The significance of elevated CSF lactate.

The final diagnosis of 158 patients who had a cerebrospinal fluid (CSF) lactate concentration greater than 2 mmol/l was ascertained. The conditions included seizures, inflammatory changes, and proven metabolic disorders. For the diagnosis of congenital lactic acidoses, CSF lactate should ideally be measured in a seizure free patient after any acute illness.     

Creatine kinase BB and lactate in the cerebrospinal fluid of neonates and infants with perinatal injuries of the CNS

A study was made of the content of creatine kinase-BB (CK-BB) and lactate in cerebrospinal fluid (CSF) of 202 neonates and infants with perinatal CNS injuries. The relationship was found between the rise of the CK-BB content and the gravity of perinatal CNS injuries. The highest content of CK-BB in CSF was marked in neonates with cerebral disorders complicated by infectious and inflammatory diseases (pneumonia, sepsis). Within the first 5 days of life, the children of this group demonstrated the relationship between the content of CK-BB and lactate of CSF. The measurement of the content of CK-BB in CSF should be used for early diagnosis, assessment of the gravity and course of perinatal CNS injuries in neonates and in infants.     

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children

Objective

To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation.

The Diagnostic and Predictive Value of Cerebrospinal Fluid Lactate in Children with Meningitis

ABSTRACT. One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n=18), aseptic meningitis (n=28), and a control group (n=87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p<0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

The diagnostic and predictive value of cerebrospinal fluid lactate in children with meningitis. Its relation to current diagnostic methods

One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n = 18), aseptic meningitis (n = 28), and a control group (n = 87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p less than 0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

新生儿缺氧缺血性脑病血浆及脑脊液乳酸的临床研究

目的　围产期窒息是引起新生儿脑损伤的重要原因之一 ,目前仍无确切的方法早期预测其预后。本实验研究缺氧缺血性脑病 (HIE)患儿血浆和脑脊液 (CSF)乳酸 (Lac)的变化 ,观察Lac与HIE及窒息的关系。方法　对 2 6例HIE患儿 (轻度 8例 ,中度 10例 ,重度 8例 )和 8例正常对照组 ,在生后 0～ 2 4h、4 8～ 72h及 7～ 10d抽取动脉血测Lac含量 ,HIE患儿生后 4 8～ 72h腰穿取CSF测Lac含量 ,并于生后 7～ 10d做头部MRI检查。结果　对照组和病例组血浆Lac均随日龄增加呈下降趋势 ,有统计学差异。生后 0～ 2 4h ,4 8～ 72hHIE组血浆Lac较对照组显著升高 (均P <0 .0 1)。重度HIE组血浆Lac(9.11± 3.2 9mmol/L)与轻、中度HIE组 (6 .0 3±2 .6 6mmol/L ,6 .5 6± 1.4 2mmol/L)相比较仅在 0～ 2 4h明显升高 (均P <0 .0 5 )。重度组CSFLac(2 .5 3±0 .2 7mmol/L)与轻、中度HIE(1.80± 0 .2 0mmol/L ,1.91± 0 .2 8mmol/L)相比有显著增高 (均 P <0 .0 1)。 5minApgar评分≤ 5分组CSFLac含量 (2 .4 3± 0 .34mmol/L)较 >5分组 (1.83± 0 .2 5mmol/L)明显升高 (t =5 .2 2 ,P<0 .0 1)。重度MRI改变的HIE患儿CSFLac较轻、中度MRI改变的HIE患儿CSFLac明显升高 (2 .36±0 .4 4mmol/Lvs 1.72± 0 .2 4mmol/L ,2 .14± 0 .2 6mmol/L     

“Cerebral” lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis

Six patients are described with a combination of early onset of neurological symptoms, gross cerebral changes and elevated concentrations of pyruvate and lactate in cerebrospinal fluid. Although at least five of the six patients appear to have a generalised defect in pyruvate metabolism, reflected in deficient pyruvate dehydrogenase activity in cultured fibroblasts, systemic acidosis was not a problem clinically and blood pyruvate and lactate concentrations were only slightly raised. The localisation of significant clinical and biochemical problems to the central nervous system, coupled with the difficulties in making the diagnosis if analysis of cerebrospinal fluid (CSF) is not performed, lead us to term this condition cerebral lactic acidosis.Abbreviations PDH pyruvate dehydrogenase - CSF cerebrospinal fluid     

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.     

Cerebrospinal fluid lactic acidosis in bacterial meningitis.

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.     

Malignancy markers in the cerebrospinal fluid

The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant.Abbreviations AAT alpha-1-antitrypsin - AFP alpha fetoprotein - ALL acute lymphoblastic leukaemia - ASAT aspartate aminotransferase - B-2-m peta-2-microglobulin - CEA carcinoembryonic protein - CK creatine kinase - CNS central nervous system - CSF cerebrospinal fluid - FN fibronectin - GFAP glial fibrillary acidic protein - HCG human chorionic gonadotrophin - LD lactate dehydrogenase - MBP myelin basic protein - NGF nerve growth factor - NSE neuronespecific enolase - PA plasminogen activator - PG prostaglandin - TdT terminal deoxynucleotidyl transferase - TX thromboxane     

Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue.

A patient is described with subacute necrotizing encephalomyelopathy proven by autopsy. A slight increase of blood pyruvate and lactate levels with an increased lactate/pyruvate ratio and frequently increased beta-hydroxybutyrate/acetoacetate ratio suggested a disorder of mitochondrial oxidation. A cytochrome c oxidase deficiency was shown in peripheral muscle tissue with some residual cytochrome c oxidase activity in heart muscle. Normal cytochrome c oxidase activity was present in liver tissue. Because of the markedly higher levels of pyruvate and lactate in CSF compared with blood and an increased lactate/pyruvate ratio in CSF, there may also have been defective activity of cytochrome c oxidase in brain tissue. After a period of apparently normal development, the child's clinical condition gradually deteriorated and she died at age 6 years due to respiratory insufficiency. This study illustrates the fact that Leigh's disease is not linked to a single inherited molecular defect.     

Brain carbohydrate metabolism during experimental Haemophilus influenzae meningitis.

Five-day-old infant rats which acquire Haemophilus influenzae b bacteremia and meningitis after intranasal inoculation have a transient depression in weight gain (2 days), but then continue to grow at the same rate as strain U--11 inoculated controls. Brain lactate, glucose, and glycogen concentrations increase during the first 5 days of disease in infected animals. The increase in brain glycogen can be accounted for by an influx of glycogen containing polymorphonuclear leukocytes. The increased concentrations of glucose and lactate were found not to be due to a change in brain weight to dry weight ratio or the volume of entrapped blood. The mean cerebrospinal fluid (CSF) glucose concentration was higher in animals with meningitis (2.7 mM) in comparison to U-11 inoculated controls (1.8 mM). This increase in brain and CSF glucose concentration appeared secondary to an increased brain uptake of hexoses as manifested by an increased [3H]mannitol uptake. Brain lactate accumulation was not explicable from the data available. There was no evidence of cerebral cortical cellular damage because in vitro oxygen uptake and lactate production were equivalent in control and meningitic animals. The ability of the infant rat brain to maintain cerebral adenosine triphosphate (ATP) content in menigitis and the failure of CSF glucose concentration to decrease might be a reflection of the importance of alternative oxidative substrate (e.g., beta-hydroxybutyrate) to the cerebral metabolism of the developing rat brain.     

Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.     

Pyruvate-dehydrogenase deficiency. Lethal course of the disease during infancy (author's transl)]

The course of pyruvate dehydrogenase deficiency in an infant is described. During pregnancy fetal movements were reduced, and since birth severe neurologic involvement was noticed. Permanent metabolic acidosis due to lactic acidemia as well as hyperpyruvic acidemia and hyperalaninemia were present. Alanine accumulated in CSF and urine, urinary excretion of lactate and pyruvate was highly elevated. Pyruvate dehydrogenase activity in a liver biopsy was only 5% of that for normal controls, and pyruvate decarboxylation by cultured fibroblasts was equally decreased. Therapy required permanent administration of bicarbonate. The administration of thiamine had no effect. The infant died within three months. Recently prenatal diagnosis during a subsequent pregnancy of the mother revealed normal results when pyruvate degradation with cultured amniotic fluid cells was investigated, and a healthy child was born.     

Mannitol treatment in experimental Haemophilus influenzae type b meningitis

A study was undertaken to evaluate hypertonic mannitol treatment in experimental lapin Haemophilus influenzae type b meningitis and to compare these results with those in normal rabbits. Increased intracranial pressure, brain water content, and concentrations of lactate and hypoxanthine in cerebrospinal fluid (CSF) were measured as a reflection of altered cerebral perfusion and hypoxia and potential brain injury associated with meningitis. A single dose of mannitol reduced transiently the CSF pressure of uninfected rabbits from 2.15 +/- 0.20 to 1.34 +/- 0.10 mm Hg (maximum reduction 34.9 +/- 8.4%; p less than 0.005). The time to the lowest pressure was 38.7 +/- 2.7 min after initiation of the infusion and the time to return of CSF pressure to initial values was 76.7 +/- 5.6 min. In infected mannitol-treated animals the CSF pressure was reduced from 4.78 +/- 0.53 to 2.61 +/- 0.55 mm Hg (maximum reduction 42.0 +/- 7.7%; p less than 0.005). Time to maximum pressure decrease was 44.0 +/- 5.6 min. CSF pressure returned to the initial level after 178.5 +/- 25.2 min. Four h after initiation of mannitol infusion the mean brain water content in infected mannitol-treated animals was 412 +/- 4 g H2O/100 g dry weight and in infected untreated animals it was 415 +/- 3 g H2O/100 g dry weight (p greater than 0.05). CSF lactate and hypoxanthine concentrations were significantly increased during the 20 h of meningeal inflammation (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Central lactic acidosis,hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma

Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected. Blüher and Schulz both contributed equally to the study.     

Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children.

Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion.     

A clear CSF is not always a normal CSF

A normal initial cerebrospinal fluid (CSF) study has been traditionally used to exclude the potential diagnosis of bacterial meningitis. However, cases of pyogenic meningitis in the absence of CSF pleocytosis have been reported in which smears for gram stain or CSF culture revealed the diagnosis of meningitis. In the presence of clinical signs of meningitis, an abnormal initial CSF study indicates a diagnosis of bacterial meningitis but a normal result may not necessarily exclude it and therefore, should not delay early institution of appropriate antimicrobial therapy.     

The clinical value of follow-up examinations in childhood T-cell acute lymphoblastic leukemia and T-cell non-Hodgkin's lymphoma

BACKGROUND: The aim of this study was to evaluate the value of follow-up investigations of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL), including cerebrospinal fluid (CSF) examination, bone marrow (BM) aspiration, peripheral blood (PB) count, serum lactate dehydrogenase (LDH) and chest X-rays in patients with an initial mediastinal enlargement. PROCEDURE: We reviewed clinical records of all T-ALL patients from 1987 to 2002 and all T-NHL patients from 1977 to 2002, seen at a single institution. RESULTS: Of 48 T-ALL patients, 15 suffered from a relapse, 6 (40%) were asymptomatic at the time of relapse. T-ALL (13/30) with mediastinal enlargement at first diagnosis relapsed versus 2/16 of those without mediastinal enlargement. However, at relapse, only one patient had a mediastinal mass, which in addition was symptomatic. Of 39 T-NHL patients, 6 patients relapsed. Forty percent of relapsed T-ALL and 17% of relapsed T-NHL were asymptomatic. The seven asymptomatic relapses were detected by CSF (n = 4), BM (n = 2) or blood count (n = 1) examinations. All T-ALL and T-NHL patients with a mediastinal relapse were symptomatic. CONCLUSIONS: This study suggests that routine CSF examinations during treatment can detect relapses of T-ALL and T-NHL before onset of symptoms, which might be of clinical value. Relapses are rarely detected by BM or blood examinations and whether this translates in a clinical benefit is unlikely. Routine chest X-rays are not useful.     

Rapid diagnosis of bacterial meningitis in children with fluorescence quantitative polymerase chain reaction amplification in the bacterial 16S rRNA gene

Polymerase chain reaction (PCR) techniques have been increasingly used to detect microbial DNA in cerebrospinal fluid (CSF) for the diagnosis of bacterial meningitis. In order to determine the rapidity, sensitivity and specificity of 16S rRNA-based fluorescence quantitative polymerase chain reaction (FQ-PCR), 16S rRNA-based FQ-PCR, CSF bacterial culture and CSF routine analysis were compared in the diagnosis of bacterial meningitis in children. Twenty children who were clinically suspected of bacterial meningitis were included in this study. A total of 2.0 ml of CSF was collected from every child and was subjected to 16S rRNA-based FQ-PCR, CSF culture and CSF routine analysis. Bacterial DNA copies and the cycle threshold (CT) value of the 16S rRNA-based FQ-PCR was recorded, and the results were compared with CSF culture and CSF routine analysis. Seven children were found to be positive with a rate of 35% (7/20) when detected with 16S rRNA-based FQ-PCR and four children displayed a positive rate of 20% (4/20) with the CSF culture method. These two groups displayed a significant difference, with a p-value of 0.002. The method of 16S rRNA-based FQ-PCR demonstrated a high specificity when compared to the standard microbes. A negative correlation was noted between the CT value and the bacteria DNA copies, and the CT value was indicative of the seriousness of bacterial meningitis. 16S rRNA-based FQ-PCR was proved to be a more rapid, sensitive and specific method compared with CSF culture and it should have promising usage in the diagnosis of bacterial meningitis.