Epilepsy

31 Epilepsy



J.W. Sander, S. Dhillon




Key points



• An epileptic seizure is a transient paroxysm of uncontrolled discharges of neurones causing an event which is discernible by the person experiencing the seizure and/or an observer.

• The incidence of epileptic seizures is around 50 cases per 100,000 of the population.

• About 70–80% of all those who develop epilepsy will become seizure free on treatment and about 50% will eventually withdraw their medication successfully.

• Generalised seizures result in impairment of consciousness from the onset; they include tonic clonic convulsions, absence attacks and myoclonic seizures.

• Focal seizures include simple partial seizures, complex partial seizures and secondarily generalised seizures.

• Treatment of epilepsy is usually for at least 3 years and, depending on circumstances, sometimes for life.

• Treatment aims to control seizures using one drug without causing side effects and minimising the use of polypharmacy.

• Management of epilepsy requires empowering patients to understand their condition and medication and helping them develop effective partnerships with health professionals.

An epileptic seizure is a transient paroxysm of uncontrolled discharges of neurones causing an event that is discernible by the person experiencing the seizure and/or by an observer. The tendency to have recurrent attacks is known as epilepsy; by definition, a single attack does not usually constitute epilepsy. Epileptic seizures or attacks are a symptom of many different diseases, and the term epilepsy is loosely applied to a number of conditions that have in common a tendency to have recurrent epileptic attacks. A patient with epilepsy will show recurrent epileptic seizures that occur unexpectedly and stop spontaneously.



Epidemiology


There are problems in establishing precise epidemiological information for a heterogeneous condition such as epilepsy. Unlike most ailments, epilepsy is episodic; between seizures, patients may be perfectly normal and have normal investigations. Thus, the diagnosis is essentially clinical, relying heavily on eyewitness descriptions of the attacks. In addition, there are a number of other conditions in which consciousness may be transiently impaired and which may be confused with epilepsy. Another problem area is that of case identification. Sometimes the person may be unaware of the nature of the attacks and so may not seek medical help. People with milder epilepsy may also not be receiving ongoing medical care and so may be missed in epidemiological surveys. Furthermore, since there is some degree of stigma attached to epilepsy, people may sometimes be reluctant to admit their condition. Indeed, epilepsy is still one of the world’s most stigmatised conditions. In today’s society, in both developed and developing countries, fear, misunderstanding, discrimination and social stigma still exist and these affect the quality of life for people with the disorder and their families.


Epilepsy does impact on an individual’s human rights, for example, access to health and life insurance is affected. A person who suffers from epilepsy may not be able to obtain a driving licence and it has an impact on the choice of career. In addition, legislation can impact on the life of individuals with epilepsy, for example, in some countries epilepsy may deter marriages. Legislation based on internationally accepted human rights standards can prevent discrimination and rights violations, improve access to health care services and raise quality of life (WHO, 2009). A global campaign has been established to raise awareness about epilepsy, provide information and highlight the need to improve care and reduce the disorder’s impact through public and private collaboration. This is supported through a partnership established between WHO, the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).


Epilepsy is recognised as a priority in effective health care delivery and there are still a number of issues that health professionals should consider:


• Epilepsy is a chronic neurological disorder that affects people of all ages.

• Around 50 million people worldwide have epilepsy.

• Nearly 90% of the people with epilepsy are found in developing regions.

• Epilepsy responds to treatment 70% of the time. Despite this, approximately 75% of affected people in developing countries do not get the treatment they need.

• People with epilepsy and their families suffer from stigma and discrimination in many parts of the world.


Incidence and prevalence


Epileptic seizures are common. The incidence (number of new cases per given population per year) has been estimated at between 20 and 70 cases per 100,000 persons, and the cumulative incidence (the risk of having the condition at some point in life) at 2–5%. The incidence is higher in the first two decades of life but falls over the next few decades, only to increase again in late life, due mainly to cerebrovascular diseases. Currently, the elderly are the group in the populations with the highest incidence of epilepsy. Most studies of the prevalence of active epilepsy (the number of cases in the population at any given time) in developed countries cite figures of 4–10 per 1000 with a rate of 5 per 1000 population most commonly quoted. In developed countries, annual new cases are between 0.4 and 0.7 per 1000 general population.


In developing countries, the prevalence of epilepsy is higher with rates of 6–10 per 1000 population cited and reported annual new cases twice those seen in developed countries, presumably due to the higher risk of experiencing conditions that can lead to permanent brain damage. Overall, nearly 90% of epilepsy cases worldwide are found in developing regions.



Prognosis


Up to 5% of people will suffer at least one seizure in their lifetime. The prevalence of active epilepsy is, however, much lower and most patients who develop seizures have a very good prognosis. About 70–80% of all people developing epilepsy will eventually become seizure free, and about half will successfully withdraw their medication. Once a substantial period of remission has been achieved, the risk of further seizures is greatly reduced. A minority of people (20–30%) will develop chronic epilepsy and in such cases, treatment is more difficult. People with symptomatic epilepsy, more than one seizure type, associated learning disabilities or neurological or psychiatric disorders are more likely to have a poor outcome. Of people with chronic epilepsy, fewer than 5% will be unable to live in the community or will depend on others for their day-to-day needs. Most people with epilepsy are entirely normal between seizures but a small minority of patients with severe epilepsy may suffer physical and intellectual deterioration.



Mortality


People with epilepsy, especially younger patients and those with severe epilepsy are at an increased risk of premature death. Most studies have given overall standardised mortality ratios between two and three times that of the general population. Common causes of death in people with epilepsy include accidents such as drowning, head injury, road traffic accidents, status epilepticus, tumours, cerebrovascular disease, pneumonia and suicide. Sudden unexpected death, an entity which remains unexplained, is common in chronic epilepsy, particularly among the young who have convulsive forms of epilepsy.



Aetiology


Epileptic seizures are produced by abnormal discharges of neurones that may be caused by any pathological process which affects the cortical layer of the brain. The idiopathic epilepsies are those in which there is a clear genetic component, and they probably account for a third of all new cases of epilepsy. In a significant proportion of cases, however, no cause can be determined and these are known as the cryptogenic epilepsies. Possible explanations for cryptogenic epilepsy include as yet unexplained metabolic or biochemical abnormalities and microscopic lesions in the brain resulting from brain malformation or trauma during birth or other injury. The term ‘symptomatic epilepsy’ indicates that a probable cause has been identified.


The likely aetiology of epilepsy depends upon the age of the patient and the type of seizure. The commonest causes in young infants are hypoxia or birth asphyxia, intracranial trauma during birth, metabolic disturbances and congenital malformations of the brain or infection. In young children and adolescents, idiopathic seizures account for the majority of the epilepsies, although trauma and infection also play a role. In this age group, particularly in children aged between 6 months and 5 years, seizures may occur in association with febrile illness. These are usually short, generalised tonic clonic convulsions that occur during the early phase of a febrile disease. They must be distinguished from seizures that are triggered by central nervous system infections which produce fever, for example, meningitis or encephalitis. Unless febrile seizures are prolonged, focal, recurrent or there is a back-ground of neurological handicap, the prognosis is excellent and it is unlikely that the child will develop epilepsy.


The range of causes of adult-onset epilepsy is very wide. Both idiopathic epilepsy and epilepsy due to birth trauma may also begin in early adulthood. Other important causes are head injury, alcohol abuse, cortical dysplasias, brain tumours and cerebrovascular diseases. Brain tumours are responsible for the development of epilepsy in up to a third of patients between the ages of 30 and 50 years. Over the age of 50 years, cerebrovascular disease is the commonest cause of epilepsy, and may be present in up to half of patients.



Pathophysiology


Epilepsy differs from most neurological conditions as it has no pathognomonic lesion. A variety of different electrical or chemical stimuli can easily give rise to a seizure in any normal brain. The hallmark of epilepsy is a rather rhythmic and repetitive hyper-synchronous discharge of neurones, either localised in an area of the cerebral cortex or generalised throughout the cortex, which can be observed on an electroencephalogram (EEG).


Neurones are interconnected in a complex network in which each individual neurone is linked through synapses with hundreds of others. A small electrical current is discharged by neurones to release neurotransmitters at synaptic levels to permit communication with each other. Neurotransmitters fall into two basic categories: inhibitory or excitatory. Therefore, a neurone discharging can either excite or inhibit neurones connected to it. An excited neurone will activate the next neurone whereas an inhibited neurone will not. In this manner, information is conveyed, transmitted and processed throughout the central nervous system.


A normal neurone discharges repetitively at a low baseline frequency, and it is the integrated electrical activity generated by the neurones of the superficial layers of the cortex that is recorded in a normal EEG. If neurones are damaged, injured or suffer a chemical or metabolic insult, a change in the discharge pattern may develop. In the case of epilepsy, regular low-frequency discharges are replaced by bursts of high-frequency discharges usually followed by periods of inactivity. A single neurone discharging in an abnormal manner usually has no clinical significance. It is only when a whole population of neurones discharge synchronously in an abnormal way that an epileptic seizure may be triggered. This abnormal discharge may remain localised or it may spread to adjacent areas, recruiting more neurones as it expands. It may also generalise throughout the brain via cortical and subcortical routes, including collosal and thalamocortical pathways. The area from which the abnormal discharge originates is known as the epileptic focus. An EEG recording carried out during one of these abnormal discharges may show a variety of atypical signs, depending on which area of the brain is involved, its progression and how the discharging areas project to the superficial cortex.



Clinical manifestations


The clinical manifestation of a seizure will depend on the location of the focus and the pathways involved in its spread. An international seizure classification scheme based on the clinical features of seizures combined with EEG data is widely used to describe seizures. It divides seizures into two main groups according to the area of the brain in which the abnormal discharge originates. If it involves initial activation of both hemispheres of the brain simultaneously, the seizures are termed ‘generalised’. If a discharge starts in a localised area of the brain, the seizure is termed ‘partial’ or ‘focal’.



Generalised seizures


Generalised seizures result in impairment of consciousness from the onset. There are various types of generalised seizures.



Tonic clonic convulsions


Often called ‘grand mal’ attacks, these are the commonest of all epileptic seizures. Without warning, the patient suddenly goes stiff, falls and convulses, with laboured breathing and salivation. Cyanosis, incontinence and tongue biting may occur. The convulsion ceases after a few minutes and may often be followed by a period of drowsiness, confusion, headache and sleep.



Absence attacks


Often called ‘petit mal’, these are a much rarer form of generalised seizure. They happen almost exclusively in childhood and early adolescence. The child goes blank and stares; fluttering of the eyelids and flopping of the head may occur. The attacks last only a few seconds and often go unrecognised even by the child experiencing them.



Myoclonic seizures


These are abrupt, very brief involuntary shock-like jerks, which may involve the whole body, or the arms or the head. They usually happen in the morning, shortly after waking. They may sometimes cause the person to fall, but recovery is immediate. It should be noted that there are forms of non-epileptic myoclonic jerks that occur in a variety of other neurological diseases and may also occur in healthy people, particularly when they are just going off to sleep.



Atonic seizures


These comprise a sudden loss of muscle tone, causing the person to collapse to the ground. Recovery afterwards is quick. They are rare, accounting for less than 1% of the epileptic seizures seen in the general population, but much commoner in patients with severe epilepsy starting in infancy.



Partial or focal seizures



Simple partial seizures


In these seizures, the discharge remains localised and consciousness is fully preserved. Simple partial attacks on their own are rare and they usually progress to the other forms of partial seizure. What actually happens during a simple partial seizure depends on the area of the discharge and may vary widely from person to person but will always be stereotyped in one person. Localised jerking of a limb or the face, stiffness or twitching of one part of the body, numbness or abnormal sensations are examples of what may occur during a simple partial seizure. If the seizure progresses with impairment of consciousness, it is termed a complex partial seizure. If it develops further and a convulsive seizure occurs, it is then called a partial seizure with secondary generalisation. In attacks which progress, the early part of the seizure, in which consciousness is preserved, may manifest as a sensation or abnormal feeling and is called the aura or warning.



Complex partial seizures


The person may present with altered or ‘automatic’ behaviour: plucking his or her clothes, fiddling with various objects and acting in a confused manner. Lip smacking or chewing movements, grimacing, undressing, performing aimless activities, and wandering around in a drunken fashion may occur on their own or in different combinations during complex partial seizures. Most of these seizures originate in the frontal or temporal lobes of the brain and can sometimes progress to secondarily generalised seizures.



Secondarily generalised seizures


These are partial seizures, either simple or complex, in which the discharge spreads to the entire brain. The person may have a warning, but this is not always the case. The spread of the discharge can occur so quickly that no feature of the localised onset is apparent to the person or an observer, and only an EEG can demonstrate the partial nature of the seizure. The involvement of the entire brain leads to a convulsive attack with the same characteristics as a generalised tonic clonic convulsion.


There have been recent proposals to revise the concepts, terminology and approaches for classifying seizures and forms of epilepsy (Berg et al., 2010). In this proposal, the so-called natural classes, for example, specific underlying cause, age at onset, associated seizure type; or pragmatic groupings, for example, epileptic encephalopathies, self-limited electroclinical syndromes, serve as the basis for classification.



Diagnosis


Diagnosing epilepsy can be difficult as it is first necessary to demonstrate a tendency to recurrent epileptic seizures. The one feature that distinguishes epilepsy from all other conditions is its unpredictability and transient nature. The diagnosis of epilepsy is clinical and depends on a reliable account of what happened during the attacks, if possible both from the patient and from an eyewitness. Investigations may help and the EEG is usually one of them. These investigations, however, cannot conclusively confirm or refute the diagnosis of epilepsy.


There are other conditions that may cause impairment or loss of consciousness and which can be misdiagnosed as epilepsy; these include syncope, breath-holding attacks, transient ischaemic attacks, psychogenic attacks, etc. In addition, people may present with acute symptomatic seizures or provoked seizures as a result of other problems such as drug intake, metabolic dysfunction, infection, head trauma or flashing lights (photosensitive seizures). These conditions have to be clearly ruled out before a diagnosis of epilepsy is made. Epilepsy must only be diagnosed when seizures occur spontaneously and are recurrent. The diagnosis must be accurate since the label ‘suffering with epilepsy’ carries a social stigma that has tremendous implications for the person.


The EEG is often the only examination required, particularly in generalised epilepsies, and it aims to record abnormal neuronal discharges. EEGs have, however, limitations that should be clearly understood. Up to 5% of people without epilepsy may have non-specific abnormalities in their EEG recording, while up to 40% of people with epilepsy may have a normal EEG recording between seizures. Therefore, the diagnosis of epilepsy should be strongly supported by a bona fide history of epileptic attacks. Nevertheless, the EEG is invaluable in classifying seizures.


The chance of recording the discharges of an actual seizure during a routine EEG, which usually takes 20–30 min, is slight and because of this, ambulatory EEG monitoring and EEG video-telemetry are sometimes required. Ambulatory EEG allows recording in day-to-day circumstances using a small cassette recorder. EEG video-telemetry is useful in the assessment of difficult cases, particularly if surgery is considered. The person is usually admitted to hospital and remains under continuous monitoring. This is only helpful in a very few cases, and it is best suited for people who have frequent seizures.


Neuroimaging with magnetic resonance imaging (MRI) is the most valuable investigation when structural abnormalities such as stroke, tumour, congenital abnormalities or hydrochephalus are suspected. MRI should be carried out in anyone presenting with partial seizures or where a structural lesion on the brain may be responsible for seizures.



Treatment


National Institute for Health and Clinical Excellence (2004a) issued guidance on the diagnosis and treatment of the epilepsies in adults and children in primary and secondary care. The guidance covered issues such as when a person with epilepsy should be referred to a specialist centre, the special considerations concerning the care and treatment of women with epilepsy and the management of people with learning disabilities. The key points of the guidance are summarised in Box 31.1.



Box 31.1 Key points on the diagnosis and management of epilepsy (National Institute for Health and Clinical Excellence, 2004a)



• Diagnosis to be made urgently by a specialist with an interest in epilepsy

• EEG to be used to support diagnosis

• MRI to be used in people who develop epilepsy as adults, in whom focal onset is suspected, or in whom seizures persist

• Seizure type(s) and epilepsy syndrome, aetiology and co-morbidity to be determined

• Initiation of appropriate treatment to be recommended by a specialist

• Treatment individualised according to seizure type, epilepsy syndrome, co-medication and co-morbidity, the individual’s lifestyle and personal preferences

• The individual with epilepsy, and their family and/or carers, to participate in all decisions about care, taking into account any specific need

• Comprehensive care plans to be agreed

• Comprehensive provision of information about all aspects of condition

• Regular structured review at least once a year

• Patient to be referred back to secondary or tertiary care if:
– Epilepsy inadequately controlled

– Pregnancy considered or pregnant

– Antiepileptic drug withdrawal considered

• MRI, magnetic resonance imaging; EEG, electroencephalogram.


Treatment during seizures


Convulsive seizures may look frightening but the person is not in pain, will usually have no recollection of the event afterwards and is usually not seriously injured. Emergency treatment is seldom necessary. People should, however, be made as comfortable as possible, preferably lying down (ease to the floor if sitting), cushioning the head and loosening any tight clothing or neckwear. During seizures, people should not be moved unless they are in a dangerous place, for example, in a road, by a fire or hot radiator, at the top of stairs or by the edge of water. No attempt should be made to open the person’s mouth or force anything between the teeth. This usually results in damage, and broken teeth may be inhaled, causing secondary lung damage. When the seizure stops, people should be turned over into the recovery position and the airway checked for any blockage.


Partial attacks are usually less dramatic. During automatisms, people may behave in a confused fashion and should generally be left undisturbed. Gentle restraint may be necessary if the automatism leads to dangerous wandering. Attempts at firm restraint, however, may increase agitation and confusion. No drinks should be given after an attack, nor should extra antiepileptic drugs (AEDs) be administered. It is commonly felt that seizures may be life-threatening, but this is seldom the case. After a seizure, it is important to stay with the person and offer reassurance until the confused period has completely subsided and the person has recovered fully.


If a seizure persists for more than 10 min, if a series of seizures occur or if the seizure is particularly severe, then intravenous or rectal administration of 10–20 mg diazepam for adults, with lower doses being used in children, is advisable.



Status epilepticus


Initial management of status epilepticus is supportive and may include:


• positioning the person to avoid injury

• supporting respiration

• maintaining blood pressure

• correcting hypoglycaemia

Drugs used include intravenous lorazepam or diazepam. Alternative medicines include midazolam in cases where the person has not responded to first-line drugs. Alternatively, buccal midazolam has been advocated and is increasingly being used, although it is not licensed in the UK. In severe cases, phenytoin, clonazepam or phenobarbital sodium may be required.



Febrile convulsions


Convulsions associated with fever are termed febrile convulsions and may occur in the young. Brief febrile convulsions are managed conservatively with the primary aim of reducing the temperature of the child. Tepid sponging and use of paracetamol is usual. Prolonged febrile convulsions lasting 10–15 min or longer or in a child with risk factors require active management to avoid brain damage. The drug of choice is diazepam by intravenous or rectal (rectal solution) administration. Prophylactic management of febrile convulsions may be required in some children, such as those with pre-existing risk factors or a history of previous prolonged seizures.



Long-term treatment


In most cases, epilepsy can only be treated by long-term, regular drug therapy. The objective of therapy is to suppress epileptic discharges and prevent the development of epileptic seizures. In the majority of cases, full seizure control can be obtained, and in other patients drugs may reduce the frequency or severity of seizures.


Initiating treatment with an AED is a major event in the life of a person, and the diagnosis should be unequivocal. Treatment options must be considered with careful evaluation of all relevant factors, including the number and frequency of attacks, the presence of precipitating factors such as alcohol, drugs or flashing lights, and the presence of other medical conditions (Feely, 1999). Single seizures do not require treatment unless they are associated with a structural abnormality in the brain, a progressive brain disorder or there is a clearly abnormal EEG recording. If there are long intervals between seizures (over 2 years), there is a case for not starting treatment. If there are more than two attacks that are clearly associated with a precipitating factor, fever or alcohol for instance, then treatment may not be necessary.


Therapy is long-term, usually for at least 3 years and, depending on circumstances, sometimes for life. A full explanation of all the implications must be given to the person and they must be involved in all stages of the treatment plan. It is vital that the person understands the implications of treatment and agrees with the treatment goals. Empowerment of the person with epilepsy to be actively involved in the decision-making process will encourage adherence and is essential for effective clinical management. Support for people so that they understand the implications of the condition and why drug therapy is so important is crucial to ensure effective clinical management.


Health professionals have a key role in supporting people with epilepsy to ensure they are able to manage their medicines appropriately. AED treatment will fail unless the patient fully understands the importance of regular therapy and the objectives of treatment. Poor adherence is still a major factor which results in hospital admissions and poor seizure control and leads to the clinical use of multiple AEDs.



General principles of treatment


Therapy aims to control seizures using one drug, with the lowest possible dose that causes the fewest side effects possible. The established AEDs, carbamazepine, ethosuximide and sodium valproate, are still important parts of the antiepileptic armamentarium. Acetazolamide, clobazam, clonazepam, phenobarbital phenytoin and primidone are also still used. In the last two decades, new AEDs such as vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, zonisamide, lacosamide and eslicarbazepine acetate have been introduced. The choice of drugs depends largely on the seizure type, and so correct diagnosis and classification are essential. Table 31.1 lists the main indications for the more commonly used AEDs, and Table 31.2 summarises the clinical use of the newer AEDs.


Table 31.1 Antiepileptic drugs for different seizure types

















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Jun 18, 2016 | Posted by in PHARMACY | Comments Off on Epilepsy

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Partial seizures
  Carbamazepine Topiramate
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