Epilepsy

Original article by Tom Leach | Last updated on 16/5/2014
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Summary

Definitions

Seizure – spontaneous uncontrolled abnormal brain activity
Epilepsy – a tendency to have seizures. Epilepsy is a symptom, and not a true condition. Epilepsy can be diagnosed after a minimum of 2 seizures.
Ictus – can refer to any acute event, in this situation, refers to the epilepsy attack itself.
Prodrome - a set of not specific symptoms that precede the onset of a disease, in this case, epilepsy
Aura – sensory disturbances that precede an attack, usually just by a few minutes. Can be visual, tactile, olfactory – pretty much any sensation.
 

Epidemiology

  • The lifetime risk of having a seizures is about 1-2%
  • Prevalence of epilepsy is about 0.5% - i.e. it is very common!
  • 70% of cases have no identified cause
  • 70% of cases are well controlled with drug treatment
  • Normally presents in childhood/teenage years
  • 5x more common in developing countries
 

Aetiology

  • Genetic component
    • 30% of patients will have a first degree relative with epilepsy. But in most cases, there is no specific syndrome present
    • >200 rare inherited syndromes all have epilepsy as a component
  • Developmental abnormalities
  • Trauma / Surgery
  • Hypoxia
  • Pyrexia – particularly in children
  • Mass lesion in the skull
  • Drugs
  • CNS infection
  • Vascular abnormalities – particularly in the elderly; including stroke.
  • Metabolic disturbance
 

Pathology

In epilepsy there is an abnormal synchronised discharge of neurons. Normal inhibitory mechanisms fail. Individuals are said to have a seizure threshold – this is the level of excitability at which cells will discharge uncontrollably. In epileptic patients we say that the seizure threshold is lowered, and the neurons are hyperexcitable. The main neurotransmitters involved are glutamate (excitatory) and GABA (inhibitory).
Triggers that push neuron excitation past the seizure threshold are:
  • Sleep deprivation
  • Alcohol (alcohol intake AND alcohol withdrawal)
  • Drug misuse
  • Physical/mental exhaustion
  • Flickering lights –e.g. on TV/video games - cause primary generalised epilepsy only
  • Infection / metabolic disturbance
  • Less common:
    • Loud noises
    • Hot bath
    • Reading
    • Strange shapes
    • Strange smells
    • Strange sounds

 

Epilepsy Classification

Partial Epilepsy

This refers to focal seizures – that remain confined to one part of the brain.

Simple partial seizure

  • Patient remains conscious
  • Isolated limb jerking is common
  • May be isolated head turning (away from the side of the seizure)
  • May be isolated parasthesia - There can be any isolated motor/sensory sign
  • Weakness of the limbs may follow – Todd’s paralysis

Complex partial seizure – aka temporal lobe seizure

  • May impair consciousness
  • Déjà vu
  • Jamais vu – feelings of unfamiliarity
  • Vertigo
  • Visual/auditory hallucinations
  • Lip smacking / other motor disturbances
  • Tachycardia
  • Emotional disturbance
  • Automatism – patients have impaired consciousness, but motor function may still be intact, so they can often wander off.
  • Drowsiness and confusion after the attack

Secondary generalised seizures – these are partial seizures that spread to lower brain areas, which results in the initiation of a generalised seizure. The resulting generalised seizures is usually tonic clonic.

 

Generalised Epilepsy

These seizures originate in the midbrain or brainstem. They spread simultaneously to both the cortices.

Absence seizures – aka petit mal

  • Childhood onset
  • 3Hz spike and wave pattern on EEG
  • Patient unresponsive to stimuli, but still conscious
  • Patient stares, may go pale
  • May be some muscle jerking
  • Many attacks can occur on the same day
  • Can affect school performance - All primary school teachers educated to recognise attacks
  • After attack – normal function quickly resumes
  • Patients likely to develop tonic-clonic seizures later in life
  • 40% of cases have relatives with epilepsy
  • May appear clinically similar to temporal lobe seizures – but:
    • There is quick recovery after the attack (in petit mal)
    • They generally last <15s, whereas temporal lobe last >30s.

Tonic Clonic Seizures – aka grand mal

  • Often aura before attack
  • Tonic phase (10-60s)
    • Rigidity
    • Epileptic cry
    • Tongue biting
    • Incontinence
    • Hypoxia/cyanosis – no breathing during this phase
  • Clonic Phase (seconds-minutes)
    • Convulsions / limb jerking
    • Eye rolling
    • Tachycardia
    • No breathing / random, uncoordinated breaths
  • Seizures are usually self-limiting. The patient may sustain physical injury the attack. Afterwards, the patient may feel drowsy, confused, and have a headache. Some patients enter a coma.

Tonic only seizures
Atonic seizure (aka akinetic seizure) – can be difficult to distinguish from a ‘faint’
Myoclonic seizure – clonic symptoms only

______________________________________________________________________________

Status Epilepticus

Said to exist when:
Seizure that lasts >30minutes
OR
Multiple seizures, inbetween which, consciousness is not recovered, lasting > 30 minutes
Status epilepticus is a medical emergency.
Ultimately the brain cells swell, and cause herniation of the brain. The swelling is a result of electrolyte imbalance that occurs when the body is no longer able to meet the massive energy demands of the rapid discharging neurons.
 
Treatment
  • Benzodiazepines – useful acutely, but not chronically. Immediate action and many administration route (rectal IM, IV)
  • Phenobarbital – 2nd line
  • 3rd line – phenytoin
    • Given IV – but this can cause severe cardiac arrhythmia – so be careful!
______________________________________________________________________________

Diagnosing epilepsy

  • ECG
  • Neurological Exam
  • Serum Clacium
  • Urine dipstickdiabetes
  • EEG
  • CT/MRI – can show focal lesions
  • PET scan
  • Bloods
    • Sugar - hypoglycaemia
    • U+E’s – renal problems
    • Calciumhypoglycaemia
    • LFT’s
    • CK - Serum muscle enzymes – raised in true epileptics after clonus and tonic seizures, normal in pseudoseizures
    • Serum prolactin – to check for pseudoseizures

 

Management

Avoiding trigger factors can reduce the frequency (and in some patients completely alleviate attacks) – e.g. in cases caused by flashing lights.
 
Drug therapy
Only start after a minimum of two fits. Only use one drug at a time, and begin with a small dose, and gradually increase it, until control is achieved, toxic affects occur, or the maximum dose is reached.
Drug
Mechanism
Side effects
Clinical uses
Phenobarbital
Inhibits sodium channels, thus reducing action potential propagation. Does not lower the seizure threshold.
Sedation, impairment of motor and cognition systems after long term use, megaloblastic anaemia
Rarely used due to sedation – been superceeded by phenytoin
Phenytoin
Inhibits sodium channels, thus reducing action potential propagation. Acts on voltage dependent channels, and selectively binds when they are in the open state.
Vertigo, nystagmus, headaches, megaloblastic anaemia, hypersensitivity, confusion and cognition problems (high dose). Teratogenic, gum hypertrophy, arrythmias
Partial and generalised attacks, but not in absence. High doses my precipitate attacks
Carbamazepine
Inhibits sodium channels, thus reducing action potential propagation. Acts on voltage dependent channels, and selectively binds when they are in the open state.
Ataxia, drowsyness, dizziness, GI disturbance, cardio effects, water rention (and subsequent hyponatraemia), alter metabolism of other drugs, skin rash
First line for partial seizures
Also often tried as a 2nd or third line drug, when other treatments have been unsuccessful.
Lamotrigine
Inhibits sodium channels, thus reducing action potential propagation.
Nausea, dizziness, ataxia
Generalised seizures – 2nd line treatment
Ethosuximide
Calcium channel inhibitor – inhibits calcium channels of the T-type – thought to be involved in the 3Hz rhythmic discharge seen in absence seizures
Dizziness, nausea, anorexia, lethargy. Can precipitate tonic/clinic attacks
Useful for absence seizures
Sodium valproate
-          Increases GABA concentration
-          Inhibits sodium channels
-          Inhibits glutamate decarboxylase
Very few side effects.
Highly teratogenic
10% will have hair loss
Reduces efficacy of contraceptive pill
First line treatment for:
-          Absence seizures
-          Generalised seizures
second line treatment for partial seizures

Surgery

May be considered when:
  • Mass lesion in the brain
  • Uncontrolled epilepsy
There are various type of surgery, all involve removing part of the brain, with possible consequences on functioning. Examples include:
  • Temporal lobectomy
  • Corpus collosal section
  • Hemispherectomy
  • Selective amygdalo-hippocampectomy

Driving and epilepsy

The law in the UK
  • The doctor is obliged to tell the patient to inform the DVLA – but the doctor does not have to directly inform the DVLA – UNLESS – after continued reminders to the patient, the patient continues to drive, the doctor then has a duty to break confidentiality to inform the DVLA.
  • Patients CANNOT drive if:
    • They have changed their medication in the last 6 months
    • They have had a seizure in the last 12 months
    • HOWEVER - If the patient has ‘night-time’ only seizures, they can drive, if they have not had a ‘day time’ seizure for the last 3 years. Note that a nocturnal seizure can occur in the day – it is just any seizure when the patient is asleep.

 

More Information

Epilepsy is not a true condition in itself. It refers to a tendency to have spontaneous abnormal brain activity, resulting in seizures. Technically to have epilepsy you have to have had a minimum of 2 seizures. It is a symptom of brain dysfunction. It may be the only symptom, or it can be part of a whole group of other problems.
In the vast majority of cases no cause can be found
There is a mortality associated with epilepsy. Usually, the epilepsy causes some traumatic injury that results in death; e.g. crashing the car, fitting in the bath and drowning. This is rare!
A more common cause of death in epilepsy is status epilepticus.
 

Epidemiology

Epilepsy is very common:

  • 1-2% of people will have at least one fit in their lifetime
  • 0.5% of the population have active epilepsy at any one time
  • After the first seizure, 70% of people will have a second within 12 months, usually within the first 2 months.

The disease is 5x as common in developing countries.
70% of all cases are well controlled with drugs
30% are at least partially resistant to treatment
Normally presents in childhood or teenage years.

  • When presents in adulthood – you should be more suspicious of organic cause / lesion / trauma.

Genetic factors

  • About 200 genetic disorders can cause epilepsy, and there are some complicated and rare syndromes. However, as these syndromes only account for 2% of cases of epilepsy, there are other genetic factors at work.
  • About 30% of epilepsy patients have a first degree relative with epilepsy – but in the vast majority of cases, there is no distinct genetic syndrome present.
  • Petit-mal and primary generalised seizures can be inherited in an autosomal dominant pattern, although the pattern is variable. this is thought to be the result of genetic abnormalities in synaptic formation and NT distribution and release.  It is also thought that migration of neurons during utero development is a major cause of epilepsy.

Developmental abnormalities

Trauma / surgery / hypoxia

This is most likely to cause epilepsy when it occurs in utero or in early childhood.

  • Brain injury can cause epilepsy within days (early epilepsy), or it may not appear for years (late epilepsy).
  • The brain injury usually resulted in coma at the time of the injury to be severe enough to cause epilepsy later.
  • 10% of neurosurgery patients will experience epilepsy at some point.

Pyrexia

Can rarely cause convulsions, usually in young children. Epilepsy is unlikely to recur.

  • When this occurs in children it is known as febrile convulsion. The brain of a child is more susceptible to seizure during fever, than that of an adult. They are rare after the age of 5. Having a febrile convulsion as a child increases the risk of further seizures, particularly in males.

Mass lesions in the skull

If the epilepsy presents in adulthood, there is a 3% chance that a mass lesion in the cause.
Drugs (particularly elicit drugs)

  • Drugs used to treat neurological and psychiatric disorders – can often lower the seizure threshold (e.g. TCA’s, MAO inhibitors, amphetamines, propofol)
  • Drug withdrawal – of anticonvulsants, and sometimes of other neuro/psychiatric drugs
  • AlcoholAlcohol induced hypoglycaemia can also be the cause
  • Alcohol withdrawal

Hydrocephalus – lowers the seizure threshold
Encephalitis

Vascular abnormalities

In the elderly, epilepsy may result from infarction

Metabolic disturbances

  • Hypoglycaemia
  • Hypocalcaemia
  • Hyponatraemia
  • hypoxia
  • uraemia
  • mitochondrial disease

Degenerative neurological disorders

Particularly:

  • Alzhemier’s
  • MS

Epilepsy trigger factors (see below)
Only about 30% of cases of epilepsy in the UK have a discovered cause:

  • 15% due to cerebrovascular disease
  • 6% due to cerebral tumour
  • 2% due to trauma
 

Causes

  • 75% - no cause found
  • 5% - CNS infection – important cause that needs investigating! Meningitis, encephalitis, brain abscess (focal brain infection).
    • Other infections can also cause episodes of epilepsy – febrile convulsions. These are particularly common in young children. Fever can alter the seizure tthreshold, and in neonates, the nerons and less stable than in older children.
  • 5% - vascular disease (including stroke)
  • 5% - head trauma
  • 4% - congenital disorder
  • 2% - neoplasm
  • 2% - anoxia
  • 2% - drugs and alcohol
  • <1% - metabolic disturbance, MS, anaesthetic agents, neuro/psychiatric medications
  • Note that old age lowers the seizure threshold – putting you at higher risk of epilepsy in later life.
 

Pathology

In normal individuals, neurons are discharging all the time, accounting for various neurological functions. They often discharge synchronously in small groups, producing normal EEG patterns. In epilepsy, there is an abnormal SYNCHRONISED discharge of many neurons – with many millions of neurons all firing at the same time. Normal inhibitory mechanisms fail.
  • On EEG this produces characteristic  wave patterns, usually with large amplitude, and sometimes in a rhythmic pattern
 
Glutamate is the main excitatory NT involved, whilst GABA in the major inhibitory NT. Dysfunctions of either or both of these have been implicated in some studies, and these may be related to the hyperexcitability phenomenon seen in epilepsy.
 

Triggers for seizures

Essentially, seizures occur because neurons are hyperexcitable. This can be a genetic tendancy, or can result from damaged brain tissue. Then, on this background of hyperexcitability, certain factor can excite the cells beyond the threshold for seizure.
Every patient has their own individual threshold for seizure. Some chemicals can induce seizures in everyone, but those with epilepsy tend to have low seizure threshold. Some triggers that can push excitability past the threshold include:
  • Sleep deprivation
  • Alcohol (alcohol intake AND alcohol withdrawal)
  • Drug misuse
  • Physical/mental exhaustion
  • Flickering lights – cause primary generalised epilepsy only
  • Infection / metabolic disturbance
  • Less common:
    • Loud noises
    • Hot bath
    • Reading
    • Strange shapes
    • Strange smells
    • Strange sounds
If known trigger factors are avoided, the probability of future seizures is reduced.
 
 

Types of epilepsy

There are lots of ways to try and classify epilepsy – I will try and keep it simple!

Partial epilepsy

These patients have seizures that occur in one localised part of the brain. Usually this part of the brain is a more superficial part of cerebral cortex.  The seizure may stay here, or it can become generalised (secondary generalised epilepsy). In these cases it is probably not possible to tell that the initial seizure was focal.

Simple partial – when this occurs, it does not result in LOC. However, there may still be other motor or sensory signs – such as a jerking limb. Usually confined to one lobe of the brain. It could occur with pretty much any motor or sensory signs/symptoms. They often result from a focal lesion (e.g. tumour or abscess). Classically, might have a tremor just of your hand – that is involuntary, and you can’t stop.

  • Jacksonian seizure – this is a type of simple partial motor seizure, which originates in the motor cortex. Typically, small jerking movements occur at the hand or face (extremities of the mouth) as these regions have the largest representation in the motor cortex, and then spread to other motor areas, as the seizure spreads in the brain. We call this the march of the seizure. Different muscle groups may twitch (clonus) in turn. Weakness of the limbs may follow for several hours, and is known as Todd’s paralysis.
  • Adverse seizures – another simple motor seizure. The patients head may rapidly turn to one side (at which point the patient is still conscious and aware). The head turns away from the side of the seizure. These then often proceed to tonic-clonic seizures.
  • Simple sensory seizures –the patient may describe parasthesia and tingling in the face, or at the extremities. There may be a ‘march’ similar to in Jacksonian  eizures. The limbs may be weak.
  • Partial seizures can be the result of a focal defect – and thus it is important to try to localised the area of the brain affected and check for underlying defects. In many cases, none will be found.

Complex partial – may result in some form of impaired consciousness. Again usually confined to one lobe of the brain.

  • Temporal lobe seizures – these can be complex or simple partial seizures, but have some other distinct features. normal complex partial seizures are temporal lobe seizures. The seizure usually originates right in the medial part of the temporal lobe, or in the hippocampus. Patients may experience:
    • Extreme déjà vu
    • Feelings of unreality and unfamiliarity – ‘jamais vu’
    • flashbacks
    • Vertigo
    • Visual/auditory hallucinations
    • Lip smacking and other motor disturbance (fidgeting, rubbing, chewing, strange limb movements)
    • Tachycardia
    • Pupillary dilation
    • Emotional disturbance – from elation to fear and displeasure.
    • Automatism – patients have impaired consciousness, but motor function may still be intact, so they can often wander off.
    • After the attack, there may be confusion and drowsyness. In some cases, the attacks may come in clusters, one shortly after another.
    • The attacks may be the result of surgery, or other defects. On autopsy/surgery, there is often hippocampal degeneration.
  • Temporal lobe epilepsy accounts for 2/3 of all new cases in adolescence and adulthood. Up to 40% don’t respond to treatment.
 
Partial Seizures evolving to Tonic-Clonic seizures – aka Secondary Generalised Seizures
Partial seizures have the ability to spread. When they spread to lower brain areas (such as the thalamus), this can start off a massive generalised seizures in both cortices simultaneously, resulting in a tonic-clonic seizure.
  • Noting the symptoms before the tonic-clonic episode can help localise where the seizure originated in these case .
  • See below for a description of a tonic-clonic attack
 

Generalised epilepsy

These seizures are bilateral, with bilateral motor effects, and impaired consciousness. The fact that they are generalised suggests that they are initiated in deep midline brain structures, (i.e. it originates in the brainstem and midbrain) and then project simultaneously to both cortices.
They can be primary or secondary:

Absence – aka petit mal. Usually generalised, usually first occurs in childhood (age 4-12), and always accompanied by the 3Hz spike and wave pattern on EEG.  Rarely presents after childhood – however, 30% of cases will go on to develop tonic-clonic seizures later in life. The main symptom is absence – e.g. patient does not respond to stimuli, but is still conscious. They may stare, and go pale, usually just for a few seconds. Many attacks can occur on the same day. The eye-lids may twitch, and there may be some muscle jerking. After an attack, the patient returns to normal functioning quickly.

  • During an attack, the patient may stop talking in the middle of a sentence, then 10 seconds later, carry on as if nothing has happened.
  • Absence attacks are never the result of acquired lesions. they are due to developmental abnormalities.
  • Children who suffer from this type of seizure tend to develop tonic-clonic seizures later in life.
  • Similar attacks can be seen with seizures of the temporal lobe, however, these attacks do not have waves at 3Hz, and thus are not the same as petit mal.
  • In 40% of cases there is a family history.
  • The first sign of this may be a reduction in academic performance at school – which can occur if the attacks are frequent.
  • EEG is particularly useful in these attacks – due to the 3Hz spike and wave. Note that similar patterns can be produced by:
    • Hyperventilation
    • Photo stimulation – flashing lights
    • And both the above can result in seizures
  • Differentiating from complex partial seizures – in petit mal:
    • There is no headache, lethargy or confusion after the attack
    • Petit mal attacks are generally less than 15 seconds, whilst complex partial seizures are usually at least 30 seconds.

Tonic-clonic – aka – grand mal seizure. These involve a major convulsion. These are primary generalised seizures – where there is no focal onset, the seizure is directly initiated in a lower brain area. There is often a vague warning before the attack, and then the tonic phase begins.

  • Tonic phase – the body becomes very stiff and rigid, for 10- 60 seconds. They may vocalise indistinguishable sounds (sometimes called the epileptic cry – and it results from rapid closure of the vocal cords), and will fall to the ground. The patient often bites their tongue, and they may have incontinence of urine or faeces (or both). The eyes will usually be open, the legs extended and the arms flexed.The patient often does not breathe during this phase, and the pupils will be dilated. There may be a slight tremor. Often there is cyanosis.
    • The tonic phase is associated with massive neuronal discharge, and the clonic phase occurs as the discharge reduces in intensity.
    • On EEG there is 10-14Hz spike activity
    • At the end of the seizure there may be a period of very little brain activity, before normal activity resumes.
  • Clonic phase – generalised convulsions and limb jerking. There may also be frothing at the mouth. This can last from a few seconds to a few minutes. The eyes can roll backwards and forwards, and there may be tachycardia. The patient still may not breathe until the end of this phase.
    • The seizure is normally self limiting. Afterwards, the patient may feel drowsy and confused, and there may be a headache. They may feel fatigued for hours or even days afterwards. This can be due to muscle damaged that occurred during the attack. There may also be other injuries. Some patients may enter a coma.
    • There may be some random unregulated breaths
  • When partial seizures progress to tonic-clonic seizures –you cannot tell it was initially a partial seizure – UNLESS the patient can remember how the seizure began and describe a partial seizure (rare as they may have some amnesia), OR you have an eyewitness account of the attack, OR you have the patient hooked up to EEG all the time – in which case you may be able to detect the two distinct patterns of brain waves.

Tonic – there is extreme rigidity, and immediate LOC, but it is not followed by a clonic phase. Rare in adults, but common in children.
Atonic aka akinetic attackthere is a sudden loss of muscle tone, and often the patient falls, and loses consciousness, but probably only very briefly. The ECG shows polyspikes, or low voltage activity.
Myoclonic – there is muscle jerking, but not the tonic phase seen in other seizures. They usually occur in the morning, and may be associated with tonic-clonic seizures. The most common cause is:Juvenile myoclonic epilepsy – which is benign, with usually onset after puberty.

  • Myoclonus is also seen in metabolic disturbance and degenerative disease.
 
Primary generalised seizures
  • Accounts for 10% of all seizures
  • Accounts for 40% of tonic-clonic seizures
  • Onset usually in childhood or young adulthood
  • No structural abnormality
  • Usually a large genetic component
  • Lots of subtypes – the main ones are described below (adapted from a table in Davidson’s Principles and Practice of Medicine, 20th Ed.):
Type
Incidence (per 100 000)
Age of onset
Seizure type
EEG
Triggers
Treatment
Prognosis
Childhood absence epilepsy
6-8
4-8 years
Frequent brief absences
Spike & wave
f= 3Hz
Fatigue, hyperventilation
Ethosuximide,
Sodium valporate
40% will develop tonic-clonic seizures. 80% will remit in adulthood
Juvenile Absense Epilepsy
1-2
10-15 years
Infrequent brief absences
Poly-Spike & wave
Sleep deprivation, hyperventilation
Sodium valporate
80% will develop some tonic-clonic seizures, but 80% will remit in adulthood
Juvenile myoclonic Epilepsy
25-50
15-20 years
GTCS, absence, morning myoclonus
Poly-spike and wave
Sleep deprivation, alcohol withdrawal
Sodium valproate
90% remission with treatment, but many relapse when treatment withdrawn
GTCS on awakening
Common?
10-25 years
GTCS, myoclonus
Spike and wave on waking and falling asleep
Sleep deprivation
Sodium valproate
65% well controlled with threatment, but high relapse rate when treatment withdrawn
GTCS – Generalise Tonic-Clonic Seizure
 

Unclassified Seizures

There are certain seizures that don’t fit the patterns described above. A few examples include:
  • West Syndrome – presents in infants, who often have tonic-clonic, myoclonic and other types of seizure. There is usually mental retardation, and mortality is high. Often the result of perinatal (immediately before and after birth) trauma or asphyxia. There is often an abnormal interictal EEG.
  • Lennox-Gastaut syndrome – similar to the above, and presents between age 1-7. Verying degress of retardation, and varying responses to treatment. Associated with lots of causes, including hypoxia and trauma.
 
Aura – strange sensations precede an attack. This can be a visual disturbance, tingling/jerking of a limb, strange smells or some other neurological sign. You can have an aura without having an attack, and you can have an attack without an aura.
 
Prodrome – a prodromal event can occur before an attack. It may be hours, or even days before an attack. A prodrome is a/a set of not specific symptoms the preceed the onset of a disease, in this case, epilepsy.
 

Status Epilepticus

Sometimes seizures can continue for many minutes, particularly tonic clonic seizures. If it continues for more than several minutes you need to do something to help.
  • Patient likely to be hypoxic – they are not breathing, but the brain actually requires more oxygen due to overactivity.
  • You can give IV/rectal diazepam
  • Don’t put your fingers in their mouth!
  • If, after diazepam, cyanosis continues, you can paralyse the patient, to intubate.
    • Be wary that in this situation, the patient may still be fitting, but you don’t know, because the physical manifestations are hidden by the paralysis
    • Once you have established the airway, you can keep giving diazepam to try and sedate, and stop the fit.
 
Status epilepticus is said to exist when:
Seizure that lasts >30minutes
OR
Multiple seizures, inbetween which, consciousness is not recovered, over a period of > 30 minutes in total
 
Status epilepticus is a medical emergency. It has a mortality of 5-10%.
Ultimately the brain cells swell, and cause herniation of the brain. The swelling is a result of electrolyte imbalance that occurs when the body is no longer able to meet the massive energy demands of the rapid discharging neurons.
 

Treatment

  • Benzodiazepines – useful acutely, but not chronically. Immediate action and many administration route (rectal IM, IV). Give diazepam – 5mg every 5 minutes. may sedate for 10-20 minutes, but then the seizure can return.
    • Can cause respiratory depression with repeated doses.
  • Phenobarbital – 2nd line
  • 3rd line – phenytoin
    • Given IV – but this can cause severe cardiac arrhythmia – so be careful! However it is useful as it does not depress respiration.
    • Monitor ECG and BP

    • Contra-indicated if known heart defect, or recent MI.

 

Diagnosis

  • Must have 2 seizures within 2 years
The most important factor in the diagnosis is was another person present to witness the seizure? – this person’s description of the pattern of events can be crucial in confirming the type of seizure. 
 
Be very careful when diagnosing – you must be sure, as the diagnosis has serious implications, including those on:
  • Driving
  • Medications (and side-effects)
  • Social stigma
  • Insurance
 

Differentials

See falls
In addition to other causes of falls, another differential is:
Pseudoseizures – which are essentially feigned attacks, usually involving limb jerking, and often feigned LOC. Individuals may have personality disorders, and/or be very suggestible. In female patients there is often a history of sexual abuse.
  • Many true epileptics may also exhibit psuedoseizures!
  • To help differentiate you can do:
    • EEG – normal
    • Serum muscle enzymes – raised in true epileptics after clonus and tonic seizures, normal in pseudoseizures
    • Serum prolactin
 

Tests

You may want to carry out many of the tests you would perform for falls to check if it really was epilepsy. Specifically, you might want to do:

ECGlooking for heart conditions that might have caused a fall – e.g. AF
Neurological exam – will usually be normal, but may point to an underlying degenerative disease, mass lesion, or other abnormality
Serum calcium
Bloods:

  • Sugar - hypoglycaemia
  • U+E’s – renal problems
  • Calciumhypoglycaemia
  • LFT’s
  • CK - Serum muscle enzymes – raised in true epileptics after clonus and tonic seizures, normal in pseudoseizures
  • Serum prolactin – to check for pseudoseizures

Urine dipstickfor diabetes, and (rarer cause of falls/epilepsy) infection.
EEG – this is useful but does have a lot of limitations. You should do an EEG after the first fit, but usually the EEG is normal inbetween fits. Also note that an abnormal EEG between fits does NOT confirm the suspected event as epilepsy either!

  • Ictal – this word refers to the epileptic event itself. Thus we refer to EEG as being ictal – recorded during the attack, or interictal – recorded between attacks.
  • You may be able to elicit an abnormal interictal EEG in some situations:
    • Sleep deprivation EEG
    • ‘Activated EEG’ – after the patient has been given procyclidine
    • 24-48 hour EEG – often with simultaneous video of patient to asses clinical signs – called videotelemetry.
  • In rare cases, you may try obtaining an EEG with implanted electrodes around the foramen ovale, or in the subdural region.
 
CT and MRI
These are indicated when:
  • Late onset disease
  • Partial seizures
  • Associated with abnormal clinical signs
They may show focal pathology, such as:
  • General lesions
  • Low grade gliomas
  • Neuron cell migration problems
 
PET scanning
May be used in rare cases where surgery is being considered. It can show functional changes in cerebral blood flow and metabolism.
  • During a seizure, metabolism and blood flow is massively increased in the affected area.
 
 

Management

Management is tricky. There are lots of epilepsy patients, and doctors don’t have time to fully explore issues. There are a growing number of special epilepsy nurses in the UK who are taking over the follow-up management of many epilepsy patients.
 
One of the first things you should try to establish is; are there any trigger factors. If these can be detected (e.g. flashing lights on TV), and avoided, then you can avoid the use of drugs.
 

Drug therapy

Most people would only recommend starting treatment after a minimum of 2 fits. Also discuss the relative risks with the patient. If they have a fit only once every year or so, and aren’t in a profession where fitting could be dangerous (e.g. operating machinery), then the patient may want to take the risk of no treatment.
Begin treatment with one drug only. Gradually increase the dose until:
  • Seizures are controlled
  • Toxic effects occur
  • The maximum dosage is reached
  • Beware of drug interactions
  • It is also best practice to only involve one doctor in these initial stages – so they can get to know the patient and their situation well.
 
Generalised seizures:
  • First line – Sodium valporate
  • Second line – lamotrigine
  • Absence seizures:
    • Try sodium valporate or ethosuximide
 
Partial Seizures – with or without secondary generalisation
  • First line – Carbamazepine
  • Second line – sodium valporate
 

Pharmacology

The mechanism of many epileptic drugs is poorly understood.
Phenobarbital
This is the oldest anti-epileptic, and closely resembles phenytoin (described below). It does not alter the seizure threshold, and has generally been superseded by phenytoin, which unlike Phenobarbital, does not cause sedation.
 
Ethosuximide
This is a calcium channel inhibitor. This drug in particular blocks T-type calcium channels – which are thought to be involved with rapid rhythmic discharge of cells – thus they help to prevent seizures. It is clinically most useful for absence seizures.
It has a half life of about 50 hours.
Side effects include:
  • Dizziness
  • Nausea
  • Anorexia
  • Lethargy
  • In some susceptible patients it may precipitate tonic/clonic attacks
  • Gabapentin is another calcium channel blocker- but this acts on L-type calcium channels – and it is not known whether this is useful for treating epilepsy. Despite its name, GABApentin has little effect on GABA receptors.
 
Phenytoin, Carbamazepine, lamotrigine
Mechanism
These are inhibitors of sodium channels, and as such, they prevent the proliferation of action potentials.They affect voltage gated sodium channels, essentially blocking the channels. They are useful because they act in such a way that the most active channels are blocked first – thus in an epileptic attack, they will stop the hyperexciteable cells, but normal cells will still function.
  • The greater the frequency and amplitude of cell firing, the greater the blockade.
The mechanism works because the drug is able to distinguish between a cell in its resting, open and blocked states, and will only bind to open channels.
 
Phenytoin specifics
  • Useful in partial and generalised attacks, but does not help absence epilepsy, and may actually make it worse
  • At high doses it can increase the frequency of attacks – so be careful!
  • Metabolised by the liver
  • Half-life is about 20 hours – this increases when the dose increases
  • Narrow therapeutic range, with wide variability in the therapeutic dose between individuals
  • Reacts with other drugs
  • Side effects:
    • Vertigo
    • Headaches
    • Nystagmus
    • Does not cause sedation
    • Megaloblastic anaemia - can be cured with folic acid supplements
    • Hypersensitivity is common
    • Causes congenital abnormalities if taken in pregnancy; notably cleft lip and palate.
    • Confusion and intellectual deterioration can occur at high doses
 
Carbamazepine specifics
Similar in structure to TCA’s. Similar in action to phenytoin. Has a half-life of 30 hours (Which is variable, and tends to reduce to about 15 hours when given regularly).
Side effects can be quite severe:
  • Ataxia
  • Drowsiness
  • Dizziness
  • Mental and motor disturbance
  • Water retention – and hyponatraemia
  • GI disturbance
  • Cardio side effects
  • Side effects are rare compared to other anti-epileptics.
  • Accelerates the metabolism of other drugs – particularly other anti-epileptics, and warfarin!
    • Do not combine it with other anti-epileptics
  • About 10% of patients cannot tolerate this drug – they most commonly come out in a skin rash.
This is a very good drug for treating trigeminal neuralgia! If someone has facial pain, and you ive them this, and it goes away, the cause is almost certainly trigeminal neuralgia!
 
Lamotrigine
Similar to carbamazepine and phenytoin, but much newer. It is thought to have a wider therapeutic range, and thus is effective in more types of epilepsy. Particularly useful in absence seizures. Causes nausea, dizziness and ataxia. Has a half life of about 24 hours.
 
Sodium valproate – trade name - Epilim This is particularly useful, because it can treat a wide range of attacks. It also has low toxicity and is not sedative.
Like carbamazepine it is used in psychiatric disorders, particularly bipolar disorder.
It is chemically unrelated to other anti-epileptics.
 
Mechanism
It has lots of effects, which are poorly understood. Causes increase in GABA concentrations in the brain, and inhibits GABA breakdown. It is also thought to enhance the action of GABA post-synaptically, and like carbamazepine and phenytoin, it is a sodium channel inhibitor.
 
Other info
  • Half life is about 15 hours
  • Has very few unwanted effects:
    • Thinning and curling of the hair in 10% of patients
    • Hepatotoxicity
    • Weight gain
    • Teratogenicity! – see below
 
Sodium valporate and pregnancy
All anti-epileptic drugs increase the risk of birth defects (particularly spina bifida).
The risk of birth defects with this drug are massively increased. The absolute risk is 6-11%, and the relative risk is 2-5x higher than with other antiepileptic drugs.
Children born to mother who took sodium valporate during in pregnancy have on average an IQ of 9 points lower than those who did not. However, it is important to remember that some patient’s epilepsy can only be controlled with valporate – and that the consequences of seizure for both mother and baby may be severe. i.e. – having a seizure is worse than the risk of teratogenesis.
  • You should recommend to all epileptic women of childbearing age
  • If they plan to become pregnant, they should try a different treatment regimen before they start trying for a baby. Bear in mind this may take several months to become effective.
 
Phenytoin is also thought to have other effects that cause a general reduction in membrane excitability and synaptic function.
 
Excitory amino acid receptor antagonists
In the past, many animal trials have shown these drugs to look useful. However, in clinical trials, the therapeutic range is usually too narrow, and motor co-ordination is affected at low doses.
 
Withdrawing treatment
After a period of 3-5 years of absence of seizures on medication, you may consider withdrawing treatment.
However, 50% of cases will relapse within 2 years after withdrawal of treatment. EEG does not predict the further risk of attacks. Discuss thoroughly the options with the patient.
 

Alternative Treatments

In some patients, drug treatment is not enough to control the epilepsy. In severe cases where fits prevent normal functioning, and the foci of the epilepsy can be identified, then surgery may be considered to remove the foci. The foci can be identified with:
  • CT/MRI – an obvious lesion may be present
  • PET – more subtle lesions can be identified with their abnormal metabolic requirements and unusual bloodflow.
  • It may be some sort of mass lesion – in which case, surgery may be indicated without, or with only mild epilepsy
  • In severe cases of epilepsy, even if there is no mass lesion, the removal of the foci may still be appropriate.
 

Types of surgery

Temporal lobectomy – part or all of the temporal lobe may be removed in temporal lobe epilepsy.

  • 50% of patients have no further seizures
  • 30% of patients have better seizure control

Corpus collosal section

  • Prevents seizures from spreading between hemispheres. Useful in patients with generalised seizures (usually tonic or myoclonic). Helps to control sezirures, but patient rarely become seizure free.

Hemispherectomy

  • Used in children who have irreversible damage to the whole hhemisphere.
    • 80% become seizure free.
    • Obviously has serious implications on functioning – alothugh, interestingly, crude limb movements, and even walking can be preserved in the contralateral limb.
    • In such cases, severe disease exists even before the surgery, and thus as little functioning is lost as possible.

Selective amygdalo-hippocampectomy

  • When this is confirmed as the foci for seizures, this can be performed.
  • Less tissue removed than in temporal lobectomy.
  • Mild cognitive changes often result
  • Not great results
 
Wada test – used in many type of neuro surgery. A catheter is inserted into the arteries of the brain, and it can target a very localised region of the brain. A local anaesthetic is then released. This then simulates the effects of removing this particularly part of the brain, and can help patients and doctors make an informed decision before they perform any sort of -ectomy of brain tissue.
 
Driving and epilepsythe law in the UK
  • The doctor is obliged to tell the patient to inform the DVLA – but the doctor does not have to directly inform the DVLA – UNLESS – after continued reminders to the patient, the patient continues to drive, the doctor then has a duty to break confidentiality to inform the DVLA.
  • Patients CANNOT drive if:
    • They have changed their medication in the last 6 months
    • They have had a seizure in the last 12 months
    • HOWEVER - If the patient has ‘night-time’ only seizures, they can drive, if they have not had a ‘day time’ seizure for the last 3 years. Note that a nocturnal seizure can occur in the day – it is just any seizure when the patient is asleep.
    • If the risk is >2% if having a seizure, then you are not allowed to drive (normal lifetime risk is 1-2%)
 
Flying and epilepsy
Patients are fine to travel as passengers. Pilots very rarely allowed to fly, even if the seizures were a long time in the past. Exceptions may be made in cases where the pilot has only experienced one or a very small number of seizures, and the cause was identified and treated.