Pauline Anderson

December 15, 2017

WASHINGTON, DC — Seizure onset is not only linked to the start of menarche but spans several years before, and after, it occurs, according to findings that suggest at-risk girls may benefit from preventive therapy during this timeframe.

Investigators found that 49% of women with epilepsy had their first seizure 2 years before and 6 years after the start of their first menstrual period.

The results suggest that girls at risk for epilepsy should potentially be treated to prevent seizures, Andrew G. Herzog, MD, professor of neurology, Harvard Medical School and director, Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, told Medscape Medical News.

The findings were presented here at the American Epilepsy Society (AES) 71st Annual Meeting 2017.

Adolescent Peak

Adolescence represents one of three periods of "peak" seizure onset over the life span. The other two peaks occur in the first year of life and after midlife, said Dr Herzog.

The peak in adolescent girls has been linked to the development of female hormones, some of which, particularly estrogen, are highly neuro-excitatory. However, research into the association between hormones and seizures has been "inconsistent," he noted.

To investigate further, Dr Herzog and colleagues used retrospective data from the Epilepsy Birth Control Registry, a Web-based survey of 1144 women with epilepsy, aged 18 to 47 years. Registry participants provide information on demographics, epilepsy type, and use of antiepileptic drugs, as well as reproductive and contraceptive data.  

The study showed that the average age of menarche among women in the survey was 12.55 years (95% confidence interval [CI], 12.45 - 12.65 years). The mean age was a little later in women who had their seizures before menarche compared with after menarche.

Seizure onset occurred in more women during the year of menarche than any other year. This was four times more than expected (8.3% vs a randomly expected 2.1%).

The researchers looked at whether there was a grouping of years rather than just 1 year that was related to the seizure onset.

"Menarche is a clinically readily identifiable point in time, but it really represents a process of hormone development over years," said Dr Herzog.

This analysis identified three clusters. The one with the highest frequency for seizure onset spanned 9 continuous years that included 2 years before, through the 6 years after, menarche. This span accounted for 49.3% of seizure onset, he added.

"So almost half of the women, in fact, had seizure onset during this span — that's 2.5 times greater than expected."

Would Progesterone Help?

This finding, said Dr Herzog, "correlates very closely with the process of adrenarche, during which time there is a 10-fold increase in neuro-excitatory steroids."

Adrenarche refers to the early stage of sexual maturation that typically occurs in early puberty, around 10 or 11 years. During this stage, the adrenal cortex secretes increased levels of androgens.

The new findings may influence treatment approaches for children at risk for epilepsy, such as those with an inherited tendency to develop seizures, or with a traumatic brain injury, said Dr Herzog.

"In these patients, the question is, Should you consider suppressing some of these excitatory steroids in late childhood?"

In children with absence seizures who tend to remit during adrenarche, "maybe you could have them remit earlier if you introduce them to some of these hormones earlier on if other treatments don't work," he said.

Another issue is whether to introduce progesterone. Anecdotally, progesterone suppresses seizures, something that has been confirmed in open-label studies, although a larger randomized controlled trial did not bear this out.

"The question is, in girls who are at risk of seizures, should you cycle them with natural progesterone during the early anovulatory cycles, or, if they already have seizures that become intractable, should you then cycle them with progesterone?"

"Intriguing" Findings

Commenting on this research for Medscape Medical News, Jacqueline French, MD, Professor, NYU Comprehensive Epilepsy Center, New York City, described it as "intriguing."

However, she noted that the study was retrospective, with information coming from a self-report registry.

"Now that they have a registry and people are writing the information in that registry, they somehow believe that it's more valid than just asking people in the clinic, but it seems to me that it's kind of the same thing," said Dr French.

"This needs to be looked at prospectively."

Dr Herzog acknowledged that tracking menses and seizure activity though charts is "primitive." He said he would like to see a "biochemical marker" developed.

It looks like the research aims to determine whether estrogen, which is believed to lower the seizure "threshold," actually produces epilepsy, said Dr French.

"But if that was the case, you would expect there would be more women with epilepsy than men, and that's not the case, as far as we know."

She said she would like to see more research on age of seizure onset in boys.

"It would be good to know when epilepsy onset is in boys and whether it differs from epilepsy onset in girls."

The study was funded by the Epilepsy Foundation and Lundbeck. Dr Herzog and Dr French have disclosed no relevant financial relationships.

American Epilepsy Society (AES) 2017 Annual Meeting. Abstract 1.216. Presented December 2, 2017.

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