Cognitive Effects of Treatment of Interictal Discharges

Subjects with seizures will be studied with electroencephalography (EEG) and offered
medication for prevention of recurrent seizures. Those with focal seizures will be treated
with levetiracetam, and those with generalized seizures will be treated with lamotrigine.
Subjects will undergo repeated EEG with concurrent cognitive testing before and after
initiation of treatment. The proposed study tests 3 hypotheses: 1. that treatment with
levetiracetam will reduce focal interictal epileptiform activity, 2. that treatment with
lamotrigine will reduce generalized interictal epileptiform activity, and 3. that the extent
of interictal epileptiform activity is inversely associated with performance on
neuropsychological batteries and computerized cognitive testing. Repeated
cognitive/neuropsychological testing obtained at steady state of the study drug and again
after approximately 2 months on the final dosage will serve to evaluate the timecourse of
potential cognitive benefits.

Inclusion Criteria

- 18-55 years of age

- Normal Intelligence Quotient (IQ ≥ 80) as estimated by the Wechsler Test of Adult
Reading (WTAR)

- Able to give consent

- The subject's treating physician is planning to prescribe levetiracetam for focal or
lamotrigine for generalized seizure prevention

- Either symptomatic or idiopathic seizures.

Exclusion Criteria:

- Non-native English speaking and/or multilingual

- Frequent seizures, since seizures themselves impair cognitive function and present a
confounding variable. Subjects may have no more than one seizure or one cluster of
seizures per month, with a cluster of seizures including more than one seizure, but
between which the patient returns to baseline. The cluster may occur over no more than
two consecutive days in one month.

- Seizure(s) must not have occurred within 3 days of enrollment and testing.

- Those with focal seizures who have evidence of renal disease (creatinine clearance
less than 80) will be excluded from participation, as levetiracetam is cleared by the
kidney.

- Those with focal seizures who have neutrophil counts <1000/microliter will be excluded
from participation, as levetiracetam may lower white blood cell counts.

- Those with focal seizures and irritability or mood swings will not be eligible for
participation, as levetiracetam may exacerbate these symptoms. This will be determined
by self-report, information obtained from the referring physician and medical record.

- Those with generalized seizures who have moderate to severe liver dysfunction
(Child-Pugh Grades B and C) will be excluded from participation, as lamotrigine is
cleared by the liver and the proposed dosing may not be tolerable in this population.
This will be determined by self-report, information obtained from the referring
physician, a comprehensive metabolic panel (routinely obtained in new-onset seizures)
and the medical record.

- Subjects who are pregnant will not be eligible to take part in the study, as
levetiracetam and lamotrigine are classified as Pregnancy Category C drugs and may
pose risk to the fetus. Women of childbearing potential will have a urine pregnancy
test prior to participation in the study. The urine pregnancy test will be repeated at
the final study visit. Subjects with epilepsy who are of childbearing potential must
use acceptable methods of birth control during the study, to be continued until one
month after discontinuation of the study drug. If a subject does become pregnant
during this time period, she must notify the investigators.

- Women who are breastfeeding may not participate in this study. Levetiracetam and
lamotrigine may pass into the breastmilk of nursing mothers, posing a risk to the
baby.

- Hypersensitivity to lamotrigine, levetiracetam or any components of these products