Clinical Implications of Small Sharp Spikes in Mesial Temporal Lobe Epilepsy: Controversies and Opportunities

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of focal epilepsy, marked by significant comorbidities including memory impairment, depression, panic, and bipolar disorders, rendering it highly incapacitating. However, early diagnosis remains challenging due to a prolonged latent period, subtle prodromal symptoms, and scant scalp EEG manifestation of hippocampal epileptiform activity. Consequently, identification of early biomarkers for mTLE is crucial. Small sharp spikes (SSSs) have traditionally been considered benign EEG patterns as they are inconsistently correlated with epilepsy, almost equally occurring in patients with and without epilepsy. Recent studies, however, have demonstrated a time-locked association between SSS and hippocampal spikes in patients with mTLE, which strongly suggests that SSS represent pathologic EEG biomarkers of mTLE, challenging the prevailing belief that SSS are benign EEG patterns. Nonetheless, the clinical significance of SSS remains controversial, particularly in patients without a diagnosis of epilepsy. Considering that patients without a diagnosis of epilepsy displaying SSS often exhibit prodromal symptoms reminiscent of those seen in mTLE, prompting EEG investigation, which raises the possibility that these patients are likely in the latent period of mTLE and suspicious for epilepsy. Therefore, SSS might be early biomarkers for mTLE. A correlation between SSS and hippocampal spikes might also exist among these patients. The implication of SSS as early EEG biomarkers is profound, enabling early diagnosis and providing a window for antiseizure and disease-modifying interventions for patients with mTLE. Here, we critically reappraise the clinical significance of SSS and explore the perspectives of SSS as early pathologic EEG markers for mTLE.