PT - JOURNAL ARTICLE AU - di Michele, F AU - Verdecchia, M AU - Dorofeeva, M AU - Costamagna, L AU - Bernardi, G AU - Curatolo, P AU - Romeo, E TI - GABA<sub>A</sub> receptor active steroids are altered in epilepsy patients with tuberous sclerosis AID - 10.1136/jnnp.74.5.667 DP - 2003 May 01 TA - Journal of Neurology, Neurosurgery &amp; Psychiatry PG - 667--670 VI - 74 IP - 5 4099 - http://jnnp.bmj.com/content/74/5/667.short 4100 - http://jnnp.bmj.com/content/74/5/667.full SO - J Neurol Neurosurg Psychiatry2003 May 01; 74 AB - Background: The neuroactive steroid 3α, 5α-tetrahydroprogesterone is the most potent endogenous positive modulator of γ-amino-butyric acid (GABA)A receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility. Objective: To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis. Methods: Plasma concentrations of the enantiomers 3α, 5α- and 3α, 5β-tetrahydroprogesterone (3αs-THP), which are positive modulators of GABAA receptors, were measured in 18 patients, along with their endogenous functional antagonists 3β, 5α- and 3β, 5β-THP (3βs-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method. Results: In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3αs/3βs-THP ratio than in seizure-free patients or control subjects. Conclusions: The reduced 3αs/3βs-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.