Epilepsy

1. ABDULLAEVA NADIRA, MD, NEUROLOGIST
Epilepsy
LECTURE
Epilepsy is defined as the repeated occurrence of sudden, excessive and/or synchronous discharges in cerebral
cortical neurons resulting in disruption of consciousness, disturbance of sensation, movements, impairment of
mental function, or some combination of these signs.
Because of their sudden nature, seizures are called ictal events, from the Latin ictus meaning ‘to strike’.
The terms epilepsy, seizure and convulsion are not synonymous.
The incidence and prevalence of epilepsy
Epilepsy is the commonest neurological condition affecting people of all ages, race and social class.
There are an estimated 50 million people with epilepsy in the world, of whom up to 75% live in resource-poor
countries with little or no access to medical services or treatment
Aetiology
The cause of epilepsy is unknown in up to one third of patients.
Seizures are common and often occur secondary to an acute insult.
These types of ‘provoked’ seizures usually occur at the time of acute illness (e.g. acute stroke, head trauma,
hypoglycaemia) or in temporal relationship with the insult.
An acute symptomatic seizure secondary to a defined cause needs to be differentiated from the recurrent,
unprovoked seizures that occur in epilepsy.

2. The cause of epilepsy can be broadly divided into six groups:
• 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.
Pathophysiology
Seizures develop due to an imbalance between inhibitory and excitatory signals in the brain.
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.
Overtime, there is transformation within neural networks that promote excitability. This is associated with long-
lasting structural and/or biochemical changes that promotes development of epilepsy.
Risk factors
Several known factors increase the risk of developing epilepsy.
• Cerebrovascular disease
• Head trauma
• Cerebral infections
• Family history: epilepsy or neurological illness
• Premature birth
• Congenital malformations of the brain
• Genetics conditions associated with epilepsy

3. Classification
The classification of epilepsy is based on recommendations by the International League Against Epilepsy
(ILAE).
There are many types of seizures and associated syndromes.
Classification is based on:
• Seizure type
• Epilepsy type
• Epilepsy syndrome.
ILAE Classification of Seizures
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily
Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
10
ILAE – International League Against Epilepsy
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American Epilepsy Society 2015
ILAE Classification of Seizures
Seizures
Partial Generalized
Simple Partial
With somatosensory
or special sensory symptoms
With motor signs
With autonomic
symptoms or signs
With psychic or
experiential symptoms
11
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American Epilepsy Society 2015
Seizure type
This refers to the exact type of seizure that occurs.
Seizure type can be determined using a three step process that focuses on the area of onset, presence of
awareness and associated clinical features.
Area of onset
• 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.
• Awareness: fully aware of themselves and their environment throughout seizure.
• Impaired awareness: any impairment of awareness during course of seizure.

4. Clinical features
• 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.
Epilepsy type
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. If one of these criteria is met, epilepsy can be classified to a
particularly type.
• 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.

5. Clinical features of seizures
Epilepsy is characterised clinically by seizures, which can manifest in numerous ways.
The clinical features associated with a seizure depend on the affected location and function of the brain.
Each individual seizure is composed into four distinct stages: prodromal, early-ictal, ictal, post-ictal.
Prodromal
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.
Early-ictal
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.
Ictal
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'.
Post-ictal
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.
Diagnosis
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:
• 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

6. Differential diagnosis
There are numerous epilepsy mimics, which can be grouped into several categories:
• 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
A seizure always is a symptom of abnormal function in the central nervous system (CNS) rather than a disease in
itself.
A seizure discharge may be initiated in an entirely normal cerebral cortex by a variety of acute insults, such as
withdrawal from alcohol, low blood sodium, or certain toxins.
Seizures are to be distinguished from epilepsy, which is a chronic condition in which seizures occur repeatedly
due to an underlying brain abnormality which persists between seizures.
A convulsion is a forceful involuntary contraction of skeletal muscles. A convulsion is a physical manifestation
of a seizure, but the term is inappropriate as a synonym for epilepsy when epilepsy may consist only of a
temporary alteration of consciousness or sensation.
Epilepsy has many causes, but in most patients a cause cannot be identified.
Among the pathologies most commonly considered to give rise to epilepsy are cerebro- vascular lesions,
perinatal or postnatal trauma, infections of the CNS, and tumours or congenital malformations of the brain.
It provides information on aetiology, treatment and prognosis.
Modern classification of the epilepsies is based on how the seizures begin.
Two broad categories are recognized depending upon whether the entire brain (generalized seizure) or only a restricted
part of the brain (partial seizure) is involved in the discharge at its onset. Each category is further subdivided, depending
on the symptoms displayed by the patient during the seizure. Many patients have more than one seizure type, but it is
rare to have both partial onset and primary generalized seizures.
Classification of Seizures and Epilepsy

7. Partial seizures
Partial seizures begin in a discrete cortical area.
They are categorized as simple when consciousness is preserved and complex when consciousness is altered.
Simple partial seizures may evolve into complex partial seizures or secondarily generalized tonic–clonic seizures as a result
of the spread of abnormal electrical activity.
Simple partial seizures
Simple partial seizures are the primary complaint in 10% of patients with epilepsy. They can occur frequently
and may result in little disability. Simple motor seizures result from a discharging lesion in the precentral gyrus
of the frontal lobe of the cerebral hemisphere opposite the muscle contractions. Some are sustained (tonic) and
others intermittent (clonic), and they may involve any body part depending on the location of the abnormal brain
discharge.
Simple sensory seizures indicate discharging nerve cells in the appropriate primary sensory cortex of the
hemisphere.
Simple somatosensory seizures usually result from an epileptogenic zone in or near the postcentral gyrus of the
opposite cerebral hemisphere
Somatosensory seizures are usually described by the patient as the sensation of ‘pins- and-needles’. A simple
seizure may remain restricted or ‘march’ to other parts of the body in a sequence determined by the somatotopic
organization of the cortex, or it may spread through other axonal pathways. Visual seizures indicate an
epileptogenic zone in or near the primary visual cortex of the occipital lobe. Spots or patterns are experienced in
the visual field opposite the side of the seizure focus. Seizures eliciting auditory, vestibular, olfactory or visceral
sensations can also occur.
Complex partial seizures
Complex partial seizures are the predominant seizure type in about 20% of patients with epilepsy. The terms
psychomotor, temporal lobe and limbic system seizure are older terms, somewhat synonymous with the term
complex partial seizure, all designating a form of partial seizure in which consciousness is altered but not
necessarily lost. During these seizures there is a period of altered behaviour for which the patient is later
amnesic.
The amnesia for ictal events is a key factor for the diagnosis of a complex partial seizure.
A typical complex partial seizure consists of several phases. About 70% begin with an ‘aura’, a sometimes
complex psychic experience that may be manifest in one or more of a wide variety of vivid forms: as an illusion,
hallucination, dyscognitive state or emotional (affective) experience. This usually lasts a few seconds. Such
psychic experiences may comprise the entire seizure, which is then a simple partial seizure.

8. When the seizure progresses into a second phase with alteration of consciousness, it is defined as a complex
partial seizure. Dystonic (twisted, stiff) posturing of the arm or leg on the side opposite to where the seizure
occurs is often observed. Primitive movements occur frequently. These are referred to as spontaneous
automatisms, and may include aimless fumbling with clothing or walking in a daze, and chewing or swallowing.
Primary generalized seizures
Primary generalized seizures (also called generalized seizures) involve widespread areas of the cerebral cortex
from the onset. These terms must not be confused with the term secondary generalized seizure, which refers to a
partial onset seizure that spreads to wide areas of cortex. The abnormal electrical activity is the same in both the
left and right hemispheres (bilaterally symmetrical).
Generalized seizures are further subdivided into convulsive and nonconvulsive types. Convulsive seizures are
characterized by sometimes violent and sustained contractions of muscles.
Nonconvulsive seizures lack prominent motor activity. Generalized tonic–clonic, clonic, and some tonic seizures
are referred to as convulsive generalized seizures. The most common nonconvulsive generalized seizure is the
absence seizure, but the category also includes atonic, brief tonic, and myoclonic seizures.
Convulsive seizures
Tonic–clonic convulsions often begin with a piercing cry or choking as the entire body musculature is seized in a
strong contraction and air is forced out through partially closed vocal cords. Patients fall to the ground in an
unconscious state. Initial motor signs include brief flexion of the trunk, an opening of the mouth and eyelids,
upward deviation of the eyes, and elevation of the arms. These are followed by a rigid extension phase,
involving the back, neck, arms and legs, which lasts for 15–20 s. Involvement of the respiratory muscles in the
spasm results in a suspension of breathing, and in a few seconds the skin and mucous membranes become
cyanotic. The patient often loses bowel and bladder control during this phase. This tonic phase of the convulsive
seizure is followed by the clonic phase, which consists of rhythmic muscle contractions lasting for 20– 30s.
Autonomic signs are conspicuous: the pupils are dilated, blood pressure is raised, the pulse is rapid, and
salivation and sweating occur.

9. When the seizure is over, the patient does not immediately return to normal. This postictal state, which lasts for
minutes to hours, is first characterized by the patient lying still and limp, and breathing quietly.
The patient slowly regains consciousness, usually over the next several minutes, but is obviously confused.
The patient may remain sleepy for several hours; if left undisturbed, the patient may fall into a deep sleep for
hours and awaken with a postictal headache and fatigue. Once recovered, the patient may have no memory for
any part of the seizure.
However, the patient is aware that something troublesome has happened because of a bitten tongue, injury from
the fall, concern expressed by others, regaining consciousness in different surroundings, and aching muscles
from the violent contractions.
Absence seizures
Absence (petit mal) seizures occur without warning and consist of a sudden interruption of consciousness. The
hallmarks of absence seizures are their brevity, general lack of motor activity, frequency, and lack of a postictal
period.The seizures usually last from 2 to 10 s, occasionally longer.
Patients are often unaware of them. An observer may interpret an absence as a moment of daydreaming.
The person stops talking briefly in midsentence, stares, or stops responding. As many as several hundred such
seizures may occur in 1 day. Absence seizures almost always begin in childhood or adolescence.
They often disappear before adulthood, presumably because of the biochemical or structural changes associated
with brain maturation. When they occur with high frequency in school, they often lead to poor performance.
During short absences the patient may be completely motionless. With longer absences, subtle automatisms are
often observed such as blinking.
Atonic seizures
Atonic seizures (drop attacks) manifest themselves as a sudden loss of tone in postural muscles. In a mild
variant, only the head drops. However, in the severe form, all of the postural muscles lose tone, and the patient
suddenly collapses to the ground. Frequent falls may result in injury, especially to the head, so protective
headgear may be needed. The duration of the attack is usually only a few seconds, but the seizure may be more
prolonged. When the attack is brief, no notable postictal symptoms occur.

10. Myoclonic seizures
Myoclonus is a nonspecific term applied to a class of motor signs characterized by fast involuntary muscle jerks. Many forms
of myoclonus are nonepileptic, but the myoclonic seizure is considered to be a type of primary generalized epilepsy. It is the
predominant seizure type in approxi- mately 4% of patients with epilepsy. Myoclonic seizures consist of bilaterally
synchronous involuntary muscle jerks that occur singly or in a brief salvo of repeated jerks. Some myoclonic jerks can be
restricted to only one muscle, while others involve large muscle masses including both arms and legs or even the entire body.
Repetitive massive myoclonic jerks can occur without any alteration in consciousness, indicating that the mechanism and
anatomy underlying myoclonic seizures is different from that in other types of generalized epilepsy.
Motor manifestations at the onset of focal seizures are optionally further classified as automatisms, hyperkinetic,
atonic, clonic, myoclonic, tonic, or epileptic spasms, if they are the predominant feature of the entire seizure.
Automatisms are coordinated repetitive movements such as chewing, licking, lip smacking, fumbling, laughing,
or crying that may appear somewhat purposeful but out of situational context.
Hyperkinetic manifestations are proximal, ballistic like movements such as thrashing and kicking.
A myoclonic jerk is a brief contraction of a muscle or a muscle group. A myoclonic jerk generated in the cortex
can be distinguised from subcortically generated movements by its brief duration (usually less than 50 msec).
Clonic movements are those generated by repetitive rhythmic stereotypical jerks.
Tonic movements are characterised by sustained stiffening of a muscle or a muscle group. Atonic behaviour
reflects the sudden loss of tone in a muscle or a muscle group.
Investigations
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.
EEG
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.
Common recommendations:
• Focal seizures: 1st line - Carbamazepine or lamotrigine. 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 valoproate. 2nd line - levetiracetam or topiramate.
• Juvenile myoclonic epilepsy: 1st line - sodium valproate*. 2nd line - lamotrigine , levetiracetam or topiramate.