Pharmacotherapy of epilepsy

1. Epilepsy
RVS Chaitanya Koppala

2. Epidemiology
 Epilepsy is a chronic neurological disorder that affects people of all ages.
Around 50 million people worldwide have epilepsy.
Nearly 90% of the people with epilepsy are found in developing regions.
Epilepsy responds to treatment 70% of the time. Despite this, approximately 75% of
affected people in developing countries do not get the treatment they need.
People with epilepsy and their families suffer from stigma and discrimination in many
parts of the world.

3. Incidence and prevalence
Epileptic seizures are common. The incidence has been estimated at between 20
and 70 cases per 100,000 persons, and the cumulative incidence at 2–5%.
Most studies of the prevalence of active epilepsy in developed countries cite figures
of 4–10 per 1000 with a rate of 5 per 1000 population most commonly quoted.
In developed countries, annual new cases are between 0.4 and 0.7 per 1000
general population.

4. Prognosis (course /opinion on medical )
Up to 5% of people will suffer at least one seizure in their lifetime.
The prevalence of active epilepsy is, however, much lower and most
patients who develop seizures have a very good prognosis.
About 70–80% of all people developing epilepsy will eventually become
seizure free, and about half will successfully withdraw their medication.
A minority of people (20–30%) will develop chronic epilepsy and in such
cases, treatment is more difficult.
People with symptomatic epilepsy, more than one seizure type, associated
learning disabilities or neurological or psychiatric disorders are more likely
to have a poor outcome.
People with chronic epilepsy, fewer than 5% will be unable to live in the
community or will depend on others for their day-to-day needs.
Most people with epilepsy are entirely normal between seizures

5. Mortality
younger patients with severe epilepsy are at risk of premature death.
Common causes of death in people with epilepsy include accidents
such as drowning, head injury, road traffic accidents, status
epilepticus, tumours, cerebrovascular disease, pneumoni and suicide.
Sudden unexpected death, an entity which remains unexplained, is
common in chronic epilepsy, particularly among the young who have
convulsive forms of epilepsy.

6. Aetiology
Epileptic seizures are produced by abnormal discharges of neurones
that may be caused by any pathological process which affects the
cortical layer of the brain.
The idiopathic epilepsies a clear genetic component (third of all new
cases of epilepsy.
In a significant proportion of cases, however, no cause can be
determined and these are known as the cryptogenic epilepsies.
(unexplained metabolic or biochemical abnormalities and microscopic
lesions in the brain resulting from brain malformation or trauma
during birth or other injury.)
The term ‘symptomatic epilepsy’ indicates that a probable cause has
been identified.

7. Depends upon the age of the patient and the type of seizure.
The commonest causes in young infants are hypoxia or birth asphyxia,
intracranial trauma during birth, metabolic disturbances and congenital
malformations of the brain or infection.
In young children and adolescents, idiopathic seizures account for the
majority of the epilepsies, 6 months and 5 years, These are usually
short, generalised tonic clonic convulsions that occurs (damage to brain
like meningitis or encephalitis)

8. The range of causes of adult-onset epilepsy is very wide.
Both idiopathic epilepsy and epilepsy due to birth trauma may also
begin in early adulthood.
Other important causes are head injury, alcohol abuse, cortical
dysplasias, brain tumours and cerebrovascular diseases.
Brain tumours are responsible for the development of epilepsy in up to
a third of patients between the ages of 30 and 50 years.
Over the age of 50 years, cerebrovascular disease is the commonest
cause of epilepsy, and may be present in up to half of patients.

9. Clinical manifestations
• The clinical manifestation of a seizure will depend on the location of
the focus and the pathways involved in its spread.
• An international seizure classification scheme based on the clinical
features of seizures combined with EEG data is widely used to
describe seizures.
• It divides seizures into two main groups
Both hemispheres of the brain =‘generalised’.
Localised area of the brain= ‘partial’ or ‘focal’.

10. Generalised seizures
• Generalised seizures result in impairment of consciousness from the
onset. There are various types of generalized seizures.
Tonic clonic convulsions
• Often called ‘grand mal’ attacks, these are the commonest of all
epileptic seizures.
• Without warning, the patient suddenly goes stiff, falls and convulses,
with laboured breathing and salivation.
• Cyanosis, incontinence and tongue biting may occur.
• The convulsion ceases after a few minutes and may often be followed
by a period of drowsiness, confusion, headache and sleep.

11. Absence attacks
Often called ‘petit mal’,
These are a much rarer form of generalized seizure.
They happen almost exclusively in childhood and early adolescence.
The child goes blank and stares; fluttering of the eyelids and flopping
of the head may occur.
The attacks last only a few seconds and often go unrecognized even
by the child experiencing them.

12. Myoclonic seizures
These are abrupt, very brief involuntary shock-like jerks,
involve the whole body, or the arms or the head.
Occurs in morning, shortly after waking.
Causes the person to fall, but recovery is immediate.
It should be noted that there are forms of non-epileptic myoclonic
jerks that occur in a variety of other neurological diseases

13. Atonic seizures
These comprise a sudden loss of muscle tone, causing the person to
collapse to the ground.
Recovery afterwards is quick.
They are rare, accounting for less than 1% of the epileptic seizures
Seen in the general population, but much commoner in patients with
severe epilepsy starting in infancy.

14. Partial or focal seizures
Simple partial seizures
In these seizures, the discharge remains localised and consciousness is fully
preserved.
Simple partial attacks on their own are rare and they usually progress to
the other forms of partial seizure.
Localised jerking
stiffness or twitching
numbness or abnormal sensations
Complex partial seizure:
If the seizure progresses with impairment of consciousness, it is termed a
If it develops further and a convulsive seizure occurs, it is then called a
partial seizure with secondary generalisation.

15. Complex partial seizures
Altered or ‘automatic’ behavior: plucking his or her clothes,
Fiddling with various objects and acting in a confused manner.
Lip smacking or chewing movements,
grimacing, undressing, performing aimless activities, and wandering
around in a drunken fashion.
Most of these seizures originate in the frontal or temporal lobes of
the brain and can sometimes progress to secondarily generalised
seizures.

16. Secondarily generalised seizures
These are partial seizures, either simple or complex, in which the
discharge spreads to the entire brain.
The person may have a warning, but this is not always the case.
Only EEG can demonstrate the partial nature of the seizure.
The involvement of the entire brain leads to a convulsive attack with
the same characteristics as a generalised tonic clonic convulsion.

17. Diagnosis
The one feature that distinguishes epilepsy from all other conditions is its
unpredictability and transient nature.
The diagnosis of epilepsy is clinical and depends on a what happened during the
attacks, if possible both from the patient and from an eyewitness.
Investigations may help and the EEG is usually one of them.
These investigations, however, cannot conclusively confirm or refute the
diagnosis of epilepsy.

18. Other conditions : misdiagnosed as epilepsy
1. Syncope (fall in blood pressure)
2. Breath-holding attacks
3. Transient ischaemic attacks
4. Psychogenic attacks
5. Drug intake
6. Metabolic dysfunction
7. Infection, head trauma or flashing lights (photosensitive seizures).
These conditions have to be clearly ruled out before a diagnosis
Only be diagnosed when seizures occur spontaneously and are
recurrent.
The diagnosis must be accurate since the label ‘suffering with epilepsy’
has tremendous implications for the person.

19. The EEG is often the only examination required, particularly in
generalised epilepsies, and
It aims to record abnormal neuronal discharges.
EEGs have, however, limitations that should be clearly understood.
Up to 5% of people without epilepsy may have non-specific
abnormalities in their EEG recording,
While up to 40% of people with epilepsy may have a normal EEG
recording between seizures.

20. The chance of recording the discharges of an actual seizure during a routine EEG takes
20–30 min
Ambulatory EEG monitoring and EEG video-telemetry are sometimes required.
Recording in day-to-day circumstances using a small cassette recorder.
EEG video-telemetry is useful in the assessment of difficult cases, particularly if surgery is
considered.
The person is usually admitted to hospital and remains under continuous monitoring
best suited for those who have frequent seizures.

21. Neuroimaging with magnetic resonance imaging (MRI) is the most
valuable investigation when structural abnormalities such as
1. Stroke,
2. Tumour,
3. Congenital abnormalities
4. Hydrochephalus are suspected.
MRI should be carried out in anyone presenting with partial seizures or
where a structural lesion on the brain may be responsible for seizures.

22. Treatment
National Institute for Health and Clinical Excellence (2004) issued
guidance on the diagnosis and treatment of the epilepsies in adults
and children in primary and secondary care.
The guidance covered issues such as
When a person should be referred to a specialist centre,
Care and treatment of women with epilepsy and
The management of people with learning disabilities.

23. Treatment during seizures
Convulsive seizures may look frightening but the person is not in pain will
usually have no recollection of the event afterwards and is usually not
seriously injured.
1. Emergency treatment is seldom necessary.
2. Make the patient comfortable by lying down (ease to the floor if sitting),
3. Cushioning the head and loosening any tight clothing or neckwear.
4. Should not be moved unless they are in a dangerous place (in a road, by
a fire or hot radiator, at the top of stairs or by the edge of water)
5. No attempt to open the person's mouth or force anything between the
teeth.
6. When the seizure stops, people should be turned over into the recovery
position and the airway checked for any blockage.

24. Status epilepticus
Initial management of status epilepticus is supportive and may include:
Positioning the person to avoid injury
Supporting respiration
Maintaining blood pressure
Correcting hypoglycaemia
Drugs used include intravenous lorazepam or diazepam /midazolam.
Buccal midazolam has been advocated and is increasingly being used.
In severe cases, phenytoin, clonazepam or phenobarbital sodium may
be required.

25. Febrile convulsions
Primary aim of reducing the temperature of the child.
Tepid sponging and use of paracetamol is usual.
Prolonged febrile convulsions lasting 10–15 min =management to avoid
brain damage.
The drug of choice is diazepam by intravenous or rectal (rectal solution)
administration.

27. Initiation of therapy in newly diagnosed patients
• The first-line AED most suitable for the person's seizure type should
be introduced slowly, starting with a small dose.
• This is because too rapid an introduction may induce side effects that
will lose the person's confidence.

28. Maintenance dosage
There is no single optimum dose of any AED that suits all patients.
The required dose varies from person to person, and from drug to
drug.
Drugs should be introduced slowly and then increased incrementally
to an initial maintenance dosage.
Seizure control should then be assessed, and the dose of drug changed
if necessary.
For Phenytoin (serum level fluctuates)

29. Altering drug regimens
If the maximal tolerated dose of a drug does not control seizures,
or
if side effects develop
The first drug can be replaced with another first-line AED.
To do this, the second drug should be added gradually to the first.
Once a good dose of the new drug is established, the first drug should
then slowly be withdrawn.

30. Withdrawal of drugs
AEDs should not be withdrawn abruptly.
With barbiturates and benzodiazepines, in particular, rebound seizures may
occur.
Withdrawal of individual AEDs should be carried out in a slow stepwise
fashion to avoid the precipitation of withdrawal seizures.
Barbiturates, for example, phenobarbital and primidoze,
Benzodiazepines, for example, clobazam and clonazepam.

31. Examples of withdrawal regimens are given
below.
• Carbamazepine
• 100–200 mg every 2 weeks (as part of a drug change)
• 100–200 mg every 4 weeks (total withdrawal)
• Phenobarbital
• 15–30 mg every 2 weeks (as part of a drug change)
• 15–30 mg every 4 weeks (total withdrawal)
• Phenytoin
• 50 mg every 2 weeks (as part of a drug change)
• 50 mg every 4 weeks (total withdrawal)
• Sodium valproate
• 200–400 mg every 2 weeks (as part of a drug change)
• 200–400 mg every 4 weeks (total withdrawal)
• Ethosuximide
• 125–250 mg every 2 weeks (as part of a drug change)
• 125–250 mg every 4 weeks (total withdrawal)

32. Thank you