Epilepsy

Question 1

Epilepsy is a chronic neurological disorder, which is characterised by recurrent seizures.

Answer 1

Epilepsy is characterised by development of multiple seizures.

A seizure refers to a transient neurological change due to synchronous, hyperexcited neuronal activity in the brain. Clinically, this manifests as a transient occurrence of seizure-like activity. This ‘activity’ may refer to a disturbance of consciousness, motor function, emotion, behaviour, cognition or sensation.

Epilepsy is a common neurological disorder that affects > 70 million people globally. The lifetime risk of having a single seizure is 1 in 10, whereas the lifetime risk of having epilepsy is 3%.

Question 2

The cause of epilepsy can be broadly divided into six groups:

Answer 2

Genetic: known or presumed genetic mutation that predisposes to recurrent seizures.
Structural: visible neurological abnormalities that predispose to seizures (e.g. chronic cerebrovascular disease, congenital malformation)
Metabolic: known or presumed metabolic disorder that predisposes to seizures
Immune: underlying immune disorder that predisposes to recurrent seizures
Infectious: chronic infection predisposing to seizures (e.g. HIV). This must be differentiated from seizures associated with an acute infection (e.g. meningitis)
Unknown: up to one third of patients.

Question 3

Seizures develop due to an imbalance between inhibitory and excitatory signals in the brain.

Answer 3

A seizure may initiate due to high-frequency bursts of excitatory action potentials in neurons. This leads to synchronous, hyperexcitable activity within a neuronal population. If this activity is propagated to other neuronal populations it can lead to clinically apparent seizures. The seizure phenotypes (i.e. clinical features) relate to the location and function off the neuronal network that have been recruited into this abnormal synchronous activity.

In epilepsy, acquired or genetic factors effect the balance between inhibitory (i.e. gabanergic) and excitatory (i.e. glutamatergic) signals.

Gabanergic: inhibitory, characterised by gamma-aminobutyric acid (GABA) receptors. Ligand-gated ion channel that allows flow of chloride ions. GABA is the main inhibitory neurotransmitter that binds to these receptors.
Glutamatergic: excitatory, characterised by glutamate receptors (multiple types: ion-channels and G-coupled protein). Glutamate is a small neurotransmitter that can active these receptors.

Question 4

Several known factors increase the risk of developing epilepsy.

Answer 4

Cerebrovascular disease
Head trauma
Cerebral infections
Family history: epilepsy or neurological illness
Premature birth
Congenital malformations of the brain
Genetics conditions associated with epilepsy

Question 5

The classification of epilepsy is based on recommendations by the International League Against Epilepsy (ILAE).

Answer 5

Classification is based on:

Seizure type
Epilepsy type
Epilepsy syndrome.

Question 6

Area of onset - SEIZURE

Answer 6

Focal: localised to a network of neurons in one hemisphere of the brain.
Generalised: affecting both hemispheres of the brain and associated neuronal networks
Focal to bilateral tonic-clonic: a focal seizure may spread to affect a wider network of neurons involving both hemispheres.Traditionally termed a secondary generalised seizure.

Question 7

Awareness - seizure

Answer 7

Awareness: fully aware of themselves and their environment throughout seizure.
Impaired awareness: any impairment of awareness during course of seizure. Complex partial seizures was the old term for focal onset impaired awareness seizures.

Question 8

Clinical features. -seizure

Answer 8

Motor:
Tonic (generalised muscle stiffening)
Clonic (rhythmic muscle jerking)
Myoclonic (brief, ‘shock-like’ involuntary jerks)
Atonic (loss of motor tone)
Spasms (sudden flexion and/or extension movements).
Non-motor:
Focal onset associated with sensory, cognitive, emotional, autonomic or behavioural changes.
Generalised onset with symptoms typical of an absence seizure.

Question 9

Following diagnosis, the actual type of epilepsy can be determined.
The development of recurrent seizure types may lead to the diagnosis of epilepsy. Diagnosis is based on one of three criteria (see chapter on diagnosis). If one of these criteria is met, epilepsy can be classified to a particularly type.

Answer 9

Focal epilepsy: any focal seizure types.
Generalised epilepsy: generalised seizure types.
Generalised and focal epilepsy: combination of both.
Unknown epilepsy: insufficient evidence to conclude whether focal, generalised or both.

Question 10

An epilepsy syndrome is characterised by the recurrent propensity to a specific seizure type or series of seizure types. Determining an epilepsy syndrome is important to guide medical therapy with anti-epileptic drugs (AEDs). Classic epilepsy syndromes include West syndrome, Lennox Gastaut syndrome and juvenile myoclonic epilepsy among many others.

Answer 10

An epilepsy syndrome is characterised by the recurrent propensity to a specific seizure type or series of seizure types. Determining an epilepsy syndrome is important to guide medical therapy with anti-epileptic drugs (AEDs). Classic epilepsy syndromes include West syndrome, Lennox Gastaut syndrome and juvenile myoclonic epilepsy among many others.

Question 11

Epilepsy syndromes usually have important characteristics:

Answer 11

Epilepsy syndromes usually have important characteristics:

Typical age of onset
Specific seizure types
Specific electroencephalogram (EEG) features
Additional clinical or radiological features

Question 12

Each individual seizure is composed into four distinct stages: …

Answer 12

Each individual seizure is composed into four distinct stages: prodromal, early-ictal, ictal, post-ictal.

Question 13

Prodromal - seizures

Answer 13

This describes a period of subjective feeling or sensation that occurs before the onset of a seizure. It only occurs in some patients and may present with features such as confusion, irritability or mood disturbances.

Question 14

Early-ictal - seizure

Answer 14

This phase is characterised by aura. An aura is the earliest sign of seizure activity and refers to subjective symptoms experienced by the patient. These can include sensory, cognitive, emotional or behaviour changes. Not all patients will experience an aura (e.g. generalised seizure onset).

An aura is suggestive of focal epilepsy (occurring in one part of the brain) and may progress to affect a wider area, or develop into a focal to bilateral tonic-clonic seizure.

Question 15

Ictal - seizure

Answer 15

The ictal phase is highly variable depending on seizure type.

In layman terms, ‘seizure’ usually refers to a generalised tonic-clonic seizure. This is characterised by stiffening and subsequent rhythmic jerking of the limbs. It may be associated with urinary incontinence and tongue biting, and normally lasts 1-2 minutes.

When a single seizure lasts > 30 minutes in duration, or two seizures occur without regaining consciousness after the first, it is termed status epilepticus or ‘status’. Status is broadly divided into convulsive (i.e. movement) and non-convulsive (i.e. no movement).

Question 16

Post-ictal - seizure

Answer 16

This is the recovery period, when the seizure has abated. There may be an extended recovery period, which is dependent on seizure type. During the period of recovery there may be altered consciousness, confusion, memory loss, drowsiness or general malaise.

This period may last hours, particularly with tonic-clonic seizures.

Question 17

The diagnosis of epilepsy is based on one of three criteria.

A diagnosis of epilepsy is made if any of the following three criteria apply:

Answer 17

Criteria 1: ≥2 unprovoked (or reflex) seizures occurring more than 24 hours apart
Criteria 2: 1 unprovoked (or reflex) seizure with a probability of further seizures felt to be at a similar recurrence risk to patients with ≥2 unprovoked seizures over the next 10 years.
Criteria 3: A diagnosed epilepsy syndrome

Question 18

There are numerous epilepsy mimics, which can be grouped into several categories:

Answer 18

Syncope and anoxic seizures: transient loss of consciousness from impaired cerebral blood flow.
Behavioural, psychological and psychiatric: non-epileptic seizures (i.e. pseudoseizures)
Sleep-related conditions
Paroxysmal movement disorders
Migraine associated disorders
Other

Question 19

Investigations for seizures

Answer 19

Neuroimaging and an EEG can help support the diagnosis of epilepsy.

Following a seizure, baseline investigations should be used to look for a precipitating cause. In adults, a series of baseline investigations including an ECG and bloods is essential.

ECG
Bloods: FBC, U&E, LFT, Glucose, Bone profile
Other: depending on suspected aetiology and age of presentation.

Question 20

EEG

Answer 20

A non-invasive method of assessing and recording the electrical activity of the brain. Epilepsy, or the propensity towards seizures, is associated with particular waveform activity on an EEG. They are usually analysed by neurophysiologists.

Question 21

Main uses of EEG

Answer 21

Support a diagnosis of epilepsy
Assess risk of seizure recurrence
Determine seizure type of epilepsy syndrome
It is not used as a sole diagnostic tool and cannot be used to exclude epilepsy, particularly if the clinical presentation supports a diagnosis of epilepsy.

Question 22

Neuroimaging - seizure

Answer 22

Typically involves magnetic resonance imaging (MRI), but computed tomography (CT) can be used where MRI is not available or suitable. Able to look for structural abnormalities that cause certain epilepsies.

MRI essential in patients who develop epilepsy before two years old, there is a suggestion of focal onset seizures or poor seizure control with anti-epileptics.

Question 23

Management of seizurez

Answer 23

Management of epilepsy is broadly divided into acute control of seizures and long-term prevention of seizures with AEDs.
The overall goal for managing a patient with epilepsy should be for no seizures and no side-effects from medications. This will not be possible in every patient due to the complexity of epilepsy.

The key aspects of management are education and safety, treating acute seizures, role of the first fit clinic and long-term treatment with AEDs.

Question 24

It is vital to educate patients, family and carers about epilepsy, provide information regarding safety precautions and how to provide pre-hospital care for seizures. This may be in the form of a formal first-aid course or guidance on epilepsy society websites.

Safety precautions:

Answer 24

Driving: see the section below on driving rules
Water safety: a seizure whilst in water can be life-threatening. Use a buddy system. Showers instead of baths.
Fire safety: be careful with heat or flames, particularly with frequent seizures.
Environmental safety: arranging the home or work environment to be safe in case of seizures
Other: care with heights, high risk recreational activities, contraception for certain mediations, etc.

Question 25

First fit clinic

Answer 25

After initial presentation and management of a suspected epileptic seizure, patients should be referred to a ‘first fit’ clinic where they will be seen by a specialist who manages patients with epilepsy (i.e. neurologist).

The clinic involves formal assessment (history and examination) and organisation of relevant investigations (e.g. MRI, EEG) to determine whether the seizure is likely to represent epilepsy. If the diagnosis of epilepsy is made, patients are given education and started on AEDs.

As a general rule, following a single seizure patients are not routinely started on AEDs unless there is felt to be considerable risk for another seizure.

Question 26

Anti-epileptic drug choices

AEDs are the hallmark of long-term treatment of epilepsy. They reduce the risk of developing seizures. There are different choices, which depend on the type of epilepsy, patient demographics, side-effect profiles and patient choice.

Common AEDs:

Answer 26

Sodium valproate: unclear mechanism. Teratogenic. Key side-effects: drug-induced liver injury, pancreatitis, increased suicide risk.
Carbamazepine: sodium channel antagonist. Increased teratogenic risk. Key side-effects: agranulocytosis, SIADH.
Lamotrigine: sodium channel antagonist. Increased teratogenic risk (but low). Key side-effects: severe skin reactions
Levetiracetam: unclear mechanism. Not enough evidence re. teratogenicity. Key side-effects: CNS disturbance (somnolence, decreased energy, headache), neuropsychiatric disturbance.
Phenytoin: sodium channel antagonist. Teratogenic. Key side-effects: multiple. Arrhythmia with parenteral use. Classic cause of gum hypertrophy and cerebellar atrophy.

Question 27

…: unclear mechanism. Teratogenic. Key side-effects: drug-induced liver injury, pancreatitis, increased suicide risk.

Answer 27

Sodium valproate: unclear mechanism. Teratogenic. Key side-effects: drug-induced liver injury, pancreatitis, increased suicide risk.

Question 28

…: sodium channel antagonist. Increased teratogenic risk. Key side-effects: agranulocytosis, SIADH.

Answer 28

Carbamazepine: sodium channel antagonist. Increased teratogenic risk. Key side-effects: agranulocytosis, SIADH.

Question 29

…: sodium channel antagonist. Increased teratogenic risk (but low). Key side-effects: severe skin reactions

Answer 29

Lamotrigine: sodium channel antagonist. Increased teratogenic risk (but low). Key side-effects: severe skin reactions

Question 30

…: unclear mechanism. Not enough evidence re. teratogenicity. Key side-effects: CNS disturbance (somnolence, decreased energy, headache), neuropsychiatric disturbance.

Answer 30

Levetiracetam: unclear mechanism. Not enough evidence re. teratogenicity. Key side-effects: CNS disturbance (somnolence, decreased energy, headache), neuropsychiatric disturbance.

Question 31

…: sodium channel antagonist. Teratogenic. Key side-effects: multiple. Arrhythmia with parenteral use. Classic cause of gum hypertrophy and cerebellar atrophy.

Answer 31

Phenytoin: sodium channel antagonist. Teratogenic. Key side-effects: multiple. Arrhythmia with parenteral use. Classic cause of gum hypertrophy and cerebellar atrophy.

Question 32

Most importantly, sodium valproate is highly teratogenic (30-40% developmental disorder / 10% congenital malformation) and should NOT be given to women and girls of childbearing potential. This includes girls who are likely to need treatment into their childbearing years. They provide recommendations for other AEDs. A clear risk/benefit discussion of these AEDs should always be discussed with the patient.

Answer 32

Most importantly, sodium valproate is highly teratogenic (30-40% developmental disorder / 10% congenital malformation) and should NOT be given to women and girls of childbearing potential. This includes girls who are likely to need treatment into their childbearing years. They provide recommendations for other AEDs. A clear risk/benefit discussion of these AEDs should always be discussed with the patient.

Question 33

Anti-epileptic drug indications

The NICE CG137 guidelines (last updated May 2021, last accessed November 2021) provide guidance on the first-line and adjuvant medications that can be used for different types of epilepsy. The general rule is the initiation of monotherapy at the lowest possible dose to control seizures. Doses can be increased, and if ineffective, can be weaned down and a new medication introduced. Combination (i.e. adjunctive) therapy may be needed.

Common recommendations:

Answer 33

Focal seizures:
1st line - Lamotrigine (if childbearing potential), alternative carbamazepine (if no childbearing potential)
2nd line - Levetiracetam, oxcarbazepine or sodium valproate*
Generalised tonic-clonic seizures:
1st line - sodium valproate* or lamotrigine.
2nd line - clobazam, lamotrigine, levetiracetam or topiramate.
Absence seizures:
1st line - ethosuximide or sodium valproate.
2nd line - lamotrigine.
Myoclonic seizures:
1st line - sodium valproate.
2nd line - levetiracetam or topiramate.
Juvenile myoclonic epilepsy:
1st line - sodium valproate.
2nd line - lamotrigine , levetiracetam or topiramate.

Question 34

Patients should be advised that oxcarbazepine and .. can impair the effectiveness of hormonal contraceptives.

Answer 34

Patients should be advised that oxcarbazepine and topiramate can impair the effectiveness of hormonal contraceptives.

Question 35

The two major complications of epilepsy are…

Answer 35

The two major complications of epilepsy are status epilepticus and sudden unexpected death in epilepsy (SUDEP).

Question 36

Complications

The two major complications of epilepsy are status epilepticus and sudden unexpected death in epilepsy (SUDEP).

Answer 36

Several complications may develop due to seizures including trauma, drowning, road traffic accidents and falls. A sustained seizure > 30 minutes or recurrent seizures without regaining consciouses describes status epilepticus. This is a life-threatening medical emergency. For more details see our notes on status epilepticus.

Question 37

SUDEP

Answer 37

Sudden unexplained death in epilepsy is the result of sudden death in a patient with epilepsy with no identifiable cause. It is the most common cause of death in young adults with epilepsy. SUDEP has been linked to uncontrolled epilepsy and nocturnal seizures. Seizure control is pivotal to reduce risk.

Question 38

Driving and seizures

Answer 38

Following a seizure, patients need to stop driving and inform the DVLA.

Question 39

There are certain rules to driving in the context of having a seizure. These depend on the timing of the seizure(s) (i.e. day or night) and whether the person has a group 1 (cars, motorcycles) or 2 (large lorries, buses) license. Always consult the DVLA for further advice.

Answer 39

In general:

First seizure - impaired consciousness (group 1): do not drive for six months, reapply
Epileptic seizure - impaired consciousness (group 1): do not drive for one year, reapply
Seizures - no loss of consciousness (group 1): seek DVLA advice
Nocturnal seizures: seek DVLA advice
First seizure (group 2): do not drive for 5 years, but seek DVLA advice (depends on type)
≥1 seizure (group 2): do not drive for 10 years, but seek DVLA advice (depends on type)