Definition & Key Features

What is Epilepsy?

Epilepsy is a neurological condition characterised by a predisposition to generate epileptic seizures, which are transient occurrences of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. A diagnosis of epilepsy is typically made after a person has had two or more unprovoked seizures.

Core Pathophysiology:

The core pathophysiology involves a disruption of the normal balance between excitatory and inhibitory neurotransmission in the brain, leading to an imbalance that results in a state of hyperexcitability and the generation of spontaneous seizures. This can be due to genetic factors, structural brain abnormalities, or other underlying conditions.

Hallmark Features, Typical Signs/Symptoms:

The hallmark feature of epilepsy is the recurrent, unprovoked seizure. Seizures can manifest in various ways depending on the part of the brain affected. Key types of seizures include:

• Generalised Tonic-Clonic (GTC) seizures: Characterised by a loss of consciousness, muscle stiffening (tonic phase), and jerking of the limbs (clonic phase).
• Focal seizures: Originate in one area of the brain. They can be simple (with no loss of awareness) or complex (with impaired awareness). They may evolve into a bilateral tonic-clonic seizure.
• Absence seizures: Typically occur in children and are characterised by brief periods of unresponsiveness, staring, and sometimes subtle body movements.
• Myoclonic seizures: Brief, shock-like jerks of a muscle or group of muscles.
• Tonic seizures: Involve sudden muscle stiffening.
• Atonic seizures: Cause a sudden loss of muscle tone, leading to a ‘drop attack’.

Important Complications or Side Effects if Untreated:

Untreated epilepsy can lead to significant complications, including:

• Physical injury: Seizures can cause falls, burns, drowning, and other injuries.
• Status epilepticus: A medical emergency where a seizure lasts longer than 5 minutes, or when a person has more than one seizure within a 5-minute period without returning to a normal level of consciousness between them.
• Sudden Unexpected Death in Epilepsy (SUDEP): A rare but serious complication, the risk of which is increased with uncontrolled seizures, particularly GTC seizures.
• Psychosocial difficulties: Including anxiety, depression, social stigma, and problems with education and employment.
• Cognitive impairment: Epilepsy and its treatment can affect memory, attention, and other cognitive functions.

Epidemiology & Risk Factors

Who is most affected?

• Prevalence: Epilepsy is one of the most common serious neurological conditions. The prevalence is highest in early childhood and in older adults.
• Age/Gender Patterns: Epilepsy can affect people of any age, with peaks in incidence in childhood and old age. There are no significant overall gender differences in the prevalence of epilepsy, though some specific epilepsy syndromes may be more common in one gender.

Risk Factors:

• Modifiable Risk Factors for a second seizure in adults:
  • Underlying mental health problems (e.g., depression, anxiety, psychosis, alcohol or substance misuse).
  • Vascular risk factors (e.g., diabetes, hypertension, atrial fibrillation).
  • Sepsis.
• Non-Modifiable Risk Factors:
  • Genetic predisposition: Family history of epilepsy or specific genetic mutations.
  • Structural brain abnormalities: Such as those caused by brain injury, stroke, tumours, infections (e.g., meningitis, encephalitis), or congenital malformations.
  • Previous febrile seizures: Children with a history of complicated febrile seizures are at a higher risk of developing epilepsy.
  • Developmental disabilities: Such as cerebral palsy or intellectual disability.

Clinical Presentation & Diagnosis

Typical Symptoms:

The presentation of epilepsy is highly variable and depends on the seizure type. GPs should suspect epilepsy in anyone presenting with transient neurological symptoms. Key symptoms to look for include:

• Unexplained loss of consciousness, confusion, or memory loss.
• Sudden falls or ‘drop attacks’.
• Episodes of staring or unresponsiveness.
• Involuntary jerking or twitching of limbs.
• Unusual sensations (aura), such as a rising feeling in the stomach, strange smells or tastes, or a sense of déja vu.

Red Flags (Indications for urgent referral or action):

• Urgent referral (within 2 weeks) to a specialist for assessment after a first suspected seizure.
• Urgent referral (within 2 weeks) for a seizure recurrence after a period of remission.
• Urgent referral to a tertiary paediatric neurologist within 24 hours for children under 2 years with suspected or confirmed infantile spasms.
• Urgent referral to a tertiary paediatric epilepsy service within 2 weeks for children with suspected or confirmed epilepsy who:
  • are aged under 3 years.
  • are aged under 4 years and have myoclonic seizures.
  • have a unilateral structural lesion on imaging.
  • are showing deterioration in their behaviour, speech or learning.

Diagnostic Criteria:

• A diagnosis of epilepsy is made by a specialist, usually based on a detailed clinical history from the patient and an eyewitness.
• The diagnosis typically requires at least two unprovoked seizures occurring more than 24 hours apart.
• A diagnosis may be made after a single unprovked seizure if the risk of a further seizure is high (e.g., due to a structural brain abnormality).

Differential Diagnoses:

• Syncope: Vasovagal syncope, cardiac syncope.
• Non-epileptic seizures (dissociative seizures): Psychological in origin.
• Migraine with aura.
• Transient ischaemic attack (TIA).
• Sleep disorders: Narcolepsy, parasomnias.
• Movement disorders: Tics, dystonia.
• Metabolic disturbances: Hypoglycaemia.

Investigations (including timing and rationale):

• 12-lead ECG: To be performed after a first suspected seizure to identify cardiac-related conditions that could mimic an epileptic seizure.
• Electroencephalogram (EEG):
  • Offered to support a diagnosis of epilepsy and to help classify seizure type or epilepsy syndrome.
  • Should be performed as soon as possible after a first seizure, ideally within 72 hours.
  • A normal EEG does not exclude a diagnosis of epilepsy.
  • Provoking manoeuvres (hyperventilation, photic stimulation) should be considered.
  • If routine EEG is normal, a sleep-deprived EEG or ambulatory EEG may be considered.
• Neuroimaging:
  • MRI: The investigation of choice. Offered to all children, young people, and adults diagnosed with epilepsy, unless they have idiopathic generalised epilepsy or self-limited epilepsy with centrotemporal spikes. The MRI should be performed within 6 weeks of referral.
  • CT scan: Considered if MRI is contraindicated. A CT scan is not routinely indicated for people with established epilepsy presenting to the emergency department after a typical seizure unless there are other concerns.
• Genetic testing: Considered for people with epilepsy of unknown cause, especially those with early onset, specific clinical features, or additional comorbidities like a learning disability.

Initial Management

First-line Treatment Approach:

Treatment should be initiated once the diagnosis of epilepsy is confirmed and should be individualised. Monotherapy should be used whenever possible.

Drug Names, Dosages, Formulations, Indications, Duration, Route, and Frequency:

The choice of antiseizure medication (ASM) depends on the seizure type and epilepsy syndrome.

• Generalised Tonic-Clonic (GTC) Seizures (First-line monotherapy):
  • Offer a choice of:
    • Sodium valproate: Note MHRA safety advice below.
    • Lamotrigine: Start at a low dose and titrate slowly (e.g., 25mg once daily for 2 weeks, then 25mg twice daily for 2 weeks, then titrate up).
    • Levetiracetam: Start at a low dose and titrate up (e.g., 250mg twice daily for 2 weeks, then 500mg twice daily).
  • If the first choice is unsuccessful, try another of these options.
• Focal Seizures (with or without evolution to bilateral tonic-clonic seizures) (First-line monotherapy):
  • Consider a choice of:
    • Lamotrigine: As above.
    • Levetiracetam: As above.
  • If the first choice is unsuccessful, consider the other of these options.
  • Second-line monotherapy options: carbamazepine, oxcarbazepine, zonisamide.
  • Third-line monotherapy option: lacosamide.
• Absence Seizures (First-line):
  • Offer Ethosuximide.
  • If unsuccessful, offer a choice of sodium valproate, lamotrigine, or levetiracetam as second-line monotherapy or add-on.
• Myoclonic Seizures (First-line):
  • Offer a choice of:
    • Sodium valproate: Note MHRA safety advice below.
    • Levetiracetam.
• Tonic or Atonic Seizures (First-line):
  • Offer a choice of:
    • Sodium valproate: Note MHRA safety advice below.
    • Lamotrigine.

Major Side Effects, Contraindications, and Cautions:

• All ASMs: Can cause dose-related side effects such as dizziness, drowsiness, and unsteadiness. All have the potential for idiosyncratic reactions (e.g., rash, which can be severe with lamotrigine).
• Sodium Valproate:
  • MHRA Safety Alert for women and girls of childbearing potential: High risk of birth defects and developmental disorders in children exposed to valproate in the womb. It must not be used in women and girls of childbearing potential unless the conditions of the Pregnancy Prevention Programme are met.
  • MHRA Safety Alert for men and boys: Possible increased risk of neurodevelopmental disorders in children whose fathers took valproate in the 3 months before conception. Men should be advised on the risks and the need for effective contraception.
  • Other side effects: Weight gain, hair loss, tremor, hepatotoxicity (rare but serious), pancreatitis.
• Lamotrigine:
  • Risk of severe rash: Including Stevens-Johnson syndrome. Risk is increased with rapid dose titration and concomitant use of valproate.
  • Oestrogen-containing contraceptives and HRT can reduce lamotrigine levels, potentially leading to loss of seizure control.
• Levetiracetam:
  • Behavioural side effects: Irritability, aggression, depression, psychosis.
• Carbamazepine:
  • Induces liver enzymes, leading to numerous drug interactions (including with hormonal contraceptives).
  • Risk of serious skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), particularly in people of Han Chinese, Thai, European or Japanese family background.
  • Can exacerbate certain seizure types (e.g., absence, myoclonic seizures).
• Topiramate:
  • MHRA Safety Alert: Increased risk of birth defects and fetal growth restriction. Should not be used in pregnancy for epilepsy unless there is no suitable alternative. Women of childbearing potential must use effective contraception.
  • Cognitive side effects: Word-finding difficulties, confusion.
  • Risk of kidney stones and metabolic acidosis.

Non-Pharmacological Measures, Patient Education, and Initial Monitoring Parameters:

• Patient Education:
  • Provide tailored information about epilepsy, seizure types, triggers, and the importance of medication adherence.
  • Discuss safety issues (e.g., driving, swimming, working at heights).
  • Provide information on SUDEP and risk reduction strategies.
  • Signpost to local and national epilepsy support groups.
• Non-Pharmacological Measures:
  • Lifestyle advice: Encourage regular sleep, avoidance of seizure triggers (e.g., excessive alcohol, sleep deprivation).
  • For some children with drug-resistant epilepsy, a ketogenic diet may be considered.
• Initial Monitoring:
  • Review patients regularly after starting a new ASM to assess efficacy and tolerability.
  • Monitor for side effects.
  • Routine monitoring of ASM levels is not usually necessary, but may be considered in specific circumstances (e.g., pregnancy, suspected non-adherence, toxicity).

Further Management & Escalation

Next Steps if First-line Fails or is Contraindicated:

• If first-line monotherapy is unsuccessful:
  • Review the diagnosis of epilepsy.
  • Try monotherapy with another first-line ASM. When changing ASMs, titrate the new drug up slowly while the old drug is maintained, then taper the old drug off slowly.
  • If monotherapy with a second drug fails, consider add-on therapy (two ASMs).
• Add-on therapy:
  • The choice of add-on therapy depends on the seizure type and the ASMs already tried. The guideline provides specific recommendations for add-on therapy for each seizure type.
  • Titrate the add-on ASM slowly and monitor for adverse effects.
  • If trials of add-on therapy are unsuccessful, aim for the regimen with the best balance of efficacy and tolerability.

Referral Criteria to Tertiary Epilepsy Service (within 4 weeks):

• Uncertainty about the diagnosis, seizure type, or epilepsy syndrome.
• Drug-resistant epilepsy (failure of two tolerated and appropriately chosen and used ASM schedules to achieve sustained seizure freedom).
• Treatment is associated with intolerable side effects.
• Further assessment and treatment approaches are indicated (e.g., video-EEG telemetry, neuropsychology, ketogenic diet).
• Consideration for epilepsy surgery or vagus nerve stimulation.

Red Flags for Urgent Escalation:

• Status epilepticus: A medical emergency requiring immediate treatment. In the community, give buccal midazolam or rectal diazepam. In hospital, IV lorazepam is first-line. If seizures continue, escalate to second-line agents (levetiracetam, phenytoin, or sodium valproate) and seek expert help.
• Cluster seizures (3 or more in 24 hours): A medical emergency. Follow the patient’s emergency management plan or consider giving a benzodiazepine.
• Prolonged seizures (longer than the person’s usual seizure): Manage as a medical emergency.

Surgical Options:

• Resective epilepsy surgery: An option for people with drug-resistant focal epilepsy. Patients should be referred to a tertiary epilepsy service for assessment.
• Vagus nerve stimulation (VNS): An option for people with drug-resistant epilepsy who are not suitable for resective surgery.

Follow-up & Safety Netting

Frequency of Follow-up Visits:

• Adults: Regular (at least annual) reviews for those with a learning disability, drug-resistant epilepsy, high SUDEP risk, serious comorbidities, or taking certain ASMs (e.g., sodium valproate).
• Children and Young People: At least annual reviews, with frequency tailored to individual needs.
• Review should be more frequent after starting or changing treatment.
• Patients should be advised they can request a review at any time if they have concerns.

Monitoring Requirements:

• Monitor seizure control, side effects, and overall wellbeing at each review.
• Consider monitoring ASM levels in specific clinical situations (e.g., pregnancy, renal failure, uncontrolled seizures, suspected toxicity).
• For women taking certain ASMs (e.g., lamotrigine), levels may need to be monitored during pregnancy and adjusted.
• Long-term treatment with some ASMs (e.g., carbamazepine, phenytoin, sodium valproate) is associated with decreased bone mineral density; consider vitamin D and calcium supplementation for people at risk.

Patient Advice on Self-Management, Health Promotion, and Warning Signs:

• Self-management: Encourage patients to keep a seizure diary, identify and avoid triggers, and take medication regularly.
• Health Promotion:
  • Contraception: Discuss interactions between ASMs and hormonal contraceptives.
  • Pregnancy: All women of childbearing potential should be offered pre-conception counselling. High-dose folic acid (5mg daily) is recommended before and during the first trimester of pregnancy.
  • Lifestyle: Advise on driving regulations (patients must inform the DVLA), alcohol consumption, and safety at home and work.
• Warning Signs Prompting Urgent Reassessment:
  • Increase in seizure frequency or severity.
  • Development of new seizure types.
  • Status epilepticus or cluster seizures.
  • Significant side effects from medication.
  • Pregnancy.
  • Concerns about mental health, including suicidal ideation.

Discontinuing Antiseizure Medication:

• Considered after a person has been seizure-free for at least 2 years.
• The decision should be made in discussion with the patient and specialist, considering the risk of seizure recurrence and the implications for driving and lifestyle.
• If discontinued, the ASM should be withdrawn slowly over at least 3 months (longer for benzodiazepines and barbiturates).

Key Points to Remember

• Refer urgently (within 2 weeks) after a first suspected seizure.
• Always consider the possibility of non-epileptic seizures and cardiac causes of ‘blackouts’.
• First-line treatment for GTC seizures is sodium valproate, lamotrigine, or levetiracetam. For focal seizures, it is lamotrigine or levetiracetam.
• Sodium valproate is highly teratogenic and should not be used in women of childbearing potential unless the Pregnancy Prevention Programme is in place. It also has risks for male fertility.
• Topiramate also has significant teratogenic risks and should be avoided in pregnancy where possible.
• Lamotrigine carries a risk of serious rash; titrate the dose slowly.
• Drug-resistant epilepsy (failure of two ASMs) should prompt a referral to a tertiary epilepsy service for consideration of further options, including surgery.
• Status epilepticus is a medical emergency. The first-line treatment in the community is buccal midazolam.
• Discuss SUDEP with patients and their families, and advise on risk reduction strategies (especially seizure control and medication adherence).
• All women with epilepsy of childbearing potential should receive counselling on contraception and pregnancy, and be prescribed high-dose folic acid if planning a pregnancy.

This MedDigest summary is intended for educational purposes only and should not be used for clinical purposes. It is an independent resource, prepared by MedDigest, to offer an accessible overview of information drawn from the NICE guidelines. The original NICE content is © Crown copyright and is used under the Open Government Licence v3.0. While MedDigest strives for accuracy in its educational summaries, this content has not been reviewed or produced by NICE. For comprehensive and definitive recommendations, please always refer to the complete NICE guidelines.

References

NICE (30 January 2025) Epilepsies in children, young people and adults. https://www.nice.org.uk/guidance/ng217