Decreased allopregnanolone levels in cerebrospinal fluid obtained during status epilepticus

Abstract

Neuroactive steroids are increasingly considered as relevant modulators of neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS) have been shown to possess, respectively, anticonvulsant or proconvulsant properties. In view of the potential role of these steroids, we aimed at evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples obtained from patients with status epilepticus (SE). To this purpose, we enrolled 41 patients affected by SE and 41 subjects investigated for nonepileptic neurologic disorders. Liquid chromatographic procedures coupled with electrospray tandem mass spectrometry and routine laboratory investigations were performed. Significantly lower AP levels were found in the CSF of patients affected by SE (-30%; p < 0.05, Mann-Whitney test). Notably, AP was not detectable in 28 of 41 patients affected by SE (p < 0.01 vs. controls, Fisher's exact test). In serum, AP levels did not differ in the two considered groups. Conversely, PS was present at similar levels in the investigated groups. Finally, differences in AP levels could not be explained by a variation in CSF albumin content. These findings indicate that AP is defective in the CSF of patients affected by SE. This phenomenon was not dependent on carriers for steroids, such as albumin.

Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus

“…Mass spectrometric detection was performed using an Agilent QQQ‐MS/MS (6410B) triple quadrupole operating in electrospray positive ionization mode, as described previously (Meletti et al . ). In the case of progesterone, the presence of two keto groups led to cis/trans derivatives, which eluted as two separable LC peaks; therefore, to quantitate progesterone in CSF samples, the summation of both peaks was used.…”

“…The effect size, estimated for allopregnanolone, was based on our previous study (Meletti et al . ). This calculation resulted in a sample size of 42 for each group.…”

“…We recently found that allopregnanolone and the cognate neurosteroid pregnanolone were present at reduced levels in the cerebrospinal fluid (CSF) of patients affected by SE (Meletti et al . ). This result open the question of whether other neurosteroids, especially those preceding the synthesis of allopregnanolone, could also be altered in patients who experience a SE.…”

“…In performing these studies, we considered a much larger cohort of patients in respect of our previous study (Meletti et al . ).…”

Place of neurosteroids in the treatment of status epilepticus

“…23 As the authors correctly stated, this association is not a proof of causality, and the situation is further complicated by the natural fluctuation of the neurosteroids during the cycle in women of childbearing potential (reviewed in Rogawski et al 11 ). 23 As the authors correctly stated, this association is not a proof of causality, and the situation is further complicated by the natural fluctuation of the neurosteroids during the cycle in women of childbearing potential (reviewed in Rogawski et al 11 ).…”