It is imperative to differentiate between epilepsy and seizures; epilepsy is a complex neurological condition which increases the susceptibility of individuals having gratuitous and recurring seizures. A seizure is warranted when normal electrical brain function is temporarily interrupted by burst of abnormal electrical signals. (University, 2015) Fundamentally not all seizures are due to epilepsy however, epilepsy is characterised by recurrent seizures. Epilepsy affects 450,000 people in the UK which is approximately 0.5-1% of the population. The neurons in our brain possess a balance between synaptic inhibition and synaptic excitation, this balance of synaptic excitation and inhibition is modified with individuals who have suffer from epileptic seizures resulting in pathological synchronization of neurons in the brain. Glutamate is the main excitatory neurotransmitter which propagates the firing of an action potential, comparatively GABA in an inhibitory neurotransmitter which counteracts glutamate and reduces the activity of the neural cells. Potential causes of epilepsy include brain tumours, stroke, infection or head injury. (What is epilepsy, 2020)
Epilepsy can be classified into several subgroups. The two broad categories of epileptic seizures are generalised seizures and partial seizures. Generalised seizures are also known as generalised whole cortex bilateral seizures as the whole cortex is involved. Generalised seizures can be further subdivided into absence seizures and tonic clonic seizures. As the name implies tonic clonic seizures are manifested by a period of muscle contraction and loss of consciousness followed by a period of relaxation where the muscles will commence to jerk rapidly and rhythmically. Absence seizures where the patient will experience perhaps a staring episode or altered state, brief consciousness. Patients will not recall absence seizures and essentially the individual ‘blanks out’ for approximately less than 15 seconds (Appleton, 2019).
If consciousness is not lost, it can result in a partial seizure, as the name implies only one portion of the brain is experiencing a seizure. Partial seizures can also be called focal or localised seizures, they are all interchangeable. They have a location dependent aspect to them, if the seizure occurs in an area associated with language such as: Broca's area, Wernicke's area patients may experience visual or auditory hallucinations. However, some partial seizures can result in a loss of consciousness when they manifest the patient and spread, also referred to as secondary generalised seizures.
The fundamental way of managing epileptic seizure is through the utilisation of anti-epileptic drugs (AEDs). Antiepileptic (often referred to as anti-convulsant) drugs are incredibly diverse; these drugs essentially restore the balance between inhibition and excitation by reducing the glutamate concentration and increase the GABA concentration. Many AED’s act via several mechanisms of action, very few antiepileptic drugs act via a singular, specific pathway. Unfortunately, AEDs are unable to cure epilepsy, they just attempt to reduce the frequency of seizures from occurring. Although anti-epileptics are a lifeline for many individuals who suffer from epileptic seizures, approximately two thirds of patients are unresponsive to AED’s. Optimal therapy is profoundly desired whereby patients are prescribed the fewest types of anti-epileptic drugs at lowest dose possible and experience the fewest side effects. Various factors must be taken into consideration when selecting an anti-epileptic drug such as: type of seizure, cost, co-morbidities, efficacy, expected adverse effects. If medication has failed other interventions can be practised such as vagal nerve stimulation, surgery or for children a ketogenic diet.
Carbamazepine is considered to be a first generation of anti-epileptic drug. It is a sodium channel blockade and is the first line treatment for treat focal seizures for adults, children and young people. Sodium ions play a critical role in an action potential, when a stimulus travels down an axon, voltage gated sodium ion channels open, sodium ions diffuse into the negatively charged axon down their electrochemical gradient, when the threshold is reached, depolarisation occurs. Carbamazepine works by blocking voltage gated sodium ion channels, it has been suggested that carbamazepine bind to the alpha subunit of the voltage gated sodium ion channels, resulting in the sodium channels entering an inactivated state. Ergo inhibiting the orchestration of the action potential and inhibiting the release of glutamate into the synaptic cleft (Gambeta 2016). Thus, elevating the seizure threshold.
Sodium valproate is another primary medication which is has been utilised for multiple decades to treat epilepsy. Sodium valproate acts on the GABA synapse thus affecting potentiation of GABA activity., it is a GABA transaminase inhibitor, blocks GABA breakdown, enhances GABA concentration and enhances GABA release. It is utilised to treat tonic clonic seizures, and is given to patients
Levetiracetam is one of the newest AED’s available on the market and is commonly utilised as a first line treatment in seizures for individuals in palliative care. The specific physiological role of SV2A remains ambiguous (SILLS) however it is understood levetiracetam binds to SV2A. SV2A (synaptic vesicle glycoprotein 2A) is a ubiquitous synaptic vesicle protein located in the CNS . This interaction inhibits the release of neurotransmitters which are located in the vesicle and reduces synaptic excitatory activity. There is proof to imply that levetiracetam selectively binds to SV2A, with minute affinity for SV2B and SV2C which are members of the SV protein family.
Lamotrigine possesses several mechanisms of action thus making it very diverse. It can be used to treat tonic clonic seizures and partial seizures. Like carbamazepine, lamotrigine acts on the sodium ion channels preventing glutamate excitotoxicity and is 1st line therapy for adult, children and young people experiencing focal seizures. Moreover, lamotrigine also acts on the voltage gated calcium ion channels (Twombly et al. 1988; . The influx of calcium ions into a cell can regulate neuronal excitability.