Cerebrospinal Fluid Lactate Levels Research Articles

Negative correlation between CSF lactate levels and MoCA scores in male Chinese subjects

Lactate is a product of glycolysis by astrocytes and can be generated as a primary metabolic energy source by neurons. Lactate plays multifunctional role in human brain energy metabolism and cognitive function. However, no direct evidence demonstrated the link between lactate and cognition in normal condition. In the present study, concentrations of lactate in cerebrospinal fluid (CSF) and peripheral blood were measured to investigate the association of lactate with cognitive ability, which was assessed by Montreal Cognitive Assessment (MoCA), in 99 male Chinese subjects. Correlation analyses revealed that serum lactate levels were negatively correlated with age, and CSF lactate levels were negatively correlated with MoCA scores after Box-Cox transformations. But no correlation was found between serum lactate levels and MoCA scores after Box-Cox transformations. In conclusion, the results indicate that CSF lactate levels were negatively correlated with MoCA scores in male Chinese subjects.

Predictive value of cerebrospinal fluid lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation with blood-contaminated cerebrospinal fluid

To evaluate the diagnostic value of cerebrospinal lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation (PNBM) with blood-contaminated cerebrospinal fluid (CSF). A prospective observational study was conducted. 101 patients underwent neurosurgical operation and clinically suspected PNBM admitted to neurosurgical intensive care unit (NSICU) of the First Affiliated Hospital of Sun Yat-sen University from October 2015 to December 2016 were enrolled. Based on red blood cell quantitative test in CSF, the patients were divided into blood-contaminated and non blood-contaminated CSF groups. According to the PNBM diagnostic criteria of 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN), all patients were divided into PNBM group and non-PNBM group. The biochemical indexes levels in CSF were compared among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of CSF lactate for PNBM in blood-contaminated patients. A total of 101 suspected PNBM patients were enrolled. In 77 blood-contaminated CSF patients, 39 patients were diagnosed as PNBM (account for 50.6%); in 24 non-blood-contaminated patients, 12 patients were diagnosed as PNBM (account for 50.0%). (1) In non-PNBM patients, the lactate level in blood-contaminated CSF was significantly higher than that of non-blood-contaminated CSF (mmol/L: 3.5±1.3 vs. 2.3±1.1, P < 0.01). In PNBM patients, there was no significant difference in lactate level between blood-contaminated CSF and non blood-contaminated CSF (mmol/L: 6.8±2.1 vs. 6.9±2.5, P > 0.05). (2) In both blood-contaminated and non blood-contaminated CSF, white blood cell (WBC), protein and lactate levels in PNBM group were significantly higher than those in non-PNBM group [WBC (×106/L): 660.0 (67.5, 1 105.0) vs. 41.0 (15.0, 142.5) in blood-contaminated CSF, 168.0 (86.5, 269.5) vs. 34.5 (7.0, 83.5) in non-blood-contaminated CSF; protein (mg/L): 4 757.8 (2 995.2, 10 219.8) vs. 1 292.8 (924.2, 1 936.2) in blood-contaminated CSF, 39 247.3 (14 900.6, 62 552.2) vs. 1 441.6 (977.3, 2 963.9) in non blood-contaminated CSF; lactate (mmol/L): 6.8±2.1 vs. 3.5±1.3 in blood-contaminated CSF, 6.9±2.5 vs. 2.3±1.1 in non blood-contaminated CSF, all P < 0.05], and glucose and CSF glucose/blood glucose ratio in PNBM group were significantly lower than those in non-PNBM group [glucose (mmol/L): 2.5±1.2 vs. 4.4±1.6 in blood-contaminated CSF, 1.9±1.4 vs. 3.4±0.9 in non blood-contaminated CSF; CSF glucose/blood glucose ratio: 0.28±0.15 vs. 0.46±0.16 in blood-contaminated CSF, 0.24±0.16 vs. 0.45±0.11 in non blood-contaminated CSF, all P < 0.01]. (3) It was shown by ROC curve analysis that CSF lactate level was a good diagnostic parameter for PNBM both in blood-contaminated and non blood-contaminated CSF, and the area under ROC curve (AUC) was 0.91 and 0.97, respectively. When the cutoff value of lactate in non blood-contaminated CSF was 3.35 mmol/L, the sensitivity was 100%, and the specificity was 91.7%. When the cutoff value of lactate in blood-contaminated CSF was 4.15 mmol/L, the sensitivity was 92.3%, and the specificity was 71.1%, and the combination of CSF lactate and glucose achieved better diagnostic specificity (AUC = 0.96, sensitivity was 97.4%, specificity was 84.2%). Blood in CSF led to the elevation of CSF lactate as compared with that in non-blood-contaminated CSF of patients with PNBM. CSF lactate was still a good diagnostic parameter for PNBM both in blood-contaminated patients, and the combination of CSF lactate and glucose achieved better diagnostic specificity.

Effects of age and glucose levels on lactate levels in cerebrospinal fluid examination of neurodegenerative diseases

Despite recent studies examining the association between neurodegenerative diseases and mitochondrial dysfunction, there are not sufficient data on factors that influence cerebrospinal fluid (CSF) lactate levels. Thus, we investigated factors that affect CSF lactate levels in neurodegenerative diseases. We extracted laboratory findings, including CSF lactate, glucose, and protein levels, and demographic and background information, including age and gender, from the electronic medical records of patients with neurodegenerative diseases in order to explore factors that have an impact CSF lactate levels. These patients had been admitted to our department and underwent a CSF examination between April 2007 and March 2015. Data from 83 patients (average age 64.5years; 45 males and 38 females) were analyzed. The patients' diagnoses included amyotrophic lateral sclerosis, multiple system atrophy, spinocerebellar degeneration, corticobasal syndrome, Parkinson's disease, and Huntington's disease. CSF lactate levels were higher in patients with a neurodegenerative disease who were aged 65years and older relative to those who were aged under 65years (p<0.05), and CSF lactate and glucose levels showed a moderate positive correlation (r=0.487). Age and CSF glucose levels influenced CSF lactate levels even after adjusting for gender, age, CSF protein levels, and CSF glucose levels. When investigating CSF lactate levels in neurodegenerative diseases, it is necessary to consider patients' age and CSF glucose levels.

Diagnostic accuracy of routine blood examinations and CSF lactate level for post-neurosurgical bacterial meningitis

ObjectiveTo evaluate the diagnostic accuracy of routine blood examinations and Cerebrospinal Fluid (CSF) lactate level for Post-neurosurgical Bacterial Meningitis (PBM) at a large sample-size of post-neurosurgical patients. MethodsThe diagnostic accuracies of routine blood examinations and CSF lactate level to distinguish between PAM and PBM were evaluated with the values of the Area Under the Curve of the Receiver Operating Characteristic (AUC-ROC) by retrospectively analyzing the datasets of post-neurosurgical patients in the clinical information databases. ResultsThe diagnostic accuracy of routine blood examinations was relatively low (AUC-ROC<0.7). The CSF lactate level achieved rather high diagnostic accuracy (AUC-ROC=0.891; CI 95%, 0.852-0.922). The variables of patient age, operation duration, surgical diagnosis and postoperative days (the interval days between the neurosurgery and examinations) were shown to affect the diagnostic accuracy of these examinations. The variables were integrated with routine blood examinations and CSF lactate level by Fisher discriminant analysis to improve their diagnostic accuracy. As a result, the diagnostic accuracy of blood examinations and CSF lactate level was significantly improved with an AUC-ROC value=0.760 (CI 95%, 0.737-0.782) and 0.921 (CI 95%, 0.887-0.948) respectively. ConclusionsThe PBM diagnostic accuracy of routine blood examinations was relatively low, whereas the accuracy of CSF lactate level was high. Some variables that are involved in the incidence of PBM can also affect the diagnostic accuracy for PBM. Taking into account the effects of these variables significantly improves the diagnostic accuracies of routine blood examinations and CSF lactate level.

Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis

BackgroundMeningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in this condition are scarce.MethodsRoutine CSF samples analyzed from 2001 to 2012 at the Laboratory of Clinical Neurochemistry, University of Göttingen, were re-evaluated. Patients, whose CSF contained malignant cells were included in this study.ResultsPatients (n = 132, age 59.1 ± 29.1, 58% women) were identified, whose CSF contained malignant cells. The most frequent primary tumor was breast cancer (32.6%), followed by lung cancer (25.0%) and hematologic malignancies (21.2%). The most frequent clinical symptoms were affections of cranial nerves (41.7%), psychiatric abmormalities (32.6%) and radicular lesions of the lower extremities (20.5%). CSF cell counts ranged from 0 to 4692 cells/μl (median 4 cells/μl) and were elevated in 50%. The CSF-to-serum albumin ratio was abnormal in 69.4%. It ranged from 1.8 to 330 x 10-3 (median 17.5 x 10-3). Total CSF protein ranged from 166 to 15,840 mg/l (median 1012 mg/l). CSF lactate was elevated (>2.4 mmol/l) in 65.2% [3.6 mmol/l (1.3/15.6 mmol/l); median (minimum/maximum)]. In 50% of all patients CSF lactate was ≥3.5 mmol/l. The CSF cell counts correlated significantly with the CSF lactate levels and the CSF protein contents. In 56 of 118 CSF samples (47.5%) ferritin was elevated, and in 25 of 65 carcinoma patients (38.5%) an intrathecal production of carcinoembryonic antigen (CEA) was detected. Granulocytes were found in 52.7% of the CSF samples. The percentages of granulocytes and lymphocytes were higher in samples with an elevated cell count.ConclusionIn approximately 50% of CSF samples with meningeosis neoplastica the CSF cell count is not elevated. Diagnosis may be missed when only CSF samples with elevated cell counts are subjected to cytological analysis. CSF lactate and protein and the CSF-to-serum albumin ratio are frequently increased in meningeosis neoplastica. The differential diagnosis between meningeosis neoplastica and central nervous infections, in particular tuberculous or fungal meningitis, can be difficult.

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes.

Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP). We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis. OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients. We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes.

Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia

ABSTRACT Background: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) frequently have overlapping symptoms, leading to the suggestion that the same disease processes may underpin the two disorders – the unitary hypothesis. However, studies investigating the two disorders have reported substantial clinical and/or biological differences between them, suggesting distinct pathophysiological underpinnings. Purpose: The purpose of this study was to further add to the body of evidence favoring different disease processes in CFS and FM by comparing ventricular cerebrospinal fluid lactate levels among patients with CFS alone, FM alone, overlapping CFS and FM symptoms, and healthy control subjects. Methods: Ventricular lactate was assessed in vivo with proton magnetic resonance spectroscopic imaging (1H MRSI) with the results normed across the two studies in which the data were collected. Results: Mean CSF lactate levels in CFS, FM and CFS + FM did not differ among the three groups, but were all significantly higher than the mean values for control subjects. Conclusion: While patients with CFS, FM and comorbid CFS and FM can be differentiated from healthy subjects based on measures of CFS lactate, this neuroimaging outcome measure is not a viable biomarker for differentiating CFS from FM or from patients in whom symptoms of the two disorders overlap.

Mitochondrial Encephalopathy and Transient 3-Methylglutaconic Aciduria in ECHS1 Deficiency: Long-Term Follow-Up.

We report the major diagnostic challenge in a female patient with signs and symptoms suggestive of an early-onset mitochondrial encephalopathy. Motor and cognitive development was severely delayed and brain MRI showed signal abnormalities in the putamen and caudate nuclei. Metabolic abnormalities included 3-methylglutaconic aciduria and elevated lactate levels in plasma and cerebrospinal fluid, but were transient. Whole exome sequencing at the age of 25years finally revealed compound heterozygous mutations c.[229G>C];[563C>T], p.[Glu77Gln];[Ala188Val] in the ECHS1 gene. Activity of short-chain enoyl-CoA hydratase, a mitochondrial enzyme encoded by the ECHS1 gene, was markedly decreased in lymphocytes. Retrospective urine analysis confirms that elevated levels of S-(2-carboxypropyl)cysteamine, S-(2-carboxypropyl)cysteine, and N-acetyl-S-(2-carboxypropyl)cysteine can be a diagnostic clue in the disease spectrum of ECHS1 mutations.

Leigh syndrome: A rare mitochondrial disorder

Leigh syndrome is a rare, mitochondrial disorder of childhood . In most cases dysfunction of the respiratory chain enzymes is responsible for the disease. Raised lactate levels in blood and/or cerebrospinal fluid is noted. Magnetic resonance imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the appropriate diagnosis. Here, we report a case of progressive neurologic disorders presenting with motor and intellectual regression which on MRI was diagnosed as Leigh syndrome.

Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease.

It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.

Clinical decision rules for acute bacterial meningitis: current insights.

Acute community-acquired bacterial meningitis (BM) requires rapid diagnosis so that suitable treatment can be instituted within 60 minutes of admitting the patient. The cornerstone of diagnostic examination is lumbar puncture, which enables microbiological analysis and determination of the cerebrospinal fluid (CSF) cytochemical characteristics. However, microbiological testing is not sufficiently sensitive to rule out this diagnosis. With regard to the analysis of standard CSF cytochemical characteristics (polymorphonuclear count, CSF glucose and protein concentration, and CSF:serum glucose), this is often misleading. Indeed, the relatively imprecise nature of the cutoff values for these BM diagnosis markers can make their interpretation difficult. However, there are two markers that appear to be more efficient than the standard ones: CSF lactate and serum procalcitonin levels. Scores and predictive models are also available; however, they only define a clinical probability, and in addition, their use calls for prior validation on the population in which they are used. In this article, we review current methods of BM diagnosis.

Significance of cerebrospinal fluid lactate level in diagnosing neonatal bacterial meningitis

Objective To study the significance of the cerebrospinal fluid (CSF)lactate level in diagnosing neonatal bacterial meningitis(BM). Methods The CSF samples were collected from neonates admitted to Neonatal Ward of Children's Hospital of Fudan University between January 2014 and March 2015.CSF lactate and glucose concentrations were measured with blood-gas analyzer.CSF and serum glucose levels were measured with glucometer.The enrolled neonates were divided into 2 groups based on CSF culture, CSF white blood cells(WBCs)and clinical presentation: observation group (neonates with BM)and control group (neonates without BM). Statistical analysis of data was performed with Stata 12.0. Results A total of 93 infants (16 assigned to observation group and 77 assigned to control group)met the inclusion criteria.Neonates in observation group had higher median CSF lactate level (4.2 mmol/L)and CSF lactate/glucose ratio (L/Gcsf)(2.32 mmol/L), than those in control group (1.3 mmol/L, 0.52), and there were significant differences (Z=-6.19, -5.92, all P<0.05). CSF glucose levels were lower in observation group (me-dian, 1.25 mmol/L)than those in control group (median, 2.5 mmol/L), and the difference was significant(Z=4.97, P<0.05); CSF/serum glucose ratio (CSF/Sglu)were lower in observation group (median, 0.44 vs 0.81 in control group), and the difference was significant(Z=4.43, P<0.05). The optimal CSF lactate cutoff point of 2.2 mmol/L had a positive predictive value (PPV)of 72.7% and negative predictive value (NPV)of 100.0% for bacterial meningitis.The optimal L/Gcsf cutoff point of 1.24 had a PPV of 94.1% and NPV of 100.0%.The optimal CSF glucose cutoff point of 2.0 mmol/L had a PPV of 65.0% and NPV of 95.9%.The optimal CSF/Sglu cutoff point of 0.6 had a PPV of 60.0% and a NPV of 96.9%. Conclusion CSF lactate may be an excellent biomarker for early diagnosis of neonatal BM. Key words: Bacterial meningitis; Cerebrospinal fluid lactate; Cerebrospinal fluid/serum glucose ratio

Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression.

BackgroundAltered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS).MethodsOne-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored.ResultsCSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein.ConclusionsMeasurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity.

Leigh's disease (subacute necrotising encephalo myelopathy): a rare mitochondrial disorder

Leigh syndrome is a rare progressive neurodegenerative, mitochondrial disorder of childhood with only a few cases documented from India. Raised lactate levels in blood and/or cerebrospinal fluid along with neuroimaging, mainly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem confirms the diagnosis. MRS can also be used to detect raised level of Lactate. Here, we report a case of 11 months old female child who presented with seizures, delayed milestones and regression of the already achieved milestones with abnormal choreoathetoid movements and dystonia.

Does MRS Lactate Peak Correlate with Lactate in the CSF and Blood?

Purpose Cerebrospinal fluid (CSF) or brain parenchyma lactate detection is important for the diagnosis of some diseases with aerobic cellular metabolism compromise. Our purpose is to correlate intraventricular magnetic resonance spectroscopy (MRS) lactate detection and quantification to CSF and blood lactate concentration. Methods Twenty-one patients (13 females; mean age 5 years) suspected of having mitochondrial disorders underwent proton MRS with point-resolved spectroscopy (TE = 144 ms). The volume of interest was positioned in the lateral ventricles, and LCModel was used for the MRS lactate peak detection and quantification. CSF and venous blood samples were obtained for lactate quantification immediately after MRS. Comparisons between MRS, CSF, and blood lactate detection and quantification were performed. p Results In our series, CSF lactate levels were high in 11 patients (52%) and blood serum lactate levels were high in 3 patients (14%). MRS was able to detect a lactate peak in all patients. A positive correlation between MRS lactate quantification and CSF lactate was observed (Pearson correlation coefficient = 0.750; p Conclusion If MRS shows increased lactate levels in the ventricles, CSF puncture is not needed for lactate increase confirmation.

CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease

ObjectivesTo investigate, in patients with Alzheimer's Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD neurodegenerative...

Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children

BackgroundCerebrospinal fluid (CSF) lactate is a potential biomarker for bacterial meningitis in children. To this end, we performed a single-center retrospective cohort study of children from Sao Paulo, Brazil, with CSF pleocytosis to evaluate the ability of CSF lactate to distinguish between children with bacterial and aseptic meningitis. We determined the optimum cutoff point for CSF lactate using receiver-operator curve (ROC) analysis.FindingsWe identified 451 children of whom 40 (9%) had bacterial meningitis. Children with bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l, interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l, IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of 94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%) for bacterial meningitis.ConclusionsIn combination with a validated meningitis clinical prediction rule, the CSF lactate level can be used to distinguish between bacterial and aseptic meningitis in children with CSF pleocytosis.

Muscle Disease

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Lactate and Pyruvate Levels in Blood and Cerebrospinal Fluid in Patients with Menkes Disease

To examine levels of lactate (LA) and pyruvate (PA) in both blood and cerebrospinal fluid (CSF) in patients with Menkes disease (MNK). A nationwide survey involving a retrospective review of medical records or medical record summaries of 42 male patients with MNK born between 1993 and 2008 were performed, and the genetic analysis of their ATP7A gene was reviewed. In these patients, LA and PA levels and the lactate vs pyruvate ratio (L/P ratio) at diagnosis in both blood and CSF were abnormally high. There were no significant differences in LA levels, PA levels, and the L/P ratio between blood and CSF at diagnosis (P > .05). There was also no correlation between LA levels, PA levels, and the L/P ratio, and age at measurement (P > .05). There was no or slight metabolic acidosis, as analyzed by blood gas analysis, in 7 patients. During treatment with subcutaneous injections of copper-histidine, LA and PA levels and the L/P ratio in both the blood and CSF decreased. Our findings suggest that LA and PA levels, and in particular, the L/P ratio, and blood gas analysis can be used to guide the diagnosis and management of MNK.

Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndrome

GLUT1 deficiency syndrome is a treatable neurometabolic disorder, characterized by a low concentration of glucose in cerebrospinal fluid (CSF) and a decreased CSF to blood glucose ratio. Reports of patients with apparently normal CSF glucose levels, however, have raised the question whether CSF analysis is a reliable screening tool for GLUT1 deficiency syndrome. To determine the value of CSF analysis in the workup of GLUT1 deficiency syndrome. PubMed was searched until July 2012 by using the terms glucose transporter 1 (GLUT-1) deficiency syndrome, glucose transporter defect, and SLC2A1-gene. Relevant references mentioned in the articles were also included. The CSF results of all patients with genetically proven GLUT1 deficiency syndrome described in literature were reevaluated. The levels of glucose in CSF, the CSF to blood glucose ratios, and the levels of lactate in CSF were reported for 147 (94%), 152 (97%), and 73 (46%) of 157 patients, respectively. The CSF glucose levels ranged from 16.2 to 50.5 mg/dL and were at or below the 10th percentile for all 147 patients. The CSF to blood glucose ratios ranged from 0.19 to 0.59 and were at or below the 10th percentile for 139 of 152 patients (91%), but they could be within the normal range as well. The CSF lactate levels ranged from 5.4 to 13.5 mg/dL and were at or below the 10th percentile for 59 of 73 patients (81%). A typical CSF profile for GLUT1 deficiency syndrome, which is defined as a CSF glucose level at or below the 10th percentile, a CSF to blood glucose ratio at or below the 25th percentile, and a CSF lactate level at or below the 10th percentile, was found in only 35 of 4099 CSF samples (0.9%) present in our CSF database of patients who received a diagnosis other than GLUT1 deficiency syndrome. We conclude that if age-specific reference values are applied, CSF glucose and lactate levels are adequate biomarkers in the diagnostic workup of GLUT1 deficiency syndrome. Future availability of whole-exome sequencing in clinical practice will make the existence of a reliable biomarker for GLUT1 deficiency syndrome even more important, in order to interpret genetic results and, even more importantly, not to miss SLC2A1-negative patients with GLUT1 deficiency syndrome.