Journal of neurology, neurosurgery, and psychiatry · 2003
GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis.
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di Michele F, Verdecchia M, Dorofeeva M, Costamagna L, Bernardi G, Curatolo P, Romeo E
Аннотация
BACKGROUND: The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-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 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-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 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects.
CONCLUSIONS: The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.
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 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-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 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects.
CONCLUSIONS: The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.