The upside of epilepsy: Theories of an evolutionary paradox.

Publication date: Jun 30, 2025

The persistence of common, heritable conditions, like epilepsy, that are associated with reduced reproductive fitness is an evolutionary paradox. Endogenous analgesic, anti-depressant, and inflammatory mechanisms able to repair compromised functions can offer advantages in unexpected crises. Here, we challenge current thinking about the detrimental effects of seizures and epilepsy and suggest that (1) seizure-driven neuroplasticity might provide a protective mechanism, (2) seizure-induced neurotransmitter release not only helps to stop seizures but also increases resilience to pain, and (3) innate immune mechanisms triggered by recurrent seizures might neutralize novel viruses, like SARS-CoV-2, more rapidly, and so provided protection during the recent pandemic. PLAIN LANGUAGE SUMMARY: We explore the idea that epilepsy may activate the brain’s natural repair systems, despite its risks. These include brain processes that help people recover from injury, infections, and reduce pain. Understanding these less frequently discussed aspects of seizures may help researchers develop novel questions and improve treatment.

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Concepts Keywords
Epilepsy epilepsy
Increases evolutionary
Neuroplasticity immune
Therapy pain
Viruses plasticity

Semantics

Type Source Name
disease MESH epilepsy
disease MESH seizures
disease MESH infections
drug DRUGBANK Coenzyme M
disease MESH morbidity
disease MESH generalized epilepsies
pathway REACTOME Reproduction
disease MESH sequelae
disease MESH polygenic risk score
disease MESH Dravet syndrome
disease MESH premature mortality
drug DRUGBANK Spinosad
disease MESH anemia
disease MESH cystic fibrosis
disease MESH cholera
disease MESH death
disease IDO organism
disease IDO immune response
disease MESH drug refractory epilepsy
disease MESH pain thresholds
pathway REACTOME Release
pathway REACTOME Innate Immune System
disease MESH depression
disease MESH COVID 19
disease MESH temporal lobe epilepsy

Original Article

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