The role of air pollution in epilepsy: a better understanding is needed

Abstract

Social determinants of health, including neighborhood and built environment factors, play a crucial but underexplored role in epilepsy incidences. Among these, air pollution emerges as a potentially-preventable driver of epilepsy and adverse health outcomes. Evidence is accumulating on the effects of air pollution on the brain, especially in stroke and neurodegenerative disorders; however, the specific impact on epilepsy remains underresearched, potentially due to the complexities of studying this condition. The present narrative review addresses a critical knowledge gap by exploring: 1) the role of air pollution in epilepsy epidemiology; 2) the biological mechanisms of air pollution in the brain in the context of epilepsy; and 3) how air pollution affects the management of people living with epilepsy. We outline vital questions and actionable interventions regarding the role of air pollution in epilepsy.

Figure 1

Notes: The circle indicates poverty; the triangle indicates air pollution; and different shades of blue indicate the quality of the best available evidence for positive associations. Epilepsy risk factors, comorbidities, and seizure precipitants associated with exposure to air pollutants.

Figure 2

Air pollutants may predispose to seizures and epilepsy by disrupting normal neuronal function, network excitability, and cortical development. Air pollutants can affect the brain at all developmental stages. (Top Right) Acting directly in the brain, they can cause direct and indirect damage through oxidative stress, inflammation, mitochondrial dysfunction, altered myelination and alterations in normal cell signaling. Air pollutants indirectly affect the brain through systemic inflammation driven by chronic lung inflammation and damage to vital organs essential for healthy brain function. (Middle Right) Network excitability may be increased through multiple complex pathways that result in net excitatory-inhibitory imbalance, such as through modulation of glutamatergic, GABAergic transmission, ion channel, and neuronal excitability. Pollutants also indirectly modulate seizure threshold through autonomic disturbance, inflammation, sleep disturbance, and endocrine disruption. (Bottom) In the developing brain, disruption of normal neuronal migration pathways, increases in somatic mutation rates, maternal immune activation, placental impairment, and maternal thyroid dyshomeostasis are potential mechanisms through which air pollutants can cause permanent structural changes (that is, cortical malformations, MCDs).