Epilepsy : Don ’ t get too excited

Epilepsy is a brain disorder experienced by 65 million people worldwide. It is characterized by the overstimulation or hypersynchrony of neurons that leads to epileptic seizures. Physical symptoms include weakness, inability to communicate clearly, and excessive exhaustion. Epilepsy can be categorized based on two factors: if the disorder is idiopathic or symptomatic, and if the disorder is generalized or partial. Idiopathic epilepsy is genetic-based, while symptomatic epilepsy has no known cause or is developed from a traumatic brain injury. If the epilepsy is generalized it occurs in multiple parts of the brain, while partial is specific to a particular brain region. A variety of ions, neurotransmitters, and extracellular components affect the level of excitation experienced by the cell, leading to the different types of epilepsy. In this review, we cover the dysfunctions in the central nervous system that can lead to the development of idiopathic generalized and idiopathic partial epilepsy. Additionally, we investigate the recent research and insights into these mechanisms and determine possible therapeutic targets. Introduction Dating back at least 4 millennia, epilepsy is a disease with a long history. Early theories of epilepsy correctly identified the brain as the site of the problem, but wrongly believed it was caused by too much phlegm in the brain or the result of evil influences (Gross, 1992). It wasn’t until the Enlightenment and advances in anatomy, chemistry, and physiology that epilepsy was seen in a modern light (Gross, 1992). In addition to these advances, Hippocrates is credited with giving the first formal description identifying it using a scientific approach, forming the base of what we know about epilepsy today (Magiorkinis, 2012). Epilepsy affects an estimated 65 million people worldwide, with infants and people over 60 being the most at risk (Epilepsy Foundation). Epilepsy can be described as the state resulting from an abnormal and excessive neuronal discharge within the central nervous system (Epilepsy Foundation). It is possible for the seizure to occur in any area of the brain and it may or may not spread to other parts (Penfield & Erickson, 1941). This hyperexcitability of neurons causes chronic, unpredictable seizures and can even lead to other neurological problems (Epilepsy Foundation). While there are two major known causes of epilepsy, traumatic brain injury (TBI) and chemical imbalances, in over half of the cases of epilepsy, the cause is unknown (Fischer, 2015). The type of injury that leads to a seizure is age-dependent. For example, seizures in children are often linked to birth traumas or infections, such as meningitis, or high fevers, while seizures in the elderly are likely due to tumors or strokes (Fischer, 2015). This review will focus on epilepsies caused by chemical imbalances and the mechanisms of dysfunction of different receptors, such as receptors for glutamate, GABA, potassium, sodium, and calcium. A. Healthy Neuron B. Epileptic Neuron Figure 1. Neuronal Excitability in an Epileptic Model A) In a healthy neuron, receptors are working properly and allow the correct amount of ion flow in and out of the cell. This results in the appropriate amount of stimulation in the cell. B) In an epileptic neuron, the K+ channels do not allow enough K+ into the cell, while the Ca+2, Na+2, GABA, and glutamate receptors allow too many ions into the cell, causing hyper-excitability.