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A seizure may be defined as ‘a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain’. Whilst many causes of seizures exist, the first task for the clinician is to determine if the event was provoked or not. A seizure that is provoked may occur due to many causes, including: Electrolyte disturbances, hypoglycaemia, and sudden withdrawal from alcohol or other drugs. Such symptomatic seizures are common, and up to 15 per cent of the population will experience a seizure at some point in life. When a patient presents with a suspected seizure, other seizure mimics, such as convulsive syncope or cardiac arrhythmia, also need to be considered.
Whilst there are many causes for a single seizure, a diagnosis of epilepsy can only be made when certain features are identified: (i) At least two unprovoked seizures occurring more than 24 hours apart; (ii) one unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60 per cent) after two unprovoked seizures, occurring over the next 10 years; and (iii) diagnosis of an epilepsy syndrome.
The World Health Organisation (WHO) estimates that 50 million people worldwide have epilepsy and that treatment is effective approximately 70 per cent of the time. In order to start an appropriate anti-epileptic medication in a newly-diagnosed patient, the type of epilepsy must be classified. The International League Against Epilepsy (ILAE) recently provided an updated classification of epileptic seizures and this helps to both communicate the exact nature of the seizures and provide a basis for treatment.
Focal-onset seizures originate from one cerebral hemisphere, and in practice the history may provide a basis for suspecting a particular lobe in the brain these may considered as seizures in a ‘part of the brain’. The earliest prominent feature at the onset of the seizure is what determines the classification. Focal seizures may have either maintained awareness or impaired awareness.
The term ‘awareness’ refers to knowledge of self and environment; this is to avoid confusion with the term ‘consciousness’, which is often unaffected during a focal seizure. The term ‘focal aware’ replaces ‘simple partial’ of the older classification. Focal with impaired awareness, ‘complex partial or dialeptic’. Following classification of a seizure as focal, further terms may be used to explain the nature of the seizure; two broad descriptions are applied: ‘Motor’ or ‘non-motor’.
Motor-onset focal seizures may be subclassified as follows: Automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic. The description of movement of a body part during a focal seizure is often obtained from the collateral history or in some instances, review of video footage made by a family member. In some instances, when awareness is maintained, the patient may recall the nature of the movements or be able to simulate the movements in clinic to aid with diagnosis. If it is not possible to classify the type of movement, the seizure may be termed ‘focal with motor onset’.
Non-motor onset seizures may be subclassified as: Autonomic, behaviour arrest, cognitive, emotional, and sensory. A history of behaviour arrest is typically obtained from collateral history from the family or eyewitness account of the seizure, as patients frequently have impaired awareness during this phenomenon. The other non-motor features are more commonly (but not universally) obtained from the patient’s account of events.
Autonomic features may include: Gastrointestinal symptoms, sense of temperature change, goose bumps, or respiratory changes. Cognitive features represent a deficit in thinking, language or higher cortical function and may include features such as déjà vu or sensory hallucinations. Emotional seizures result in a subjective overwhelming feeling of anger, joy, anxiety or other emotions that do not result from any other external stimuli.
The classification of focal seizures and corresponding anti-epileptic drugs used in treatment are summarised in Table 1. Either focal motor or non-motor seizures may progress to bilateral tonic-clonic seizures. The ILAE have also dispensed with the terms ‘secondary generalisation’ and ‘convulsion’. Whilst any focal seizure may progress to bilateral tonic-clonic, it is the patient’s history, and in particular previous focal seizures rather than tonic-clonic seizures, that often aids classification to ensure an appropriate treatment is started.
Generalised seizures are defined as ‘originating at some point within and rapidly engaging, bilaterally distributed networks’. In other words, the ‘whole brain’ is involved rather than a ‘part of the brain’, as in a focal seizure. Due to the more extensive involvement in a generalised seizure, it is implicit that awareness is impaired, so unlike focal seizures, this does not need to be explicitly stated. Generalised seizures may then also be subclassified as motor or non-motor.
Generalised motor seizures may contain the following descriptive terms: Tonic-clonic, clonic, myoclonic, atonic or epileptic spasms. In such seizures, an eyewitness account is crucial, as the patient will have little or no recollection of the event. In such seizures, a tonic movement refers to a prolonged abnormal stiffening of a limb and may be isolated or followed by clonic (jumpy or jerky) limb movements. Less commonly, an atonic event may occur where the muscle loses all tone and may result in a ‘drop attack’. Myoclonus may be difficult to discriminate from clonus retrospectively; patients frequently give a history of isolated myoclonic jerks. These may be more noticeable in the morning time in the setting of juvenile myoclonic epilepsy. Again, the term ‘grand mal’ has been dispensed with to describe generalised motor seizures.
Generalised non-motor seizures are most commonly seen in the form of absence seizures. These were previously described as ‘petit mal’ seizures, but this term has also now been discontinued. Absence seizures are featureless, with a momentary loss of awareness, and are most commonly seen in young children. They can be confused with daydreaming or lack of attention in the setting of school. Absence seizures can be precipitated by hyperventilation. In the context of a person with a learning disability, such seizures have a slower onset, or termination and tone may change. These seizures are referred to as ‘atypical absence seizures’. Other variants of a non-motor seizure include: Absence with myoclonic activity or eyelid myoclonia, both of which are less common.
The classification of generalised epileptic seizures and possible anti-epileptic treatments are summarised in Table 2.
In the context of a first seizure or suspected new-onset epilepsy, a critical component of the assessment is a detailed history from the patient and any eyewitness about the onset of the presenting event and a detailed history of any previous unexplained events. As in the case report outlined on this page, our patient had over a decade of ongoing focal seizures. It was only when these spread to bilateral tonic-clonic seizures that a diagnosis of epilepsy was made, and, in our experience, this is not an uncommon phenomenon.
The first investigation to consider in the context of the emergency department, once metabolic abnormalities or seizure mimics are excluded (pulse, blood pressure, ECG and holter), is a CT brain scan.
If possible, an MRI scan is preferable but in the acute setting, this is not always possible and an MRI may be obtained at a later time point. A CT may be useful to identify acute haemorrhage or a large glioma or meningioma. An MRI may provide a more detailed view of the anatomy of the brain parenchyma or more specific features, such as mesial temporal sclerosis. If the person is back at baseline and has no residual focal neurological deficits, an emergency brain CT may not be necessary and an MRI may be obtained in the first instance.
After imaging, the other investigation frequently performed is an EEG. However, it is important to understand the limitations of a routine outpatient department investigation. Unless a seizure or typical event is captured, which often occurs, then no diagnostic electrographic abnormalities or epileptiform discharges may be seen. It is important to note that a ‘normal’ EEG does not exclude a diagnosis of epilepsy, which is always made clinically.
By classifying the seizures as ‘focal’ or ‘generalised’, it allows refinement of the choice of an appropriate anti-epileptic drug. In choosing an anti-epileptic drug, a number of other factors should also be considered, including: Age, gender, reproductive status, learning disability, medical comorbidities, and medication interactions that may arise.
In general terms, the following drugs may be considered for treatment of a focal epilepsy: Levetiracetam, eslicarbazepine, and lamotrigine. This list is far from exhaustive, and a number of other possible drugs may be used in the context of a specialist clinic. These three drugs are likely the most commonly-initiated drugs in a newly-diagnosed focal epilepsy. Their use is summarised in Table 1, with the corresponding most commonly seen side-effects.
For generalised seizures, so called ‘broad spectrum’ drugs are typically used. These include: Levetiracetam, valproate, topiramate and zonisamide. It is extremely important to note that valproate is highly teratogenic, and should not be prescribed to a female patient with child-bearing potential, unless no other effective option exists for a particular patient. As with treatment of a focal epilepsy, a number of other drug treatment options are possible and the list provided again represents only the more frequently-used drugs, rather than every available option.
For patients who continue to have epileptic seizures despite a trial of two appropriate anti-epileptic drugs, their epilepsy may be defined as refractory. Such cases represent approximately one-third of all patients, and specialist treatment may include a combination of anti-epileptic drugs, resective surgery or a vagal nerve stimulator.
Whilst epilepsy is a common neurological disorder, and is estimated to affect approximately 40,000 people in Ireland, seizures are not the only manifestation of the disease. A number of other factors are considered in the management of a person with epilepsy. Whilst the possible comorbidities are extensive, only the more commonly-encountered issues are discussed.
Psychological or psychiatric comorbidities are among these and depression is one of the most frequently encountered. Whilst most antidepressant medications list seizures as a side-effect, the benefit of treating depression in epilepsy far outweighs the risk of provoking further seizures in the vast majority of cases.
For women with epilepsy, pregnancy and childbirth are frequently discussed in clinic. As already discussed, valproate is generally contraindicated in women of child-bearing age; however, the risk of foetal anomalies is thought to be significantly lower with either levetiracetam or lamotrigine. All women with epilepsy are encouraged to take folic acid prior to conception, to reduce the risks of a neural tube defects. Although it is important to note that folic acid does not protect against valproate-associated teratogenicity. Women with epilepsy will also require more frequent antenatal monitoring.
As discussed in the case report above, driving also represents a topic that should be discussed with patients who have epilepsy. The RSA guidelines are clear in relation to epilepsy, and require that a person is free from seizures for one year before returning to driving. However, commercial vehicles (buses or trucks), or other large vehicles, have much more stringent restrictions. In practical terms, a person with epilepsy may often consider an alternate career or role in an organisation if previously employed as a commercial driver. The support group Epilepsy Ireland can provide vocational training and support in this regard.
Diet and exercise are also important considerations in epilepsy. This is particularly true in relation to bone density, as many anti-epileptic drugs contribute to osteoporosis. Weight-bearing exercise is of importance to reduce this risk and monitoring with a DEXA scan as well as calcium supplementation should be considered, in line with osteoporosis treatment guidelines.
Epilepsy is a chronic neurological disorder and requires multidisciplinary management, including: Epilepsy nurse specialist, support groups, such as Epilepsy Ireland, psychiatry, psychology, GPs and neurologists. For many people, modifications in lifestyle, such as reduced alcohol consumption and regular sleep, combined with an appropriate anti-epileptic medication, significantly reduces the risk of future seizures. Whilst seizure freedom cannot be guaranteed for any person, a holistic approach to management is recommended, as with other chronic diseases. In the minority of cases, epilepsy is refractory. However, to determine if an anti-epileptic drug choice was appropriate classification (focal versus generalised) of the person’s epilepsy is critical.
The classification of epileptic seizures has recently been updated, and the seizures are classified based on the features at onset of the seizure. Seizures are broadly classified into focal versus generalised and further descriptive terms may be used. This system of classification informs the choice of an appropriate anti-epileptic drug and provides language that is clear to people with epilepsy, researchers and physicians. Older, outdated terms such as ‘petit mal, ‘grand mal’, ‘simple partial’, ‘complex partial’ or ‘convulsion’ should no longer be used to facilitate optimum communication, treatment and research in epilepsy.
References on request
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