Kindling in humans: Does secondary epileptogenesis occur?

Area of Science:

• Neuroscience
• Epileptology
• Clinical Neurology

Background:

• Secondary epileptogenesis, the development of epilepsy in previously normal brain regions, is a controversial concept in human epilepsy.
• While established in animal models, definitive proof in humans is challenging due to ethical and practical limitations.
• Observational data from human epilepsy cases is crucial for understanding this phenomenon.

Purpose of the Study:

• To review and present observational evidence supporting the occurrence of secondary epileptogenesis in humans.
• To examine specific epilepsy types, such as hypothalamic hamartoma-related epilepsy and hippocampal sclerosis, as models for secondary epileptogenesis.
• To explore the underlying mechanisms and potential therapeutic targets for secondary epileptogenesis.

Main Methods:

• Review of contemporary surgical series and observational data from human epilepsy patients.
• Analysis of cases with hypothalamic hamartoma-related epilepsy to identify stages of secondary epileptogenesis.
• Examination of findings from bitemporal and dual pathology series, considering hippocampal sclerosis.
• Consideration of recent experimental data and the role of synaptic plasticity versus neuronal injury.
• Evaluation of the postoperative running-down phenomenon as evidence for a kindling-like process.

Main Results:

• Hypothalamic hamartoma-related epilepsy offers the strongest evidence for secondary epileptogenesis, displaying all observable stages.
• The case for secondary epileptogenesis in hippocampal sclerosis is less conclusive due to limited longitudinal data and conflicting experimental findings.
• Synaptic plasticity is proposed as a more likely mechanism driving secondary epileptogenesis than seizure-induced neuronal injury.
• The postoperative running-down phenomenon in some patients provides compelling evidence for an in-vivo kindling-like process.

Conclusions:

• Observational data strongly suggests that secondary epileptogenesis occurs in humans, particularly in specific conditions like hypothalamic hamartoma-related epilepsy.
• Synaptic plasticity is the probable mechanism underlying secondary epileptogenesis, rather than solely seizure-induced damage.
• Further research, including network analysis and exploration of subcortical interventions, is warranted to understand and manage secondary epileptogenesis.