Neurosteroids such as
allopregnanolone may play a role in
epilepsy as positive modulators of inhibitory currents mediated by γ-
aminobutyric acid type A (GABAA ) receptor. Indeed, these molecules have been consistently shown to be
anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated
neurosteroids in the cerebrospinal fluid (CSF) of patients with
status epilepticus (SE) by liquid chromatography tandem-mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007-2017 period. Seventy-three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls (n = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work-up.
Progesterone was 64% lower in patients with SE (p < 0.001). With respect to progesterone, upstream
pregnenolone sulfate and
pregnenolone did not change. Instead, downstream 5α-dihydroprogesterone,
pregnanolone and
allopregnanolone were, respectively, 49% (p < 0.001), 21% (p < 0.01) and 37% (p < 0.001) lower than in controls. Duration or type of SE, age and sex did not consistently affect CSF
neurosteroid levels in the SE cohort. Instead,
pregnenolone sulfate (Spearman's ρ = 0.4335, p < 0.01),
allopregnanolone (ρ = 0.4121, p < 0.05) and
pregnanolone (ρ = 0.592, p < 0.001) levels significantly increased by aging in controls. We conclude that neurosteroidogenesis is defective in patients with SE.