Objective:

Investigation of prevalence and impact of neurodegenerative protein accumulation in epilepsy.

Background:

Emerging evidence indicates abnormal accumulation of neurodegenerative proteins such as tau and amyloid-β in epilepsy, though their role in cognitive impairment independent of Alzheimer’s disease is uncertain.

Design/Methods:

Review included peer-reviewed articles from PUBMED MEDLINE, Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials published before July 7, 2024. Eligible studies included neurodegenerative protein pathology in epilepsy. Only English-language articles were included. This review adhered to PRISMA guidelines, and the risk of bias was assessed using the ROBANS 2 tool.

Results:

Of 2,071 articles screened, 42 met inclusion criteria, with the majority being retrospective cohorts(n=26). Most studies involved temporal or mesial temporal lobe epilepsy(TLE/MTLE) or drug-resistant epilepsy(DRE) with hippocampal sclerosis. Across studies, 57% of 1,544 patients were male, with mean onset ages ranging from 4.3–25.1 years, mean age at analysis 9–56.5 years, and disease durations of 9.2–42.3 years. Focal impaired awareness seizures predominated, often with secondary generalization. Fourteen studies included DRE populations, with carbamazepine and phenytoin most used. Phosphorylated tau was detected in 3–95% of epilepsy cases across 33 studies, typically elevated in MTLE/HS and associated with older age, longer duration, and poorer cognition. Amyloid pathology appeared in 14 of 25 studies. Cognitive impairment coexisted with neurodegenerative protein accumulation but showed inconsistent correlations.

Conclusions:

Neurodegenerative protein accumulation, including tau, amyloid-β, is common in epilepsy, especially with chronic or drug-resistant disease. Tau and amyloid were associated with older age, longer epilepsy duration, and cognitive impairment, though correlations with cognition were inconsistent. Epilepsy chronicity, rather than seizure type, appears most strongly linked to protein pathology.