Seizing an opportunity: broader definitions of epilepsy may lead to better treatments

Abstract

There is not just one type of epilepsy. While some forms of the disease are characterized by convulsive seizures, others involve seizures that are barely noticeable. Seizures can occur for many reasons: they can be caused by genetic mutations, injury, or infection early in life. In addition, events in daily life, such as stress, or normal variations in hormones, such as estrogen and testosterone, can influence brain activity and therefore influence seizures. By considering the powerful interactions between the brain and the endocrine system, this influence of hormones on seizures can be understood and new treatment options can be considered.

Diagram 1.

The estrogen/progesterone hypothesis for catamenial epilepsy. A diagram of the time line of the menstrual cycle, which lasts 28 days, and is divided into a follicular phase and a luteal phase. The excitatory effects of estrogen and the inhibitory effects of progesterone have been used to explain the two times during the menstrual cycle when symptoms usually worsen: the periovulatory period, at approximately day 14, and the perimenstrual period, at approximately day 28 (yellow bars). Progesterone “withdrawal” has also been suggested as an explanation of perimenstrual seizures.

Diagram 2.

Indirect effects of estrogen and progesterone that are excitatory (green) or inhibitory (red) provide an explanation for catamenial epilepsy. Indirect excitatory effects of estrogen include those mediated by brain-derived neurotrophic factor (BDNF). BDNF synthesis in the brain is induced by estrogen, and BDNF increases neuronal activity. Indirect inhibitory effects of progesterone (red) are mediated by its metabolite allopregnanolone, which increases the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. During the periods marked by the yellow bars, the excitatory effects (green) are greater than the inhibitory effects (red), which could lead to a decrease in seizure threshold.