Epilepsy

What is Epilepsy?

Epilepsy is neurological condition where we see the repeating discharge of neurons in the cerebral cortex of the brain, resulting in the disruption of normal neurological function. This results in a variety of effects including abnormal sensations, changes in consciousness and uncontrolled muscle movements. It is estimated that around 600,000 people have epilepsy in the UK[3] and 60 million worldwide.

We can record neuronal activity using an electroencephalogram (EEG) and when cerebral cortex neuronal activity is measured in an epileptic patient a common pattern occurs. After a neuron is excited and an action potential arises, this must be extinguished (this is called hyperpolarisation) to allow the cell to return to normal resting conductions. However, when these mechanisms fail, then an action potential is not extinguished and this can lead to a spiking epileptic seizure event. This hyperexcitability in a single neuron can spread to surrounding neurons increasing the intensity of the epileptic event.

Epileptogenesis

Epileptogenesis is the development of epilepsy within the brain[4]. As mentioned above the failure of hyperpolarisation is thought to form the basis of this, although precise mechanisms are still debated. However, it is thought there are three simple reasons contributing to epileptogenesis[5].

  • The first are changes in a cells own intrinsic properties. For example, if sodium channel activity is elevated within a cell, this will cause more excitability and mask any attempt to extinguish an action potential. Alternatively, if potassium channel activity is reduced, we might see an insufficient ability to eliminate an action potential and so epilepsy develops.

  • Secondly, there might also be changes in the synaptic efficacy between neurons. We have both excitatory and inhibitory synaptic processes between neurons. If we see an increase in the amount of excitatory receptor activation (e.g., NMDA Receptors) then we run the risk of allowing hyperexcitability within a cell to propagate more easily to nearby tissue, causing an epileptic event.

  • Finally, epileptogenesis might occur due to alterations in synaptic connectivity within neurons. For example, Hippocampal sclerosis is the loss of many neurons within the hippocampus, this can prompt changes in neuronal circuitry and might allow additional excitatory connections to develop and therefore, may result in epilepsy.

Epilepsy and Global Warming

Sisodiya et al in 2019 shed light on the worrying links between global warming and neurological conditions, specifically focusing on epilepsy as an example. Dravet Syndrome is a type of epilepsy and occurs due to mutations which build up in SCN1A, a sodium channel encoding gene [1]. The sodium channel protein which is then constructed from this mutated gene is greatly affected by temperature. As Sisodiya et al described, when heatwaves occur in the summer carers of patients with Dravet Syndrome report that the number and length of epileptic seizures greatly increases. Not only is this alarming for people with Dravet Syndrome, but as global temperatures continue to rise neurologists are undoubtedly going to see many further links between other forms of epilepsy and temperature.

However, recently the link between climate change and neurological conditions is generating more and more publicity. The Epilepsy Society, a recognised national UK charity published an article in 2019 called ‘Climate change and epilepsy: Time to take action[2]. This landmark paper outlined not only the problem we are currently facing, but also what we can already do to combat it. For example, large orangisations are recommended to start reducing emissions, improve their sustainability and support funding for more research. Although these seem like insignificant steps now, the hope is in the future a collective response will reverse the effects of global warming and make an impact on our lives for the better.

 

References

[1] Sisodiya SM, Scheffer IE, Lowenstein DH, Free SL. Why should a neurologist worry about climate change?. The Lancet Neurology. 2019;18(4):335-6.

[2] Sisodiya SM, Fowler HJ, Lake I, Nanji RO, Gawel K, Esguerra CV, Newton C, Foley A. Climate change and epilepsy: Time to take action. Epilepsia open. 2019 Dec;4(4):524-36.

[3] Epilepsy Statistics | Epilepsy Research UK [Internet]. Epilepsyresearch.org.uk. 2021 [cited 23 August 2021]. Available from: https://epilepsyresearch.org.uk/about-epilepsy/epilepsy-statistics/

[4] Goldberg EM, Coulter DA. Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. Nature Reviews Neuroscience. 2013 May;14(5):337-49.

[5] Professor M. Farrant. Anti-Epileptic Drugs. 2020-21 PHAR0007 UCL Lecture.