Overview

Seizures and epilepsy

A seizure is a set of transient signs and symptoms that arise due to abnormal excessive or synchronous activity in the brain.

Epilepsy describes a person’s tendency to have seizures and is defined as any of the following:

  • At least two unprovoked seizures occurring more than 24 hours apart
  • One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures over the next 10 years
  • Diagnosis of an epilepsy syndrome

Non-epileptic seizures are seizures that do not occur due to epilepsy and abnormal neuronal discharge. They are discussed more in Non-Epileptic and Other Seizures.

Provoked and unprovoked seizures

In general, seizures associated with epilepsy and have no identifiable reversible cause are called unprovoked seizures. Seizures that are caused by a reversible stimulus (e.g. drugs or toxins) are called provoked seizures.

Therefore, not all seizures are due to epilepsy.

Status epilepticus

Status epilepticus describes a seizure lasting 5 minutes or longer, or recurrent seizures without recovery in between. It is a medical emergency that is discussed more here.

Epidemiology

  • Epilepsy is one of the most common serious brain conditions
  • High-risk groups are infants and those aged >50 years
  • Structural causes are the most common cause of epilepsy in the elderly
  • People with learning difficulties have higher rates of epilepsy

Risk Factors

Classification

International League Against Epilepsy (ILAE) 2017 classification

Seizures and epilepsy syndromes are classified according to three major components:

  • Where did the seizure originate?
    • Generalised seizures:
      • Affect both hemispheres to begin with
    • Focal seizures (previously known as ‘partial’ seizures):
      • Affect one hemisphere of the brain to begin with
    • They have the potential to spread and affect both hemispheres (become generalised)
  • For focal seizures, were they aware (did they retain normal consciousness)?
    • In generalised seizures, consciousness is lost immediately
  • What characteristic features are there?
    • Are there motor features?
      • Automatisms – involuntary behaviour (e.g. lip smacking, Jacksonian march)
      • Atonic – sudden loss of muscle strength and tone
      • Clonic – involuntary, regular (rhythmic) muscle jerks
      • Epileptic spasms – sudden, involuntary tightening of a muscle
      • Hyperkinetic – irregular sequential movement of limb/axial muscles
      • Myoclonic – involuntary, irregular (non-rhythmic) muscle jerks
      • Tonic – increased tone (stiffness) of muscles
  • Are there non-motor features?
    • Autonomic – Changes in blood pressure, heart rhythm, bowels or bladder, gastric uprising, sweating, going pale, turning red, or drooling
    • Cognitive – out-of-body feeling, déjà vu, jamais vu
    • Behaviour arrest – patients ‘freeze’
    • Emotional – changes in mood/emotion
    • Sensory – touch, taste, hearing, vision, smell

Presentation

Overview

Seizures can be difficult to diagnose. Collateral histories from witnesses and video recordings are often used:

  • Pre-seizure warning signs (‘auras’ such as epigastric rising) suggest a focal seizure
  • Tongue-biting and urinary incontinence:
    • These are non-specific regarding the type of seizure but can help to determine if a seizure has truly occurred
  • Post-ictal phase – a period after the seizure where the patient gradually returns to normal
    • This may last between 5-30 minutes
  • Patients may be confused, drowsy, or depressed, and may have headaches or nausea

Features suggesting generalised seizures are discussed in more detail here. Features suggesting focal seizures are discussed in more detail here.

Investigations

  • Blood glucose:
    • Hypoglycaemia can cause provoked seizures
  • Full blood count:
    • Leukocytosis may suggest a central nervous system (CNS) infection
  • Urea and electrolytes (U&Es):
  • ECG:
    • To identify cardiac-related conditions that can mimic seizures
  • Toxicology screen:
    • Considered if illicit substances are suspected
    • Examples are cocaine, amfetamines, and opioids
  • Serum prolactin:
    • Consider if there is doubt that an actual seizure occurred
    • Prolactin is elevated within 10-20 minutes
  • Neuroimaging – ideally an MRI brain:
    • To identify structural abnormalities, intracranial masses etc.
    • A CT may be performed if an MRI is contraindicated
  • Electroencephalogram (EEG):
    • May show epileptiform activity that corresponds with a specific epilepsy syndrome
    • A normal EEG does not rule out epilepsy:
      • Sleep-deprived EEGs or manoeuvres provoking a seizure (e.g. hyperventilation or photic stimulation) may be performed
      • Ambulatory EEG monitoring for up to 48 hours may be considered

Management

Overview

In most cases, antiepileptic drugs (AEDs) are started after a second epileptic seizure:

  • AEDs are prescribed by brand – this is because there are slight differences in bioavailability between different brands which could risk seizures occurring

The choice of AED depends on:

  • The type of epilepsy the patient has
  • What other medications the patient takes:
    • AEDs can induce/inhibit the P450 system and affect the metabolism of other medications such as contraceptives or warfarin
  • If the person is of childbearing potential and may become pregnant
    • AEDs are generally teratogenic, particularly sodium valproate
    • Breastfeeding while taking AEDs (except barbiturates) is generally safe

Generalised seizures

  • Generalised tonic-clonic seizure:
    • 1st-line: sodium valproate
    • 2nd-line: lamotrigine or carbamazepine
  • Absence seizures:
    • 1st-line: sodium valproate or ethosuximide
    • 2nd-line: lamotrigine
    • Do not offer carbamazepine or phenytoin
      • Carbamazepine may worsen absence seizures
  • Myoclonic seizures:
    • 1st-line: sodium valproate or levetiracetam or topiramate (e.g. if person of childbearing potential/pregnant)
      • Carbamazepine may worsen myoclonic seizures
  • Tonic or atonic seizures:
    • 1st-line: sodium valproate or lamotrigine

Focal seizures

  • 1st-line: carbamazepine or lamotrigine
  • 2nd-line: levetiracetam, oxcarbazepine, or sodium valproate

Withdrawal

Withdrawal of antiepileptic drugs should be considered when a patient has been seizure-free for at least 2 years:

  • This should be done slowly at least over 2-3 months, with one drug being withdrawn at a time

Pregnancy, Breastfeeding, and Contraception

Pregnancy

In regards to pregnancy, data regarding managing epilepsy is limited. Some general points using our current data are:

  • Aim for monotherapy in pregnant patients
  • Patients should take 5mg folic acid per day from before conception until the end of the 1st trimester
  • Drugs not associated with an increased risk of major congenital malformations are:
    • Lamotrigine
    • Levetiracetam
  • Drugs that are associated with an increased risk of major congenital malformations are:
    • Sodium valproate – highly teratogenic
    • Topiramate
    • Phenytoin
    • Phenobarbital
    • Carbamazepine – least teratogenic

Breastfeeding

In general, breastfeeding is considered safe in nearly all epileptics

  • Phenobarbital may cause drowsiness in the neonate and withdrawal if it is stopped and should be used with caution.

Contraception

Some antiepileptic drugs may be enzyme-inducing and reduce the effectiveness of hormonal contraception. Some common drugs are carbamazepine, phenytoin, topiramate, and phenobarbital. Some general points are:

  • Copper intrauterine devices (IUDs) and the levonorgestrel-releasing intrauterine system (LNG-IUS or Mirena coil) are not affected by enzyme-inducing drugs
  • The combined oral contraceptive pill (COCP) and progesterone-only pill (POP), transdermal patches, vaginal rings, and implants may be affected
  • In emergency contraception, levonorgestrel and ulipristal acetate may be affected
    • The copper IUD is the preferred method for emergency contraception
  • People taking lamotrigine and oestrogen-containing contraceptives may be at an increased risk of seizures due to reduced levels of lamotrigine

Monitoring and Patient Advice

Monitoring

  • All patients with epilepsy should have a thorough care plan and are followed up regularly – usually every 3-12 months
  • Regular antiepileptic drug blood test monitoring is not done routinely unless in specific circumstances:
    • Suspected non-adherence
    • Suspected toxicity
    • Adjusting phenytoin dose
    • Management of interactions
    • Specific scenarios such as status epilepticus, organ failure, or certain situations in pregnancy
  • Inpatient EEG monitoring may be useful for people where the diagnosis is difficult

Patient Advice

Complications

  • Social stigma and occupational problems
  • Psychosocial problems – anxiety/depression
  • Developmental problems in children with early-onset seizures
  • Increased mortality rate due to:
    • Accidents during seizures
    • Sudden unexpected death in epilepsy (SUDEP)
    • Status epilepticus

Prognosis

  • Remission is less likely the longer seizures go on for
  • Mortality may be due to many reasons, such as accidents, alcohol misuse, drug poisoning, vehicle accidents, or suicide
  • Factors associated with a poorer prognosis are:
    • Focal impaired awareness seizures
    • Tonic-clonic seizures
    • Abnormal physical signs
    • Learning difficulties

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