The upside of epilepsy: Theories of an evolutionary paradox

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.