CSF lactate

L2. Leib, S. L., Boscacci, R., Gratzl, O., and Zimmerli, W., Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery. Clini. Infect. Dis. 29, 69-74 (1999). 

A neonatal form of hepatic failure has a rapidly fatal course and frequently includes severe hypotonia, myoclonus epilepsy, and psychomotor retardation [39]. Another type (found in children aged 2-18 months) has a milder clinical course with infrequent fatal outcome [11]. Abnormal histology (steatosis, micro and macro-nodular cirrhosis) and elevated plasma or cerebrospinal fluid (CSF) lactate are consistent features of the disease, regardless of the clinical subtype. The brain is often involved in these presentations, but other organs could also be involved. Dwarfism... 

Al. Abe, K., Fujimura, H., Nishikawa, Y., Yorifuji, S., Mezaki, T., Hirono, N., Nishitani, N., and Kameyama, M., Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Acta Neurol. Scand. 83, 356-359 (1991). 

If the history, physical findings, and laboratory results are suggestive but not conclusive of a particular mitochondrial disease (e.g., MELAS), then a second tier of tests is performed. These include blood and CSF lactate and pyruvate, as well as the lactate/pyruvate ratio timed or random measurement of amino acids in blood, urine, and CSF organic acids in urine and CSF and ketones and free and total carnitine in blood and urine. 

Another report has provided more details from physical assessments and laboratory and radiological (MRI and MRS) data, and more information about the course of this heroin-related effect (21). The three cases showed raised concentrations of intracerebral lactate (reflecting mitochondrial dysfunction), which suggests a conversion of aerobic to anaerobic metabolism seen in hypoxic-ischemic conditions, including stroke. One patient recovered quite well after antioxidant therapy, supporting a metabolic effect of the heroin-related toxin a similar response to co-enzyme Q has been found in other mitochondrial disorders with a high CSF lactate. Thus, the authors recommended that although the role of antioxidant therapy in this condition is unclear, it may be prudent to administer oral co-enzyme Q supplemented with vitamins C and E to patients with this syndrome. 

Lactate in CSF normally parallels blood levels, but not in children. With biochemical alterations in the CNS, however, CSF lactate values change independently of blood values. Increased CSF concentrations are noted in cerebrovascular accidents, intracranial hemorrhage, bacterial meningitis, epilepsy, inborn errors of the electron transport chain, and other CNS disorders. In aseptic (viral) menmgitis, lactate concentrations in CSF are not usually increased hence, CSF lactate has been used to help discriminate between viral and bacterial meningitis,but the clinical utility has been questioned. In a few children with inherited metabolic diseases, CSF lactate concentrations may be increased despite a plasma lactate in the reference interval. 

Lactate in spinal fluid normally parallels blood levels. In cases of biochemical alterations in the central nervous system, however, CSF lactate values change independently of blood values. Increased CSF levels may be seen in intracranial hemorrhage, bacterial meningitis, epilepsy, and other CNS disorders. ... 

In the current example, cerebral spinal fluid (CSF) lactate concentration was considered to be the biomarker. A model linking the PK exposure to the biomarker and another model linking biomarker to clinical response were estimated and then applied by Monte Carlo simulation to evaluate competing clinical trial designs for a Phase 3 study. 

In the PK/PD part of this study, 52 volunteer patients received from 1 to 3 doses of DCA ranging from 45 to 150mg/kg (18). In total, 1041 DCA concentrations of which 284 were of CSF origin and 1052 lactate concentrations of which 312 were of CSF origin were measured. The CSF lactate concentrations were related to the serum CSF DCA concentrations by an indirect physiologic response model, which is schematically presented in Figure 17.2. 

For the purpose of the analysis, lactate concentrations were assumed be pseudosteady-state at the beginning of the first DCA dose, so that A i was set to equal the lactate concentration at time 0 multiplied by the estimated A out (A m= A out lactate). A link between the 24 hour post-trauma CSF lactate and 6 month postinjury Glasgow Coma Score (GCS) was also estimated by application of logistic regression to literature data (20). Thus, a PK-exposure-PD-CSF lactate-outcomes model was constructed with the biomarker, CSF lactate, in the center. It must be recognized that this modeling and evaluation of power and efficiency could not be executed without a biomarker. 

An increased lactate concentration in CSF is an important indicator for CNS involvement. Increased lactate concentrations in blood are also indicative, but can easily be caused by stress (fear of venapuncture), excessive muscle contractions (status epilepticus), anoxia and other conditions. A reliable value is only obtained from two or more blood lactate determinations. Some patients with a proven mitochondrial defect do not show lactate accumulation in blood or urine, but CSF lactate is frequently increased. Urinary lactate excretion can be secondarily increased in some types of organic aciduria [2]. 

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