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.

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.

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.

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.

Diagnosis of disease-specific proteins in cerebrospinal fluid of children infected with tuberculous meningitis

BACKGROUND： Isolated mycobacterium tuberculosis from cerebrospinal fluid （CSF） is regarded as the ＂gold standard＂ for diagnosis of tuberculous meningitis （TBM）. However, culture of CSF specimens is time-consuming and lacks sensitivity. There is a strong need to determine complementary disease-specific markers, which are essential for increasing early diagnosis and improving prognosis in patients with TBM OBJECTIVE： To establish proteomic profiles of CSF in TBM and normal children using two-dimensional polyacrylamide gel electrophoresis, and to screen for disease-specific proteins. DESIGN, TIME AND SETTING： The case-control study was conducted at the Department of Pediatrics, Xiangya Hospital of Central South University and the Key Laboratory of Cancer Proteomics of Ministry of Public Health of China between January 2008 and January 2009. PARTICIPANTS： The TBM group included three patients with a strongly positive tuberculin skin test, as well as positive CSF mycobacterial staining and culture, who were admitted to the Department of Pediatrics, Xiangya Hospital from January 2008 to January 2009. Three healthy, age- and gender-matched children served as the control group. METHODS： CSF proteins were separated using two-dimensional polyacrylamide gel electrophoresis in both groups. Gels were scanned using Image scanner and LabScan software. Differentially expressed proteins were analyzed using PDQuest 7.0 software. The clearly discernible spots, which were expressed only in the TBM group, were chosen to perform matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. MAIN OUTCOME MEASURES： Differentially expressed spots on CSF profiles of TBM and normal children were measured. RESULTS： Following comparison of two-dimensional polyacrylamide gel electrophoresis maps between TBM and control groups, 546 and 533 spots were detected, respectively. A total of 64 differentially expressed proteins were observed between the groups, including 15 upregulated spots, eight downregulated spots, 27 spots that were exclusively expressed in the TBM group, and 14 spots that were exclusively expressed in the control group. At total of 20 spots that were exclusively expressed in the TBM group were chosen for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and 20 peptide mass fingerprints were obtained. After searching the data base, 16 proteins were matched. CONCLUSION： Two-dimensional polyacrylamide gel electrophoresis profiles of the CSF proteome were successfully established in the TBM and normal children. Parts of these differentially expressed proteins were identified through mass spectrometry and bioinformatics. Results indicated that apolipoprotein A I, anti-tumor necrosis factor-alpha antibody, crystal structure of MRP14 and HLA class II histocompatibility antigen DRB1-4 could be closely correlated with TBM pathogenesis.

Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients

In this study, the levels of soluble delta-like ligand 1 in cerebmspinal fluid and serum of 50 patients with tuberculous meningitis, 30 patients with viral meningitis, 20 patients with purulent meningitis and 40 subjects without central nervous system disease were determined using an enzyme-linked immunosorbent assay. The mean levels of soluble delta-like ligand 1 in both cerebrospinal fluid and serum from patients with tuberculous meningitis were significantly higher compared with those from patients with viral meningitis or purulent meningitis or from subjects without central nervous system disease. Meanwhile, the level of soluble delta-like ligand 1 gradually decreased as tuberculous meningitis patients recovered. If patients deteriorated after treatment, the level of soluble delta-like ligand 1 in cerebrospinal fluid gradually increased. There was no correlation between the level of soluble delta-like ligand 1 and the protein level/cell number in cerebrospinal fluid. Our findings indicate that the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum are reliable markers for the diagnosis of tuberculous meningitis and for monitoring treatment progress. At the same time, this index is not influenced by protein levels or cell numbers in cerebrospinal fluid.

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.

Cerebrospinal fluid analysis,predictors of bacterial meningitis:a study in 312 patients with suspected meningial infection

Objective:Patients with cerebrospinal fluid(CSF)pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics,although few have bacterial meningitis(BM).The aim of this study was to evaluate predictors to differentiate BM from aseptic meningitis(ASM).Methods:The study was conducted in Razi hospital,a training center affiliated to Ahvaz Joundishapoor University of Medical Sciences in Iran.and all patients were 18 years old or above and were treated in the hospital between 2003 and 2007.Data of those who had meningitis,tested as CSF pleocytosis but had not received antibiotic treatment before lumbar puncture were retrospectively analyzed.Results:Among 312 patients with CSF pleocytosis,two hundred fifteen(68.9%)had BM and ninety seven(31.1%)had ASM.The mean age for patients with BM was(34.7±17.7)years(P=0.22,NS).Sixty percent of the BM cases and 61.2% of the ASM cases occurred in men(P=0.70,NS).We identified the following predictors of BM:CSF-WBC count>100 per micro liter,CSF-glucose level<40 mg/dL,CSF-protein level>80 mg/dL.Sensitivity,specificity,PPV,NPV of these predictors,and LR for BM are 86.5%,52.6%,80.2%,63.7% and 104.1 for CSF-WBC count and 72.1%,83.5%,90.6%,57.4% and 164.2% for CSF glucose,and 49.7%,91.8%,93.4%,45.2% and 104.5% for CSF protein.Conclusion:The CSF WBC count should not be used alone to rule out bacterial meningitis.When it is combined with other factors such as CSF glucose and protein improved decision making in patients with suspected BM may occur.

Effect of successive irrigation of subarachnoid cavity on body temperature and cerebrospinal fluid-related index in suppurative meningitis model dogs

BACKGROUND： At present, suppurative meningitis is mainly treated through anti-infection with antibiotics, depressing encephalic pressure with mannitol , lowering body temperature with drugs , supporting treatment, etc. However, Jt takes a long course of treatment and has poor therapeutic effect. Successive irrigation of subarachnoid cavity maybe have better effect on suppurative meningitis.OBJECTIVE： We compared the successive irrigation of subbarachnoid cavity with routine therapeutic methods to observe the effect of successive irrigation of subarachnoid cavity on the body temperature, cerebrospinal fluid pressure, the number of white blood cell and the level of protein of suppurative meningitis dogs. DESIGN： A randomized and controlled animal experiment SETTING： Institute of Neuroscience, Taihe Hospital Affiliated to Yunyang Medical College MATERIALS： Totally 17 healthy adult male Beagle dogs, of common grade, weighing 9 to 10 kg, were involved in the experiment, and raised in the 20 ℃ temperature with relative humidity of 50% for 1 week. They were randomized into 3 groups： normal group （n=5）, control group （n=5） and irrigation group （n=6）. Artificial cerebrospinal fluid was prepared according to the level of glucose and chloride of cerebrospinal fluid of normal dogs, and then it was sterilized with high pressure. METHODS ： This experiment was carried out in the experimental animal center of Yunyang Medical College from April to August 2001. ① After the dogs were anesthetized,1 mL fresh staphylococcus aureus liquid [（1.5-1.6）× 10^9 L 1] was injected into medullary cistern to establish suppurative meningitis models. ② After models were successfully established, intravenous drip infusion of 1.2 ×10^6 U/（kg.d）, muscular injection of sulfadiazine sodium of 100 mg/（kg.d ）and intravenous injection of 200 g/L mannitol of 5 g/（kg .time） for 3 times a day were performed in the control group. The irrigation of subarachnoid meningitis was conducted in the irrigation group besides the routine treatments in the control group： Artificial cerebrospinal fluid was successively injected into the epidural catheter in the waist part. The mixtures of artificial cerebrospinal fluid and inflammatory cerebrospinal fluid flowed out incessantly from epidural catheter of medullary cistern. Irrigation was ended 48 hours later. Dogs were routinely raised in the control group. ③ From the first day after being modeled to the 14^th day after treatment, the rectal temperatures were daily measured in the morning, at noon and in the evening respectively, then the mean temperatures were calculated. From the 2^nd day after being modeled to the 14^th day after treatment, puncture at waist was given once, and the cerebrospinal fluid pressure, the number of white blood cells and the level of protein were measured. MAIN OUTCOME MEASURES ： The body temperature, cerebrospinal fluid pressure, the number of white blood cells and the level of protein were measured on suppurative meningitis model dogs. RESULTS＂ Totally 17 Beagle dogs were involved in this study.①The body temperatures of dogs were significantly reduced in the control group and in irrigation group on the 1^st day after treatment and lower than suppurative meningitis model dogs on the 2^nd day after being modeled （P 〈 0.05）. The body temperatures were gradually decreased in control group from the 2^nd day after being modeled to the 14^th day after treatment （P 〈 0.01）, but were significantly higher than those of dogs in normal group on the 14^th day after treatment （P 〈 0.05）. The body temperatures of dogs were gradually decreased in irrigation group on the 2^nd day or 3^rd day after treatment （P 〈 0.01） and then were close to the normal body temperature on the 14^th day after treatment. ②There was the same cerebrospinal fluid pressure in control group as in irrigation group on the 2^nd day after being modeled （P 〉 0.05）, but significantly decreased in two groups from the 1s＇ day or 2^nd day after treatment （P 〈 0.01）, and cerebrospinal fluid pressure was close to the normal level in irrigation group. Although the cerebrospinal fluid pressure raised a little on the 3^rd day or 4^th day after treatment in the irrigation group （P〈 0.05）, but recovered to the normal level on the 9^th day after treatment again. It decreased slowly in the control group and still was sig- nificantly higher than normal group on the 14^hd day after treatment （P〈 0.01 ）. ③No significant difference existed in number of white blood cell and the level of protein between control group and irrigation group on the 2^nd day following modeled. Both of them began to significantly decrease on the 1^st and 2^nd day after treatment （P 〈 0.01 ）. Although the number of white blood cell and the level of protein rebounded a little in irrigation group 3 or 4 days after treatment （P〈 0.05）, they were gradually decreased and recovered to normal levels on the 13^th day after treatment. The number of white blood cell and the level of protein slowly decreased in the control group compared with irrigation group and were still significantly higher than normal group on the 14^th day （P〈 0.01 ）. EONELUSEON ： Irrigation of subarachnoid cavity can decrease the body temperature, cerebrospinal fluid pressure, the number of white blood cells and the level of protein at early stage of suppurative meningitis, and the therapeutic effect is better than that of routine treatment.

The characteristics of cerebrospinal fluid tumor microenvironment in a patient with leptomeningeal metastases from cancer of unknown primary

Cancer of unknown primary(CUP)is a rare disease characterized by metastases in which the primary tumor is of unknown origin.The cerebrospinal fluid(CSF)tumor microenvironment of CUP is still unknown.A Chinese male was diagnosed with leptomeningeal metastases from CUP(CUP-LM)based on the following medical examination results:partial leptomeningeal enhancement by brain magnetic resonance imaging,few malignant cells of diverse morphology in CSF,and no abnormalities or lymphadenopathy by systemic examination.

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.

Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome

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.

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.

Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

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.

Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy

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.

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 blood biomarkers in Alzheimer’s disease

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.