Fast Ripples
Making Waves as First Reliable Biomarker for Epilepsy
Caroline
Cassels
Medscape Medical
News 2006. © 2006 Medscape
December
12, 2006 (San Diego) — Fast ripples — brief, high-frequency, interictal
oscillations — are showing promise as the first reliable biomarker for
epilepsy, says a leading expert.
Here at the First North American
Epilepsy Regional Congress, Jerome Engel, MD, PhD, whose group at the
David Geffen School of Medicine at the University of California, Los
Angeles, first described fast ripples in 1999, told delegates attending
the presidential symposium that fast ripples not only may provide
clinicians with an accurate diagnostic tool but also may have the ability
to predict epilepsy, assess treatment efficacy in a timely manner, and aid
in the development of rapid screening methods to identify new
antiepileptic compounds.
"Currently, there are no reliable
surrogate markers for epilepsy, which is one of the holy grails in all
diseases. Right now we use interictal EEG spikes [to diagnose epilepsy],
but they tend to be nonspecific and don't indicate where seizures
originate, so they are less than ideal," Dr. Engel told
Medscape.
Animal models of temporal lobe epilepsy (TLE), as well as
human data, show that fast ripples are specific to the area of the brain
that generates seizures. Furthermore, said Dr. Engel, research has also
shown fast ripples correlate with the severity of epilepsy and are able to
predict which animals will develop seizures following brain
injury.
If fast ripples ultimately turn out to be a reliable
biomarker, and particularly if a method to record them noninvasively can
be found, this could revolutionize epilepsy diagnosis, treatment, and
research, particularly in TLE, the most common and most
treatment-resistant form of the disease, he said.
Dr. Engel noted
that medical treatment of epilepsy currently consists of a trial-and-error
strategy. "We give a drug and we don't know whether it works or not until
it is confirmed by the presence or absence of another seizure. This
approach can take months or even years. In the meantime, another seizure
could be devastating and even result in death," he said.
A study
conducted by Anne Berg, PhD, from Northern Illinois University, in DeKalb,
and published in Neurology
in 2003 (Berg AT et al. Neurology.
2003;60:186-190)
found that among
patients with intractable epilepsy, it took an average of 9 years to prove
medical therapy was ineffective.
Furthermore, the same study found
that among patients who eventually received surgical treatment, it took an
average of 22 years before they were referred.
According to the American
Epilepsy Society, 60% to 70% of theUS
epilepsy population has good seizure control with medication. Of the
remaining 20% to 30%, half are potential surgical candidates. Even though
surgical success rates are in the range of 70% to 90%, only a very small
percentage of these patients are ever referred for surgery.
Surgery
Underutilized
Right now, said Dr. Engel, surgery is
greatly underutilized. Part of the reason for this is that presurgical
evaluation is time consuming, expensive, and due to the fact that
electrodes have to be placed directly into the brain to record seizures,
is frequently associated with considerable risk.
He estimated there
are probably "a few hundred thousand patients" in the United States alone who are potential surgical
candidates but maybe only 3000 a year actually receive this form of
treatment.
"A good biomarker that could accurately detect the
presence and severity of epilepsy would allow us to make a definitive
diagnosis and localize the area of the brain that needs to be resected
with a single test. This would greatly increase the number of patients who
would receive and benefit from surgery," he said.
In addition, Dr.
Engel noted, there is a great deal of ongoing research investigating ways
of preventing epilepsy in individuals who are at high risk because they
have suffered traumatic brain injury or had an intracranial infection.
Although such treatments are still in the experimental stages, it is
feasible that in the future an accurate biomarker could help identify
which patients would be most likely to benefit from epilepsy
prophylaxis.
Next
Challenge
Finally, said Dr. Engel, if fast ripples live
up to their expected potential, it would provide scientists with a rapid,
inexpensive method of identifying new drug compounds.
"Testing drug
compounds in animal models of epilepsy is time consuming and expensive. If
we had a cheap surrogate marker of temporal lobe epilepsy, we could screen
thousands of drugs very quickly and cheaply," he said.
However,
before any of this can occur, researchers' face the challenge of finding a
noninvasive method of measuring fast ripples.
"Right now, fast
ripples can be recorded only with electrodes implanted directly into the
brain. Obviously, it is not practical or desirable to do this in large
numbers of patients," he said.
One possible method is to use
magnetoencephalography, which has the capability of recording signals deep
within the brain that cannot be picked up with EEG. Another possible
method he said is to use a combination of functional MRI and EEG
testing.
First North American Epilepsy Congress: 60th Annual
Meeting of the American Epilepsy Society: Presented December 3, 2006.
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