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1. Definition of terms
5-10% of the general
population has had a seizure
during their lifetime.
Incidence of epilepsy is 0.3
–0.5 % worldwide and the
prevalence 5-10 per 1000
According ILAE 1981
(i) partial seizures
a) simple partial – motor
b) complex partial
c) partial seizures
(ii) generalized seizures
a) grand mall (tonic
b) clonic) – 10% of all
c) absence (petit mal) –
15-20 % of childhood
- neonatal seizures
- infantile spasms
3 points to note about
- status epileptics
a) Juvenile myoclonic
They may also have tonic
clonic seizures. 1/3 have petit
mal also .It comes in early
b) Lennox Gestaut syndrome
Occurs in children,
characterized by multiple
seizures - tonic clonic, atonic,
- EEG shows slow < 3 Hz
spike and wave discharge
and other abnormalities .
- Impaired cognitive
function in most cases
- Associated with CNS
disease or dysfunction
c) Mesial temporal lobe
epilepsy syndrome (MTLE)
Has typical clinical, EEG
and pathologic features. It is
the most common syndrome
associated with complex
partial seizures. There’s
hippocampal sclerosis, it is
resistant to drugs and is
usually cured by surgery.
d)West’s syndrome – A
clinical triad of infantile
spasms, arrest of
and hypsarrhythmia on EEG.
Causes can be prenatal,
perinatal or post natal. Upto
40% no cause. Onset usually
before 1 year, peaks at 3-7
months. Prognosis very poor
for those with infantile
spasms. Drug of first choice
is vigabatrin. Others are
valproate, clonazepam and
zonisamide. ACTH and
corticosteroids are used when
others fail. Focal lesions
respond to surgery.
syndrome. Presents as an
acquired aphasia with
seizures. Several seizure
types occur including GTC,
partial and myoclonic.
word deafness despite normal
hearing. EEG shows spike
activity over temporo-central
regions. Occurs at 3-9 years.
Responds to standard drugs.
Language recovery variable.
Two types of epilepsy
- acute CNS infection
- metabolic disturbances decreased ca, mg, glucose
- drugs withdrawal
- developmental diseases
- genetic abnormalities
IN INFANTS/CHILDREN (1/12 – 12
IN ADOLESCENTS (12-18YRS)
Illicit drug use
YOUNG ADULTS (18-35 YRS)
Illicit drugs use
Metabolic diseases – anemia,
liver failure, electrolyte
- Alzheimers disease, other
DRUGS + OTHER SUBSTANCES
- Antibiotics – β-lactams, quinolones,
INH, acyclovir, gancyclovir
- Anesthetics /analgesics –
meperidine, tramadol, Local
- Immunomodulatory drugs Cyclosporin, tacrolimus, interferons
- Psychotropcis - Antidepressants,
- Radiocontrast agents
- Sedative/hyphotics withdrawal Alcohol, benzodiazepines,
- Drugs of abuse
- Amphetamine, cocaine,
1. Inhibition of sodium Channels Phenytoin, carbamazepine
topiramate, zonisamide, felbamate
2. Inhibition of voltage gated calcium
Channels – phenytoin,
3. Decrease of glutamate release –
lamotrigin, topiramate – act on
AMPA receptors, felbamate – act
on NMDA receptors
4. Potentiation of GABA receptor
function - benzodiazepines,
barbiturates, topiramate , they
5. Increase in availability of GABA valproate, gabapentine inhibits
GABA transaminase, tiagabine
inhibits GABA reuptake.
1. Hydantoins – Phenytoin,
methotoin, ethotoin, phenacemide
2. Imminostilbenes – carbamazepine,
3. Barbiturates - phenobarbital,
4. Benzodiazepines - diazepam,
5. Carboxylic acids(fatty acids)valproic acid, Sodium valproate
6. Succinamides –ethosuximide,
7. Oxazolidinediones -trimethadione, dimethadione,
8. Steroids - ACTH, Prednisone
9. Amino acids – 5-0H tryptophan
10. Miscellaneous – vigabatrin,
TREATMENT OF EPILEPSY
1. Carbamazepine (Tegrettol,
zheptol)- 400-1600mg/d, in 2-3
First line or adjunctive therapy
in partial and generalized seizures
(except petit mal and myoclonus),
Lennox Gestaut syndrome,
childhood epilepsy syndromes.
Therapeutic levels 20-50 μmol/l
2. Clobazepam - 10-30mg/d, in 1-2
- Adjunctive therapy for partial
and generalized seizures.
- Also for intermittent therapy,
on/off prophylactic therapy, non
convulsive status epilepticus,
- Excellent second line for some
3. Clonazepam(rivotril) - initially
0.25mg, maintainance 0.5- 4mg
per day in 1-2 doses, or 0.1- 0.2
mg /kg in adults, children 0.01 –
Therapeutic levels, 5-70ng/ml
Adjunctive therapy in partial
and generalised seizures, including
absence and myoclonus, Lennox
Gestaut syndrome, status epilepticus.
4. Lamotrigine (lamictal) - initially
12.5-25mg/d, maintenance 100200mg/d.
Monotherapy or comedication
with valproate, Comedication with
enzyme inducers 200 – 400mg/d
Adjunctive or mono therapy in
partial and generalized epilepsy,
Lennox Gestaut syndrome.
5. Phenytoin(dilantin) - initially
300mg, maintainance 100-300mg/d in
adults, children 5mg/kg,
maintainance 3-8mg /kg. Adjustment
guided by serum levels. Therapeutic
levels – 40-80μmol/l (10-20μg/ml)
Given orally or I.V in 1-2 doses.
First line or adjunctive therapy for
partial and generalized seizures,
excluding absence and myoclonus,
Lennox Gestaut syndrome (LGS),
childhood epilepsy syndromes.
Use limited by adverse effects.
Valproate (depakene, depakote,
epilim) – initially 400 - 600mg/d in
adults in 2-3 divided doses,
maintenance 500-2500mg/d in adults.
20mg/kg/d in children < 20kg,
40mg/kg/d in children >20/kg
Therapentic levels - 300-600
Drug of choice in primarily
generalised epilepsy and useful in
many others – myoclonus,
Felbamate (felbatol) - initially
1200mg/d in adults, in 3-4 divided
doses, maintenance 1200-
3600mg/d. Children - initially
15mg/kg/d, maintenance 45-80
Adjunctive therapy in refractory
partial and secondarily generalized
seizures, Lennox Gestaut
syndrome, highly effective in severe
resistant epilepsy but use limited
by rare but severe hepatic and
Therapeutic levels 200460μmol/l.
Gabapentin (neurontin) - 3001800mg/d
Adjunctive therapy for refractory
partial and secondarily generalised
seizures. Well tolerated.
Levetiracetam (keppra) – 10003000mg/d
Adjuctive therapy in partial ±
secondarily generalised seizures
10. Oxcarbazepine (trileptal) initially 600mg/d in 2 divided doses.
Maintenance 900 – 2400 mg/d.
Structure similar to carbamazepine
but better tolerated with fewer
Adjunct or monotherapy in partial
and secondarily generalised seizures.
11. Primidone (mysolin) - initially
125mg/d in 1-2 divided doses
Maintenance 500-1500 mg/d.
Children < 2yrs – 250 - 500mg, 2-5
yrs 500-700mg, 6 - 9 yrs 7501000mg.
Adjunctive therapy in partial and
secondarily generalised seizures,
absence, myoclonus, L.G.S. Active
metabolite is phenobarbital.
12. Tiagabine (gabatril) - initially
15mg/d in 2-3 divided doses
Maintenance 30 – 45 mg/d ( and in
combination with enzyme inducers)
15-30 mg/d combined with
Adjunct therapy for partial and
secondarily generalized seizures,
especially refractory cases.
13. Vigabatrin - initially 1000mg /d
in 2 divided doses, maintenance 10003000mg/d, children 40mg/kg /d
Adjunct therapy in partial and
secondarily generalised seizures. Use
limited by neuropsychiatric side
effects and visual field constriction.
14. Topiramate (topamax) –
Initially 25-50 mg/d in 2 doses,
Adjuct therapy in partial and
secondarily generalised seizures, LGS
and grand mal seizures.
15. Ethosuximide (zarontin) –
initially 250mg in 2-3 divided doses,
children 10-15 mg/kg,
Maintenance – 750 – 2000mg in
20-40mg/kg /d in
Therapeutic levels 300-700μmol/l
16. Piracetam- initially 7.2 g/d in 23 divided doses, maintenance upto
For some patients with refractory
17. 5-OH Tryptophan
For intention myoclonus
18. Steroids - ACTH 25-40 units/d,
upto 240 units/d
prednisone - 15- 60 mg/d
prednisolone 2 mg/kg /d
dexamethasone 0.3 mg/kg/d
For refractory infantile spasms
19. Trimethadone – 900-2400 mg /d
children 30mg /kg/d
Therapeutic level >700μg/ml
Not used because of severe adverse
effects on bone marrow, kidney
and liver. It used to be the drug
choice for petit mal.
20. Lorazepam - 2-3 mg b.d I.V in
normal saline infusion.
For status epilepticus.
21. Clorazepate dipottasium –
45mg/d in 2-3 divided doses,
- initially 7.5 – 22.5 mg
For infantile spasms and
Less potent than clonazepam.
23. Acetazolamide – 250 500mg/d. or 10/kg, max 1000mg
Effective as adjunct therapy in
catamenial epilepsy, started 7-10days
prior to onset of menses and until
24. Phenobarbital ( gardenol, luminal)
– 30 – 180mg/d in 1-2 divided doses
in adults, 3 - 8mg /d in children, 3 – 4
mg/d in neonates PO.
IM or IV 50 – 200mg repeated PRN,
maximum 600mg, in status
Adjunct or first line therapy in partial
or generalized seizures + absence +
myoclonus, status epilepticus, Lennox
Gestaut syndrome, childhood epilepsy
syndromes, febrile seizures, neonatal
Therapeutic levels 40 – 170 μmol/l
MANAGEMENT OF EPILEPSY
1. Early diagnosis and treatment of
seizure disorders with a single
appropriate agent offers the best
prospect of achieving prolonged
seizure free periods with the
lowest risk of toxicity.
2. An attempt should be made to
ascertain the cause, as it may be
correctable. This is most likely in
the very young and those with the
first episode in adulthood.
3. The goal of therapy is to keep
patient seizure free without
interfering with normal function.
Drug adjustments are best assisted
by drug plasma levels.
4. Treatment should be initiated with
a single drug. Adjust doses
upwards for control until maximal
doses are reached or until
toxicities are intolerable.
Large doses are started only if
there is urgency in controlling the
5. First substitute another drug if
maximum doses have not achieved
control before using combinations.
In substituting, gradually reduce
dose of the first drug as you
gradually increase the dose of the
Consider AEDS acting on new
Combinations should be as rational as
6. Once control achieved with
polytherapy, attempt to come back
to monotherapy. Any drug should
be withdrawn only gradually
7. After seizure free period of 3yrs,
you can start withdrawing the
drugs. 70% children, 60% adults
will have seizures controlled and
can do without drugs after this
SIMPLE, COMPLEX PARTIAL
GENERALISED TONIC CLONIC
(a) Carbamazepine and phenytoin are
the most effective single drug
therapy of partial and generalized
tonic clonic epilepsies. The choice
depends on toxicity considerations.
Long term use of Phenytoin causes
untoward cosmetic effects e.g
hirsutism, coarsening of facial
features, gingival hypertrophy, so it
is often avoided in young patients.
Carbamazepine can cause
leukopenia, aplastic anemia or
hepatotoxicity and is therefore not
appropriate for patients predisposed
to these conditions.
(b) Valproic acid is broad spectrum
and is preferred for patients with
mixed seizures especially the epilepsy
syndromes. It is an effective
alternative for partial seizures
especially with secondarily
generalised seizures. It rarely causes
reversible bone marrow suppressions
and hepatotoxicity which may be
fatal. Avoid in those with bone
marrow or liver disease. Risk of the
fatal liver failure is higher in those <
2yrs age, those on multiple drugs
and those with inborn errors of
It is used in infants and young
children only if benefit outweighs
risk. It more commonly causes
tremors and weight gain.
(c) Lamotrigin, gabapentin,
topiramate, tiagabine and
Phenobarbital and primidone are
additional drugs used for partial
seizures with or without secondary
generalization. Lamotrigine is as
effective as the standard drugs and is
used as monotherapy. It may cause
rash in children especially. It is
introduced gradually from small doses
when added to valproate. It inhibits its
metabolism. Gabapentin has no
significant drug interactions making it
a useful add on therapy. Phenobarbital
and primidone cause sedation in
adults, hyperactivity in children and
other subtle cognitive changes.
Primidone causes more toxicity
including nausea, dizziness, ataxia,
somnolence and decreased libido.
Their use should be limited to
situations in which there is no suitable
(d) Oxcarbazepine is as effective as
carbamazepine with less adverse
effects. Benzodiazepines are used for
limited periods as tolerance to them
(e) Clobazepam, tiagabine,
vigabatrin, piracetum, felbamate,
topiramate, levetiracetam are
currently reserve drugs, for resistant
Felbamate rarely causes severe
hepatic and hematological toxicity.
The drug of first choice is
ethosuximide. Valproate is equally
effective. It is of second choice.
Clonazepam is useful especially in
those with myoclonic component.
Ethosuximide rarely causes bone
Valproate is the drug of first choice.
Clonazepam is equally effective and
its effect can be dramatic.
Nitrazepam is also effective.
2-3% of cases become epileptic in
later years. Factors associated with
risk of epilepsy are:
- neurological disease
- developemental delay
- family history of epilepsy
- complicated febrile seizure i.e >
15min, one sided, several in a day
Phenobarbital prophylaxis has been
used before but now only rectal
diazepam during fever is
SEIZURES IN INFANTS AND
Infantile myoclonic spasms with
hypsarrhythmias are refractory to the
usual anti-seizure agents. ACTH and
adrenal corticosteroids are the drugs
of choice. Valproate and clonazepam
may be effective. Valproate is
effective for akinetic myoclonic and
atonic seizures in young children.
It is a medical emergency. Mortality
is 3-35%. Signs become subtle after
30-45 min continuous fits, therefore
monitor with EEG.
1. Benzodiazepines are the drugs of
first choice for initial treatment.
(a) Diazepam 0.2mg/kg. 10-20mg
bolus iv stat then 40mg in 500mls
5% dextrose to run slowly over 6
hours. If it recurs you can give
another bolus. At the same time
start a longer acting drug like
phenytoin IV or orally.
(b) Lorazepam 0.1mg/kg at
2. Phenytoin i.v 15-20 mg/kg at
50mg/min. Additional doses of 510mg/kg can be given if fits
3. Phenobarbital 20mg/kg i.v at 5075mg/min. Additional doses of 510mg/kg can be given if fits
4. Anaesthetic agents - thiopentone
sodium, midazolam, or propofol
for G.A with assisted respiration if
fits still persist.
Should be in I.C.U with EEG
monitor. Attend to acute cardio
TREATMENT OF REFRACTORY
About 1/3 patients of epilepsy are
resistant to a single drug and require
multiple drug therapy. The most
likely are :
- Focal epilepsy related to a structural
- Multiple seizures patients
- Those with developmental delay
In most cases, the initial combination
therapy, combine the first line drugs
i.e carbamazepine, phenytoin,
If these are unsuccessful then addition
of a newer drug like topiramate,
gabapentin is indicated.
In resistant absence seizures,
valproate can be added to
ethosuximide. Potential drug