Epilepsy - Clinical review

How to identify, assess and manage epilepsy, and differentiate it from other neurological disorders.

CT and PET scans:epilepsy is shown by extended orange region (right)
CT and PET scans:epilepsy is shown by extended orange region (right)

Section 1: Epidemiology and aetiology

Epilepsy is a group of disorders characterised by two or more unprovoked seizures. The average prevalence of epilepsy is 5.5 per 1,000 people in Europe, 6.8 per 1,000 people in the US and 7.5 per 1,000 people in Australia.

Prevalence rates reported in developing countries vary considerably, with rates as high as 74.4 per 1,000 people for sub-Saharan Africa.

The annual incidence rates of epilepsy are 24-56 per 100,000 people in Europe. Reported incidence rates for developing countries are considerably higher. Approximately 3% of people will be diagnosed with epilepsy during their lifetime.

Seizures are broadly classified into focal onset (simple focal, complex focal and secondary generalised tonic-clonic seizures) and generalised onset (categorised as generalised tonic-clonic, absence, myoclonic, tonic and atonic seizures).

Epilepsy may be caused by a variety of disorders affecting the brain and can be classified by cause. Genetic (previously termed idiopathic): where epilepsy is the direct result of a presumed genetic defect.

Structural/metabolic (previously termed symptomatic): resulting from tumour, infection, head injury, cerebrovascular disease, degenerative or demyelinating conditions.

Unknown (previously termed cryptogenic): where the nature of the underlying cause is unknown.1

Temporal lobe epilepsy accounts for 60-70% of all focal epilepsies and may result from viral or autoimmune encephalitides, mesial temporal sclerosis (MTS) or tumour. Juvenile myoclonic epilepsy and childhood absence epilepsy account for most presumed genetic epilepsies.

Epilepsy is associated with comorbidities, particularly in the subset of patients with chronic epilepsy, who are more at risk of sudden unexplained death. Depression occurs in approximately one-third of all patients with epilepsy and is the second most important predictor of quality of life. Identifying chronic epilepsy early may allow early implementation of aggressive treatment, minimising long-term sequelae.

Section 2: Making the diagnosis

Patients presenting with a first seizure or epilepsy should be seen within two weeks by a specialist with clinical expertise in epilepsy.2 However, a proportion of patients will be diagnosed by other healthcare professionals because of variable access to epilepsy clinics or specialists in some parts of the UK.3

Epilepsy is a clinical diagnosis based on an accurate and detailed clinical history. A witness account should be sought wherever available. The clinician needs to distinguish between seizures, syncope and non-epileptic attack disorder (NEAD). Syncope can be physiological (vasovagal), cardiogenic or related to autonomic dysfunction. Myoclonic jerks (which may be multifocal and high amplitude) can occur during a syncopal event and may mimic seizure activity. Bradyarrhythmias can occur as part of seizures and may cause syncope.

NEAD accounts for one in five patients presenting to the epilepsy clinic. These events are thought to have an underlying psychological basis.

Neuropsychological assessment may unveil previous exposure to physical or sexual abuse and maladaptive illness behaviour.

See table 1 for a list of the clinical features distinguishing the three main diagnostic groups. Other important differential diagnoses include hypoglycaemic attacks, parasomnias and migraine.




Non-epileptic attack disorder

Posture Upright Any posture Any posture
Onset Gradual Sudden/aura Gradual
Pallor and sweating Invariable Uncommon Uncommon
Injury Unusual Not uncommon Not uncommon
Convulsive jerks Not uncommon Common Common (wax and wane) non-rhythmical
Incontinence Rare Common Not uncommon
Unconsciousness Seconds Minutes Minutes to hours
Recovery Rapid Often slow Often rapid
Postictal confusion Rare Common Rare (tearful, emotional)
Tongue biting Rare Common (lateral border) Rare Common Rare (tip of tongue)
Precipitating factors Crowds, lack of food, unpleasant circumstances Sleep deprivation  Stress, anxiety, medical situations

During history taking, information on child development and any illnesses (febrile convulsions, meningitis or head injuries) needs to be sought. Family history of blackouts or epilepsy, alcohol and drug use and current medications are also important. Establishing whether the patient holds a driving licence and pregnancy plans in women of childbearing age, are important facets of the history.

All patients presenting with seizure should have a 12-lead ECG to ascertain any underlying arrhythmia or long QT syndrome.

Interictal electroencephalography (EEG) is used in the setting of first epileptic seizure to provide prognostic information on the risk of further seizures over the next two years (27% versus 58% in patients with normal versus abnormal EEG).

In patients with newly-diagnosed epilepsy, EEG may provide information on classification and seizure type. In patients with suspected NEAD, EEG may confirm the diagnosis, demonstrating a lack of epileptiform correlate during a clinical event.

Interictal EEG is normal in about 50% of patients with epilepsy and is not a diagnostic tool for epilepsy. Video-EEG, where the patient is monitored during a five-day hospital stay, is used in cases where there are frequent events of diagnostic uncertainty.

MRI (T1, T2, fluid attenuated inversion recovery sequences) is used to identify a structural lesion (for example, hippocampal sclerosis, cortical dysplasia or low-grade glioma) causing seizures. Early identification of lesions provides opportunity for timely surgery and treatment planning.

Other imaging techniques are also used in UK epilepsy centres to provide further diagnostic information in presurgical evaluation.

Section 3: Managing the condition

The MRC multicentre trial for early epilepsy and single seizures ascertained that there was no long-term treatment advantage in commencing patients presenting with first seizure on antiepileptic drugs (AEDs).

However, AEDs may be offered to patients following a generalised tonic-clonic seizure if there is a neurological deficit, the EEG shows unequivocal epileptic discharges, there is a structural abnormality on imaging, or the patient (or carer) considers the risk of seizure recurrence unacceptable.4

The main aim of treating epilepsy is to achieve seizure freedom with minimal side-effects. In patients with non-lesional epilepsy, this is achieved via AEDs. All are widely considered to be effective in controlling focal onset seizures, although some drugs (for example, carbamazepine) may exacerbate certain forms of generalised seizures (for example, myoclonus and absences).

The largest randomised clinical trial to date, Standard And Newer Anti-epileptic Drugs (SANAD I) in newly-diagnosed epilepsy patients demonstrated that lamotrigine was most effective for patients with newly diagnosed focal onset epilepsy and sodium valproate was most effective for patients with newly diagnosed generalised onset epilepsy.5,6 SANAD II, is examining newer AEDs with the most effective AEDs from the first trial.

Choosing an AED
There needs to be special consideration when choosing AEDs in patients of childbearing age and in women on the combined oral contraceptive pill (COC).

In patients who fail their first monotherapy, an alternative trial of monotherapy should be considered. In patients failing two trials of appropriate treatment, a second AED may be added to the current regimen.

The proportion of patients achieving a reduction in seizure frequency by 50% varies between 30% and 50% for newer AEDs used as add-on therapy.

There is no clear evidence on which to base a choice among AEDs at present. Some advocate the combination of AEDs with mechanistic actions, but there is no clear evidence that mechanism of drug influences the response to treatment.

Surgical options
In patients with MTS who do not achieve seizure control with AEDs, surgery should be considered. Predictors of achieving seizure freedom include shorter duration of epilepsy, younger age at surgery, absent secondary generalisation and concordance between MRI and EEG.

Vagal nerve stimulation (VNS) is used as adjunctive treatment in patients with focal onset epilepsy who are medically refractory to AEDs and are not suitable for surgery. Studies show that approximately 30% of patients may have a reduction of seizures by 50% with VNS.

VNS also appears to improve depressive symptoms, with patients experiencing enhanced psychological wellbeing. Adverse effects commonly include hoarse voice, coughing and pharyngitis. Trigeminal nerve stimulation (TNS) via transcutaneous patch has been licensed for use in Europe and the US. It is thought to work by modification of thalamocortical pathways. TNS is yet to be evaluated by NICE for use in the UK.

Table 2: Annual review checklist for epilepsy patients suitable for primary care review
1. Seizure control (number of attacks, type of attack – use diary if necessary)
2. Date of last seizure 
3. Any adverse effects of AEDs 
4. Any cognitive problems as an adverse effect of AEDs
5. Consider checking folate/FBC in patients on enzyme-inducing AEDs whose diet might be low in folate 
6. Consider checking vitamin D levels in patients on enzyme-inducing AEDs who have other risk factors for osteoporosis
7. Compliance (monitoring of AED levels is only recommended to check compliance if seizure control is poor and in patients treated with phenytoin) 
8. Continued education about epilepsy (refer to community epilepsy nurse where available)
9. Address lifestyle factors (driving, contraception, pregnancy planning, employment, benefits)
10. Date of next review 
11. Adjust AEDs according to agreed management plan

Section 4: Prognosis

Approximately 60-70% of patients with epilepsy can expect to achieve seizure remission. The remaining 30-40% develop chronic (medically refractory) epilepsy, which may require multiple trials of treatment or co-medications to control seizures.

Risk factors for recurrent seizures include high pretreatment seizure frequency, earlyto mid-adult onset epilepsy, generalised and myoclonic seizures and an abnormal EEG.

Patients who achieve full control or have infrequent seizures may be suitable for follow-up care in the community. (see table 2) Table 3 lists the suggested criteria for re-referral of patients back to secondary care.

Table 3: Criteria for Re-referral to a Secondary Care Epilepsy Specialist
1. Poor seizure control
2. Problems with AEDs
3. Neurological deterioration or impact of epilepsy on cognitive function
4. Further advice on management is required (for example, preconception counselling)
5. Acute problems, for example, recent admission for status epilepticus
6. Patients who are seizure-free wish to discuss possible withdrawal of AEDs
7. Patients with a diagnosis acquired elsewhere and new to the practice

Section 5: Case study

A 35-year-old attended the epilepsy clinic with a 12-month history of episodes which he described as 'a memory rush associated with altered awareness'.

These episodes had been witnessed by his wife, who described him going pale with a glazed expression on his face and some associated orofacial movements and hand rubbing. They would last a minute and afterwards he would appear dazed and tired and would often need to go to bed. They were occurring on a weekly basis, although they tended to cluster. In the past week, he had attended A&E in the evening with a generalised tonic-clonic seizure.

He had a past medical history of febrile convulsions but was otherwise fit and well. He did not take any regular medication. He drank about 30 units of alcohol per week and held a driving licence. His neurological examination was normal.

The patient was diagnosed with temporal lobe epilepsy and commenced on lamotrigine. He was advised to stop driving and inform the DVLA, and to reduce his alcohol intake. An ECG in the clinic was normal. An MRI and EEG were arranged as an outpatient.

Finding the best treatment
Within three weeks, the patient had developed an allergic skin rash, resulting in the discontinuation of lamotrigine and commencement of sodium valproate.

At his next clinic appointment, he reported continuing seizures, despite being compliant with the medication.

His MRI was reported to show right MTS and his interictal EEG was reported to show epileptiform discharges within the right anterotemporal leads.

His medication dose was increased and reviewed over the next few months. He continued to have complex focal seizures.

Levetiracetam was added to his regimen and his seizures started to improve. He had a period of approximately six months without clear seizures, but relapsed.

He was unfortunately unable to tolerate the higher doses, which caused irritability and low mood. He underwent video-EEG, which showed that the seizure onset was from the right temporal area.

He underwent a right amygdalohippocampectomy seven months later and at his 12-month follow-up, was seizure free.

Section 6: Evidence base

Clinical trials

  • SANAD I (Standard And Newer Anti-epileptic Drugs trial)
  • MESS (MRC Multicentre trial for Early Epilepsy and Single Seizures)


  • NICE. The epilepsies: The diagnosis and management of epilepsies in adults and children in primary and secondary care. NICE, London, January 2012. www.nice.org.uk/cg137.
  • Both guidelines are available online. The guidelines cover the management of epilepsies.

Key text

  • Shorvon S, Guerrini R, Cook M et al. Oxford Textbook of Epilepsy and Epileptic Seizures. Oxford, Oxford University Press, 2012.

Chapters seven and eight cover clinical features of epileptic seizures and differential diagnosis.


This resource provides information summaries on guidelines, general management information and tools and templates.

  • Maguire M, Marson AG, Ramaratnam S. Partial Epilepsy. Clinical Evidence (online) 2011; 6: 1214-43.


  • Maguire MJ, Marson AG, Ramaratnam S. Generalised Epilepsy Clinical Evidence (online) 2012; 6: 1201-13.

http://clinicalevidence.bmj.com/x/ systematic-review/1201/overview.html

Contributed by Dr Melissa Maguire, consultant neurologist at Leeds General Infirmary, Leeds

Click here to take a test on this article and claim a certificate on MIMS Learning


These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Arrange a clinical meeting to discuss AEDs and write a practice protocol for choice of AED.
  • Review contraception advice and pre-pregnancy counselling for epilepsy patients of child-bearing age.
  • Consider patients on the epilepsy register and the criteria for re-referral to secondary care.


1. Berg AT, Berkovic SF, Brodie MJ et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51(4): 676-85.
2. Nunes VD, Sawyer L, Neilson J. Diagnosis and management of the epilepsies in adults and children. BMJ 2012; 344: e281.
3. Epilepsy Action. A Critical Time for epilepsy in England. Epilepsy: A study of epilepsy service provision in England by Epilepsy Action.
4. Marson A, Jacoby A, Johnson A; Medical Research Council MESS Study Group. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures. Lancet 2005; 365(9476): 2007-13.
5.. Marson AG, Al-Kharusi AM, Alwaidh M. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy. Lancet 2007; 369(9566): 1016-26.
6. Marson AG, Al-Kharusi AM, Alwaidh M; SANAD Study Group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy. Lancet 2007; 369(9566): 1000-15.

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