Epilepsy is a neurological and a systemic disorder.

Area of Science:

• Neurology
• Pathophysiology
• Systemic Diseases

Background:

• The fundamental pathophysiology of epilepsy remains incompletely understood.
• Epidemiological data suggest epilepsy encompasses more than seizure propensity, indicated by high comorbidity rates.
• Premature mortality persists even in epilepsy patients in long-term remission, hinting at a systemic component.

Purpose of the Study:

• To propose a novel perspective on epilepsy pathophysiology.
• To highlight the role of systemic dysfunction in epilepsy comorbidities and mortality.
• To advocate for integrated management strategies addressing both seizures and systemic factors.

Main Methods:

• Review of existing epidemiological and pathophysiological evidence for epilepsy.
• Conceptual framework development linking systemic processes to epilepsy outcomes.
• Analysis of fundamental pathophysiological processes including inflammation, oxidative stress, glycation, and methylation capacity.

Main Results:

• A systemic component, characterized by inflammation, oxidative stress, glycation, and methylation capacity, is implicated in epilepsy.
• This systemic dysfunction contributes significantly to epilepsy comorbidities.
• It also explains the elevated risk of premature mortality in individuals with epilepsy, even in remission.

Conclusions:

• Epilepsy should be conceptualized as seizures plus comorbidities stemming from systemic dysfunction.
• Comprehensive epilepsy care must incorporate management of these underlying systemic issues.
• Addressing systemic dysfunction offers a pathway to improve long-term outcomes and reduce mortality in epilepsy patients.