Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression

Abstract

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.

Mitochondrial functionality and metabolism in T cells from progressive multiple sclerosis patients

“…Although we are well aware that lactate in plasma can derive from different sources, differences observed in T cell metabolism can account, at least in part, for plasma concentration of glycolytic metabolism. Lactate has been nowadays recognized as an important molecule that bridges metabolism and inflammation , and it has been shown that lactate in cerebrospinal fluid and serum is associated with the progression of MS . T cells sense lactate using specific transporters, that inhibit their motility, with a mechanism dependent upon lactate interference with glycolysis.…”

Lactate at the crossroads of metabolism, inflammation, and autoimmunity

“…Conversely, other authors found increased extramitochondrial glucose metabolism in the cerebrospinal fluid [74] as well as in the serum of MS patients with higher levels of lactate as compared to controls [75,76]. These parameters were positively correlated and associated with disease progression and activity [75,76]. …”

Neuroprotection by central nervous system remyelination: Molecular, cellular, and functional considerations

“…This change in energy demand is associated with mitochondrial accumulation that matches that of healthy unmyelinated axons (Mutsaers and Carroll, ). Importantly, a number of changes that affect lactate dynamics occur in MS, including an increase in cerebrospinal fluid lactate concentrations (Albanese et al, ), which may be mediated by infiltrating macrophages (López‐Villegas et al, ). Demyelinated lesions exhibit changes in astrocytic and neuronal expression of lactate‐permeable MCTs (Nijland et al, ), which as noted above could impact energy status in axons.…”