Basics of Epilepsy for Esproute

1. Basics Of
Epilepsy

2. Definition of Epilepsy
A transient, sudden, abnormal and excessive
neuronal activity in the brain which may alter the
behavior of the person is a Seizure
Recurrent unprovoked seizures is known as
Epilepsy
ILAE 2005
Epilepsia. 2014; 55: 475-482

3. Current Definition of Epilepsy
Task force proposed that epilepsy be considered to be a disease of
the brain defined by any of the following conditions:
1.At least two unprovoked (or reflex) seizures occurring more than
24 hours apart;
2.One unprovoked (or reflex) seizure and a probability for further
seizures similar to general recurrence risk (at least 60%) after
two unprovoked seizures, occurring over next 10 years;
3.Diagnosis of epilepsy syndrome
ILAE 2014
Epilepsia. 2014; 55: 475-482

4. Epidemiology
• Epilepsy is one of the most common neurological disorders affecting at
least 50 million people worldwide and carrying a point prevalence of 1%,
and every year around 50-70 patients per 100,000 of population is added,
mostly affecting children and the elderly.
• It is estimated that there are more than 10 million persons with epilepsy in
India. The prevalence is higher in the rural (1.9%) compared to urban
population (0.6%)
• Most patients can be managed with anti-epileptic drugs (AEDs), however
10-40% of patients would still continue to have seizures despite optimal
treatment.
Neurosciences 2011; 16 (1): 3-9
Ann Indian Acad Neurol. 2014; 17: S3-S11

5. Mechanism During a Seizure?
Seizures happens when there is excessive excitatory activity &
decreased inhibitory activity
Excitatory
(increase activity)
factors
Inhibitory
(decreased activity)
factors

6. Mechanism During
Epilepsy
a) Increase release of
glutamate
b) Increase stimulation of
NMDA receptors
c) Increased entry of Na+ &
Ca 2+
d) Decrease GABA and
GABA receptor activity

7. Classification of Seizures
ILAE Revised Terminology for Organization of Seizures and Epilepsies 2011 - 2013

8. Proportion of Incidence cases
according to seizure type
Most common
type of epilepsy
is the Complex
Partial followed
by GTC epilepsy
36
147
3
6
23
8 3
0 0
0
Complex partial
Simple partial
Partial unclassifies
Myoclonic
Absence
Generalized tonic
clonic
Other generalized
Unclassified

9. 61%
15%
6%
6%
3%
8%
Idiopathic or Cryptogenic Vascular Alcohol Tumor Posttraumatic Others
Etiology (causes)
Symptomatic: 22-53%
Idiopathic (genetic) & Cryptogenic: approx 60%

10. Pharmacological Treatment of Epilepsy
Anti-epileptic Drugs (AEDs) are the Mainstay of Treatment
Conventional AEDs 2° AEDs 3° AEDS
Carbamazepine Oxcarbazepine Lacosamide
Valproate Lamotrigine Eslicarbazepine
Phenobarbital Levetiracetam Brivaracetam
Phenytoin Topiramate Retigabine
Primidone Tiagabine Ganaxolone
Ethosuximide Zonisamide Perampanel
Vigabatrin
Gabapentine
Rufinamide

11. Mechanism of action Drugs
Blockers of Na⁺ channels
Phenytoin, Carbamazepine, Valproate,
Oxcarbazepine, Lamotrigine, Topiramate
GABA receptor enhancers Phenobarbital, Benzodiazepines
Increased GABA production & release Valproate
Decrease glutamate release Lamotrigine, Topiramate
Blockers of Ca²⁺ channels
Lamotrigine, Oxcarbazepine,
Carbamazepine, Phenobarbital,
Phenytoin, Valproate
Blocker of special type of
Ca²⁺ channel (T-calcium channel)
Ethosuximide, Valproate
Binding to protein SV2A thereby
inhibiting neurotransmitter release
Levetiracetam

12. Refractory Epilepsy
• The International League Against Epilepsy proposed a definition of drug resistant
epilepsy as failure of adequate trials of two tolerated, appropriately chosen and
used AED schedules (whether as monotherapies or in combination) to achieve
sustained seizure freedom
• The chances of achieving seizure control with the third drug once the patient has
failed 2 AEDs for correct seizure type in an adequate dose is not more than 5-
10%.
• So, such patients, although they still have up to a 10% chance of seizure control,
can be practically considered as a drug failure and may be considered for other
treatment options.
Neurosciences 2011; 16 (1): 3-9
Seizure. 2000; 9:464-468

13. What is Status Epilepticus?
• Seizure lasting beyond 15-30 mins is termed status epilepticus (Sneurcrit
Care. 2012; E)
• GTC lasting for more than 5 mins is termed SE
• Status epilepticus is an emergency and must be treated promptly
• It can result in major complications and even death
Neurocrit Care. 2012: DOI 10.1007/s12028-012-9695-

14. Causes of Status Epilepticus
according to age
Among adults, majority of cases
of SE, that occurred in
previously non-epileptic patients
are due to acute brain insult.
In patient with previous history
of epilepsy, most cases are due
to AED withdrawal.

15. Treatment of Status Epilepticus
Neurocrit care 2012; 17: 3-23
Neurology Asia 2013; 18: 67-71

16. Effects of Epilepsy on Pregnancy
• GTC seizures increase risk of hypoxia, asphyxia and acidosis
as well as injury from blunt trauma
• Maternal seizures during gestation, increases the risk of
developmental delay
• Generalized convulsions can lead to abortions or stillbirths
• Status epilepticus can carry a high mortality rate for both
mother and foetus
• GTC seizures during labour -profound effect on fetal heart rate
• Partial seizures – no such effect seen
• Complex partial seizures- foetal bradycardia and also
miscarriages

17. Preferred Regimens in Pregnancy
Always monotherapy is preferred over Polytherapy
Polytherapy is proven to be associated with higher rates on congenital
malformation
Results of a EURAP registry on pregnancy and epilepsy have shown that
compared with lamotrigine monotherapy at doses less than 300 mg per day,
risks of malformation were significantly higher with valproic acid and
phenobarbital at all doses, and with carbamazepine at doses greater than
400 mg per day
Valproate should be strictly avoided in Women with Epilepsy (WWE)
The preferred drugs for monotherapy in women with epilepsy in child-
bearing age or during pregnancy would be:
LAMOTRIGINE OXCARBAZEPINE LEVETIRACETAM

18. Epilepsy In Paediatrics
Worldwide it is estimated that 10.5 million children under 15 years
have active epilepsy. This represents about 25% of the global epilepsy
population.
Causes of epilepsy in children may be
• Symptomatic- prenatal brain injury/ trauma
• High fever
• Lack of oxygen to the brain
• Brain infection
• Cryptogenic or idiopathic
Lancet. 2006; 367(9509):499-524.

19. Drugs Preferred
Childhood Absence Seizures Ethosuximide, Valproate, Lamotrigine
Lennox Gastaut Syndrome
Valproate, benzodiazepines- 1st line
Lamotrigine, Levetiracetam, Topiramate
Infantile Spasms
ACTH-Prednisolone, Vigabatrin- 1st line
Pyridoxine, Valproate, ketogenic diet
Neonatal Seizures Phenobarbital, Valproate, Lorazepam
Febrile Seizures
Rectal Diazepam- DOC
Valproate- first line preventive treatment
Complex Partial Seizures Carbamazepine, Oxcarbazepine, Valproate
European Expert Opinion (2007): Treatment of pediatric epilepsy
Epileptic Discord Vol. 9, No.4, December 2007

20. Epilepsy In Elderly
• Old age is the most common time to
develop seizures.
• Most new seizures in elderly patients
are partial in onset with or without
secondary generalization
• Causes are mainly cerebrovascular
disease- stroke, brain tumor or brain
injury.
• Drug-induced seizures are most likely
to be associated with use of more
than one drug, high doses, parenteral
administration, and coexisting

21. Lamotrigine can be used as first line monotherapy since it is
better tolerated and has fewer side effects than carbamazepine
and phenytoin.
Gabapentin is well-tolerated as adjunctive treatment for seizures
of partial onset.
Oxcarbazepine is another reasonable choice
Levetiracetam has got evidence of its use in elderly population.
Also, less likely to have drug interactions & is well tolerated

22. Epilepsy
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