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May 2008: Assessing suspected epilepsy in primary care

What are the risk factors for epilepsy?

What are the differential diagnoses?

Which patients should stop driving?

What are the risk factors for epilepsy?

What are the differential diagnoses?

Which patients should stop driving?

Epilepsy is the most common serious neurological disorder and affects about 0.7% of the population.1 Patients are usually diagnosed after a generalised seizure, or following recurrent stereotyped attacks, which may or may not disturb consciousness (complex and simple partial seizures respectively).

Assessment

Epilepsy is a clinical diagnosis. A careful history is essential and should cover the following for each attack:

• Time of day, situation and presence of any provoking factors, such as acute illness, sleep deprivation, alcohol or recreational drug use and exposure to flashing lights

• Presence of any prodrome, particularly if it is similar in all attacks

• A detailed description of the event itself. If the patient loses consciousness, enquire about tongue/cheek biting and other injuries, incontinence and the duration of any postictal confusion. A collateral history from a friend or relative is invaluable, even if the patient retained consciousness. If the attacks are recurrent, it may be possible for observers to record a video, for example on a camera phone.

41190508Patients should also be asked about risk factors for epilepsy (see table 1, left), employment, home circumstances and driving status. Bupropion can cause seizures, and beta blockers commonly cause syncope in older patients, which may be mistaken for epilepsy.

Neurological examination is usually normal between attacks in patients with epilepsy, and focal abnormalities suggest underlying structural CNS pathology.

Patients should have a cardiovascular examination and a routine 12-lead ECG to investigate cardiovascular differential diagnoses.

Blood should be taken as soon as possible after an event and sent for urea and electrolytes, glucose, calcium and magnesium levels to rule out significant metabolic abnormalities.

A full blood count and liver function tests need to be carried out to serve as baselines before antiepileptic drug therapy is initiated.

Differential diagnosis

41190509Epilepsy has a wide differential diagnosis, which is summarised in table 2, left.

It is important to avoid making a ‘diagnosis' of epilepsy in people who have provoked or acute symptomatic seizures, for example seizures in the context of alcohol withdrawal or acute metabolic disturbance. In these patients the underlying condition needs to be treated.

Vasovagal syncope

The most common differential diagnosis is vasovagal syncope, which is often indicated by the three Ps:

• Provocation – typical provoking factors include a warm, crowded environment and emotion
• Posture – the patient is usually standing or sitting during the attack
• Prodrome – the patient experiences a prodrome, which may last several minutes. This usually includes lightheadedness, sweating, nausea, tinnitus, a sensation of ‘closing in' and blurred vision.

Observers may note that the patient looks pale and sweaty before losing consciousness and falling to the ground. However, once supine, skin colour and consciousness usually return quickly. Patients do not normally experience prolonged confusion or amnesia, and tongue biting, injury and incontinence are rare.

Myoclonic jerks while unconscious may cause diagnostic confusion. If these are brief and the history is otherwise typical for syncope, it is likely that the patient has experienced ‘convulsive syncope', or reflex anoxic seizure, caused by brief cerebral anoxia. Such attacks should not be considered epileptic seizures.2

Patients with vasovagal syncope should be advised to avoid trigger factors and to lie down if presyncopal symptoms occur. If attacks remain frequent, referral to a falls and syncope service should be considered.

Cardiac causes of syncope

Cardiac causes of syncope are important as they may require urgent management. A history of palpitations, chest pain or heart disease can indicate cardiac arrhythmia.

If the arrhythmia is paroxysmal, an ECG is usually normal between attacks. However, it may provide vital clues, such as a prolonged QT interval, which is often familial or drug-induced, or delta waves, indicating Wolff-Parkinson-White syndrome.

Exercise-induced syncope, angina or dyspnoea may indicate cardiac outflow obstruction, for example by aortic stenosis or hypertrophic obstructive cardiomyopathy, and a systolic murmur may be detected on examination.

Hypoglycaemia

Hypoglycaemia usually causes a prodrome of autonomic features (such as sweating, tremor and palpitations) and neuroglycopenic features (diplopia and alterations in conscious level and personality) before progressing to loss of consciousness and convulsions. It should mostly be considered in patients with diabetes treated with insulin, sulphonylureas or metformin, or those who have access to such drugs and might use them surreptitiously.

Ideally, hypoglycaemia is diagnosed acutely by taking a capillary blood glucose level. However, if this is not possible and events are recurrent, referral to a diabetes specialist may be indicated.

Complex partial seizures can mimic hypoglycaemia, and if glucose levels are found to be normal the patient should be referred to a neurologist.

Seizure

If a diagnosis of seizure is suspected after initial assessment in primary care, the patient should be referred to the local neurology service, usually to a dedicated first seizure clinic.

In the interim, patients should be instructed to:

• Avoid heights and deep water. The patient should leave the bathroom door unlocked when taking a bath and ask a responsible adult to remain in the vicinity. Showers can be taken unsupervised

• Stop driving and operating dangerous machinery until further notice

• Bring a witness to their neurology appointment.

This safety advice should be given to the patient even if the attacks do not involve any alteration of conscious level, as partial seizures can spread and generalise unpredictably. Any advice should be recorded clearly in the patient's notes.

Driving status

The neurologist will discuss driving status with the patient. After any seizure, including epileptic ‘auras' or partial events and myoclonic seizures, holders of a group 1 licence must stop driving for one year and inform the DVLA and their motor insurance provider. By contrast, clear, simple, provoked faints usually entail no driving restrictions.

Further details are available in the DVLA guide on medical standards of fitness to drive,3 which also includes guidelines for loss of consciousness or altered awareness where the diagnosis is unclear.

Patients who experience frequent seizures should also be advised not to ride a bicycle.

Types of epilepsy

Focal epilepsies

The majority of epilepsies are focal or localisation-related and arise from a localised area of electrically abnormal cortex. Clinical features may suggest the area of onset (see table 3, attached). Seizure activity may remain localised in a partial seizure or spread through the cortex, ultimately causing a generalised seizure. Such generalisation may occur rapidly, and many focal epilepsies do not appear to begin with focal symptoms.

Idiopathic generalised epilepsies

Idiopathic generalised epilepsies almost invariably begin in childhood and early adulthood, and are associated with several seizure types. The most common of these is juvenile myoclonic epilepsy, which represents 6% of adult epilepsies4 and manifests as generalised tonic-clonic seizures, myoclonic jerks on waking and, in about 30% of cases, absences. Up to 40% of patients are photosensitive.5

In patients who present with isolated, generalised tonic-clonic seizures in later adulthood, focal epilepsy with rapid generalisation is often misdiagnosed as idiopathic generalised epilepsy. The distinction between focal and idiopathic generalised epilepsies is important in determining the course of investigation and treatment.

Investigations

All patients with focal epilepsy should undergo MRI to determine whether there is any underlying structural abnormality (see figure 1, attached). If MRI is contraindicated, a CT scan with contrast should be performed.

An EEG is helpful if epilepsy is suspected, as it can support the diagnosis, help to classify seizure type and epilepsy syndrome, and determine the risk of seizure recurrence after a first unprovoked seizure. However, an EEG can neither exclude epilepsy nor diagnose it in isolation, and should not be performed if the diagnosis is thought to be syncope.

Most routine EEGs include a period of photic stimulation with a strobe light. If this does not result in clinical or electrographic seizure activity, there is no need for the patient to avoid strobe illumination in the future. However, occasionally patients can be pattern-sensitive, which is not identified by strobe testing.

If the diagnosis remains in doubt, videotelemetry may be required. This involves a continuous, synchronised video and EEG recording of the patient for a prolonged period in order to capture the clinical and electrical features of an attack simultaneously. This is usually performed during admission to hospital.

Treatment

Before any treatment is started, the diagnosis must have been established beyond reasonable doubt. If the diagnosis remains uncertain, it is best to seek further clinical information or to wait; therapeutic trials should not be performed.

Antiepileptic drugs form the mainstay of therapy (see table 4, attached), and are selected according to the type of epilepsy and the patient's requirements. These should normally be instituted in secondary care, and a joint management plan should be established for dose adjustment or change of medication.

Focal epilepsy

Traditionally, the treatment of choice for focal epilepsy is carbamazepine. However, the SANAD study6 found that lamotrigine is equally effective and is associated with fewer side-effects. Topiramate was found to have a higher risk of treatment failure because of side-effects or poor seizure control. Some of the newest antiepileptic drugs, for example levetiracetam, were not included in SANAD and further studies are required.

Idiopathic generalised epilepsy

The SANAD study7 confirmed the established view that valproate is the best agent in terms of efficacy and side-effects for the treatment of idiopathic generalised epilepsy. Other useful agents include lamotrigine and topiramate. Clonazepam may be used for patients with prominent myoclonus that do not respond to valproate alone.

In patients who suffer from clusters of seizures, clobazam 10mg bd is sometimes added for short periods as required.

If frequent, prolonged, generalised seizures occur, rectal diazepam can be used to terminate the seizure. Buccal midazolam, although unlicensed, is equally effective and more socially acceptable, but relatives or carers need to be trained to administer it.8

It is important that the needs of the individual are taken into account. See table 5, attached, and table 6, attached, for guidance in managing epilepsy in women of childbearing age and older people respectively.

Long-term care

Monitoring

Regular monitoring for long-term side-effects of antiepileptic drugs is unlikely to be beneficial in the majority of cases. It is more important to warn patients to report changes such as bruising/bleeding, jaundice, nausea and changes in mental state.

If monitoring is performed, the following blood tests may be considered:

• Full blood count, to ensure the absence of drug-induced cytopenias
• Folate/calcium levels, as enzyme inducers can accelerate the metabolism of folate and vitamin D. Testing is most relevant in older patients.

Liver function tests should not usually be performed, as laboratory confirmation of hepatic enzyme induction does not influence management. Measuring drug levels is not usually helpful, as the plasma levels of most drugs do not correlate well with therapeutic efficacy (except for phenytoin).

Follow-up

Every patient with epilepsy should have an annual review.11 The following points should be discussed:

• Date of last seizure, seizure frequency
• Safety, work, driving status, contraception and pregnancy
• Current treatment and further treatment options
• Availability of advice from voluntary organisations.

Patients with stable epilepsy without active management issues are usually discharged from the hospital clinic. However, the occurrence of any new problems may necessitate further discussion with the neurologist or re-referral. Patients whose seizures fail to respond to appropriate medication should be referred back to specialist services for review.

Conclusion

The presentation of epilepsy is variable and a wide differential diagnosis needs to be considered. Patients with suspected epilepsy should be referred for investigation and treatment.

Authors

Dr Stephan R Jaiser
MA MB BChir MRCP
academic clinical fellow

Dr Margaret J Jackson
MD FRCP
consultant neurologist, Department of Neurology, Newcastle General Hospital

Epilepsy in primary care Key points Table 3: Epilepsy syndromes Table 4: Common antiepileptic drugs Table 5: Treatment of epilepsy in women of childbearing age Table 6: Treatment of epilepsy in older people tab1ep Tab2epi MRI of a brain of a patient with tuberous sclerosis, showing subependymal nodules (arrowheads) and white matter abnormalities Figure 1 Carbamaepine-induced drug rash Figure 2

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