2. Epilepsy
• International League Against Epilepsy (ILAE)
defined epilepsy as “a disorder of the brain
characterized by an enduring predisposition to
generate epileptic seizures, and by the
neurobiologic, cognitive, psychological, and
social consequences of this condition”.
• It is characterized by repetitive, unprovoked
epileptic seizures .

3. • Seizure- a paroxysmal abnormal discharge at
high frequency from neurons in cerebral
cortex.
• Convulsions- involuntary, violent, spasmodic
contractions of skeletal muscles.

4. Etiology
1.Structural etiologies
Structural etiologies could be primitive (for instance
congenital malformations), or acquired (from a stroke,
head trauma, infection, hypoxic-ischemic encephalopathy)
2.Genetic etiologies
The syndrome of Benign Familial Neonatal Epilepsy (KCNQ2
or KCNQ3 mutations)
The Dravet syndrome (SCN1A mutations)
3.Infectious etiologies
infectious etiologies include neurocysticercosis,
tuberculosis, HIV, cerebral malaria, subacute sclerosing
panencephalitis, cerebral toxoplasmosis, and congenital
infections such as Zika virus and cytomegalovirus

5. 4.Metabolic etiologies
porphyria, uremia, aminoacidopathies,
or pyridoxine-dependent seizures
5.Immune etiologies
anti-NMDA (N-methyl-D-aspartate) receptor
encephalitis and anti-LGI1 encephalitis

6. Primary
Types of
s
(focal)

7. Ideal Properties for an Antiepileptic Drug :-
• Broad spectrum activity against all seizure types
• High Efficacy
• Good tolerability
• No risk of allergic or idiosyncratic reactions
(including teratogenicity)
• Low interaction potential
• Favorable pharmacokinetics ( linear kinetics, half
life compatible with once or twice daily dosage

8. Ideal Properties for an Antiepileptic Drug :-
• No tolerance to antiepileptic effects
• No withdrawal seizures
• No need for intensive laboratory
monitoring
• Availability of convenient formulations
(pediatric and parenteral )
• Low cost

9. “Older” Anti-Epileptic drugs
Phenobarbital 1912
Phenytoin 1938
Ethosuximide 1960
Carbamazepine 1974
Valproate 1978

10. • Despite a broad range of AEDs currently
available, about 30 % of patients with
epilepsy are uncontrolled with available
treatment and a further 25 % suffer from
manifestation of drug toxicity.

11. Newer Antiepileptic drugs
• Equally effective as older AEDs
• Better tolerated than older AEDs
• Most have fewer interactions with other
medications than older AEDs
• Expensive compared to older drugs

12. Newer Antiepileptic drugs
• Lamotrigine 1994
• Topiramate 1996
• Levetiracetam 1999
• Oxcarbazepine 2000
• Zonisamide 2000
• Lacosamide 2008
• Rufinamide
• Vigabatrin

13. • NEWER AGENTS DIFFER FROM OLDER
DRUGS BY
Relatively lack of drug-drug interaction
(simple pharmacokinetic profile) Improved
tolerability
HOWEVER THEY ARE
Costly with limited clinical experience

26. LAMOTRIGINE
MOA – Lamotrigine is another broad spectrum AED
which acts by blocking the voltage dependent sodium
channels and thus blocks the release of glutamate
through stabilization of presynaptic membrane
Primary Indications –
- It is an effective adjunct to refractory partial and
generalized epilepsy
-It is particularly useful in typical and atypical
absence seizure in Lennox Gastaut syndrome and in
children with myoclonic-astatic epilepsy

27. LAMOTRIGINE
Usual dosages –
Lamotrgine is started at 1-2 mg/kg followed by slow
hiking biweekly to 3-8 mg/kg/day
ADR - somnolence, sleep disturbances, dizziness,
diplopia, ataxia, nausea and vomiting, skin rash and
rarely Steven Johnson syndrome and toxic epidermal
necrolysis

28. TOPIRAMATE
MOA Topiramate is a sulphamate substituted
monosaccharide, a broad spectrum AED acting on
voltage dependent sodium channels, enhancement of
GABA, decrease in glutamate and inhibition of
carbonic anhydrase.
Primary Indications –
- Topiramate is a useful adjunct in refractory partial or
generalized epilepsy

29. TOPIRAMATE
Usual dosages –
Pediatric dosage is 1-3 mg/kg/day (divided
twice daily) hiked bi-weekly to 3-8 mg/kg/day
ADRs dizziness, mental slowing, somnolence,
ataxia, impaired concentration and confusion ,
metabolic acidosis, nephrolithiasis, decreased
sweating and resultant hyperthermia
SAFE IN PREGNANCY.

30. LEVETIRACETAM
MOA – It inhibits high-voltage-activated calcium
channels and reduces calcium release from
intraneuronal stores.It also binds to a specific target
in the brain, the synaptic vesicle protein 2A (SV2A),
an integral membrane glycoprotein, which is involved
in the control of vesicle fusion and exocytosis.
Primary Indications –
-partial onset seizures and in primary generalized
tonic-clonic seizures.
-Intravenous preparation has recently shown efficacy
in neonatal seizures and status epilepticus .

31. LEVETIRACETAM
Usual dosages
Pediatric dose start from 10 mg/kg/day (divided tweice
daily) to be hiked by 10-20 mg/kg every two weeks to a
maximum dose of 40-60 mg/kg/day.
ADR headache, anorexia, and somnolence.
behavioural side effects like aggression, emotional
lability, oppositional behavior, and psychosis in
children
LEVETIRACETAM IS AN AED THAT IS MOST FREE
FROM ADRs. MOST OF ADRs ARE DOSE DEPENDENT
AND REVERSIBLE.

32. OXCARBAZAPINE
MOA – Oxcarbazepine is the 10-keto analogue of
carbamazepine which blocks high frequency voltage
dependent repetitive firing of sodium channels.
Primary Indications –
- first line drug for partial and secondarily
generalized seizures
- monotherapy for children with partial-onset
seizures and focal epilepsy.

33. OXCARBAZAPINE
Usual dosages –
Oxcarbazepine can be started with initial dose of 5 to
8 mg/kg/day in 2 divided doses increasing by 5 to 8
mg/kg after 5 to 7 days up to a maximum of 30 mg/kg.
ADR – hyponatremia, headache, dizziness, and
ataxia

34. VIGABATRIN
MOA – Vigabatrin is a structural analogue of
gammaaminobutyric acid (GABA), which irreversibly
inhibits the enzyme GABA transaminase
Primary Indications –
- infantile spasms in children with tuberous sclerosis
VIGABATRIN
Usual dosages –
Pediatric doses range from 50 mg/kg/day to 150 mg/
kg/day . The dose may be increased by 30-40 mg/
kg/day every 4-5 days till the maximum dose is
reached
ADR –
bilateral concentric peripheral visual field constriction,

35. ZONISAMIDE
MOA Zonisamide is a sulphonamide derivative, a
broad spectrum AED that acts through : facilitation
of dopaminergic and serotoninergic
neurotransmission through the blockade of T-type
calcium channels, prolongation of sodium channel
inactivation and as a weak inhibitor of carbonic
anhydrase.
Primary Indications –
-progressive myoclonic epilepsy syndromes such as
Unverricht-Lundborg disease and Lafora body
disease
-Useful as a second-line agent for infantile spasms,
Lennox-Gastaut syndrome, and juvenile myoclonic
epilepsy

36. ZONISAMIDE
Usual dosages –
The usual starting dose is 2–4 mg/kg/day, and the
maintenance dose is 4–8 mg/kg/day;divided once or
twice daily
ADR –Somnolence, poor appetite, weight loss,
headache, pruritus, and skin rash, kidney stones,
oligohydrosis and hyperthermia

37. LACOSAMIDE
MOA – Lacosamide is a functionalized amino acid
that selectively enhances slow inactivation of
voltage-gated sodium channels, increasing the
proportion of sodium channels unavailable for
depolarization.
Primary Indications –
- Lacosamide is used in children with refractory
epilepsy

38. LACOSAMIDE
Usual dosages –
Starting dose – 1-2 mg/Kg/day
Maintenance – 6-9 mg/Kg/day
ADR – irritability, oral tics, and prolonged crying

39. RUFINAMIDE
MOA prolonging the inactive state of sodium
channels and therefore limiting excessive
firing of sodium-dependent action potentials.
Primary Indications –
- children (>4 yrs) is with refractory Lennox
Gastaut syndrome.
RUFINAMIDE
ADR - headache, dizziness, fatigue,
somnolence, and nausea.

40. SURGERY IN RESISTANT EPILEPSY
The surgical options include resective surgery and palliative
surgery.
Few of the resective surgical procedures include temporal
lobe resections, extra temporal lobe resections and
hemispherectomy. Palliative epilepsy surgical procedures
include corpus callasotomy and Multiple Subpial
Transections (MST). Minimally invasive procedures include
neurostimulation procedures including Deep brain
stimulation, Vagal Nerve stimulation and Responsive
neurostimulation.
Other minimally invasive surgical interventions include
Stereotactic Radiosurgery and Stereotactic Laser
Ablation (SLA).

41. NEW FORMULATIONS
INTRANASAL
- DIAZEPAM
- MIDAZOLAM
Absorption from nasal mucosa within 2 – 5
minutes
Rapid penetration into the central nervous
system
Cost effective and feasible to administer to
adults as well

42. Clinical Advices for the Use of Drugs in the
Treatment of Epilepsy.
• General features:
• It is essential to have an accurate and
comprehensive diagnosis.
• Must treat underlying causes e.g. hypoglycemia ,
infection and tumor
• Diagnosis: Adequate description of symptoms both
from patient and eye witness.
• EEG( supportive)

43. Clinical Advices ( Cont. )
• EEG should not be an indication for confirming
epilepsy nor to stop treatment for seizure free
patients.
• 20% of pts admitted after positive recording with
EEG did not have the disorder

44. Common Causes of Failure of Antiepileptics
1. Improper diagnosis of the type of seizures
2. Incorrrect choice of drug
3. Inadequate or excessive dosage
4. Poor compliance

45. REFERENCES
INDIAN JOURNAL OF PRACTICAL PEDIATRICS
INDIAN PEDIATRICS VOLUME 50,2013