Biochemical Analysis Of Cerebrospinal Fluid Research Articles

Biochimie du liquide cérébrospinal

AbstractBasic biochemical analysis of cerebrospinal fluid (CSF) is limited to the dosages of proteins (proteinorrhachia) and glucose (glycorrhachia), always completed with cytological and bacteriological examination of CSF and with notation of its aspect. They form the basic examination of CSF for the diagnosis of infectious meningitidis or sub-arachnoid haemorrhage. A number of other biochemical analyses were developed with electrophoresis, the study of immunoglobulins, and application of index for transudation or intrathecal synthesis, also isoelectric focalisation searching for oligoclonal bands characteristic of multiple sclerosis as well as the development of biomarkers of inflammatory neurological diseases and in particular neurodegenerative diseases. Tau and phosphorylated-tau proteins help in the differential diagnosis of Alzheimer’s disease. The elevation of angiotensin-converting enzyme activity in CSF helps in the diagnosis of neurosarcoidosis. Neurotransmitters allow the study of paediatric neurological diseases with abnormal movements.

The 500th case: pain in both hip joints, headache, and diplopia

A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.

Lipocalin-type Prostaglandin D Synthase Concentration Gradients in the Cerebrospinal Fluid in Normal-tension Glaucoma Patients with Optic Nerve Sheath Compartmentation.

ObjectiveTo report on the lipocalin-type prostaglandin D synthase (L-PGDS) concentrations in the cerebrospinal fluid (CSF) of the perioptic and lumbar subarachnoid space (SAS) in patients with radiologically proven optic nerve (ON) sheath compartmentation presenting as normal-tension glaucoma (NTG).MethodsRetrospective biochemical analysis of CSF in thirteen patients with ON sheath compartmentation presenting as NTG (four females, mean age 70±8 years). CSF was sampled from the SAS of the ON during ON sheath fenestration for ON sheath compartmentation and from the lumbar SAS at the time of lumbar puncture. Nephelometry was used for the quantification of L-PGDS and albumin concentration. Albumin was measured in order to assess the amount of contamination with serum in the CSF samples taken from the ON SAS. Main outcome measures were L-PGDS concentrations in the CSF of the perioptic and lumbar SAS.ResultsMean L-PGDS concentration was 24±8 mg/L in the lumbar SAS compared to 33±27 mg/L without correction of serum contamination and 45±39 mg/L after correction of serum contamination in the perioptic SAS. The difference between the lumbar and the perioptic SAS was statistically significant (P=0.0047 without correction of serum contamination, P=0.0002 with correction of serum contamination; Mann–Witney U-test).ConclusionThis study demonstrates a concentration gradient of L-PGDS levels within the CSF with a statistically significant higher concentration in the compartmentalized perioptic SAS compared to that in the lumbar SAS. Biochemical changes in the perioptic SAS might be involved in the pathophysiology in NTG patients with ON sheath compartmentation.

Clinical, molecular, and biochemical delineation of asparagine synthetase deficiency in Saudi cohort

PurposeAsparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease. Patients may not demonstrate low asparagine levels, which highlights the advantage of molecular over biochemical testing in the initial work-up of ASNSD. We aimed to further delineate the ASNSD variant and phenotypic spectrum and determine the value of biochemical testing as a frontline investigation in ASNSD. MethodsWe retrospectively collected the clinical and molecular information on 13 families with ASNSD from the major metabolic clinics in Saudi Arabia. ResultsThe major phenotypes included congenital microcephaly (100%), facial dysmorphism (100%), global developmental delay (100%), brain abnormalities (100%), spasticity (86%), and infantile-onset seizures (93%). Additional unreported phenotypes included umbilical hernia, osteopenia, eczema, lung hypoplasia, and hearing loss. Overall, seven homozygous variants accounted for ASNSD. The p.Tyr398Cys and p.Asn75Ile variants accounted for 54% of the cases. The clinical sensitivity and specificity of the proposed biochemical analysis of cerebrospinal fluid (CSF) for the detection of patients with ASNSD were 83% and 98%, respectively. ConclusionOur study describes the largest reported ASNSD cohort with clinical, molecular, and biochemical characterization. Taking into consideration the suboptimal sensitivity of biochemical screening, the delineation of the phenotype variant spectrum is of diagnostic utility for accurate diagnosis, prognosis, counseling, and carrier screening.

A novel, robust method for quantification of multiple kynurenine pathway metabolites in the cerebrospinal fluid.

Aim:Kynurenine metabolites are potential modulators of psychiatric disease. We aimed to develop a highly sensitive biochemical analysis of cerebrospinal fluid (CSF) tryptophan (TRP) metabolites, to investigate the stability of metabolites and to confirm our previous findings of aberrant CSF quinolinic acid (QUIN) and picolinic acid (PIC) in suicide attempters using this method.Methodology & results:Ten CSF TRP metabolites were analyzed with ultraperformance LC–MS/MS. The method showed small intra- and interassay variation. Metabolites were stable following freeze–thaw cycles. A decreased CSF PIC/QUIN ratio was found in suicide attempters.Conclusion:The feasibility of reliably determining CSF TRP metabolites were demonstrated, including separation of the two isomers PIC and nicotinic acid (NA) and the finding of a reduced PIC/QUIN ratio replicated in suicide attempters.

New Insights in the Mechanisms of Impaired Redox Signaling and its Interplay With Inflammation and Immunity in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination and axonal damage and resulting in a range of physical, mental or even psychiatric symptoms. Key role of oxidative stress (OS) in the pathogenesis of MS has been suggested, as indicated by the biochemical analysis of cerebrospinal fluid and blood samples, tissue homogenates, and animal models of multiple sclerosis. OS causes demyelination and neurodegeneration directly, by oxidation of lipids, proteins and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. In this review, we discuss the interrelated mechanisms of the impaired redox signaling, of which the most important are inflammation-induced production of free radicals by activated immune cells and growth factors, release of iron from myelin sheath during demyelination and mitochondrial dysfunction and consequent energy failure and impaired oxidative phosphorylation. Review also provides an overview of the interplay between inflammation, immunity and OS in MS. Finally, this review also points out new potential targets in MS regarding attenuation of OS and inflammatory response in MS.

Rett Syndrome: Search for Prognostic Factors

Rett (RTT) syndrome is primarily a disorder of synaptic plasticity. The maturation of neurons is blocked resulting arrest of brain growth. Clinical signs of excitatory activity occur in early age but reduced in later childhood. Correcting this imbalance may be reflected in molecular changes. Our aim was to find prognostic factors using combination of clinical examination, neuroradiological and biochemical analysis of cerebrospinal fluid (CSF). The evaluation of 15 children with RTT included careful clinical examination, measurement of serum- and CSF-insulin-like growth factor-1 and -nerve growth factor, CSF-glutamate, - adrenocorticotropin (ACTH) and -acetyltransferase, genetic analysis, and single photon computed tomography (SPECT) studies. Predictive data for poor outcome of six children were early onset of clinical signs, early deceleration of head growth, and hypometabolism in SPECT images corresponding low CSFNGF found in patients with RTT. These signs correlated with severity of later gross motor signs (no gait). Favorable outcomes were seen in nine children with late onset of the clinical symptoms and late deceleration of head growth. Two of these patients had the highest CSF-acetylcholinesterase and mutation R294X, and five had R306C mutation. ACTH/glutamate-ratio was significantly higher in the early onset-group compared to the late onset-group. This might mean an attempt to restore the balance between excitatory and inhibitory transmission. In conclusion, the clinical signs and hypo-perfusion in SPECT were the most predictive outcome measures. Our findings might be valuable because they impact the understanding of mechanisms of RTT and the potential to discovery of biological markers for proper diagnosis and treatment.

Performance of lactate in discriminating bacterial meningitis from enteroviral meningitis

ABSTRACTThe cytological and biochemical examination of cerebrospinal fluid (CSF) has been used for the presumed diagnosis of bacterial meningitis until the final microbiological results are achieved. We assessed the ability of CSF lactate in comparison with other CSF parameters to discriminate bacterial and enteroviral community acquired meningitis. We included 1,187 CSF samples of acute community-acquired meningitis, being 662 cases of bacterial and 525 of enteroviral meningitis. Lactate concentration (mg/dL), leukocyte count/mm3, protein (mg/dL), and glucose (mg/dL) were compared between bacterial and viral meningitis. Receiver operator characteristic (ROC) curves were used to assess diagnostic performance. CSF leukocytes, CSF protein and CSF lactate were significantly higher in bacterial meningitis cases (P<0.0001). CSF glucose was significantly lower in bacterial meningitis cases (P<0.0001). CSF lactate showed the best predictive ability with an area under the curve of 0.944 (95% CI 0.929 – 0.959). Considering a cut off of CSF lactate of 30 mg/dL, the sensitivity and specificity for bacterial meningitis were 84.1% and 99%, respectively. In the cytological and biochemical CSF analysis, CSF lactate was the most accurate marker for bacterial meningitis.

Importance of CSF lactate concentration in the diagnosis of acute bacterial meningitis

Editor – We read with interest the recent Clinical Medicine review by Griffiths et al [1][1] on management of acute meningitis, but were disappointed to note that there was no reference to the importance of biochemical analysis of cerebrospinal fluid (CSF) lactate concentration in the diagnosis of

Clinical profile of pediatric neurotuberculosis patients at a tertiary care center of Western India

Aim: The aim of this study is to determine the clinical profile of neurotuberculosis in the age group of 6 months to 10 years and its association with biochemical analysis of cerebrospinal fluid (CSF) and neuroradiological findings. Methods: Retrospective assessment of the medical records of confirmed cases of neurotuberculosis from January 2010 to June 2014 was carried out. Results: Of the 46 cases studied, mean age at presentation was 3.4 years. Male-to-female ratio was 1.55:1. Fever, vomiting, headache, seizures, and focal neurological deficits were the most common presenting clinical symptoms. Protein–energy malnutrition (PEM) was detected in 39 cases. On systemic examination, the order of involvement of cranial nerves was VII, II, III, IV, VI, and V. Positive Mantoux test was present in only 11 cases. CSF findings showed lymphocytic predominance, raised protein levels with a decreased to normal glucose levels. Neuroimaging by computed tomography scan/magnetic resonance imaging of the brain gave a definite diagnosis in thirty cases of which hydrocephalus, basal exudates, tuberculoma, and infarctions were the most common findings. The primary focus of tuberculosis was found in the lungs on chest roentgenogram in 12 cases. Conclusions: Neurotuberculosis occurs with increased frequency in the age group of 1–5 years. Fever may be of short duration at presentation in contradiction to current medical literature. PEM is a predisposing factor for the development of the disease. A tuberculin sensitivity test may be negative in cases of neurotuberculosis. CSF analysis and neuroimaging are pivotal in the establishment of a diagnosis.

Biochemical analysis of cerebrospinal fluid in healthy and neurological affected dromedary camels (Camelus dromedarius)

Biochemical analysis of cerebrospinal fluid in healthy and neurological affected dromedary camels (Camelus dromedarius)

Prior treatment with non anti-TB antibiotics, and the duration of symptoms have no effect on diagnostics of tuberculous meningitis

PurposeOur objective was to investigate whether diagnosis of tuberculous meningitis (TBM) with microbiological and molecular analysis was affected by prior empirical non anti tuberculosis antibiotics or by duration of symptoms before lumbar puncture. Materials and methodsWe retrospectively evaluated medical records of patients with TBM confirmed by positive culture, nucleic acid amplification techniques (NAATs) or Ehrlich–Ziehl–Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) or by characteristic results of biochemical analysis of CSF combined with a typical clinical manifestation. Results68 adult patients were analyzed. The isolation rates for NAATs, Lowenstein–Jensen (LJ) culture, BACTEC and EZNs were 70.6%, 69.1%, 67.6% and 26.5%, respectively. Biochemical analysis of CSF samples revealed: pleocytosis (median 224 [range 78–380]cells/mm3) with lymphocyte predominance (76 [45–90]%), elevated levels of protein (2.43 [1.50–3.84]g/l) and lactic acid (5.0 [3.9–7.2]mmol/l). Forty (65%) patients received no anti-tuberculosis antibiotic treatment before the diagnostic lumbar puncture. The were no significant differences in the microbiological and biochemical CSF analyses, between the patients who received and those who did not receive non anti-TB empirical antibiotic treatment. The median duration of symptoms before the diagnostic lumbar puncture was 24 (range 11–61) days. No significant differences in microbiological and biochemical analysis of CSF where found when comparing patients with duration of symptoms lasting above and less than the median time. ConclusionsNeither prior non anti-TB antibiotic therapy, nor the duration of symptoms before diagnostic lumbar puncture have any effect on confirmation of TBM by microbiological and biochemical CSF analysis.

Biochemical analysis of cerebrospinal fluid in the laboratories of deployed medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?

IntroductionDuring military deployment, the diagnosis and the management of acute bacterial meningitis can be problematic, as deployed Medical Treatment Facilities (MTFs) often have a limited laboratory diagnostic capability. However, French...

Levels of selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in patients with hydrocephalus.

<i>Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) absorption and treated by surgical shunt insertion. The early diagnosis of NPH is difficult because of various manifestations of the disease. One of the most promising research directions is biochemical CSF analysis. The aim of this study was to determine the CSF levels of cytokines. The levels of various cytokines (IL-6, IL-8, IL-12, IL-10 and TNF-α) were measured in patients with idiopathic active normal pressure hydrocephalus, arrested hydrocephalus and hydrocephalus with brain atrophy compared to controls. Our study showed that the concentrations of IL-6 and IL-8 were significantly elevated in the group with idiopathic active hydrocephalus compared to control patients. Moreover, we observed that the levels of IL-6 and IL-8 in the group with idiopathic active hydrocephalus were significantly higher compared to patients with arrested hydrocephalus and hydrocephalus with brain atrophy.</i>.

Accuracy of universal polymerase chain reaction (PCR) for detection of bacterial meningitis among suspected patients

IntroductionCentral nervous system (CNS) infections are life-threatening diseases caused by viral, bacterial, parasitic and fungal microorganisms. The aim of this study was to determine the accuracy of universal polymerase chain reaction (PCR) for the detection of bacterial meningitis among patients who were referred to Koodakan Hospital in Bandar Abbas because they were suspected of having the disease.MethodsThis study was conducted in 2013 on the patients who were admitted to Bandar Abbas’ Koodakan Hospital because they were suspected of having meningitis. A questionnaire, including demographic data, was completed for each patient. Universal PCR, Cerebrospinal fluid (CSF) analysis, and gram staining and cultures were done for all the patients. The data were analyzed using SPSS software.ResultsAmong the 100 patients studied 59 (59%) were male and 41 (41%) were female. No patient in our study had a positive smear and culture for meningitis. Among the patients with negative smears and cultures six (6%) had positive universal PCR, and 94 (94%) had negative universal PCR. Based on these results, PCR had 95% specificity and 100% negative predictive value for the prediction of meningitis. In 30 patients (30%), the biochemical analysis of CSF were in favor of meningitis. Among the 30 patients, six patients (20%) had positive universal PCR and 24 patients (80%) had negative universal PCR.ConclusionBased on our results, the universal PCR test is useful in the diagnosis of bacterial meningitis in children. We recommend using it in combination with other tests, such as CSF analysis, for diagnosis of bacterial meningitis.

Research Symposium Showcases Great Minds, Great Science

Research Symposium Showcases Great Minds, Great Science

Tuberculous meningitis in Denmark: a review of 50 cases

BackgroundTuberculous meningitis is the most severe manifestation of extrapulmonary tuberculosis with a high mortality rate and a high rate of sequelae among survivors. The aim of this study is to assess the current epidemiology, clinical features, diagnostic procedures, treatment and outcome in patients with tuberculous meningitis in Denmark, a country with a low tuberculosis incidence.MethodsA nationwide retrospective study was conducted, comprising all patients notified with tuberculous meningitis (TBM) in Denmark from 2000-2008. Medical records were reviewed using a standardised protocol.ResultsFifty patients, including 12 paediatric patients, were identified. 78% of the patients were immigrants from countries of high tuberculosis endemicity. 64% of all patients had a pre-existing immunosuppressive condition; 10% were HIV positive, 48% were HIV seronegative and 42% had an unknown HIV status. Median symptom duration before admission was 14 days in the Danish patient population and 20 days in the immigrant group. Biochemical analysis of cerebrospinal fluid (CSF) samples revealed pleocytosis in 90% with lymphocyte predominance in 66%. Protein levels were elevated in 86%. The most common findings on neuro-radiological imaging were basal meningeal enhancement, tuberculomas and hydrocephalus. Lumbar puncture was performed on 42 patients; 31 of these specimens (74%) had a positive CSF culture for mycobacteria and 9.5% were smear positive for acid-fast bacilli. The overall mortality rate was 19% and 48% of the remaining patients had neurological sequelae of varying degree.ConclusionTBM is a rare but severe manifestation of extrapulmonary TB in Denmark. The clinician must be prepared to treat empirically if the suspicion of TBM has arisen to improve treatment outcome.

Diagnosis and biomarkers of predementia in Alzheimer's disease.

In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.

Cerebrospinal fluid: the role of biochemical analysis

Biochemical analysis of cerebrospinal fluid may provide answers to important clinical questions. This review summarizes these questions and outlines the value and limitations of cerebrospinal fluid analysis.

Acquired choroidal folds: a sign of idiopathic intracranial hypertension

Choroidal folds may be caused by several underlying ocular and orbital diseases; they are classified as idiopathic when no obvious cause is found. The objective of this study was to determine whether acquired choroidal folds are associated with idiopathic intracranial hypertension. In this observational case series, three patients with normal fundus examination later developed choroidal folds. They underwent complete ocular examination, B-scan ultrasonography, fluorescein angiography, optic coherent tomography (OCT) and magnetic resonance imaging. A neurological consultation, lumbar puncture and measurement of opening pressure of cerebrospinal fluid (CSF) were also obtained for all patients. Three patients with previously normal ocular fundus developed choroidal folds, and optic nerve subarachnoid space enlargement was seen on B-scan. Clinical and radiological evaluations identified elevation of intracranial pressure, and biochemical analysis of CSF was normal, suggesting a diagnosis of pseudotumour cerebri, which was later confirmed. The first patient developed choroidal folds in one eye first, and 4 years later in the fellow eye. The second patient presented with bilateral optic disk swelling secondary to intracranial hypertension. After treatment, which lowered CSF pressure, bilateral choroidal folds were identified by OCT, fluorescein angiography and ocular fundus photograph. The third patient also developed choroidal folds in one eye, but his fellow eye was difficult to evaluate due to a chorioretinitis scar on the macula. OCT identified choroidal folds in all three patients and in the second patient, it also revealed retinal nerve fiber layer damage. Acquired choroidal folds and optic nerve subarachnoid space enlargement may be signs of idiopathic intracranial pressure elevation. Nevertheless, this diagnosis should be confirmed by lumbar puncture. Comprehensive imaging studies should be performed to rule out expanding tumors. The lower CSF pressure in our first two patients suggests that choroidal folds or optic disk swelling may depend on the level of intracranial pressure and may be points in a continuum of clinical presentations.