A Prospective, Phase 4, Open-Label, Twelve-Week Study to Examine the Cognitive Impact and Tolerability of Levetiracetam (Keppra) in Elderly Patients With Seizures of Partial Onset

This is a prospective, phase 4, open label, twelve week study. The study will consist of a 4 week titration phase followed by an 8 week assessment phase. All clinic visits will be conducted at Drexel University College of Medicine Department of Neurology at 219 N. Broad St., Phila., PA.

Visit one will include reviewing and signing the written informed consent form, obtaining relevant demographic data, and then routine blood work. The baseline frequency, duration and type of seizures our subjects experience will be documented, as will their current antiepileptic medications. Baseline history and a physical and neurological examination will be performed, including vital signs. Testing will include baseline measurements of cognition, function (activities of daily living), and behavior. Cognitive testing will include Folstein's Minimental State examination (MMSE), and the ADAS-cog. Our overall assessment will include the Modified Schwab and England Activities of Daily Living Scale. Behavioral assessment will include Tariot's Behavior Ratings Scale and the Cohen-Mansfield Agitation Inventory (CMAI; long form). Levetiracetam will be initiated and instructions for follow up will be given. Because the goal is cognitive tolerability, Levetiracetam will be used as either an add-on agent or as primary monotherapy.

During week two, a follow up telephone assessment will be done to review the instructions and to determine whether any medical changes or adverse events occurred. Adverse events will be assessed by direct questioning and spontaneous patient/caregiver reports. The date, number, duration and type of seizures any of our subjects experience will also be documented.

At the third assessment (week 4), a follow up physical and neurological examination will be done, including vital signs, and the mental testing, including the tests of cognition, function and behavior will be repeated. An assessment will be made to determine whether adverse events occurred. Adverse events will be assessed by review of the subject's seizure log, physician observation, direct questioning and spontaneous reports. The date, number, duration and type of seizures any subject experiences will also be documented. In cases where levetiracetam is an add-on agent, we will attempt to taper the preceding medications if seizure control has been demonstrated. Cognitive testing will be done when subjects are not in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to another day within one week.

At week twelve, a full follow up mental status assessment will be done for the final assessment. Testing will be the same as that done at weeks 1 (baseline) and 4. Again, cognitive testing will not be done when subjects are in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to the next available day, within one week.