Epilepsy drug may help adults learn pitch

Results from a study shows that an epilepsy drug can help adults learn the rare skill of having perfect pitch.

Perfect pitch, also called absolute pitch, is the ability to accurately name any pitch you hear. People with perfect pitch can sing any note of the chromatic scale without hearing reference pitches first.

Until recently, perfect pitch was thought to be an innate ability that very few children possessed. The American Psychological Association estimates that only one in 10,000 Americans have the gift.

But according to a research report published last week, scientists have discovered that Valproate, a drug used to treat epilepsy, can help adults develop perfect pitch.

Research had shown that the drug enabled adult mice to learn habits that were previously only possible for mice to learn during youth.

Harvard researcher Takao Hensch and an international team of scientists, then, decided to give Valproate to a group of adult men who had no prior musical training. They asked the group to complete an online ear-training course that lasted for two weeks.

At the end of the trial, those who took Valproate were significantly better at identifying pitches than those taking a placebo.

Hensch, who is a professor of molecular and cellular biology at Harvard, recently discussed the research team's findings with Linda Wertheimer of NPR. "It's a mood-stabilizing drug, but we found that it also restores the plasticity of the brain to a juvenile state," Hensch said.

In other words, the drug seems to restore the ability to learn certain tasks that were once thought impossible to learn outside of childhood.

Of course, the implications of such a drug are enormous. It could help adults learn a new language and speak that language without an accent, abilities which are thought to peak in early childhood.

For a long time, perfect pitch was thought to be a result of nature, not nurture.

In the NPR interview, Hensch acknowledges that there is a genetic component. But he and many other researchers believe that perfect pitch can be acquired, through early musical training before age seven.

Other researchers disagree, saying that the ability to develop perfect pitch is genetic and can't be taught.

However, there is one point on which researchers tend to agree: It is impossible for adults to develop perfect pitch.

Many musicians regard perfect pitch as the holy grail, the ultimate musical gift. Mozart had perfect pitch, and many experts think Beethoven had it also.

The ability to instantly identify whether any pitch is sharp or flat can help string players play in tune. The ability to sing any pitch can help singers navigate densely chromatic music.

And perfect pitch can help any musician sight-read a difficult score. A drug that could aid adults in developing this ability would probably prove extremely popular among musicians.

But Hensch warns that scientists are only beginning to understand how Valproate affects the brain's ability to learn new things. And the drug is known to have side effects.

So, it may be a long time before Valproate is available to consumers for this purpose. And those who take such a medication may find that perfect pitch has its downside.

Those who have it might not enjoy listening to an orchestra that tunes to a concert "A" that is a little sharp or flat, as some orchestras do. And hearing the out-of-tune pitches of electric appliances, train whistles and other background noises in our environment could become annoying for a whole new reason.

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Research on women, pregnancy, and the effects of epilepsy

Research looks into women, pregnancy and folic acid supplementation, and how valproate, an antiepileptic drug, effects them.

New research pertaining to the latest findings on the effects of epilepsy on both the mother and child were presented at the American Epilepsy Society's 67th Annual Meeting in Washington DC. These studies explore folic acid use, the effect of surgery with intractable focal epilepsy, and antiepileptic drug exposure during breastfeeding.

Researchers from the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Boston, Massachusetts investigated the frequency of folic acidsupplement use by women with epilepsy in the community and factors that may predict its use (Platform B.04 / Abstract 1722353). Folic acid deficiency in early pregnancy is known to cause birth defects and increase the risk of miscarriages, which can occur most with enzyme-inducing antiepileptic drugs (AED). Neural tube malformations are most common with the use of Valproate, a folic acid antagonist.

Data for this study was collected through the Epilepsy Birth Control Registry (EBCR), a web-based survey and educational site used to gather key information from 626 women with epilepsy in the community. The study found that 44% of respondents took folic acid.

"Our findings show that only about half of the women surveyed are taking folic acid, despite their high risk of unintended pregnancies. Additionally, we found that many of the respondents who were not taking precaution of neural tube malformation were taking Valproate, a folic acid antagonist," said Andrew G. Herzog, MD, principal investigator of the study. "Overall the women at risk, regardless of antiepileptic drugs or contraceptive use, did not differ significantly from women not at risk and on no antiepileptic drugs."

In a related study, researchers from The Mayo Clinic-Rochester presented evidence to support the importance of early surgery in women with intractable focal epilepsylooking to get pregnant (Poster 3.250 / Abstract 1750307). One hundred and thirteen women were included in this study. An average of 0.93 pregnancies and 0.73 births were identified prior to surgery, compared to a significantly higher success rate of 1.27 pregnancies and 0.96 births post-surgery. A total of 17 women had a total of 35 pregnancies and 25 births after surgery. Those patients who received fewer medications prior to surgery were more likely to have additional children following surgery.

"While the significance of these findings is uncertain, we believe that they support a role for earlier surgical intervention in the management of intractable focal epilepsy and the relationship it has to conceiving and giving birth," said Rachel R. Fabris, MD, the lead author of this study.

A third study was presented as a follow up to previous research determining the effects of antiepileptic drug exposure via breast milk on IQ at age 3 years old. The new data collected was from a cohort of children at the age of 6, which the researchers deemed an age more predictive of school performance and adult abilities (Poster 2.213 / Abstract 1732174). While breastfeeding is known to have beneficial effects for both the child and the mother, there is concern regarding whether breastfeeding while taking antiepileptic drugs could be harmful to the cognitive development of the infant.

Results of the study were analyzed as a function of whether the children had been breastfed or not. Overall, 43% of the children were breastfed, but the results failed to show adverse effects of AED exposure: children who breastfed exhibited higher IQ and Verbal Index scores even though their mothers used AEDs.

"Our results are encouraging in that women with epilepsy can be less fearful of breastfeeding their baby," said the leader of this study, Kimford Meador, MD. "Nevertheless, this is a limited study and additional research is needed."

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Mechanism that valproate uses to block seizures understood

The mechanism by which the anti-epileptic drug valproate works is finally understood 50 years after the discovery of the drug.

50 years after valproate was first discovered, research published today in the journalNeurobiology of Disease, reports how the drug works to block seizure progression.

Valproate (variously labelled worldwide as Epilim, Depacon, Depakene, Depakote, Orlept, Episenta, Orfiril, and Convulex) is one of the world's most highly prescribed treatments for epilepsy. It was first discovered to be an effective treatment for epilepsy, by accident, in 1963 by a group of French scientists. In thousands of subsequent experiments, animals have been used to investigate how valproate blocks seizures, without success. Scientists from Royal Holloway and University College London have now identified how valproate blocks seizures in the brain, by using a simple amoeba.

"The discovery of how valproate blocks seizures, initially using the social amoeba Dictyostelium, and then replicated using accepted seizure models, highlights the successful use of non-animal testing in biomedical research," said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.

"Sodium valproate is one of the most effective antiepileptic drugs in many people with epilepsy, but its use has been limited by side-effects, in particular its effect in pregnant women on the unborn child," said Professor Matthew Walker from the Institute of Neurology at University College London. "Understanding valproate's mechanism of action is a first step to developing even more effective drugs that lack many of valproate's side-effects.

"Our study also found that the decrease of a specific chemical in the brain at the start of the seizure causes even more seizure activity. This holds important implications for identifying underlying causes," added Professor Williams.

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Children of pregnant women who use anti-epileptic drug may have increased risk of autism

Pregnant mothers who use valproate, an anti-epilepsy drug, may have children with an increased risk of autism. Dont jump to assume causation.  With the finding that autism is noted in families with other neuro-psychiatric illness, there may be some confounding variables in this observation. - JR

Maternal use of valproate (a drug used for the treatment of epilepsy and other neuropsychological disorders) during pregnancy was associated with a significantly increased risk of autism in offspring, according to a study in the April 24 issue of JAMA. The authors caution that these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

"Anti-epileptic drug exposure during pregnancy has been associated with an increased risk for congenital malformations and delayed cognitive development in the offspring, but little is known about the risk of other serious neuropsychiatric disorders," according to background information in the article.

Jakob Christensen, Ph.D., of Aarhus University Hospital, Aarhus, Denmark, and colleagues evaluated the association between maternal use of valproate during pregnancy and the risk of autism spectrum disorder and childhood autism in offspring. The population-based study included all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). Data were analyzed and adjusted for potential confounders (factors that can influence outcomes) such as maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity. Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.

The analysis included 655,615 children born from 1996 through 2006. The average age of the children at end of follow-up was 8.8 years. During the study period, 5,437 children were diagnosed with autism spectrum disorder, including 2,067 with childhood autism. The researchers identified 2,644 children exposed to antiepileptic drugs during pregnancy, including 508 exposed to valproate. The authors found that use of valproate during pregnancy was associated with an absolute risk of 4.42 percent for autism spectrum disorder and an absolute risk of 2.50 percent for childhood autism.

"In this population-based cohort study, children of women who used valproate during pregnancy had a higher risk of autism spectrum disorder and childhood autism compared with children of women who did not use valproate. Their risks were also higher than those for children of women who were previous users of valproate but who stopped before their pregnancy," the researchers write.

"Because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance. Still, the absolute risk of autism spectrum disorder was less than 5 percent, which is important to take into account when counseling women about the use of valproate in pregnancy."

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Link Found Between Epilepsy Drug in Pregnancy and Lower IQ

A study found that mothers who took the epilepsy drug valproate resulted in a lower IQ of the child at age 6. This effect was proportional to the dosage of valproate.

Children of mothers who take the antiepileptic drug valproate during pregnancy have lower IQ scores at age 6, a new study says.

And the higher the dose of valproate during pregnancy, the greater the effect on a child's IQ, according to the report published in the Jan. 22 issue of The Lancet Neurology.

For the study, the researchers looked at 305 pregnant women in the United States and United Kingdom who took a single drug to treat the seizure disorder -- either valproate (Depakote), carbamazepine (Tegretol), lamotrigine (Lamictal) or phenytoin (Dilantin).

At age 6, the IQ of children whose mothers took valproate during pregnancy was seven to 10 points lower than children whose mothers took another antiepileptic drug. Exposure to valproate was also associated with poorer speaking and memory abilities.

"These results build on our earlier work to show that valproate usage during pregnancy has a significant negative effect on children's IQ, which lasts beyond their earliest years," said study leader Kimford Meador, a professor in the neurology department at Emory University in Atlanta.

"IQ at age 6 is strongly predictive of adult IQ and school performance, so our research suggests that valproate use during pregnancy is likely to have long-term negative effects on a child's IQ and other cognitive [mental] abilities," Meador added in a journal news release.

Another expert said the study is practice-changing.

"This important work has changed the way we practice neurology, leading us to conclude that valproate should not be used, if at all possible, in women of child-bearing potential," said Dr. Cynthia Harden, chief of the division of epilepsy and electroencephalography at the Cushing Neuroscience Institute in Manhasset, N.Y.

"The risks of valproate during pregnancy are clearly demonstrated, as the children in this research cohort continue to grow," said Harden.

However, the researchers also found that over time IQ may improve for children exposed to valproate in the womb, and that folic acid supplementation in mothers-to-be may improve children's IQ scores.

Harden called the finding about folic acid's mitigating effect "reassuring and fascinating, since the mechanism of how intrauterine valproate exposure causes cognitive [thinking] and behavioral problems in children is unknown."

For some patients, valproate is the only drug that can control their seizures. This may give particular importance to the findings that higher drug doses have a greater impact on IQ and that folic acid supplementation may have a positive effect on IQ, the researchers said.

Meador said more research in this area is urgently needed, given that many women with epilepsy do not have the option of stopping medication during pregnancy.

After a 2009 study found that taking valproate during pregnancy affected children's IQ at age 3, the U.S. Food and Drug Administration issued a warning that valproate exposure in the womb is associated with impaired mental function in children.

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