly injuring the dura,and 1 case after posterior cervical double-door laminoplasty without observed dural injury during surgery.Of the 5 CSFL cases,4 cases occurred at 1-3 days after operation and 1 case at 9 days after operation.All 5 postoperative CSFL cases were treated through wound drainage removal,wound sutures,prophylactic antibiotics,and continuous subarachnoid drainage in the elevated head position.Results All 5 CSFL cases experienced leakage cessation within 1-3 days and wound healing within 4-8 days,and subarachnoid drainage lasted 11-16 days with an average volume of 320 mL(range,150-410 mL).Four cases experienced headache,nausea and vomiting,1 case suffered from somnolence and hyponatremia,and symptoms subsided after symptomatic treatment and intravenous fluid administration.All patients were followed up for an average of 32 months(range,22-50 months).No occurrence of cerebrospinal fluid cyst or wound infection was observed.CSFL produced no significant negative effects upon neuromuscular function recovery.Conclusion Continuous subarachnoid cavity drainage in combination with elevated head position is a simple and safe non-surgical method in treatment of CSFL following cervical surgery.

Serial lumbar puncture reduces cerebrospinal fluid (CSF) infection during removal of hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling

The present study aimed to compare the complications and clinical outcomes of serial lumbar puncture（LP） and lumbar cerebrospinal fluid（CSF） drainage（LD） of patients with aneurysmal subarachnoid hemorrhage and provide more evidence to guide clinical management.In this retrospective study,41 and 39 aneurysmal subarachnoid hemorrhage patients were enrolled in the LP and LD group,respectively.Clinical outcomes,including CSF infection,intracerebral hemorrhage,vasospasm,hydrocephalus,death,length of stay,duration of drainage and the Glasgow Outcome Scale score were compared between the two groups.By comparing with the LP group,the LD group showed a significantly higher rate of CSF infection（P= 0.029） and shorter duration of drainage（P〈 0.001）.Both groups displayed similar rates of vasospasm,hydrocephalus,intracerebral hemorrhage,the Glasgow Outcome Scale score one month after endovascular coiling and length of stay（P〉 0.05,respectively）.In conclusion,both LD and serial LP are effective methods in the treatment of aneurysmal subarachnoid hemorrhage; besides,serial LP can reduce the incidence of CSF infection in draining hemorrhagic CSF in aneurysmal subarachnoid hemorrhage after endovascular coiling.

Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid（CSF） T‐SPOT.TB test for the diagnosis of TB meningitis（TBM）. A retrospective analysis of 96 patients with manifested meningitis was conducted; T‐SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value（PPV）, and negative predictive value（NPV）. A receiver operating characteristic（ROC） curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T‐SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients（54.2%） of the 96 enrolled patients. The area under the curve（AUC） was 0.910, and the sensitivities of CSF T‐SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T‐SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM.

Cognitive impairment in multiple sclerosis: lessons from cerebrospinal fluid biomarkers

Cognitive impairment is a common clinical manifestation of multiple sclerosis,but its pathophysiology is not completely understood.White and grey matter injury together with synaptic dysfunction do play a role.The measurement of biomarkers in the cerebrospinal fluid and the study of their association with cognitive impairment may provide interesting in vivo evidence of the biological mechanisms underlying multiple sclerosis-related cognitive impairment.So far,only a few studies on this topic have been published,giving interesting results that deserve further investigation.Cerebrospinal fluid biomarkers of different pathophysiological mechanisms seem to reflect different neuropsychological patterns of cognitive deficits in multiple sclerosis.The aim of this review is to discuss the studies that have correlated cerebrospinal fluid markers of immune,glial and neuronal pathology with cognitive impairment in multiple sclerosis.Although preliminary,these findings suggest that cerebrospinal fluid biomarkers show some correlation with cognitive performance in multiple sclerosis,thus providing interesting insights into the mechanisms underlying the involvement of specific cognitive domains.

Cerebrospinal fluid and neural stem cell niche control

Neurogenesis from inner brain neural stem cells （NSCs） is a process which takes place continuously in mammals through- out their life. However, the main ontogenic difference is the intensity of neurogenesis, which commences as a very intensive and global activity in the early embryonic brain （neural tube）, persists in fetal and newborn stages, and declines significantly in adulthood, becoming restricted to specific places with low neurogenic activity such as the subventricular zone （SVZ） and the subgranular zone （SGZ） in the dentate gyrus （DG） of the hippocampus.

Hepatitis B virus in cerebrospinal fluid of a patient with purulent bacterial meningitis detected by multiplex-PCR:A case report

BACKGROUND Bacterial meningitis(BM)is a common central nervous system inflammatory disease.BM may cause serious complications,and early diagnosis is essential to improve the prognosis of affected patients.CASE SUMMARY A 37-year-old man was hospitalized with purulent meningitis because of worsening headache for 12 h,accompanied by vomiting,fever,and rhinorrhea.Head computed tomography showed a lesion in the left frontal lobe.Infectious disease screening showed positivity for hepatitis B surface antigen,hepatitis B e antigen,and hepatitis B core antigen.Cerebrospinal fluid(CSF)leak was suspected based on clinical history.Streptococcus pneumoniae(S.pneumoniae)was detected in CSF by metagenomic next-generation sequencing(mNGS)technology,confirming the diagnosis of purulent BM.After treatment,multiplex PCR indicated the presence of hepatitis B virus(HBV)DNA and absence of S.pneumoniae DNA in CSF samples.CONCLUSION We report a rare case of HBV in the CSF of a patient with purulent BM.Multiplex PCR is more sensitive than mNGS for detecting HBV DNA.

Secretion of nerve growth factor,brain-derived neurotrophic factor,and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

The present study co-cultured human embryonic olfactory ensheathJng cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7-10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid （10%, 20% and 30%） in the growth medium caused a decrease of neurotrophic factor secretion Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.