Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

Area of Science:

• Neuroscience
• Epileptology
• Critical Care Medicine

Background:

• Spreading depolarization (SD) involves massive ion shifts and neuronal swelling, distinct from epileptic seizures characterized by sustained sub-threshold depolarization.
• Historical animal studies suggested a link between SD and seizure-like activity under specific conditions.
• The occurrence of spreading convulsions in human patients remained largely unconfirmed until recent investigations.

Purpose of the Study:

• To investigate the presence and characteristics of spreading convulsions in human patients with subarachnoid hemorrhage (SAH) and epilepsy.
• To explore the potential protective role of GABAergic inhibition against spreading convulsions.
• To assess the relationship between SD events and the risk of developing late post-hemorrhagic seizures.

Main Methods:

• Monopolar subdural recordings in 25 SAH patients and in vitro neocortical slices from 12 epilepsy patients.
• Analysis of electrocorticographic (ECoG) data for spreading depolarization (SD) and ictal epileptic events.
• Correlation of SD frequency and duration with patient outcomes and seizure development.

Main Results:

• Spreading convulsions were identified in 2/25 SAH patients and in epilepsy patient slices, with epileptic potentials superimposed on the SD slow potential.
• GABAergic inhibition appeared to protect against spreading convulsions in vitro.
• SAH patients exhibited significantly more SD events than isolated ictal events; higher SD burden correlated with poor outcome and increased risk of late seizures.
• Arterial pulse artifacts mimicking epileptic activity were noted in some SAH patients.

Conclusions:

• This study provides unequivocal evidence of spreading convulsions in human patients, bridging observations from animal models to clinical reality.
• Early and frequent spreading depolarizations in SAH patients may serve as a biomarker for increased risk of developing late post-hemorrhagic seizures.
• Findings highlight the complex interplay between SD and epileptic activity in neurological disorders and suggest potential therapeutic targets.