Endogenous Neurosteroids Levels are Decreased in CSF During Status Epilepticus

Purpose: Neuroactive steroids, such as allopregnanolone (AP), are positive allosteric modulators of GABA-A receptors enhancing both synaptic and extrasynaptic GABA-A mediated inhibition and might be effective in the treatment of benzodiazepine-resistant status epilepticus (SE). No data are available on AP levels in central nervous system (CNS) of patients suffering from SE. This lack of information hampers the possibility to correctly design a rational therapeutic approach to SE. We designed a study to evaluate AP in serum and cerebrospinal fluid (CSF) of patients affected by SE. Method: We retrospectively (2007–2015) evaluated blood and CSF samples from 41 adult patients with diagnosis of SE who received lumbar puncture at SE onset (median of 4 days) for clinical purposes and for whom a CNS infection was finally excluded. 41 subjects (matched for age and sex) that had negative results after lumbar puncture for suspected idiopathic intracranial hypertension, CNS infection, or inflammatory disease served as control group. Quantitative analysis of neurosteroids was performed by liquid chromatography-electrospray tandem mass spectrometry. Results: Serum AP levels did not revealed significant differences between controls and SE patients. However, CSF AP levels were decreased by approximately 30% (p < 0.05, Mann-Whitney test) in patients compared with controls. Interestingly, linear regression did not reveal a relationship between serum and CSF levels for AP in controls (R2 = 0.06, p = 0.27). On the contrary, a significant relationship (R2 = 0.57, p = 0.003) was present in patients affected by SE. Conclusion: We demonstrated that endogenous allopregnenolone is significantly reduced during SE in CSF. Administration of AP to patients suffering of SE could be useful to reestablish AP level in the CNS. In addition, exogenously administered AP may result to have a privileged access to brain tissue by virtue of the higher permeability of the blood- brain barrier during SE.