Cerebrospinal Fluid Biochemistry Research Articles

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase

Glutamine synthetase (GS), encoded by GLUL, catalyzes the conversion of glutamate to glutamine. GS is pivotal for the generation of the neurotransmitters glutamate and gamma-aminobutyric acid and is the primary mechanism of ammonia detoxification in the brain. GS levels are regulated post-translationally by an N-terminal degron that enables the ubiquitin-mediated degradation of GS in a glutamine-induced manner. GS deficiency in humans is known to lead to neurological defects and death in infancy, yet how dysregulation of the degron-mediated control of GS levels might affect neurodevelopment is unknown. We ascertained nine individuals with severe developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry with de novo variants in GLUL. Seven out of nine were start-loss variants and two out of nine disrupted 5' UTR splicing resulting in splice exclusion of the initiation codon. Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif, resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine. Analysis of human single-cell transcriptomes demonstrated that GLUL is widely expressed in neuro- and glial-progenitor cells and mature astrocytes but not in post-mitotic neurons. One individual with a start-loss GLUL variant demonstrated periventricular nodular heterotopia, a neuronal migration disorder, yet overexpression of stabilized GS in mice using in utero electroporation demonstrated no migratory deficits. These findings underline the importance of tight regulation of glutamine metabolism during neurodevelopment in humans.

Where to Draw Cerebrospinal Fluid from an External Ventricular Drain? Comparison of Cerebrospinal Fluid Parameters between Two Different Collection Sites

Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag.

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

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. To assess the efficacy of cerebrospinal fluid (CSF) lactate in diagnosing meningitis in critically ill patients. 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. 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. 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.

Evaluation of Magnetic Resonance Findings of Circumventricular Organs in Idiopathic Intracranial Hypertension Patients.

Idiopathic intracranial hypertension (IIH) is the increased pressure with normal cerebrospinal fluid (CSF) composition, not due to a secondary cause. However, the need for lumbar puncture, an invasive method in diagnosis, leads to research on noninvasive diagnostic methods. This study aims to examine the role of the size of the pituitary gland and the previously unevaluated pineal glandin radiological diagnosis in patients with IIH. The study retrospectively included 57 patients aged 18-80 years, who were followed up in our clinic with the diagnosis of IIH, and 52 control patients without central nervous system disease and cranial MR pathology. CSF pressure measurement values, CSF biochemistry, and cytology examinations were recorded as a result of lumbar puncture performed in the lateral decubitus position of all patients. In addition, the pineal gland and pituitary dimensions were measured by a neuroradiologist on cranial MR imaging of both groups. Pituitary gland height, anteroposterior (AP), and transverse dimensions were found to be significantly lower in the IIH patient group than in the control group (p<0.05). There were a significant reduction in pineal gland AP and height measurements in the IIH patient group compared to the control group. Still, we found no significant difference between the two groups in transverse measurements (p>0.05). Our findings suggest that measurement of pituitary and pineal gland sizes in neuroimaging may be a guide as a noninvasive method in diagnosing and treating IIH.

Investigation of Methods and Influencing Factors to Increase the Positive Rate of Cytological Pathology of Cerebrospinal Fluid from Lung Cancer Leptomeningeal Metastases

In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM. The fixation treatment of cerebrospinal fluid samples has a significant impact on the positive cytology detection rate, and how to improve the positive cytopathology detection rate of cerebrospinal fluid is a hot topic in clinical research. From June 2019 to November 2021, 105 cases diagnosed with LM based on clinical symptoms and positive imaging were collected and retrospectively evaluated in the second ward of the Department of Oncology of The Second Affiliated Hospital of Harbin Medical University. The effect of different fixation methods on the positive rate of cerebrospinal fluid cytopathology was investigated, and specimens of cerebrospinal fluid were collected and sent for examination using different delivery methods, including the application of the TIB cell preservation solution kit (experimental group) and the routine application of sterile plastic tubes in lumbar puncture bags (control group). Biochemical assays (glucose and total protein) were performed on the cerebrospinal fluid fluid, and Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the supplementary diagnostic value for LM patients with lung cancer. The relevance of chemical indexes in the assessment of therapeutic efficacy was examined, and biochemical (glucose, total protein) indices and cytological changes in cerebrospinal fluid fluid after pemetrexed intrathecal injection therapy were dynamically monitored. In the control group, 24 (45.28%) patients were positive for the first time, while 42 (80.77%) patients were positive for the first time and 10 (19.23%) patients were negative for the first time in the experimental group. Significant differences existed between the two groups (P<0.001). The results of Logistic regression analysis of patients with the first cerebrospinal fluid biochemical test showed that the risk of positive cerebrospinal fluid biochemical pathology with less than 2.5 mmol/L was 2.456 times greater than 2.5 mmol/L of cerebrospinal fluid glucose (OR=2.456, P<0.05), and total cerebrospinal fluid biochemical protein greater than 430 mg/L was 2.647 times less than 430 mg/L (OR=2.647, P>0.05). The ROC curve showed glucose sensitivity of 76.9% in cerebrospinal fluid, the specificity of 54.5%, Youden index of 0.315 and area under the curve (AUC) of 0.620, total protein sensitivity in cerebrospinal fluid of 44.4%, 90.6%, Youden index of 0.350 and AUC of 0.671. After 2 cycles of pemetrexed intrathecal treatment with complete cerebrospinal fluid cytology and cerebrospinal fluid biochemical (glucose, total protein) tests in 73 and 50 patients, respectively, the rate of cerebrospinal fluid cytology turning negative was gradually increased. Cerebrospinal fluid glucose levels increased after 2 cycles of treatment compared with the first time, with a statistically significant difference (P<0.001). The use of a cell preservation solution kit to immediately fix cerebrospinal fluid samples following isolation in patients with clinical symptoms and positive imaging greatly enhances the rate of positive cerebrospinal fluid cytology detection. The effect of treatment can be assessed and predicted by continuous dynamic monitoring of cerebrospinal fluid biochemistry and cytology.

Varicella zoster virus: an under-recognised cause of central nervous system infections?

Varicella zoster virus (VZV) causes infections of the central nervous system (CNS) manifesting as meningitis or encephalitis. It is not commonly tested in CNS infections when compared with enterovirus (EV) and herpes simplex virus 1 (HSV-1) and 2 (HSV-2). Cerebrospinal fluid (CSF) findings of viral CNS infections are thought to be comparable. To describe the manifestations of VZV CNS infections and ascertain if there is a predominant syndrome. To compare CSF parameters of VZV with EV, HSV-1 and HSV-2. Retrospective study at two hospitals in Brisbane, reviewing medical notes and laboratory information system for results between January 2001 and 2019. The following parameters were recorded - disease classification, presence of rash, duration of symptoms prior to hospitalisation, length of admission, duration of antiviral treatment and 30-day mortality. CSF biochemistry, cell count (differential), PCR for VZV, EV, HSV-1 and HSV-2 were recorded. Statistical analysis of CSF parameters included Student's t-test and linear regression. Incidence of meningitis was comparable to encephalitis (44 vs 39%) in 52 cases. CSF protein in VZV was significantly elevated compared with EV (median 1121 vs 569 mg/L; P < 0.001) as was CSF monocytosis (96% vs 61%; P < 0.001). CSF parameters between VZV, HSV-1 and HSV-2 were similar. VZV had a higher incidence than HSV-1 or 2, while it was tested one-third as often. VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected.

Predictive Value of Cerebrospinal Fluid Lactate Level for the Diagnosis of Bacterial Meningitis following Cranial Surgery

Background:To distinguish post-neurosurgical bacterial meningitis (PNBM) from aseptic meningitis is difficult. Inflammatory and biochemical cerebrospinal fluid (CSF) changes mimic those classically observed after CNS surgery. CSF lactate assay has therefore been proposed as a useful PNBM marker. Objective:To determine the value of cerebrospinal fluid (CSF) lactate level for the identification of bacterial meningitis following cranial surgery. Methods:Between January 2016 and December 2016, a prospective clinical study was done in Department of Neurosurgery, in which all patients with clinical suspicion of PNBM were enrolled. Patients with clinical suspicion of bacterial meningitis BM were categorized, according to preset criteria, into 3 groups: (1) proven BM; (2) presumed BM, and (3) nonbacterial meningeal syndrome. CSF markers were plotted in a receiver operating curve (ROC) to evaluate their diagnostic accuracy. Results:The study included 70 patients. We obtained 65 CSF samples from patients with clinical suspicion of BM by CSF analysis. 20 corresponded to proven BM, 7 to probable BM and 38 to excluded BM. Mean lactate in CSF was: 8.4 ±3.0 mmol /l for proven BM, 4.8 ± 0.99 mmol /l for probable BM and 2.08 ± 0.822 mmol/l for excluded BM (P &lt; .001). Conclusion: CSF lactate level has good predictive value to distinguish BM from aseptic meningitis with sensitivity of 90% and specificity: 87% at cut-off value: 4.0 mmol/l.

Idiopathic intracranial hypertension with initial presentation of optic disc edema

Abstract Introduction: Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure in young women of childbearing age. The typical symptom is headache, and the symptom of visual obscuration tends to be overlooked. So, the patients usually visit the department of neurology for headache management. Here, we report a patient with IIH who first presented with ophthalmic symptoms. Patient concerns: A 28-year-old overweight female complained of intermittent darkened vision in both eyes lasting for 2 months. She was diagnosed with papilledema at another hospital and received local and systemic application administration of neurotrophic drugs and glucocorticoids 1 month before. Because of the poor outcomes, she visited our ophthalmology clinic for further management. She had no other medical history. Diagnosis: On ophthalmic examination, bilateral optic disc edema with blurred boundary was observed. The cranial magnetic resonance imaging and blood examination showed no obvious abnormality. A lumbar puncture was performed by a neurologist, which demonstrated an opening pressure of 30 cm of water. The cerebrospinal fluid biochemistry and bacteriology results were normal. A diagnosis of IIH was made based on the above findings. Outcomes: Oral acetazolamide, weight loss therapy and local corticosteroid treatment were initiated. At 7-week follow-up, the darkened vision and optic disc edema was obviously alleviated. Conclusion: IIH is a neurologic disease, but patients with this disease may first present to ophthalmology department because of the visual symptoms, such as blurred or darkened vision, visual loss, and even diplopia. As ophthalmologists, we should screen for this disease in a timely manner when we encounter similar patients with bilateral optic edema.

The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.

Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging. To evaluate phenotype-modifying effects of genetic variants in Klotho, a longevity gene. We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL-VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinson's Progression Markers Initiative (PPMI) for validation of genetic-clinical findings. PD patients carrying the KL-VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson´s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale. Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.

Ebola: A review and focus on neurologic manifestations

Ebolavirus disease (EVD) is a severe, highly contagious, and often fatal systemic disease in human and non-human primates. Zoonotic and human-to-human transmission have been well documented. Ebolaviruses are endemic to Equatorial and West Africa and there have been over 20 outbreaks in sub-Saharan Africa since 1976. The largest known outbreak of EVD occurred between 2013 and 2016 across several West African countries. It resulted in 28,646 suspected and confirmed cases and 11,323 deaths. There are 5 species within the genus Ebolavirus with 4 of them being clinically significant. In patients with EVD, neurologic manifestations range from mild symptoms such as confusion to severe neurologic diseases such as meningitis and encephalitis. Altered mental status, from mild confusion to delirium with hallucinations, may also occur. Rare neuropsychiatric manifestations of EVD include psychological or cognitive symptoms, including short-term memory loss, insomnia, and depression or anxiety. Although Ebolavirus RNA has been detected in cerebrospinal fluid, the body of knowledge around the pathogenic mechanisms of neurological disease is not yet fully understood. Studies are needed to understand the acute and chronic neuronal pathologic as well as biochemical cerebrospinal fluid changes in Ebolavirus infection.

Estimation of cerebrospinal fluid lactate level to differentiate between pyogenic and non-pyogenic meningitis: a prospective analytical study

Background: Meningitis is one of the common causes of serious morbidity and mortality and is one of the common causes of intensive care unit (ICU) admissions. The meningitis can be broadly divided into bacterial, viral or fungal meningitis. It is important to differentiate between pyogenic and non-pyogenic meningitis because of obvious management implications. Cerebrospinal fluid (CSF) lactate levels can be used for differentiating pyogenic and non-pyogenic (viral/tubercular) meningitis.Methods: This was a prospective analytical study in which cases diagnosed to be having meningitis were included on the basis of a predefined inclusion and exclusion criteria. Demographic details such as age, gender and socioeconomic status was note in all the cases. A detailed clinical history was taken and a through clinical examination was done. Imaging (computerized tomography) was done in selected cases. CSF cytology, biochemistry and culture sensitivity were done in all cases. CSF lactate was determined in all cases.Results: The CSF cytological examination showed that the mean total cell count was more (643.23±102.02) in pyogenic meningitis as compared to non-pyogenic (viral/tubercular) meningitis (121.76±59.74) and the difference was found to be statistically highly significant (p&lt;0.0001). The analysis of CSF lactate levels showed that pyogenic meningitis cases had a significantly high level of CSF lactate as compared to non-pyogenic meningitis cases and the difference was found to be statistically highly significant (p&lt;0.0001).Conclusions: CSF lactate level is a good indicator in differentiating pyogenic and non-pyogenic meningitis.

A case of pseudotumor cerebri secondary to acute leukemia

Introduction: Idiopathic intracranial hypertension (IIH) is a rare clinical condition in which an increase in intracranial pressure is seen without a lesion in the head. The association of IIH with haematological malignencies is not well known. Case: We present 19-year-old male with frequent episodes of headache that lasted up to 24 hours, localized to the bilateral temporal region accompanied with nausea and vomiting for two months. On the neurological exam, the lateral gaze was slightly restricted. Ophthalmological exam revealed bilateral papilledema, which was more pronounced on the right. Bilateral concentric constriction, more pronounced on the right , was observed on the computerized visual field exam. Brain Magnetic Resonance Imaging (MRI) showed swelling in the optic nerve sheats, rather than on the right. In the analysis of cerebrospinal fluid (CSF), the opening pressure was 370 mmH2 Cytological examination of the CSF showed atypical lymphoid cells. The patient was diagnosed as precursor lymphoblastic leukemia/lymphoma. Conclusion: Acute leukemia–induced clinical IIH has not been reported in the literature up to now, and the present case study will contribute to the literature in this regard. This phenomenon will be noteworthy for clinicians who encounter high CSF opening pressure, abnormal CSF biochemistry, and substantial cytology in cases presenting with clinical IIH.

EVALUATION OF THE CORRELATION BETWEEN NEUTROPHIL-LYMPHOCYTE RATIOS AND BODY MASS INDEX AND CEREBROSPINAL FLUID PRESSURE IN IDIOPATHIC INTRACRANIAL HYPERTENSION

Aim: Idiopathic intracranial hypertension (IIH) is a disease with signs and symptoms of increased intracranial pressure syndrome without a structural lesion in the brain and an abnormal finding in the cerebrospinal fluid (CSF). IIH is associated with obesity and inflammation. In our study, we aimed to evaluate the correlation between neutrophil-lymphocyte ratios (NLR) and body mass index (BMI) and CSF pressure in IIH. Method: Forty-seven patients consisting of 41 (87.2%) women and 6 (12.8%) men who had headache and papilledema, a CSF opening pressure of 25 cmH2O and above, and normal CSF biochemistry and were newly diagnosed with IHH according to the modified Dandy criteria, and 47 age-and gender-matched healthy volunteers consisting of 39 (83%) women and 8 (17%) men were included in the study, and their BMI, white blood cell counts, NLR, CSF pressures and cranial MRI findings were evaluated. RESULTS: The NLR ratio was 2.3952±1.09 in the patient group and 1.9711±0.74 in the control group and was significantly higher in the patient group (p=0.02) (p=0.02). The white blood cell counts were found to be significantly higher with 7.93±1.91 in the patient group and 7.11±1.42 in the control group (p=0.02). BMI was significantly higher with 30.23±2.84 in the patient group and 26.31±3.97 in the control group (p=0.00). Although there was no correlation between NLR and CSF pressure (p=0.58), the cut-off value for NLR was calculated to be 1.95, and a significant correlation was found between the NLR values of 1.95 and above and the CSF pressure (p=0.04). A positive correlation was found between BMI and CSF pressure and NLR ( p=0.001, r= 0.79; p=0.03, r= 0.21). Conclusion: The etiopathogenesis of IIH has not been fully understood, and the existing findings are associated with obesity and related inflammation. Our results indicate that serum NLR level can be used as a marker to show inflammation in IIH and that increased inflammation may be associated with BMI and CSF pressure.

Elevation of Postmortem Cerebrospinal Fluid Sodium and Chloride Levels Is a Potential Adjunct Test in the Diagnosis of Salt Water Drowning.

Postmortem vitreous humor biochemistry is a useful test in the diagnosis of salt water drowning (SWD). A significant limitation of vitreous humor is the potential effect of prolonged immersion. A recent animal study and case report suggested that cerebrospinal fluid biochemistry may be an alternative to vitreous because it is more resistant to the effects of immersion, given its protected anatomical location. This study compared postmortem cerebrospinal fluid sodium and chloride (PMCSC) levels collected via ventricular aspiration (PMCSC_V) and via lumbar puncture (PMCSC_L) in 13 SWD and 31 nonimmersion deaths. It showed a significant elevation in PMCSC levels in SWD deaths for both PMCSC_V and PMCSC_L (P < 0.05). The areas under the curve on the receiver operating characteristic curves for PMCSC_V and PMCSC_L were 0.73 and 0.83, respectively. The optimal cutoff for PMCSC_V was 216 mmol/L (sensitivity, 0.60; specificity, 0.72; likelihood ratio, 1.80; positive predictive value, 0.45) and for PMCSC_L was 241 mmol/L (sensitivity, 0.78; specificity, 0.73; likelihood ratio, 2.89; positive predictive value, 0.46). This study supports PMCSC levels as another biochemical test that can potentially aid in the diagnosis of SWD, particularly in cases where vitreous humor samples are unavailable or uninterpretable.

Status epilepticus associated with Mycoplasma pneumoniae encephalitis in children: good prognosis following early diagnosis and treatment.

Status epilepticus associated with Mycoplasma pneumoniae encephalitis in children: good prognosis following early diagnosis and treatment.

Clinical characteristics and cerebro-spinal fluid cytokine changes in patients with acquired immunodeficiency syndrome and central nervous system infection.

Clinical characteristics and the cerebro-spinal fluid (CSF) cytokine changes in acquired immunodeficiency syndrome (AIDS) patients with tuberculous meningitis and cryptococcal meningitis in central nervous system (CNS) infections before and after treatment were investigated. The clinical records of 80 AIDS patients with CNS infections and 40 non-CNS infection patients hospitalized in the Infection Department of the First Hospital of Changsha from February 2013 to March 2016 were retrospectively analyzed. Forty-one cases of AIDS complicated with tuberculous meningitis were enrolled as group A, 39 cases of AIDS complicated with cryptococcal meningitis as group B, and 40 cases of non-CNS infection with lumbar puncture indication as group C. The general data, clinical symptoms, CSF examination and prognosis of the three groups of patients were collected. Of the 80 patients, 56 patients were discharged from hospital (improvement group) and 24 died (death group) after treatment. The concentrations of interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in CSF were detected by enzyme-linked immunosorbent assay. There were significant differences in clinical manifestations, CSF pressure, CSF leucocyte count, CSF glucose, CSF chloride and CSF protein between group A, group B and group C (P<0.05). The concentrations of IFN-γ, IL-6, IL-10 and TNF-α in CSF of group A and group B increased significantly compared with group C (P<0.001). The IL-6, IL-10 and TNF-α levels in CSF in the improvement group were significantly lower than those in the death group (P<0.001), while the concentration of IFN-γ increased significantly (P<0.001). CSF biochemistry is characterized by increased pressure, leucocyte count and protein, and decreased chloride and glucose. IFN-γ, IL-6, IL-10 and TNF-α in CSF have certain predictive value for poor prognosis of AIDS patients with CNS infection.

Validation of multiplex PCR for the diagnosis of acute bacterial meningitis in culture negative cerebrospinal fluid.

This study evaluated the operational characteristics of the multiplex polymerase chain reaction (PCR) for cerebrospinal fluid (CSF) from patients with cellular and biochemical characteristics of acute bacterial meningitis and positive or negative CSF cultures. Multiplex PCR was performed for 36 CSF samples: culture-proven acute bacterial meningitis (n = 7), culture-negative acute bacterial meningitis (n = 17), lymphocytic meningitis (n = 8), and normal CSF (n = 4). The operational characteristics of multiplex PCR were evaluated with definite and probable bacterial meningitis, using culture positive, cytological and biochemical CSF characteristics as the gold standard. Multiplex PCR for CSF was efficient in the group with CSF cellular and biochemical characteristics of acute bacterial meningitis but with a negative CSF culture. This group demonstrated high specificity, positive predictive value, and efficiency. Multiplex PCR for CSF can improve the speed and accuracy of acute bacterial meningitis diagnosis in a clinical setting as a complement to classical immunological and bacteriological assays in CSF. It is also useful for CSF culture-negative acute bacterial meningitis.

Use of vitreous and cerebrospinal fluid biochemistry to aid the diagnosis of salt water drowning: an illustrative case report

Use of vitreous and cerebrospinal fluid biochemistry to aid the diagnosis of salt water drowning: an illustrative case report

The Role of Cerebrospinal Fluid Biomarkers in the Diagnosis of Post-Neurosurgical Meningitis.

To measure cytokine and lactate levels in the cerebrospinal fluid (CSF) of patients with suspected post-neurosurgical meningitis. Interleukin (IL)-8,-12, and -13, interferon (IFN) gamma, and lactate concentrations were determined in the CSF of patients diagnosed with meningitis, who were undergoing follow-up after neurosurgical procedures at the Neurosurgery Clinic between May 2016 and November 2017. The demographic, clinical, biochemical, CSF cell count, CSF biochemistry, and CSF culture results of 119 patients were recorded. The study group consisted of 39 patients diagnosed with post-neurosurgical meningitis. The control group comprised of 80 patients without pleocytosis, who had undergone lumbar puncture due to various indications. In the study group, 59% of the patients had fever, 66.7% had deterioration in the level of consciousness, and 35.9% had neck stiffness. The levels of IL-8 (96.5 ng/L vs. 86.6 ng/L, p < 0.001), IL-12 (10.1 ng/L vs. 3 ng/L, p < 0.001), and lactate (5.9 mmol/L vs. 2.1 mmol/L, p < 0.001) were higher in the CSF of the patient group compared to the control group. However, IL-13 (32.7 ng/L vs. 42.5 ng/L, p=0.003) and IFN gamma (73.3 ng/L vs. 260.4 ng/L, p < 0.001) levels were lower in patients compared to controls. The mortality rate in post-neurosurgical meningitis patients was estimated to be 35.9%. Post-neurosurgical meningitis prolongs the duration of hospital stay and causes long-term sequelae. Therefore, measurement of CSF cytokine and lactate levels alongside meningitis diagnostic processes may facilitate early and accurate diagnosis. Measuring CSF lactate is inexpensive and cost effective, particularly in post-neurosurgical patients.

The Effect of Alpha Lipoic Acid on Cerebrospinal Fluid Biochemistry and Brain Edema After Experimental Traumatic Brain Injury.

To investigate the effect of alpha lipoic acid on cerebrospinal fluid (CSF) osmolarity and brain tissue water ratio in a rabbit model of traumatic brain injury. Using a previously established model of traumatic brain injury using liquid nitrogen, 36 New Zealand rabbits were randomized into six groups (three treatment groups, a no trauma/no treatment group, a trauma/no treatment group, and a no trauma/treatment group). The treatment groups were administered intravenous alpha lipoic acid at different times of the experiment. Cerebrospinal fluid was obtained 96 hours after injury/treatment via cisterna magna puncture; glucose, blood urea nitrogen, and sodium levels were measured and osmolarity was calculated. Brain tissue water ratio was determined using wet and dry brain weights. The therapeutic effect of alpha lipoic acid was evaluated by comparing cerebrospinal fluid osmolarity and brain tissue water ratio between study groups. Based on cerebrospinal fluid osmolarity values, alpha lipoic acid treatment effectiveness was greatest in the group that received 3 doses after trauma. Alpha lipoic acid is effictive in the treatment of brain edema after experimental traumatic brain injury.