• 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

Management

Surgery

• Mass lesion in the brain
• Uncontrolled epilepsy

• Temporal lobectomy
• Corpus collosal section
• Hemispherectomy
• Selective amygdalo-hippocampectomy

More Information

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
• Alcohol – Alcohol 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

• On EEG this produces characteristic  wave patterns, usually with large amplitude, and sometimes in a rhythmic pattern

Triggers for seizures

• 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

Types of epilepsy

Partial epilepsy

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.

• 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

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 attack– there 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.

• 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, 20^th Ed.):

Unclassified Seizures

• 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.

Status Epilepticus

• 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.

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 – 2^nd line
  • Effective, but cause circulatory depression
• 3^rd 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

• Driving
• Medications (and side-effects)
• Social stigma
• Insurance

Differentials

• 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

ECG – looking 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
• Calcium – hypoglycaemia
• 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 dipstick – for 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.

• Late onset disease
• Partial seizures
• Associated with abnormal clinical signs

• General lesions
• Low grade gliomas
• Neuron cell migration problems

• During a seizure, metabolism and blood flow is massively increased in the affected area.

Management

Drug therapy

• 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.

• First line – Sodium valporate
• Second line – lamotrigine
• Absence seizures:
  • Try sodium valporate or ethosuximide

• First line – Carbamazepine
• Second line – sodium valporate

Pharmacology

• 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.

• The greater the frequency and amplitude of cell firing, the greater the blockade.

• 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

• 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.

• It is also used to treat psychiatric disorders.

• 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

• It is essential that all women of childbearing age are also on contraception if they are taking anti-epileptic drugs
  • Long-acting reversible contraption (LARC) methods are usually recommended – such as mirena or implanon
• 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.

Alternative Treatments

• CT/MRI – an obvious lesion may be present
• PET – more subtle lesions can be identified with their abnormal metabolic requirements and unusual blood flow.
• 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 – although, 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

• 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%)