Cerebrospinal Fluid Lactate Research Articles

Tumor metabolism and neurocognition in CNS lymphoma.

The mechanistic basis for neurocognitive deficits in central nervous system (CNS) lymphoma and other brain tumors is incompletely understood. We tested the hypothesis that tumor metabolism impairs neurotransmitter pathways and neurocognitive function. We performed serial cerebrospinal fluid (CSF) metabolomic analyses using liquid chromatography-electrospray tandem mass spectrometry to evaluate changes in the tumor microenvironment in 14 patients with recurrent CNS lymphoma, focusing on 18 metabolites involved in neurotransmission and bioenergetics. These were paired with serial mini-mental state examination (MMSE) and MRI studies for tumor volumetric analyses. Patients were analyzed in the setting of the phase I trial of lenalidomide/rituximab. Associations were assessed by Pearson and Spearman correlation coefficient. Generalized estimating equation (GEE) models were also established, adjusting for within-subject repeated measures. Of 18 metabolites, elevated CSF lactate correlated most strongly with lower MMSE score (P < 8E-8, ρ = -0.67). High lactate was associated with lower gamma-aminobutyric acid (GABA), higher glutamate/GABA ratio, and dopamine. Conversely, high succinate correlated with higher MMSE scores. Serial analysis demonstrated a reproducible, time-dependent, reciprocal correlation between changes in lactate and GABA concentrations. While high lactate and low GABA correlated with tumor contrast-enhancing volume, they correlated more significantly with lower MMSE scores than tumor volumes. We provide evidence that lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in CNS lymphomas. We identify novel metabolomic biomarkers that may be applied in future studies of neurocognition in CNS lymphomas. Elucidation of mechanistic interactions between lymphoma metabolism, neurotransmitter imbalance, and neurocognition may promote interventions that preserve cognitive function.

Elevated cerebrospinal fluid levels of beta-2-microglobulin in patients with Guillain-Barré syndrome and their correlations with clinical features.

Beta-2-microglobulin (β2-MG) levels vary in many infectious and autoimmune diseases. We investigated plasma and cerebrospinal fluid (CSF) β2-MG levels in patients with Guillain-Barré syndrome (GBS) and their correlations with clinical parameters. CSF samples from 50 patients with GBS including 19 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 10 acute motor-sensory axonal neuropathy (AMSAN), 7 Miller-Fisher syndrome (MFS), and 8 unclassified patients were collected. Moreover, 23 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 42 enrolled patients and 29 healthy individuals were also collected. The β2-MG levels were measured by immunoturbidimetry on automatic biochemical analyser. Besides, clinical data were extracted from electronic patient documentation system. CSF levels of β2-MG, lactate dehydrogenase (LDH), and lactate were significantly increased in patients with GBS (p = 0.004, p = 0.041, p = 0.040, respectively), particularly in patients with AIDP (p < 0.001, p = 0.001, p = 0.015, respectively), whereas no statistically significant difference was found in plasma levels of β2-MG. Furthermore, CSF levels of β2-MG were positively correlated with Hughes functional score (r = 0.493, p = 0.032), LDH (r = 0.796, p < 0.001), and lactate (r = 0.481, p = 0.037) but not with protein (r = - 0.090, p = 0.713) in AIDP patients. CSF β2-MG levels may help identify AIDP and indicate clinical severity. CSF LDH and lactate levels correlate with CSF β2-MG levels; interaction among these biomarkers would need further investigation.

Cerebrospinal Fluid Lactate Levels, Brain Lactate Metabolism and Neurologic Outcome in Patients with Out-of-Hospital Cardiac Arrest.

Cerebrospinal fluid (CSF) and serum lactate levels were assessed to predict poor neurologic outcome 3months after return of spontaneous circulation (ROSC). We compared arterio-CSF differences in the lactate (ACDL) levels between two neurologic outcome groups. This retrospective observational study involved out-of-hospital cardiac arrest (OHCA) survivors who had undergone target temperature management. CSF and serum samples were obtained immediately (lactate0), and at 24 (lactate24), 48 (lactate48), and 72 (lactate72) h after ROSC, and ACDL was calculated at each time point. The primary outcome was poor 3-month neurologic outcome (cerebral performance categories 3-5). Of 45 patients, 27 (60.0%) showed poor neurologic outcome. At each time point, CSF lactate levels were significantly higher in the poor neurologic outcome group than in the good neurologic outcome group (6.97 vs. 3.37, 4.20 vs. 2.10, 3.50 vs. 2.00, and 2.79 vs. 2.06, respectively; all P < 0.05). CSF lactate's prognostic performance was higher than serum lactate at each time point, and lactate24 showed the highest AUC values (0.89, 95% confidence interval, 0.75-0.97). Over time, ACDL decreased from - 1.30 (- 2.70-0.77) to - 1.70 (- 3.2 to - 0.57) in the poor neurologic outcome group and increased from - 1.22 (- 2.42-0.32) to - 0.64 (- 2.31-0.15) in the good neurologic outcome group. At each time point, CSF lactate showed better prognostic performance than serum lactate. CSF lactate24 showed the highest prognostic performance for 3-month poor neurologic outcome. Over time, ACDL decreased in the poor neurologic outcome group and increased in the good neurologic outcome group.

Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia

Background: Copper deficiency can lead to a severe myelopathy and cytopenia. The myelopathy can lead to inability to walk by paresis and deafferentation. The anemia can as well be severe with the need for blood transfusions. Beside innate reasons it occurs years after surgeries of the intestine and following disturbed resorption. It can also occur due to excessive intake of zinc that binds copper. An early diagnosis following copper substitution can lead to restitution. It can clinically be mistaken for a vitamin B12 deficiency. This circumstance can lead to a delayed treatment. Case: A 67 years old woman with severe gait disturbances, sensory ataxia was admitted to our hospital. She had the diagnosis of vitamin B12 deficiency. B12 was elevated and metabolites were in normal range. The electrophysiology showed a deafferentation of the legs. Objective: This case report provides detailed information about the course of diagnosis and the treatment of a severe copper deficiency with symptomatic myelopathy and cytopenia in an elderly woman. Methods: We performed a literature research with keywords “spinal cord disease, gait disturbances, elevated lactate in cerebrospinal fluid, anemia”. We did blood tests and CSF on a regular basis combined with clinical assessments and electrophysiology. Results: Serum copper was not detectable. CSF copper was reduced (8.7 µg/l, Ref.: 14.2-109 µg/l), CSF lactate was elevated (4.69 mmol/l, Ref.: 1.1-2.4 mmol/l). The patient had a cytopenia (Hb 6.6 g/dl, Ref.: 12-16 g/dl, MCV 130 fl, Ref.: 80-96 fl, leucocytes 2.3 10³, Ref.: 4.3-10 10³/µl). Vitamin B12 amounted to 891 pg/ml (Ref.: 191-663 pg/ml). The somatosensory evoked potential (SEP) study showed absent cortical responses after stimulation of the sural nerves bilaterally. Due to the diagnosis of a myelopathy and bone marrow dysfunction due to copper deficiency we substituted copper-histidine subcutaneously. This led to a marked improvement of symptoms, an increase of serum copper levels (141 µg/l), CSF copper levels (14.1 µg/l), hemoglobin (11.9 g/dl), leukocyte count (11.4 10³/µl) and a normalization of CSF lactate. Conclusion: Elevated CSF lactate might be an indicator for treatable myelopathy due to copper deficiency in patients with afferent gait disturbances. A timely substitution can lead to a marked improvement of even severe symptoms.

Risk Factors of Influenza-Associated Necrotizing Encephalopathy in Children

Objective: A case-control study of Influenza-Associated Necrotizing Encephalopathy (IANE) in children was conducted to explore the risk factors for the diagnosis of IANE, and to provide a predictive reference for the diagnosis of IANE. Methods: The children with IANE who received treatment in our hospital from January 2016 to December 2020 were selected as the study group, and the children with Influenza-Associated Encephalopathy (IAE) group who received treatment in the same period were selected as the control group. The blood biochemical, coagulation function and cerebrospinal fluid test results of the two groups were analyzed by univariate analysis. Receiver Operating Characteristic curve (ROC) analysis was used to determine the optimal threshold point of each index for the indicators with statistically significant differences in univariate analysis results, and multivariate Logistic stepwise regression analysis was performed according to the optimal threshold points. Results: In the IANE group, there were 32 children, including 20 males and 12 females, aged 60 (35, 84) months. There were 40 children in IAE group, including 26 males and 14 females, aged 58 (23, 97) months. Univariate results showed that serum Lactate Dehydrogenase (LDH), Cerebrospinal Fluid Lactate Dehydrogenase (CSF LDH) and Cerebrospinal Fluid Protein (CSF PRO) in the IANE group were significantly higher than those in the IAE group, and the difference between the two groups was statistically significant (P 535 U/L (OR = 31.264, 95% CI: 5.892 - 165.878, P 0.49 g/L (OR = 7.695, 95% CI: 1.052 - 56.305, P = 0.044) were independent risk factors for IANE. Conclusion: For children with influenza whose neurological symptoms appear rapidly and persist in the early stages of the disease, blood LDH > 535 U/L and CSF PRO > 0.49 g/L are independent risk factors for IANE.

Evaluation of Lactate in Differentiating Pyogenic and Non-Pyogenic Meningitis

Background : Meningitis is serious and a life-threatening condition among any age group associated with serious mortality and morbidity. The objective of the present research was to assess the efficiency of CSF lactate in differentiating bacterial/ pyogenic from non-pyogenic meningitis. Subjects and Methods: A hospital-based one-year prospective study was conducted at a tertiary care hospital in Gujarat. The study was performed at the department of General medicine for a period of one year. All the cases suspected of meningitis above 18 years of age irrespective of sex were admitted and clinically evaluated. The Diagnosis of meningitis was made on account of various clinical symptoms and signs. Like headache, nausea, presence of kernig’s sign, altered sensorium, cranial nerves palsies, hemiparesis, seizures, etc, Results: The mean total cell count was highest in cases of pyogenic meningitis with a mean of 840.50 and SD of 112.30 than viral and tubercular meningitis. However, no statistical significance was associated with total count and types of meningitis. (P&gt; 0.05) Lactate levels of the CSF were elevated than normal in both pyogenic and tubercular than viral, however, the mean CSF lactate was higher in pyogenic than tubercular. A clear statistical significance was observed in CSF sugar/blood glucose ratio and CSF lactate levels in this study (p 0.05). Conclusion: CSF lactate level is a rapid, quite inexpensive and unpretentious process, important diagnostic indicator in the premature demarcation of pyogenic meningitis and tubercular meningitis from viral meningitis, serving in the premature organization of proper action and diminishing transience and impediments. Early detection may help in early decision on the type and institution of appropriate management could reduce the mortality and morbidity of meningitis.

Population pharmacokinetics of vancomycin in patients with external ventricular drain-associated ventriculitis.

To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)-associated ventriculitis, the pharmacokinetics of vancomycin were evaluated and covariate relationships explored. For the population pharmacokinetic model patients were recruited in a neurocritical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of EVD-associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM. A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three-compartment model with linear elimination. Creatinine clearance (ClCr ) and CSF-lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on ClCr and furthermore the clearance (Cldif ) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM: Cl=5.15L/h, Q (intercompartmental clearance)=3.31L/h, Cldif =0.0031L/h, Vcentral =42.1L, VCSF =0.32L and the value of Vperipheral was fixed to 86.2L. With the developed pharmacokinetic model, area under the curve (AUC) values as well as CSF trough levels were simulated. Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from ClCr ).

Association between cerebrospinal fluid lactate concentration and central nervous system disease in dogs.

Cerebrospinal fluid (CSF) analysis is a sensitive tool for evaluating patients with neurologic diseases but is rarely specific. Biomarkers can be measured from any bodily fluid and can be useful indicators for the presence, severity, and prognosis of diseases. This study was designed to evaluate if CSF lactate can be used as a biomarker in dogs with central nervous system disease. Peripheral venous blood and CSF were collected from 49 dogs with various intracranial diseases to evaluate correlations between blood and CSF lactate levels. Total nucleated cell count (TNCC) and CSF protein concentrations were also evaluated. All samples obtained were divided into normal (NG) and abnormal (AG) dogs based on a TNCC of ≤5 and >5cells/μL and a protein concentration of ≤25 and >25mg/dL, respectively. The AG dogs were further subdivided into those having <100 TNCCs/µL (AGL) and those having >100 TNCCs/µL (AGH). They were also subdivided into groups based on seizure activity (AGS), and inflammatory (AGI), or neoplastic diseases (AGN), and the respective lactate concentrations were then compared. Lactate concentrations were significantly increased in CSF and venous blood samples in the AG compared with the NG dogs, but no differences were found among the individual disease processes. In all dogs, CSF lactate concentrations were higher than venous blood lactate levels; however, no direct correlation between CSF and blood lactate concentrations was identified. Cerebrospinal fluid lactate can be used as a biomarker in clinical settings as it can be measured via a commercially available lactometer immediately after collection without the need for special instrumentation or laboratory personnel.

Is cerebrospinal fluid lactate useful in differentiating scrub typhus meningitis from aseptic, bacterial and tuberculous meningitis?

Scrub typhus is one of the most common causes of meningo-encephalitis in endemic areas of the Indian subcontinent. Numerous studies have established the reliability of cerebrospinal fluid lactate for differentiation of bacterial meningitis from aseptic meningitis. However, there are no reported data on the predictive value of cerebrospinal fluid lactate in scrub typhus meningitis. We thus conducted a cross-sectional study to examine the diagnostic accuracy of cerebrospinal fluid lactate in the differentiation of different causes of acute meningitis. Over two years, we studied 119 patients, with almost equal gender distribution, whose mean age was 43.58 (±18) years and their overall mean duration of fever was 11.7 (±21.0) days. Commonest clinical features overall were neck stiffness; values of cerebrospinal fluid lactate were lowest in aseptic meningitis, followed by scrub typhus, TB and bacterial meningitis. We conclude that cerebrospinal fluid lactate levels may be a useful adjunct to clinical features and laboratory investigations to differentiate between bacterial, viral, tubercular and scrub meningitis.

Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis.

Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P < .0001), seizures (P = .0005), elevated intracranial opening pressure (P = .03), higher CSF white cells (P = .007), and lower CSF glucose (P = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55-7.51; P = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate.

Cerebrospinal fluid lactate level in aquaporin-4 antibody positive neuromyelitis optica spectrum disorders: a hint on differential diagnosis and possible immunopathogenesis

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) may be similar to each other in clinical features. The differential diagnosis between them remains challenging in clinical practice. This retrospective study is aimed to describe the difference of cerebrospinal fluid (CSF) lactate level between aquaporin-4 antibody (AQP4-Ab) positive NMOSD and MS, to discuss the possible explanation upon immunopathogenesis and the significance in differential diagnosis. MethodWe retrospectively analysed cerebral biochemical results from 60 AQP4-Ab positive NMOSD and 55 MS Asian patients. To assess the diagnostic ability of cerebrospinal fluid lactate for distinguishing AQP4-Ab positive NMOSD from MS using receiver operating characteristic (ROC) curve analysis. ResultsThe cerebrospinal fluid lactate level is significantly higher in AQP4-Ab positive NMOSD than in MS based on multiple linear regression (P<0.0001). The differential diagnostic efficacy of cerebrospinal fluid lactate distinguishing AQP4-Ab positive NMOSD from MS reached an area under ROC curve (AUC) of 0.8842 (95% CI 0.82-0.95, P<0.0001), using 1.50 as the diagnostic critical point of the cerebrospinal fluid lactate level, the sensitivity was 88.3%, the specificity was 78.2%. ConclusionThe cerebrospinal fluid lactate level differs between AQP4-Ab positive NMOSD and MS, which also contributes in differential diagnosis. The distinct patterns of cerebral biochemical results may cast a light on the immunopathogenesis of AQP4-Ab positive NMOSD.

Increased Cerebrospinal Fluid Uric Acid Levels in Guillain-Barré Syndrome.

Uric acid (UA) is a natural scavenger for peroxynitrite and can reflect antioxidant activity and oxidative stress in several neurological disorders. Changes in serum and cerebrospinal fluid (CSF) levels of UA have been reported in patients with multiple sclerosis and neuromyelitis optica spectrum disorders. The levels of UA in CSF are relatively poorly understood in patients with Guillain–Barré syndrome (GBS). It remains unclear whether UA can play an antioxidant role and reflect oxidative stress in GBS. The purpose of this study is to investigate CSF and serum UA levels in patients with GBS and their relationship with clinical characteristics. The CSF and serum UA levels were detected in 43 patients with GBS, including 14 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 13 with acute motor and sensory axonal neuropathy (AMSAN), 7 Miller Fisher syndrome (MFS), and 3 unclassified, and 25 patients with non-inflammatory neurological disorders (NIND) as controls. Moreover, serum UA levels were also detected in 30 healthy controls. The levels of UA were measured using uricase-based methods with an automatic biochemical analyzer. CSF UA levels were significantly increased in patients with GBS (p = 0.011), particularly in patients with AIDP (p = 0.004) when compared with NIND. Among patients with GBS, CSF UA levels were higher in those with demyelination (p = 0.022), although the difference was not significant after multiple testing correction. CSF UA levels in GBS were positively correlated with serum UA levels (r = 0.455, p = 0.022) and CSF lactate (r = 0.499, p = 0.011). However, no significant correlations were found between CSF UA levels and GBS disability scores. There were no significant differences in serum UA levels among GBS, NIND, and healthy controls. These results suggest that CSF UA may be related to the pathogenesis of demyelination in patients with GBS and may be partially determined by serum UA and the impaired blood–nerve barrier.

Cerebrospinal fluid lactate concentrations in dogs with seizure disorders.

BackgroundCerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown.Hypothesis/ObjectivesCerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures.AnimalsOne‐hundred eighteen client‐owned dogs with seizure disorders.MethodsCase series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded.ResultsDogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy.Conclusions and Clinical ImportanceCerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process.

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.

Cerebrospinal Fluid Bacillary Load by Xpert MTB/RIF Ultra Polymerase Chain Reaction Cycle Threshold Value Predicts 2-Week Mortality in Human Immunodeficiency Virus-Associated Tuberculous Meningitis.

BackgroundThe World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay’s PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. MethodsWe prospectively enrolled 102 human immunodeficiency virus (HIV)–positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters. ResultsSubjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality—worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra–negative (30%) probable TBM cases (P = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P = .48). Ct tertile was significantly associated with baseline CSF lactate (P = .03). ConclusionsHigh CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care.

The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle.

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF. A lactate receptor, the hydroxycarboxylic acid receptor 1 (HCA1), is present in the brain, but whether it is located in the CP or in other periventricular structures has not been studied. Here, we investigated the distribution of HCA1 in the cerebral ventricular system using monomeric red fluorescent protein (mRFP)-HCA1 reporter mice. The reporter signal was only detected in the dorsal part of the third ventricle, where strong mRFP-HCA1 labeling was present in cells of the CP, the tela choroidea, and the neuroepithelial ventricular lining. Co-labeling experiments identified these cells as fibroblasts (in the CP, the tela choroidea, and the ventricle lining) and ependymal cells (in the tela choroidea and the ventricle lining). Our data suggest that the HCA1-containing fibroblasts and ependymal cells have the ability to respond to alterations in CSF lactate in body–brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer’s disease biomarker).

Clinical performance of amperometry compared with enzymatic ultra violet method for lactate quantification in cerebrospinal fluid.

The differential diagnosis between acute bacterial meningitis (BM) and viral meningitis (VM) is crucial for treatment and prognosis. Cerebrospinal fluid (CSF) lactate (LA) is considered a good biomarker for differentiating BM from VM. The objective of this study was to compare the clinical performance of amperometry, which is not validated for measurement of LA in CSF samples, with a validated method (enzymatic ultra violet), for their ability to discriminate between acute BM and VM. It was a retrospective, descriptive comparative study, 320 CSF reports were included; LA was quantified in CSF using either Dimension AR machine (Dade Behring) or amperometry (RAPID Point 500, Siemens). All samples with bacteria (n=54) or virus (n=139) identified, compared with a control with normal CSF (n=127). CSF LA levels were comparable for amperometry or enzymatic methods on each group studied, in a wide range of LA levels; it was capable to distinguish BM from VM independent of the method used to quantify. The findings support the use of the amperometric method in measuring LA concentrations in CSF in a wide range of values. Amperometry is a less expensive method, validated for blood, easily available in small laboratories including in limited resources countries.

Leigh Syndrome in an Adolescent Girl: A Case Report

Leigh syndrome (LS) is a disorder of infancy and rarely late childhood. It presents with regression of mental and motor skills. Here, we present LS in an adolescent girl who presented with generalized dystonia and cognitive decline. Her infective, metabolic, endocrinal and autoimmune work up was normal. The neuroimaging showed progressive symmetric involvement of basal ganglia with focal intensity over bilateral lentiform nucleus and thalamic region. The cerebrospinal fluid (CSF) lactate level was elevated. Genetic test could not be performed; however the history of neuro-regression with extrapyramidal involvement with CSF and neuroimaging finding led to the diagnosis of Leigh’s syndrome.

Leigh Syndrome in an Adolescent Girl: A Case Report

Leigh syndrome (LS) is a disorder of infancy and rarely late childhood. It presents with regression of mental and motor skills. Here, we present LS in an adolescent girl who presented with generalized dystonia and cognitive decline. Her infective, metabolic, endocrinal and autoimmune work up was normal. The neuroimaging showed progressive symmetric involvement of basal ganglia with focal intensity over bilateral lentiform nucleus and thalamic region. The cerebrospinal fluid (CSF) lactate level was elevated. Genetic test could not be performed; however the history of neuro-regression with extrapyramidal involvement with CSF and neuroimaging finding led to the diagnosis of Leigh’s syndrome.

Cisternal versus lumbar cerebrospinal fluid lactate concentration in healthy dogs

The analysis of cerebrospinal fluid biomarkers provides a wide range of information about the neurological health of a patient. Lactate is a metabolic precursor necessary for brain gluconeogenesis. When oxidative impairment or mitochondrial damage is present, lactate alteration occurs. The rostro-caudal dynamics of cerebrospinal biomarkers along the craniospinal axis in humans and horses was demonstrated in other studies. To the authors’ knowledge, no clinical study has, so far, investigated the cerebrospinal fluid lactate concentration in dogs in association with the puncture site. The purpose of this study was to compare the cerebellomedullary cistern and lumbar cistern cerebrospinal fluid lactate concentrations in healthy dogs. Cerebellomedullary and lumbar cerebrospinal fluids were collected for the cell count, total protein determination and lactate analysis from ten healthy Beagle dogs. The results revealed a significantly increased lumbar cerebrospinal fluid lactate concentration when compared with the cerebellomedullary cistern level. The results included: the total nucleated cell count &amp;lt; 5 cells/µl, the red blood cell count &amp;lt; 500 cell/µl, the total proteins &amp;lt; 0.3 g/l, as well as the cerebellomedullary lactate values (1.44 ± 0.06 mM/l) and the lumbar cistern lactate values (1.58 ± 0.1 mM/l). The results of this study highlight useful data that help to understand the physiological lactate variations depending on the cerebrospinal fluid puncture site.