Abstracts

Rationale: Compared to patients whose epilepsy is well-controlled with anti-epileptic drugs, patients with poorly controlled epilepsy often experience worse morbidity and mortality, and accelerated aging. The plasma biomarkers P-tau217 and P-tau181 have been shown to align with CSF P-tau values, amyloid PET and correlate with both clinical and pathologic diagnoses of Alzheimer’s Disease (AD). These minimally invasive biomarkers facilitate investigations into the relationships between neurodegenerative proteins and epilepsy. In this study, we analyzed P-tau217 and P-tau181 levels in patients with poorly-controlled (PC) and well-controlled (WC) epilepsy to explore whether poor seizure control correlates with elevated biomarkers of neurodegenerative proteins.

Methods: We prospectively recruited persons with epilepsy aged 18 to 65 years from the Brigham and women’s epilepsy clinic over a 3-year period. Exclusion criteria included: 1- seizure within 24 hours of the sample, 2- Ongoing infection, 3-Seizures limited to focal aware seizures, 4- Recent surgical procedures, 5-Renal or hepatic insufficiency, and 6-antiseizure medication changes within the past 4 weeks. Demographics and time since last seizure were extracted from the electronic health records. Epilepsy-related factors were also extracted including seizure frequency, seizure location, and presence or absence of MRI lesions. Participants were divided into those who have had a seizure within the past 6 months (PC) vs. those who haven’t (WC).

Results: Plasma was collected from 103 persons with focal epilepsy 48 WC (31.3% female) and 55 (50.9% female) PC. 89% of the poorly controlled group were medically refractory and had failed at least 2 antiseizure medications. The mean age of the participants was 39.9 ±11.8 years for WC, 35.9 ± 11.7 years for PC. The mean number of days since last seizure was 1768 ± 1814 days in WC and 38.8 ± 38.6 days in PC, and 54.9% of participants had an abnormal MRI (44.7% of WC, 63.6% of PC). The most common epilepsy location was temporal in both groups (72% WC, 71% PC).

There was no significant difference in P-tau217 (p = 0.7155) or P-tau181 (p = 0.8739) levels between the two groups (The mean P-tau217 was 83.3 pg/ml (SD =118.5) in WC, and 83.7 pg/ml (SD =66.1) in PC. The mean P-tau181 was 14.3 pg/ml (SD = 13.7) in WC, and 13.9 (SD = 16.9) in PC. Further analysis revealed that P-tau217 and P-tau181 levels did not correlate significantly with age (ρ=-0.15 p = 0.14, ρ=-0.15 p= 0.13), MRI abnormality (p = 0.70, p = 0.19), duration of disease (ρ=-0.14 p = 0.07, ρ=-0.18 p= 0.15), seizure frequency per month (ρ=-0.11 p = 0.50, ρ=-0.09 p= 0.48), or log transformed days since last seizure (ρ=+0.03 p= 0.80, ρ=-0.09, p= 0.77).


Conclusions: Our results indicate that interictal biomarkers of neurodegenerative proteins are not elevated in adults with poorly controlled epilepsy, and do not correlate with the days since last seizure. Future studies need to explore whether there is a subpopulation at risk, and predictors of accelerated aging.

Funding: N/A