It is known that the neuroactive steroids (NAS) modulate the permeability of ion channels. Some NAS exert neuroprotective effects, e.g. neuronal remyelination. Multiple sclerosis (MS) is the most common cause of neurological disability in adults. Thus, we have measured the free and conjugated (after hydrolysis) circulating neuroprotective, GABAergic, glycinergic, glutamatergic acetylcholinergic and purinergic NAS, their precursors and metabolites (52 steroids) in the Δ5 and Δ4 metabolic pathways, both pregnanes (20-oxo and 20α-hydroxy) and androstanes (17-oxo and 17β-hydroxy), steroid 5α/β-reduced metabolites, 16α-hydroxyderivatives and 7α/β-derivatives of Δ5 C19 steroids using GC-MS in selected ion monitoring mode after derivatization. The samples were from 12 female MS patients- 33 (26, 44) years old (median with quartiles) and from 6 sex- and age-matched controls (both in the follicular menstrual phase). In our patients we estimated increased levels of C21 steroids. This is an evidence for an increased adrenal cortex activity as a mechanism enabling a consequent synthesis of neuroprotective steroids. When using the multivariate regression model, we have found that circulating levels of 10 most relevant steroids predict the presence of MS with CI: 91.7% (64.6% - 98.5%) sensitivity and 100% (60.9% - 100%) specificity (mean with 95% confidence intervals). The neuroprotective effects of individual steroids and a possible utilization of the results for the diagnosis and treatment of MS were discussed.

Acknowledgement: Project was supported by IGA MZCR NT/13369, NT/12349 and NT/11513 of Czech Ministry of Health.