Cerebrospinal fluid glucose levels and their association with disability, depression, and cognitive function in multiple sclerosis.

Glucose dysregulation in the CNS contributes to both inflammation and neurodegeneration in multiple sclerosis (MS). While glucose levels are routinely measured in peripheral blood, these levels do not necessarily reflect glucose levels in the central nervous system. We analysed data of n = 88 treatment-naive, newly-diagnosed MS patients. Primary outcomes included Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT), Fatigue Scale for Motor and Cognitive Functions (FSMC) and Beck Depression Inventory-II (BDI-II) as well as cerebrospinal fluid (CSF) and serum glucose levels obtained at the time of initial diagnosis. Additionally, we analysed CSF lactate concentration. All blood and CSF samples were collected before the patients received any glucocorticoid treatment. Linear regression analysis revealed that after adjusting for age, sex, BMI and CSF/serum albumin quotient, there was a significant association between CSF glucose levels and EDSS (ß=0.260, p = 0.020), SDMT z scores (ß=-0.245, p = 0.033) and BDI (ß=0.279, p = 0.026). There were no associations with serum glucose levels (ß ranging from − 0.067 to 0.170, all p > 0.05). CSF lactate concentration was not significantly associated with the clinical parameters (ß ranging from − 0.048 to 0.184, all p > 0.05). Patients with higher CSF but not serum glucose concentrations exhibited higher physical disability, more cognitive impairment and worse depressive symptoms. Increased CSF glucose in MS might be a compensatory mechanism for CNS damage but also a landmark of mitochondrial dysfunction and trigger of further neuroinflammation and neurodegeneration. More research is necessary to elucidate the role of glucose-related metabolic processes in MS.