November 2019, ScientificAmerican.com 21SCIENCE SOURCEMEDICINESeizure
Warnings
Molecules in the blood could alert
those with epilepsy hours aheadMore than 50 million people worldwide
have epilepsy, and one of its harshest as-
pects is its unpredictability. Sufferers rarely
know when a seizure will occur.
But molecular biologist Marion Hogg
of FutureNeuro, a research institute hosted
at the Royal College of Surgeons in Ireland,
and her colleagues have found molecules
whose levels in the bloodstream differ be-
fore and after a seizure. This discovery
could lead to a blood test that gauges
when seizures are likely to strike, enabling
patients to take fast-acting preventive
drugs. The study, published in July in the
Journal of Clinical Investigation, may even
offer clues about epilepsy’s causes.
The researchers analyzed plasma sam-
ples from the blood of people with epilepsy
and found that certain fragments of trans-
fer RNA (tRNA)—a molecule involved in
translating RNA into proteins—appear to
spike hours before a seizure, then return to
a normal level afterward. These fragments
form when enzymes cut tRNAs in response
to stress, possibly caused by increased
brain activity in the run-up to a seizure.
Neurologist Mark Cook of St. Vincent’s
Hospital in Melbourne, Australia, who was
not involved in the work, says the tRNA fluc-
tuations could reflect the rhythms of biologi-
cal clocks. “In adults with chronic epilepsy,we see cycles running over seven, 28, 40
days,” Cook says. “These patterns control
brain excitability, making you more or less li-
able to seizures.” The new findings may thus
ultimately lead to a better understanding of
the causes of epilepsy. “We haven’t known
what’s driving the cycles, but there may be
a clue here that there are genes driving the
system, generating these fragments, which
allow prediction of seizures,” Cook says.
“That’s very exciting because it tells you
something not only about epilepsy but about
how the brain works.”
Cook’s group previously predicted sei-
zures by monitoring brain activity, but that
required invasive surgery. FutureNeuro re-
searchers are working on a seizure-predic-
tion device that uses pinprick blood tests
at home, similar to a glucose monitor. The
study’s analysis needed relatively large
amounts of plasma separated from blood—
so an immediate challenge is developing a
device that works both with small samples
and with whole blood. “We anticipate such
a device may be available for patients to
use in the next five years,” Hogg says.
Advance warnings could make a major
difference in patients’ lives. “If you had an
indication, perhaps you wouldn’t go into
work, or drive, or go swimming,” Hogg
says. And although some epilepsy drugs
are fast-acting, most are for long-term
management—but nearly a third of pa-
tients do not respond to the latter. Cook
says that accurate seizure prediction
would encourage drug development for
acute use, which could mean fewer side
effects as compared with a daily regimen.
— Simon MakinBrain scan shows activity
caused by epilepsy.© 2019 Scientific AmericanSCIENCE SOURCEMEDICINESeizure
Warnings
Molecules in the blood could alert
those with epilepsy hours aheadMore than 50 million people worldwide
have epilepsy, and one of its harshest as-
pects is its unpredictability. Suff erers rarely
know when a seizure will occur.
But molecular biologist Marion Hogg
of FutureNeuro, a research institute hosted
at the Royal College of Surgeons in Ireland,
and her colleagues have found molecules
whose levels in the bloodstream diff er be-
fore and after a seizure. This discovery
could lead to a blood test that gauges
when seizures are likely to strike, enabling
patients to take fast-acting preventive
drugs. The study, published in July in the
Journal of Clinical Investigation, may even
off er clues about epilepsy’s causes.
The researchers analyzed plasma sam-
ples from the blood of people with epilepsy
and found that certain fragments of trans-
fer RNA (tRNA)—a molecule involved in
translating RNA into proteins—appear to
spike hours before a seizure, then return to
a normal level afterward. These fragments
form when enzymes cut tRNAs in response
to stress, possibly caused by increased
brain activity in the run-up to a seizure.
Neurologist Mark Cook of St. Vincent’s
Hospital in Melbourne, Australia, who was
not involved in the work, says the tRNA fl uc-
tuations could refl ect the rhythms of biologi-
cal clocks. “In adults with chronic epilepsy,we see cycles running over seven, 28, 40
days,” Cook says. “These patterns control
brain excitability, making you more or less li-
able to seizures.” The new fi ndings may thus
ultimately lead to a better understanding of
the causes of epilepsy. “We haven’t known
what’s driving the cycles, but there may be
a clue here that there are genes driving the
system, generating these fragments, which
allow prediction of seizures,” Cook says.
“That’s very exciting because it tells you
something not only about epilepsy but about
how the brain works.”
Cook’s group previously predicted sei-
zures by monitoring brain activity, but that
required invasive surgery. FutureNeuro re-
searchers are working on a seizure-predic-
tion device that uses pinprick blood tests
at home, similar to a glucose monitor. The
study’s analysis needed relatively large
amounts of plasma separated from blood—
so an immediate challenge is developing a
device that works both with small samples
and with whole blood. “We anticipate such
a device may be available for patients to
use in the next fi ve years,” Hogg says.
Advance warnings could make a major
diff erence in patients’ lives. “If you had an
indication, perhaps you wouldn’t go into
work, or drive, or go swimming,” Hogg
says. And although some epilepsy drugs
are fast-acting, most are for long-term
management—but nearly a third of pa-
tients do not respond to the latter. Cook
says that accurate seizure prediction
would encourage drug development for
acute use, which could mean fewer side
eff ects as compared with a daily regimen.
— Simon MakinBrain scan shows activity
caused by epilepsy.sad1119Adva3p.indd 21 9/18/19 5:19 PM
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