Perimenstrual catamenial epilepsy, the cyclical occurrence of seizure exacerbations near the time of menstruation, affects a high proportion of women of reproductive age with drug-refractory epilepsy. Enhanced seizure susceptibility in perimenstrual catamenial epilepsy is believed to be due to the withdrawal of the progesterone-derived GABA_A receptor modulating neurosteroid allopregnanolone as a result of the fall in progesterone at the time of menstruation. Studies in a rat pseudopregnancy model of catamenial epilepsy indicate that after neurosteroid withdrawal there is enhanced susceptibility to chemoconvulsant seizures. There is also a transitory increase in the frequency of spontaneous seizures in epileptic rats that had experienced pilocarpine-induced status epilepticus. In the catamenial epilepsy model, there is a marked reduction in the antiseizure potency of anticonvulsant drugs, including benzodiazepines and valproate, but an increase in the anticonvulsant potency and protective index of neurosteroids such as allopregnanolone and the neurosteroid analog ganaxolone. The enhanced seizure susceptibility and benzodiazepine-resistance subsequent to neurosteroid withdrawal may be related to reduced expression and altered kinetics of synaptic GABA_A receptors and increased expression of GABA_A receptor subunits (such as α4) that confer benzodiazepine insensitivity. The enhanced potency of neurosteroids may be due to a relative increase after neurosteroid withdrawal in the expression of neurosteroid-sensitive δ-subunit-containing perisynaptic or extrasynaptic GABA_A receptors. Positive allosteric modulatory neurosteroids and synthetic analogs such as ganaxolone may be administered to prevent catamenial seizure exacerbations, in what we call neurosteroid replacement therapy.

中文翻译：

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经期癫痫的神经类固醇替代疗法。

经期围经期癫痫是在月经临近时周期性发作的癫痫发作，影响很大一部分患有药物难治性癫痫的育龄妇女。_{围经期经期癫痫发作易感性增强被认为是由于孕酮衍生的 GABA A}受体调节神经类固醇异孕酮的撤退，这是由于月经期间孕酮下降所致。对经期癫痫大鼠假妊娠模型的研究表明，神经类固醇停药后，对化学惊厥癫痫发作的易感性增强。经历过毛果芸香碱诱导的癫痫持续状态的癫痫大鼠的自发性癫痫发作频率也会短暂增加。在经期癫痫模型中，抗惊厥药物（包括苯二氮卓类和丙戊酸）的抗惊厥效力显着降低，但神经类固醇（例如四氢孕酮和神经类固醇类似物加奈索酮）的抗惊厥效力和保护指数增加。神经类固醇戒断后癫痫易感性和苯二氮卓类药物耐药性增强可能与突触 GABA _{A受体表达减少和动力学改变以及 GABA A}受体亚基（如 α4）表达增加有关，从而赋予苯二氮卓类药物不敏感性。_{神经类固醇效力的增强可能是由于神经类固醇停药后，神经类固醇敏感的含δ亚基的突触周围或突触外GABA A}受体的表达相对增加。可以使用正变构调节神经类固醇和合成类似物（例如加奈索酮）来预防经期癫痫发作加重，这就是我们所说的神经类固醇替代疗法。