Peter is concerned about his lack of knowledge of epilepsy which his daughter Amber (16 years old) has been diagnosed with. Amber is worried she might have to give up activities she enjoys. She has also started studying for her A levels and feels like her world has been turned upside down. Both Peter and Amber are curious to find out what consequences this may cause for their future.
Epilepsy is a central nervous system disorder in which the brain activity becomes abnormal, causing seizures or periods of unusual sensations and loss of awareness. Epilepsy can affect anyone (1). Seizures are a sudden burst of electrical activity in the brain that temporarily affects how it works and cause a wide range of symptoms (2). The main symptoms of epilepsy are repeated seizures and it can affect people in different ways, depending on which part of the brain is involved. (3). Epilepsy is one of the most common serious neurological conditions in the world. Almost 1 in 100 people in the U.K. have epilepsy (4).
Epilepsy is not contagious however for many people with epilepsy, there can be triggers that cause seizures. These include; stress, lack of sleep, alcohol consumption, or some medications, and illegal drugs (4). The cause of epilepsy is unknown in about 50% of cases worldwide (5). The cause is divided into the following groups: genetic, infectious, structural, immune, and unknown. Genetic causes include congenital abnormalities or genetic defects that cause seizures due to brain malformations.
Furthermore, brain damage such as a stroke or brain tumor can cause epilepsy due to the restriction of oxygen to the brain. Also, an infection of the brain such as meningitis, encephalitis, or neurocysticercosis can cause epilepsy. Also, there are known inherited conditions that may cause epilepsy for example tuberous sclerosis. However, it is hard to determine whether a child will inherit epilepsy from its parents as there are many types of epilepsy and different factors a child might inherit (5).
Seizures can be caused by multiple mechanisms, one of them is the Glutamatergic and γ-aminobutyric acid (GABA) transmission, which is the major excitatory and inhibitory transmitters of the nervous system. Disrupting the mechanisms that inhibit firing or promoting the mechanisms that facilitate excitation can lead to seizures. Also, Defects in almost any step of the molecular mechanism of synaptic transmission can lead to seizures because of its critical role in maintaining the balance between excitation and inhibition.
For example, a high concentration of potassium exists inside a neuron and there is high extracellular sodium concentration. If the resting potential of -60mV is disturbed by sodium/potassium pumps in the plasma membrane this can lead to depolarization which promotes abnormal activity and can cause seizures. (3)
Seizures are divided into two main groups based on where the abnormal brain activity begins. Focal seizures are seizures that appear to start from one side of the brain. Focal seizures without loss of consciousness are seizures that can cause intense changes in emotions and unusual smells or tastes. They may also result in involuntary twitching or stiffness in parts of your body such as an arm or leg (1). You remain awake and aware while this happens. These seizures are sometimes known as 'warnings' because they can be a sign that another type of seizure is about to happen (2).
Focal seizures with impaired awareness are seizures that involve a loss of consciousness or awareness. Also, might involve making random body movements such as hand rubbing, chewing, swallowing, or moving arms around. During this type of seizure, you may stare into space or not respond to the environment as you normally would (2). These symptoms may be confused with other neurological disorders such as migraine or mental illness. So thorough examination and testing are needed (1).
Generalized seizures are seizures that appear to be more distributed and affect both sides of the brain. During a generalized seizure, the person may lose consciousness or have muscle spasms (1). A secondary generalized seizure is when a focal seizure spreads from one side of the brain to the other.
In the case study provided it mentions that Peter only remembers the type of epilepsy his daughter is diagnosed with “sounds like a drink you buy in a bar”. I suspect the patient has Tonic-Clonic seizures, as this is the most recognized type of seizure and its name sounds like a drink. No other information has been given about the type of seizure the patient is diagnosed with therefore it is subjective on which type of seizure sounds like a drink. It could also be Clonic, tonic, or atonic.
During Tonic-Clonic seizures there are 2 phases: the “tonic” phase, followed by the “Clonic” phase. The first phase can cause an abrupt loss of consciousness, body stiffening, or biting your tongue. The second phase can cause the limbs to jerk quickly, loss of control of the bladder or bowel. The seizure normally lasts between 1-3 minutes however if it lasts longer than 5 minutes emergency medical treatment may be needed. After the seizure has finished, the patient may have a headache or difficulty remembering what happened and feel tired or confused. The time to recover varies between each person ranging from a couple of hours to days (6).
Other generalized seizures include absence seizures which are characterized by staring into space or subtle body movements such as eye blinking or lip-smacking. These seizures may occur in clusters and cause a brief loss of awareness where the person won’t be able to remember them. Also, Atonic seizures cause a loss of muscle control, which may cause you to collapse. Finally, Myoclonic seizures usually appear as sudden brief jerks or twitches of your arms and legs (1).
The diagnosis of epilepsy is made by a neurologist and is based on the reported and observed symptoms. The specialist may suggest arranging for the patient to have some tests. These include electroencephalogram (EEG) test and magnetic resonance imaging (MRI) scan. An EEG test is used to check for unusual electrical activity in the brain that can happen in people with epilepsy. A brain scan can help spot problems in your brain that can sometimes cause epilepsy, such as brain tumors, damage to the brain, or scarring in the brain (7). Furthermore, a blood test can be taken to check the patient’s general health and look for any medical conditions causing epilepsy (8).
There is no known cure for Epilepsy. On the other hand, treatment methods aim to reduce active impairment and the severity of symptoms, hence improving the quality of life. They do this by preventing the occurrence of seizures by maintaining an effective dose of one or more antiepileptic drugs. Treatments should start with low doses and increase gradually until seizures are controlled (8).
The main treatment for epilepsy is anti-epileptic drugs. The medicine doesn’t cure epilepsy but helps to stop or reduce the number of seizures. Many people find that their seizures stop with the first or second medicine they try. But some people need to try a few medicines before they find one that works well for them. (2).
Pharmacological treatments for female patients who are newly diagnosed with tonic Clonic seizures are not recommended to use sodium valproate if they are at childbearing ages unless other treatments are not tolerated, and the pregnancy prevention program is in place (9). This is because there is an increased risk of teratogenicity with the use of antiepileptic drugs. Sodium valproate is associated with the highest risk of developing congenital malformation (approximate 10% risk) and developmental disorder (up to 40% risk). Therefore, valproate must not be used in females in childbearing age potential (10).
It is recommended to use Lamotrigine as sodium valproate is not suitable for this patient because she is of childbearing age (9). When monotherapy with a first-line antiepileptic drug has failed, monotherapy with a second drug should be tried. The change from one antiepileptic drug to another should be cautious, slowly withdrawing the first drug only when the new regimen has been established. Combination therapy with two or more antiepileptic drugs may be necessary, but this increases the risk of adverse effects and drug interactions. The diagnosis should be checked before starting an alternative drug if the first drug showed a lack of efficacy. A single antiepileptic drug should be prescribed whenever possible (11).
Lamotrigine is an antiepileptic drug belonging to the phenyl-triazine class. Lamotrigine is an anticonvulsant and prevents seizures by stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate which contribute to seizure activity. Although the exact mechanism of lamotrigine is not fully understood as it exerts cellular activity that contributes to efficacy in a range of conditions. Lamotrigine acts by inhibiting sodium currents by binding to the inactive sodium channels which suppress the release of glutamate. Also, lamotrigine enhances the actions of gamma-aminobutyric acid which may result in a reduction of pain-related transitions of signals along the nerve fibres (12).
After consumption lamotrigine is rapidly and entirely absorbed along the entire length of gastrointestinal tracts and is metabolized by glucuronidation, with minimal first-pass metabolism effects which mean that the active drug is at a high concentration when it reaches the site of action, which may be useful when the patient is at college or participating in sports activities as the seizures may be prevented. This is evident due to a bioavailability estimated at 98%. The rate and extent of Lamictal absorption are equivalent between compressed tablet form or dispersible tablets taken with water which means both formulations are suitable for the patient.
Furthermore, the average elimination half-life of lamotrigine ranges from 14-59 hours which means the dose administrated can be beneficial as the patient may only need to take it once daily instead of having more doses often. Also, the plasma protein binding of lamotrigine is estimated at 55% this means that the drug is not expected to undergo significant interaction with other drugs for protein sites due to lower protein binding. Lastly, about 94% of lamotrigine and its metabolites are recovered in urine and 2% in faeces (12).
The most common side effects of lamotrigine are dizziness, visual disturbances, nausea or vomiting, and nonserious rash. Furthermore, serious skin reactions including stevens-Johnson syndrome and toxic epidermal necrolysis may develop in the first 8 weeks. This is associated with hypersensitivity syndrome and is more common in patients with a history of allergy or rash from other antiepileptic drugs. The patient should be advised to consider withdrawal if a rash or signs of hypersensitivity syndrome develops (13). If the symptoms of epilepsy in the patients have not improved and the first-line treatment is ineffective, it is recommended to offer clobazam, levetiracetam, or topiramate as an adjunctive treatment to female patients of childbearing age (9).
Lamotrigine is commonly available as a compressed tablet and dispersible tablet formulation (13). Tablets should be swallowed with a glass of water to ensure they function as intended and to minimise adverse effects and tablets should not be chewed. For monotherapy of primary and secondary generalized tonic-clonic seizures, a child aged 12-17 the dose should be 25mg initially for 14 days, then increased to 50mg daily for further 14 days, then increased in steps of up to 100mg every 7-14 days. maintenance 100–200 mg daily in 1–2 divided doses; increased if necessary up to 500 mg daily, dose titration should be repeated if restarting after more than 5 days (13).
Other types of treatment can be implemented if the seizures are not controlled well by medication. The ketogenic diet is high in fat and low in carbohydrates. This reduces the amount of glutamate in the brain and enhances the synthesis of GABA making it less likely for a seizure to occur. Also, it can reduce inflammation due to infections like meningitis which can trigger seizures. The patient may be referred to see a tertiary pediatric specialist discuss trying this diet. Finally, brain surgery may be considered as an alternative for some patients, should they be eligible for it (14).
Lastly, a pharmacist has an important role in patient-centred care. Counselling should be given with regards to the medication, for example, the dosage instructions should be made clear. The pharmacist should advise the patient to take the medication regularly as epilepsy drugs work best when taken on time. Also, the information should be given on reporting any side effects the patient might suffer from and what to do if you miss a dose.
The pharmacist should explain the benefits of a healthy lifestyle to assist with the condition, as this reduces depression. This includes exercising, drinking enough water, and a well-balanced diet. The pharmacist should stress the importance of sleep as it can trigger seizures and stay away from underage drinking or any other seizure triggers mentioned. Lastly, the pharmacist should advise the patient to wear a medical alert bracelet as this will help emergency personnel know how to treat the patient properly (8).
