BACKGROUND Cerebrospinal fluid(CSF)leaks in the temporal bone arise from osteodural defects,resulting in an abnormal connection between the subarachnoid space and the adjacent tympanomastoid cavity,which often manifes...BACKGROUND Cerebrospinal fluid(CSF)leaks in the temporal bone arise from osteodural defects,resulting in an abnormal connection between the subarachnoid space and the adjacent tympanomastoid cavity,which often manifests as otorrhea.Patients typically exhibit symptoms such as headache,unilateral hearing impairment,aural fullness,or even meningitis.Imaging studies are critical for identifying and differentiating the location and characteristics of CSF leaks.However,when the leak's origin remains ambiguous,diagnostic surgery may be warranted to both confirm the diagnosis and facilitate treatment.This report discusses an uncommon case while reviewing relevant literature,focusing on the surgical diagnostic intervention in a 58-year-old male with spontaneous temporal bone CSF leaks.CASE SUMMARY The patient,a 58-year-old man,was admitted for evaluation of left ear fullness,hearing loss,and nasal discharge.Notably,when supine,clear fluid drained from the left nasal cavity,with improvement noted upon sitting.A nasal examination did not reveal significant findings,while the otologic evaluation indicated an intact periosteum;however,considerable fluid accumulation was identified within the left middle ear.Despite undergoing multiple periosteal punctures and conservative medical management,the middle ear effusion persisted.Imaging studies,including magnetic resonance imaging(MRI)and computed tomography,confirmed the presence of left-sided CSF otorrhea,and the head MRI indicated potential CSF rhinorrhea.This raised challenges in determining whether the CSF leak originated from the sphenoid sinus or the temporal bone.Given that CSF otorrhea may drain through the external auditory canal and CSF rhinorrhea from the sellar region can present as nasal leakage,differentiation proved complex.In this case,with an intact external auditory canal,CSF from the middle ear was observed to flow into the nasal cavity via the Eustachian tube.Therefore,leakage from both sites could be misconstrued as CSF rhinorrhea,complicating the diagnostic process.Consequently,an exploratory surgical procedure was performed,revealing an incomplete dura mater on the temporal aspect of the petrous bone,which was subsequently repaired.CONCLUSION Benign intracranial hypertension can result in meningeal protrusion or meningoencephalocele,which may lead to CSF leakage that generally responds favorably to mucosal repair.In instances where imaging fails to identify the source of the leak or when diagnostic options are limited,proactive exploratory surgery is advisable.Although surgical interventions carry inherent risks,the application of endoscopic techniques by experienced surgeons renders this approach a feasible choice for addressing both diagnostic and therapeutic challenges.展开更多
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,pat...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.展开更多
Objective This study aims to analyze metabolites in the cerebrospinal fluid(CSF)of neurosyphilis patients to identify potential diagnostic markers.Methods Untargeted metabolomics by liquid chromatography-mass spectrom...Objective This study aims to analyze metabolites in the cerebrospinal fluid(CSF)of neurosyphilis patients to identify potential diagnostic markers.Methods Untargeted metabolomics by liquid chromatography-mass spectrometry was used to analyze metabolites in CSF samples from five neurosyphilis and five syphilis/non-neurosyphilis patients.After quality control and normalization,data analyses(principal component analysis,orthogonal partial least squares-discriminant analysis,hierarchical clustering)were conducted to identify differential metabolites.Results The content of metabolites(Pro-leu,nudifloramide,N-oleoyl glycine,DMP 777,(±)-propionylcarnitine,and 3β-hydroxy-5-cholenoic acid)in neurosyphilis patients was 1.7-to 4.5-fold of that in the non-neurosyphilis patients.Conclusions The metabolites,particularly nudifloramide and N-oleoyl glycine,which have been implicated in other neurological disorders,warrant further investigation into their roles in the pathogenesis of neurosyphilis.展开更多
Previous studies show that chronic acrylamide exposure leads to central and peripheral neu- ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebr...Previous studies show that chronic acrylamide exposure leads to central and peripheral neu- ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.展开更多
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）. Transpl...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.展开更多
Cerebrospinal fluid fistulae occur when defects in dura, pla-arachnold or skull permit the cerebrospinal fluid escape from the subarachnoid space via anterior naris, nasopharynx or external acoustic meastus, Which is ...Cerebrospinal fluid fistulae occur when defects in dura, pla-arachnold or skull permit the cerebrospinal fluid escape from the subarachnoid space via anterior naris, nasopharynx or external acoustic meastus, Which is most commonly manifested as rhinorrhea or otorrhea,complicated by serious recurrent meningitis for months or years.This paper reports 20 cases of rhinorrhea and one of otorrhea, persisting longer than 3 months. All the cases were repaired successfully and there was no recurrence arter being followed up for 1 to 20 years.We compared various diagnostic methods and suggested a simple operative procedure.展开更多
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 t...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.展开更多
Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promis...Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.展开更多
Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Meth...Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Methods:A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months.The average length of follow-up was three years.The characteristics of the clinical presentations of all patients,such as self-reported symptoms,radiographic findings,surgical approaches and methods of repair,position of the leakage during surgery,and postoperative course,including the success rate of surgery,are presented.Results:The patients presented mostly with typical symptoms of meningitis,severe hearing impairment,and CSF otorrhea or rhinorrhea.All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment.The preoperative audiograms of 17 patients showed profound sensorineural hearing loss,and one patient had conductive hearing loss.Twelve patients presented with an initial onset of otorrhea,and two had accompanying rhinorrhea.Six patients complained of rhinorrhea,two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital.High-resolution computed tomography(HRCT)images can reveal developments in the inner ear,such as expansion of a vestibular cyst,unclear structure of the semicircular canal or cochlea,or signs of effusion in the middle ear or mastoid,which strongly suggest the possibility of CSF otorrhea.The children in the study suffered more severe dysplasia than adults.All 18 patients had CSF leakage identified during surgery.The most common defect sites were in the stapes footplates(55.6%),and 38.9%of patients had a leak around the oval window.One patient had a return of CSF otorrhea during the postoperative period,which did not re-occur following a second repair.Conclusions:CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults.The most common symptoms were meningitis,hearing impairment,and CSF otorrhea or rhinorrhea.HRCT has high diagnostic accuracy for this disease.The most common fistula site was around the oval window,including the stapes footplates and the annular ligament.展开更多
Neonatal encephalopathy resulting from an asphyxial episode occurring perinatally is a major cause of death and of permanent neurological disabilities worldwide. Therapeutic hypothermia(TH) started within 6 hours of l...Neonatal encephalopathy resulting from an asphyxial episode occurring perinatally is a major cause of death and of permanent neurological disabilities worldwide. Therapeutic hypothermia(TH) started within 6 hours of life and maintained for 72 hours is now well established as standard treatment for infants with moderate-to-severe hypoxicischemic encephalopathy(HIE).展开更多
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 ...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.展开更多
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 p...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.展开更多
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 mea...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.展开更多
Alzheimer＇s disease （AD） is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is...Alzheimer＇s disease （AD） is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid （CSF） biomarkers （β-amyloid, total tau, and hyperphosphorylated tau）. Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.展开更多
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 meningiti...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.展开更多
Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Ta...Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.展开更多
To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(C...To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with sAD.Then,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic risk.Receiver operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset.We measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the PRSs.We found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our cohort.The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at onset.Furthermore,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and P-tau.Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD.As genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.展开更多
Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study ...Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.展开更多
Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnos...Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnosis is not possible.Thus,an early diagnosis and identification of AD patients is critical for promising,early pharmacological interventions as well as addressing health care needs.The most advanced and most reliable markers areβ-amyloid,total tau and phosphorylated tau in cerebrospinal fluid(CSF).In blood,no single biomarker has been identified despite an intense search over the last decade.The most promising approaches consist of a combination of several bloodbased markers increasing the reliability,sensitivity and specificity of the AD diagnosis.However,contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult.In this review,we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.展开更多
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...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.展开更多
文摘BACKGROUND Cerebrospinal fluid(CSF)leaks in the temporal bone arise from osteodural defects,resulting in an abnormal connection between the subarachnoid space and the adjacent tympanomastoid cavity,which often manifests as otorrhea.Patients typically exhibit symptoms such as headache,unilateral hearing impairment,aural fullness,or even meningitis.Imaging studies are critical for identifying and differentiating the location and characteristics of CSF leaks.However,when the leak's origin remains ambiguous,diagnostic surgery may be warranted to both confirm the diagnosis and facilitate treatment.This report discusses an uncommon case while reviewing relevant literature,focusing on the surgical diagnostic intervention in a 58-year-old male with spontaneous temporal bone CSF leaks.CASE SUMMARY The patient,a 58-year-old man,was admitted for evaluation of left ear fullness,hearing loss,and nasal discharge.Notably,when supine,clear fluid drained from the left nasal cavity,with improvement noted upon sitting.A nasal examination did not reveal significant findings,while the otologic evaluation indicated an intact periosteum;however,considerable fluid accumulation was identified within the left middle ear.Despite undergoing multiple periosteal punctures and conservative medical management,the middle ear effusion persisted.Imaging studies,including magnetic resonance imaging(MRI)and computed tomography,confirmed the presence of left-sided CSF otorrhea,and the head MRI indicated potential CSF rhinorrhea.This raised challenges in determining whether the CSF leak originated from the sphenoid sinus or the temporal bone.Given that CSF otorrhea may drain through the external auditory canal and CSF rhinorrhea from the sellar region can present as nasal leakage,differentiation proved complex.In this case,with an intact external auditory canal,CSF from the middle ear was observed to flow into the nasal cavity via the Eustachian tube.Therefore,leakage from both sites could be misconstrued as CSF rhinorrhea,complicating the diagnostic process.Consequently,an exploratory surgical procedure was performed,revealing an incomplete dura mater on the temporal aspect of the petrous bone,which was subsequently repaired.CONCLUSION Benign intracranial hypertension can result in meningeal protrusion or meningoencephalocele,which may lead to CSF leakage that generally responds favorably to mucosal repair.In instances where imaging fails to identify the source of the leak or when diagnostic options are limited,proactive exploratory surgery is advisable.Although surgical interventions carry inherent risks,the application of endoscopic techniques by experienced surgeons renders this approach a feasible choice for addressing both diagnostic and therapeutic challenges.
文摘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.
文摘Objective This study aims to analyze metabolites in the cerebrospinal fluid(CSF)of neurosyphilis patients to identify potential diagnostic markers.Methods Untargeted metabolomics by liquid chromatography-mass spectrometry was used to analyze metabolites in CSF samples from five neurosyphilis and five syphilis/non-neurosyphilis patients.After quality control and normalization,data analyses(principal component analysis,orthogonal partial least squares-discriminant analysis,hierarchical clustering)were conducted to identify differential metabolites.Results The content of metabolites(Pro-leu,nudifloramide,N-oleoyl glycine,DMP 777,(±)-propionylcarnitine,and 3β-hydroxy-5-cholenoic acid)in neurosyphilis patients was 1.7-to 4.5-fold of that in the non-neurosyphilis patients.Conclusions The metabolites,particularly nudifloramide and N-oleoyl glycine,which have been implicated in other neurological disorders,warrant further investigation into their roles in the pathogenesis of neurosyphilis.
基金supported by State Key Development Program for Basic Research of China,No.2012CB525002the National Natural Science Foundation of China,No.30771823
文摘Previous studies show that chronic acrylamide exposure leads to central and peripheral neu- ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.
文摘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.
文摘Cerebrospinal fluid fistulae occur when defects in dura, pla-arachnold or skull permit the cerebrospinal fluid escape from the subarachnoid space via anterior naris, nasopharynx or external acoustic meastus, Which is most commonly manifested as rhinorrhea or otorrhea,complicated by serious recurrent meningitis for months or years.This paper reports 20 cases of rhinorrhea and one of otorrhea, persisting longer than 3 months. All the cases were repaired successfully and there was no recurrence arter being followed up for 1 to 20 years.We compared various diagnostic methods and suggested a simple operative procedure.
基金supported by the National Natural Science Foundation of China (No. 81171029)
文摘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.
基金supported by the National Natural Science Foundation of China,No.81671211,81672251(both to HLL)
文摘Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.
基金Project supported by the National Natural Science Foundation of China(Nos.81570914 and 81700925)
文摘Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Methods:A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months.The average length of follow-up was three years.The characteristics of the clinical presentations of all patients,such as self-reported symptoms,radiographic findings,surgical approaches and methods of repair,position of the leakage during surgery,and postoperative course,including the success rate of surgery,are presented.Results:The patients presented mostly with typical symptoms of meningitis,severe hearing impairment,and CSF otorrhea or rhinorrhea.All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment.The preoperative audiograms of 17 patients showed profound sensorineural hearing loss,and one patient had conductive hearing loss.Twelve patients presented with an initial onset of otorrhea,and two had accompanying rhinorrhea.Six patients complained of rhinorrhea,two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital.High-resolution computed tomography(HRCT)images can reveal developments in the inner ear,such as expansion of a vestibular cyst,unclear structure of the semicircular canal or cochlea,or signs of effusion in the middle ear or mastoid,which strongly suggest the possibility of CSF otorrhea.The children in the study suffered more severe dysplasia than adults.All 18 patients had CSF leakage identified during surgery.The most common defect sites were in the stapes footplates(55.6%),and 38.9%of patients had a leak around the oval window.One patient had a return of CSF otorrhea during the postoperative period,which did not re-occur following a second repair.Conclusions:CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults.The most common symptoms were meningitis,hearing impairment,and CSF otorrhea or rhinorrhea.HRCT has high diagnostic accuracy for this disease.The most common fistula site was around the oval window,including the stapes footplates and the annular ligament.
文摘Neonatal encephalopathy resulting from an asphyxial episode occurring perinatally is a major cause of death and of permanent neurological disabilities worldwide. Therapeutic hypothermia(TH) started within 6 hours of life and maintained for 72 hours is now well established as standard treatment for infants with moderate-to-severe hypoxicischemic encephalopathy(HIE).
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China(81102154)the Medical Scientifi c Research Foundation of Guangdong Province,China(B2012322 and A2013598)+1 种基金Shenzhen Scheme of Science and Technology(Medicine and Health)(201202086 and 201302148)a Shenzhen Special Fund Project on Strategic Emerging Industry Development of China(JCYJ20130329103949650)
文摘Alzheimer＇s disease （AD） is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid （CSF） biomarkers （β-amyloid, total tau, and hyperphosphorylated tau）. Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.
文摘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.
文摘Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.
基金supported by the National Basic Research Development Programof Ministry of Science and Technology of China (2016YFC1306401)the National Natural Science Foundation of China (91749206)。
文摘To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with sAD.Then,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic risk.Receiver operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset.We measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the PRSs.We found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our cohort.The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at onset.Furthermore,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and P-tau.Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD.As genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
基金National Natural Science Foundation of China(Grant No.81773865)the National Key R&D Program of China(Grant No.2018YFC1704500,2018YFC1704506)。
文摘Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.
文摘Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnosis is not possible.Thus,an early diagnosis and identification of AD patients is critical for promising,early pharmacological interventions as well as addressing health care needs.The most advanced and most reliable markers areβ-amyloid,total tau and phosphorylated tau in cerebrospinal fluid(CSF).In blood,no single biomarker has been identified despite an intense search over the last decade.The most promising approaches consist of a combination of several bloodbased markers increasing the reliability,sensitivity and specificity of the AD diagnosis.However,contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult.In this review,we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.
文摘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.
