CSF lactate is a brain health indicator

Albanese M, Zagaglia S, Landi D, Boffa L, Nicoletti CG, Marciani MG, Mandolesi G, Marfia GA, Buttari F, Mori F, Centonze D.

Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression. 

J Neuroinflammation. 2016 ;13(1):36. doi: 10.1186/s12974-016-0502-1.

BACKGROUND:Altered 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).

METHODS:One-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.

RESULTS:CSF 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.

CONCLUSIONS:Measurement 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.

When things go badly, they go stupendously wrong - it's a long habit that is hard to kick in life, and the human body is no different

Lactate, whether in serum or in the CSF, is one such indicator of this, and not very specific for a particular disease process (unlike the implications in the opening sentence of the abstract above). Indeed, I have found raised lactate levels to be useful in supporting my suspicions of a seizure, bacterial meningitis, stroke, and a mitochondrial disorder, in the past

CSF lactate is produced by anaerobic metabolism in the brain (see figure above) and increases in any condition that causes a decrease in brain oxygen supply. The investigators did not find any correlations with contrast-enhancing lesions on MRI (not surprising as this only a snap shot of the brain) or relapses (reporter dependent and excludes sub-clinical relapses). They do, however, report a weak correlation with markers of axonal damage Tau and neurofilament light chain (r=0.26 and 0.32, respectively).

This doesn't mean it's useless marker, in fact, it has a place as a diagnostic test for establishing rapidly and reliably that there's something wrong in the brain. Further more targeted testing can always be performed afterwards in order to establish the specifics.

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