Does Treatment-resistant Epilepsy Get Better or Worse Over Time?
Ojas Potnis1, Gabriel Biondo2, Rachel Sukonik3, Caitlin Grzeskowiak4, Gary Cutter5, Joseph Medina6, Jacqueline French7
1School of Medicine, Enmed, Texas A&M, 2University of Notre Dame, 3University of Delaware, 4Epilepsy Foundation of America, 5School of Public Health, University of Alabama At Birmingham, 6NYU Langone BRAIN Program, 7NYU Grossman School of Medicine
Objective:

Characterize focal treatment resistant epilepsy seizure frequency natural history.

Background:

Does focal treatment resistant epilepsy (FTRE) improve or worsen over time? This is an important question, as many open label long-term extension studies of anti-seizure medications (ASMs) and devices suggest improvement over time, and invoke a possible disease modifying effect. The Human Epilepsy Project 2 is a prospective, observational, multicenter US study aimed at identifying treatment response in participants with FTRE. Here, we report trends in seizure frequency for participants during the study.

Design/Methods:

All participants had FTRE, failed ≥4 ASMs, were receiving ≥1 ASM, and were followed ≤36 months. Seizure frequency data were collected via daily electronic seizure diaries, monthly coordinator check-ins, medical records. To prevent confounding by dropouts, we compared first half of follow-up to second half within each participant. Three cohorts were also created based on follow-up times of <12, 12-24, >24 months. We examined all data in a linear mixed  model with response variable of monthly seizure counts and independent variable of follow-up month to examine slopes of the seizure counts over time within each cohort.

Results:

128 actively enrolled participants provided seizure frequency data over time. 68.2% experienced seizure frequency reduction in the second half of their follow-up compared to the first half. Linear regression analysis demonstrated continued improvement of approximately 1 seizure/month. The trend in the LS Means seizure count estimated from the models for each cohort showed similar decreases in estimated seizure counts over the projected months of follow-up.

Conclusions:

Our data suggests improvement of seizures over time in FTRE. The data cannot distinguish between “natural history” and effects of ongoing active management. However, these data support the need for cautious interpretation of open-label studies that report improvement trends over time. Future analyses of our data will address impact of specific medication interventions during the study.

10.1212/WNL.0000000000206664