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