Systemic evidence of acute seizure-associated elevation in serum neuronal injury biomarker in patients with temporal lobe epilepsy

Background: Patients with drug refractory temporal lobe epilepsy frequently accumulate cognitive impairment over time, suggesting loss of neurons induced by seizures. Our objective was to determine whether there is a temporal association between changes in serum levels of neural injury markers and electroencephalographic (EEG) evidence of seizures and interictal spikes. Methods: We measured serum levels of neuron-specific enolase (NSE), a neuronal injury marker, relative to levels of S100β, a marker of glial injury, at 6 AM, 9 AM, noon, 3 PM, and 6 PM over the course of several days in 7 epilepsy patients undergoing continuous video-EEG monitoring and in 4 healthy controls. Results: All epilepsy patients exhibited significant deviations in NSE levels through time, and 4 of the epilepsy patients exhibited large sample entropy values and large signal variation metrics for NSE relative to S100β. Controls did not exhibit such changes. Correlation analysis revealed that NSE levels were significantly elevated after seizures. There was also a highly significant relationship between increased EEG spike frequency and an increase in serum NSE levels measured 24 h later. Conclusions: The detection of large but transient post-ictal increases in NSE suggests that even self-limited seizures may cause an injury to neurons that underlies cognitive decline in some patients. While this study used a small patient population, the pilot findings suggest that post-ictal assessment of serum NSE may serve as a biomarker for measuring the efficacy of future acute neuroprotective strategies in epilepsy patients.