Divergent Propagation Networks Define Two Pathophysiologically Distinct Electroclinical Phenotypes in Mesial Temporal...

Area of Science:

• Neuroscience
• Epileptology
• Clinical Neurology

Background:

• Mesial temporal lobe epilepsy (MTLE) exhibits temporal dissociation between electrographic and clinical seizure onset, suggesting underlying network heterogeneity.
• This heterogeneity implies that MTLE may comprise distinct electroclinical phenotypes characterized by different seizure propagation dynamics.

Purpose of the Study:

• To investigate the hypothesis that MTLE consists of distinct electroclinical phenotypes.
• To define these phenotypes based on divergent seizure propagation dynamics using scalp and stereoelectroencephalography (SEEG).

Main Methods:

• Retrospective analysis of 167 seizures from 13 patients with drug-resistant MTLE and Engel Class I surgical outcomes.
• Classification of patients into EEG-first (n=7) or Clinical-first (n=6) based on the predominant relationship between scalp EEG and clinical onset.
• Assessment of seizure onset patterns, propagation pathways, and temporal dynamics using scalp EEG and SEEG.

Main Results:

• EEG-first seizures showed scalp EEG changes preceding clinical signs (70.5%) with longer SEEG-to-clinical latency and specific onset patterns (rhythmic theta/low-voltage fast activity).
• Clinical-first seizures exhibited the reverse onset order (65.8%) with heterogeneous scalp patterns (theta, delta-theta, delta slowing).
• Seizure propagation differed, with anterior pathways more common in EEG-first and posterior pathways in Clinical-first, though with overlap.

Conclusions:

• MTLE comprises two distinct pathophysiological phenotypes: EEG-first (slowly propagating anterior mesial network) and Clinical-first (rapidly spreading posterior network).
• This classification provides a mechanistic framework for understanding electroclinical dissociation in MTLE.
• The findings may refine presurgical evaluation strategies for patients with MTLE.