RT Journal Article SR Electronic T1 GABAA receptor active steroids are altered in epilepsy patients with tuberous sclerosis JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 667 OP 670 DO 10.1136/jnnp.74.5.667 VO 74 IS 5 A1 F di Michele A1 M Verdecchia A1 M Dorofeeva A1 L Costamagna A1 G Bernardi A1 P Curatolo A1 E Romeo YR 2003 UL http://jnnp.bmj.com/content/74/5/667.abstract 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.