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Generalized seizures are usually of a tonic–clonic type and the patient tends to fall stiffly (tonic) and then start a coarse generalized limb shaking (clonic). This tends to go on for around 30 s, during which the patient is unresponsive to all stimuli. If examined during this period, the pupils are unreactive to light and the plantar responses are upgoing. The patient may bite his tongue and be incontinent of urine. When the patient regains consciousness he is often confused (post-ictal confusion) with aching muscles and a headache. In generalized seizures the patient can be cyanosed or look normal. It is

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common for oxygen saturations to be low during a prolonged, generalized, tonic–clonic epileptic seizure. Often convulsive seizures of this type occur singly or in groups of two or three. Prolonged series of such seizures without regaining consciousness in between is called convulsive status epilepticus and requires urgent treatment (see later)

In syncope the patient often appears pale shortly before and during the event. The period of loss of consciousness tends to be very brief (seconds). There is no confusion afterwards

Q4: What clinical examination would you perform and why?

A4

 Look in the mouth for evidence of tongue biting (this can occur during a generalized seizure).

 Cardiovascular system: a common cause for seizures in this age group is cerebrovascular disease. Evidence of ischaemic heart disease should be sought. Postural hypotension, arrhythmia or cardiac murmurs can also be associated with syncopal events.

 Neurological examination should concentrate on looking for lateralizing signs. These may occur as a result of a focal cerebral lesion, e.g. from a stroke or a space-occupying lesion. Funduscopy, if it identifies papilloedema, suggests the presence of raised intracranial pressure from a space-occupying lesion.

 Respiratory examination: the patient smokes so the possibility of a cerebral metastasis from a bronchogenic carcinoma should be considered.

 Abdominal examination: if there is a history of alcohol excess it is important to assess for signs of chronic liver disease.

Q5: What investigations would be most helpful and why?

A5

 A BM stick allows rapid measurement of glucose.

 Electrocardiogram (ECG): should be done in all patients because epilepsy and cardiac causes of loss of consciousness can be difficult to distinguish. If arrhythmias are suspected a 24-hour ECG is helpful.

 Full blood count (FBC): anaemia or infection can provoke seizures.

 Urea and electrolytes (U&Es), calcium: hyponatraemia and hypocalcaemia in particular can provoke seizures.

 Blood glucose: hypoglycaemia can provoke seizures.

 Electroencephalogram (EEG): should be performed in all patients to support the diagnosis of epilepsy in patients with a suitable history and to help with seizure classification and localization. It is important to note that a ‘normal’ EEG does not exclude epilepsy, and a ‘non-specifically abnormal’ EEG does not necessarily imply an underlying significant neurological problem. Diagnosis of epilepsy is based primarily on a clear history. One reason for the high rates of misdiagnosis in epilepsy may be inappropriate interpretation of the EEG result. A single resting EEG shows abnormalities in only 50 per cent of patients with epilepsy. Sensitivity increases if the EEG is done within 24 h of a seizure, repeated or performed after sleep deprivation. Most useful of all is if the EEG can be performed during a seizure with video monitoring of the patient (video-telemetry). Conversely, normal phenomena, artefacts and non-specific abnormalities, occurring in about 20 per cent of the general population, are open to misinterpretation and may yield ‘false-positive results’. Correct analysis of the EEG is dependent on the context in which it is performed. If an EEG

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is requested as a ‘screening tool’ for a patient with, for example, ‘funny turns’, it may yield minor abnormalities and cause more diagnostic uncertainty than it solves.

 Brain imaging: computed tomography (CT) of the brain will exclude a space-occupying lesion and may identify evidence of cerebrovascular disease. It is often used for rapid assessment. Magnetic resonance imaging (MRI) of the brain is better at identifying small structural lesions and is the brain imaging modality recommended by many authorities.

Q6: What treatment options are appropriate?

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This patient is likely to have suffered a secondary generalized seizure. However, a diagnosis of epilepsy cannot be made on the basis of a single seizure. Infection, drugs or metabolic problems can provoke seizures. Anti-epileptic drugs (AEDs) are therefore not usually started after a first seizure unless the risk of recurrence is thought to be high.

Epilepsy may be viewed as a chronic neurological condition characterized by recurrent unprovoked seizures. The nature of the seizures depends on which brain structures are affected.

Anti-epileptic drugs are usually started after the second seizure. Current indications and side-effect profiles for the various AEDs are readily available in the British National Formulary. The principles of treatment are addressed and commonly used

‘first-line’ monotherapy agents are discussed in brief.

A treatment should be effective, with minimal side effects for the patient. At present there is no clear consensus as to where the balance between efficacy and side effects lies. In circumstances where there is no urgency to start treatment, the decision should ideally be made jointly by the patient and a neurologist. Potentially ‘acceptable’ side effects will differ from patient to patient, and there are particular issues when prescribing for women, because drug interactions with the oral contraceptive pill, safety in pregnancy and breast-feeding need to be taken into account. The aim of treatment is to control seizures with a single agent (monotherapy), although a small proportion of patients may eventually require more than one AED.

There are now a large number of AEDs (including phenytoin, sodium valproate, carbamazepine, lamotrigine, levatiracetam, topiramate, oxcarbazepine, tiagabine, phenobarbital to name but a few). Some are licensed for use only as adjuncts (i.e. as an ‘add on’ treatment in patients with difficult to treat epilepsy), and should not therefore be initially used as monotherapy.

At present commonly prescribed first-line monotherapy AEDs in patients who do not require urgent treatment includes sodium valproate, lamotrigine and carbamazepine. Lamotrigine and sodium valproate are accepted as suitable for primary generalized seizures, partial/secondary generalized, and epileptic seizures of uncertain nature. Carbamazepine is not generally used for primary generalized seizures, because it may worsen this seizure type significantly.

CASE 6.2 – A 24-year-old woman who is known to have epilepsy started fitting after a family argument and an ambulance was called.

Q1: What is the likely differential diagnosis?

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 Non-epileptic seizure disorder

 Status epilepticus.

Non-epileptic seizure disorder is overwhelmingly likely in this scenario. However, before making this diagnosis it is important to be confident that the other important diagnosis of prolonged generalized tonic–clonic seizure (status epilepticus) has been excluded. Status epilepticus is defined as continuous epileptic seizures for over 30 min or recurrent seizures over 30 min with failure to regain consciousness in between events. Untreated it carries a high mortality and occurs in 3–7 per cent of patients with epilepsy.

Q2: What issues in the given history support/refute a particular diagnosis?

A2

Onset during a stressful event can be suggestive of a psychogenic factor. However, epileptic seizures can be triggered by stressful events so this feature is rather non-specific. The fact that the patient is known to have epilepsy does not help to support either an epileptic or a non-epileptic aetiology. A significant number of patients (30 per cent on average) have mixed epileptic and non-epileptic seizure disorders.

Q3: What additional features would you seek to support a particular diagnosis?

A3

This case demonstrates the importance of making a diagnosis before starting potentially dangerous treatments. Non-epileptic seizure disorder is considered to have a psychogenic basis. Non-Non-epileptic attacks are found to be most common in women between the ages of 20 and 50. Factors that may play a part in their onset often include a personal or family history of psychiatric disorder or depression, previous significant life events including bereavement, or a history of physical, sexual or emotional abuse.

Q4: What clinical examination would you perform and why?

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The fact that the eyes are screwed tightly shut suggests a volitional component to the muscle activity. This would not be expected to occur in status epilepticus. Wild thrashing, hip thrusting, normal pupillary responses, normal oxygen saturations and normal plantar responses are suggestive of non-epileptic seizures. The patient may respond to deep pain stimuli during the seizure. In status epilepticus patients are completely unresponsive.

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Q5: What investigations would be most helpful and why?

A5

An EEG – although it seems rather self-evident, it is important to emphasize that non-epileptic seizures are NOT epileptic seizures.

Correct identification of non-epileptic seizures is particularly important to prevent inappropriate transfer to an intensive therapy unit (ITU) for epilepsy management (see later).

An EEG performed during the seizure will be normal in a non-epileptic seizure, but would be expected to show epileptiform discharges during generalized status epilepticus.

Serum prolactin is often elevated during and shortly after a prolonged generalized tonic–clonic seizure. It is not generally significantly elevated by a non-epileptic seizure. However, it should be remembered that prolactin levels can also be increased by drugs (e.g. phenothiazines). This can occasionally cause diagnostic confusion.

Q6: What treatment options are appropriate?

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Patients with non-epileptic seizure disorder require a psychotherapeutic approach to help control their condition. The fits self-terminate.

Status epilepticus is a potential differential diagnosis in this situation, and the management of status epilepticus is outlined in Key concepts on p. 162.

CASE 6.3 – A 21-year-old woman presents with a history of an episode of loss of consciousness 3 months ago.

Q1: What is the likely differential diagnosis?

A1

 Syncope: simple faint (vasovagal syncope) – cardiac: cardiac arrhythmias

– metabolic: hypoglycaemia, hyperventilation, drug related/provoked

 Epilepsy.

This history is highly suggestive of syncope and is most likely to be a vasovagal event.

Q2: What issues in the given history support/refute a particular diagnosis?

A2

The symptoms related to posture, and the fact that she became pale and felt light-headed before losing consciousness (i.e.

a relatively long premonitory period), suggest impairment of cerebral blood flow. The facts that she crumpled to the floor rather than falling stiffly, and that loss of consciousness was very short-lived with rapid recovery, are also highly suggestive of a syncopal event.

The circumstances of the events (a hot, crowded situation) are highly suggestive of vasovagal syncope. The fact that she is otherwise very active would suggest that a primary cardiac arrhythmogenic or structural lesion is less likely (although it does not entirely exclude it).

A few short-lived and transient limb-jerking movements are compatible with a syncopal event (and are NOT diagnostic of epilepsy), although longer-lasting jerking movements of the limbs are more suspicious of epileptic seizures.

Q3: What additional features would you seek to support a particular diagnosis?

A3

 Is there is a past or family history of epilepsy or heart problems?

 Did she have palpitations before the event (more suggestive of an arrhythmia)?

 Was there any incontinence or tongue biting with the episode of loss of consciousness? This is common with epileptic seizures but not in syncope.

Remember that a patient may not volunteer aspects of a history that are potentially embarrassing, and ‘direct’ questioning may be needed to elicit this information.

Q4: What clinical examination would you perform and why?

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One would not usually expect to find any abnormalities in the general or neurological examination.

However, during examination, particular attention should be paid to excluding abnormalities in the cardiac system (e.g.

arrhythmias, heart murmurs). A postural blood pressure drop may sometimes be found.

Q5: What investigations would be most helpful and why?

A5

 Echocardiogram

 Tilt testing.

An ECG would help further to discount the (unlikely) possibility of a primary cardiac/arrythmogenic cause. Otherwise, no other investigations are necessary at present.

Importantly, an EEG is not indicated and if performed might complicate matters – a substantial proportion of ‘normal’ EEGs may show minor alterations in wave morphology that might confuse the unwary.

If she has further events, further investigation with a 24-h ECG may identify disorders of heart rhythm. If an arrhythmogenic cause is strongly suspected and the 24-h ECG is normal a cardiac ‘memo’ can be helpful. If a structural cause is strongly suspected an echocardiogram can identify evidence of outflow obstruction. Tilt-table testing is sometimes helpful in patients with severe and frequent episodes of syncope if cardiac abnormalities have been excluded.

Q6: What treatment options are appropriate?

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This patient requires reassurance that the episode was a faint rather than an epileptic seizure, and to try to avoid precipitating activities.

OSCE Counselling Case – Answer

OSCE COUNSELLING CASE 6.1 – The patient with epilepsy.

Epilepsy is a long-term diagnosis and issues surrounding AED choice, seizure triggers (fatigue, alcohol and other drugs, stress and occasionally photosensitivity), issues for women, driving regulations, safety in the home, cognitive effects of epilepsy and AEDs all need to be discussed with the patient. It is important to document that this has been done in the notes for medicolegal reasons. A useful checklist is available from the Scottish Intercollegiate Guidelines (www.sign.ac.uk).

Comprehensive guidelines from the National Institute for Health and Clinical Excellence (NICE) are also available from www.nice.org.uk.

The following issues need to be discussed:

 Explain what epilepsy is.

 Discuss the side effects of the various AED options.

 Discuss triggers to seizures, e.g. lack of sleep, infections, drugs, poor compliance with AED medication.

 SUDEP: SUDEP is the acronym for sudden unexplained death in epilepsy. There are around 500 cases in the UK every year, which, as a comparison, is more than the annual cases of cot deaths. The causes are not clear but SUDEP appears to be more frequent in those with poor seizure control who are non-compliant with treatment. It is considered that all patients with epilepsy should be informed of SUDEP, although clearly it is important to do this at an appropriate time, not necessarily at the time of diagnosis.

The following should also be discussed.