Epilepsy and Valproate

EPILEPSY AND VALPROATE

According to the landmark study of the Institute of Medicine (IOM), a staggering amount of one out of twenty-six people will be diagnosed with epilepsy over a lifetime. In USA alone, 150,000 are diagnosed with this chronic brain disorder annually (Aesnet 2016). Thus, it was acknowledged as the fourth most common neurological problem. Epilepsy is indicated by unpredictable and recurrent seizures which occur when the brain receives a sudden discharge of electrical signals that transiently interferes with the normal electrical brain functions. A person is only diagnosed as an epileptic if they have had two or more seizures of unknown causes (Epilepsy Foundation 2016). Seizures are divided into two main types; Focal (partial) seizures and generalized seizures (Healthline 2016). This essay will compare the biochemistry of seizures and the differences between these two types of seizures. We will also discuss the electrical activities of neurons and the alterations that occur to it which leads to epileptic seizures mentioned. A brief explanation on how action potentials are produced is given. Furthermore, discussion of how the antiepileptic drug, valproate, is used to treat seizures is also included.

Generalized seizures occur when there is epileptic activity in both hemispheres of the brain. The person experiencing this form of seizure is normally unconscious even if just for a brief moment. People will have no recollection of what happened during their spasms (Epilepsy.org.uk 2015). The most common sub-unit of generalized seizure is the tonic clonic seizure which are separated into two phases beginning with the tonic phase where muscles stiffen and the person may fall to the floor. Then comes the clonic phase where unnatural jerking and twitching of the body occurs. The person usually cries out as the muscles in the chest contract and air rushes through the vocal cords. However, this cry does not indicate pain. This type of spasm may last up to five minutes (Epilepsyontario 2016).

Focal seizures differ from generalized seizures as electrical disturbance only take place in a specific site on one cerebral hemisphere. The affected person is not oblivious to the happenings around them, they are still fully conscious and are able to remember what happened to them during this epileptic period. People with simple partial seizures can have minor jerking such as the finger, they may also hear, smell, or even hallucinate. They also have impaired speaking abilities and uncontrollable emotions. There are also people with complex partial seizures, these people are more at risk of hurting or embarrassing themselves as they perform purposeless actions, automatisms. (Epilepsy.org.uk 2014).

Nerve cells or neurons are divided into three main parts named axon, dendrites and cell body. The neurons are categorized based on their functions. Sensory neurons carry messages from external stimuli to the brain via electrical impulses. Motor neurons conveys these impulses from the brain to the muscles, glands or other effector tissues. Interneurons process the information of these impulses inside the brain. The gap between each neuron is a synaptic cleft. For these impulses to travel across this gap, a neurotransmitter is required. The messages are conveyed by the firing of an action potential (bbc.co.uk 2016).

In the cerebral cortex of a normal unaffected person, the voltage gated ion channels play a primary role for the generation of action potential. The NaV1.1, NaV1.2, and NaV1.6 sodium channels encoded by SCN1A, SCN2A and SCN8A genes are primarily responsible for the generation of action potential (Catterall, Kalume and Oakley, 2010). Upon activation, these ion channels will open causing an influx of sodium ions into the cell which results in depolarization of the membrane potential (-70mV) towards the equilibrium for sodium (+60mV). Once equilibrium is achieved, a refractory period occurs where the voltage gated sodium ion channels remain in an inactive state until the membrane repolarizes via the delayed activation of voltage gated potassium channels (Neurones, 2016). This entire process produces one action potential. This neuronal excitation is balanced with the presence of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA).

GABA is made in brain cells form alpha-keto glutarate during the Krebs cycle, it acts as an inhibitory