Exploring the impact of climate change on epilepsy: Insights from the 15th European Epilepsy Congress

This commentary is motivated by the recently held 15th European Epilepsy Congress (EEC, Rome, 7th–11th September 2024), which featured the first ever poster section dedicated to the impact of climate change on epilepsy. This initiative highlights the growing recognition of the influence that environmental changes, particularly rising global temperatures, can have on human health.1-4 Climate change represents a serious concern for people with epilepsy across the world,5, 6 since a number of climate-change related events are associated with increased seizure frequency. Elevated temperatures and extreme weather events may exacerbate seizure precipitants, such as stress, fever, sleep deprivation, and vector-borne infections.3 Indirect consequences of climate change–related conditions, such as heatwaves, may include compromising stability and effectiveness of antiseizure medications (ASMs; e.g., due to pharmacokinetic changes), aggravation of comorbidities or increase in risk of sudden unexpected death in epilepsy (SUDEP).3 Extreme climate events may be especially important for human genetic variants that influence the temperature sensitivity of neuronal networks in the brain. For example, Dravet syndrome is associated with pathogenic variants in SCN1A gene encoding a temperature-sensitive ion channel (NaV1.1), with seizures that can be precipitated by even mild increases in body temperature. Thermoregulation may be compromised in epilepsy also due to disease-associated alterations in thermoregulatory hypothalamic nuclei,7 which may extend the risk of seizure exacerbation to common form of epilepsies. Preclinical research has shown that neuronal function and excitability are significantly influenced by changes in ambient temperature, and an increase in core and brain temperature can precipitate seizures in animal models.8 We need more preclinical and clinical data to better understand the climate-driven risks for seizures and epileptogenesis, and for identifying the critical underlying cellular and molecular mechanisms. In this context, seven posters were presented at EEC in the section dedicated to the impact of climate change on epilepsy, starting to address various aspects of the relationship between climate change and epilepsy, and providing insights into potential interactions. The main findings and implications of these studies are summarized below (Figure 1). Giorgi et al.9 investigated the experience of a cohort of 10 parents of children with Dravet syndrome, a severe developmental and epileptic encephalopathy,10 during heatwaves in Spain. Families reported increased seizure susceptibility in their children during heatwaves, associated with a reduced ability to spend time outdoors. Schools and daycare centers were often inadequately equipped to handle extreme heat. In addition, families have had to invest in home adaptations, such as air conditioning or insulation, to mitigate the effects of excessive heat and alleviate sleep disturbance at night. These adjustments increased the financial burden for families and resulted in overall higher levels of energy consumption, which carried further environmental impact. Centralized solutions and providing properly equipped schools and daycare centers could reduce the need for individual adaptations and the collective environmental footprint. The study underscored the urgent need for better resources and infrastructures to support families of people with epilepsy, and for mitigation actions to prevent seizures worsening during heatwaves while minimizing negative environmental impacts. Clayton et al.9 conducted a prospective observational pilot study in people with developmental and epileptic encephalopathies,10 including seven residents living in a long-term care facility in the UK. Bedroom and outside temperatures were recorded daily, as well as forehead skin temperature and seizure frequency by care staff. They found a significant relationship between outside temperature and bedroom temperature. Higher bedroom temperatures, when outside temperatures exceeded 28°C used to define a heatwave in Buckinghamshire, UK.11 One individual experienced significantly more seizures during heatwaves, associated with increased body temperature on seizure days. This study highlights the need to gain a better understanding of the relationship between ambient temperature, body temperature, and risk of seizure. This information will help develop strategies to mitigate the impact of rising global temperatures on individuals with epilepsy. Mamad et al.9 examined the relationship between body temperature and seizures in adult mice developing epilepsy after status epilepticus induced by intra-amygdala kainic acid. Spontaneous seizures were continuously recorded via EEG telemetry, and body temperature measurement came from the telemetry unit itself. The peak number of seizures was detected at body temperatures between 35°C–36°C, with body temperature rising during seizures. Of interest, more seizures occurred in summer than winter, suggesting seasonal variations in seizure frequency.12, 13 The study highlighted the importance of monitoring body temperature for better understanding seizure dynamics, potentially offering a biomarker for seizure prediction. Bera et al.9 investigated thermoregulatory dysfunction in mice with acquired epilepsy induced by intra-amygdala kainate. They found an ~25% neuronal loss in hypothalamic regions that regulate body temperature, namely the ventromedial preoptic nucleus and dorsomedial nucleus. This was associated with reduced hypothalamic volume on magnetic resonance imaging (MRI) and an increased hippocampal temperature of 1.3°C ± 0.1°C before the onset of epilepsy in mice, an effect that persisted in chronic epilepsy. These changes may impair the body's ability to adapt homeostatically to external temperature fluctuations, potentially exacerbating seizures. The findings emphasized the importance of preserving hypothalamic function to maintain thermal homeostasis in people with epilepsy. Yılmaz et al.9 examined the effects of high temperature on absence seizures in GAERS, a genetic rat model of absence epilepsy. Rats were exposed to increased ambient temperature using an infrared heater, which raised their core temperature from 37.8°C to 39°C for 1 h. This temperature change was associated with increased anxiety levels. Although there was no change in the frequency of absence seizures overall, one rat experienced increased seizures and eventually died, suggesting that absence epilepsy may be exacerbated by increased temperature. The findings call for further studies to better understand the impact of temperature changes on absence seizures and the associated comorbidities. Mills et al.9 investigated the vulnerability of neurological diseases, including epilepsy, to elevated temperatures using an in vitro system. Several ion channel–related genes have been identified that harbor variants that could make carriers sensitive to temperature changes. Because astrocytes are essential for brain homeostasis and respond dynamically to environmental stressors, they were utilized to study the effects of temperature fluctuations on resident brain cells. Primary fetal human astrocyte cultures were exposed to elevated temperatures of 39°C for 6 h and 24 h. Transcriptomic analysis showed significant changes in gene expression, including genes associated with epilepsy phenotypes. For example, potassium voltage-gated channel subfamily A member 1 (KCNA1) was downregulated after exposure to 39°C, whereas sodium voltage-gated channel alpha subunit 9 (SCN9A) was upregulated. These findings suggest that temperature fluctuations cause dynamic transcriptional changes that may affect molecular networks in the brain. Further research is needed to extend this study to neurons, and elucidate the mechanisms by which elevated temperature influences molecular pathways in brain cells, and whether this contributes to seizures. Yilmazer et al.9 studied the effects of high temperatures on the metabolism of ASMs and their drug interactions, based on the hypothesis that extreme weather events may affect the pharmacokinetics of these drugs. They used HepG2 cells ± carbamazepine incubated at 37°C or 40°C for 3 h and 24 h as a model system to study the effect of high temperature on the expression of hepatic cytochrome P450 (CYP) enzymes, responsible for the metabolism of various ASMs.14 They found that acute heat exposure (40°C) for 3 h induced the mRNA expression of CYP3A4 and CYP2C9 enzymes in HepG2 cells. This suggests that extreme temperatures could alter ASM metabolism and their pharmacokinetic interactions, potentially impacting seizure control in patients with epilepsy. These results warrant further investigation into how climate-induced temperature changes may affect hepatic ASM metabolism and antiseizure efficacy. Although these studies have offered valuable insights into the potential relationship between climate change and epilepsy, research on this topic is still in its early stages and has significant knowledge gaps. For example, the studies have focused mainly on acute heat exposure, whereas the long-term effects of chronic or repeated heat exposure were unexplored. Additional environmental factors such as humidity and environmental pollutants should also be considered. Furthermore, the relationship between climate change-induced stress and seizure susceptibility remains poorly understood. There is a need for more in-depth investigations into the mechanisms by which environmental temperature may affect core and brain temperatures in epilepsy. In particular, how different brain cell populations may vary their phenotype and function with temperature changes, and if and how thermoregulation is impaired in genetic and acquired epilepsies, and different syndromes and patient ages15 and their relevance for seizure precipitation, both in experimental models and clinical settings. Individuals with developmental and epileptic encephalopathies may be especially vulnerable to temperature fluctuations, highlighting the need for targeted studies to better understand their specific risks. Furthermore, research is required to examine the impact of climate change on the stability, metabolism, and pharmacokinetics of ASMs, which could influence seizure control. The 15th EEC's focus on climate change and epilepsy has brought attention to a crucial intersection between environment and neurological health. Addressing the gaps in knowledge will be critical to safeguarding the health of individuals with epilepsy in the face of a changing global climate. Further focused data would help us to develop prevention or mitigation methods to protect people with epilepsy from the effects of climate change. We look forward to more posters and sessions on climate change and epilepsy in forthcoming International League Against Epilepsy (ILAE) meetings—it is a challenge we all need to address. We thank the authors of the posters for their permission to share their findings. S.M.S. is supported by the Epilepsy Society. The authors declare no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Data S1. 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