Molecular pathogenesis of alcohol withdrawal seizures: the modified lipid-protein interaction mechanism.

The phrase alcohol withdrawal seizures (AWS) refers to seizures that result from the withdrawal of alcohol after a period of chronic alcohol administration. A mechanism of AWS is postulated, namely the modified lipid-protein interaction (MLPI) mechanism. This hypothesis is based upon an evaluation of the mechanisms of membrane fluidity, calcium channels, gamma-aminobutyric acid (GABA) and glutamate in the molecular pathogenesis of AWS. The mechanism hypothesizes that acute ethanol treatment alters the neuronal membrane lipids which then perturbs protein events, such as affecting the GABAA receptors, NMDA receptors and voltage-dependent Ca2+ channels synergistically or in combination. Subsequent adaptations in these systems occur after prolonged administration of ethanol. A sudden withdrawal of ethanol then leads to hyperexcitability which results in AWS.