Updated management on epilepsy

1. EPILEPSY:UPDATED
MANAGEMENT
DR.MOHAMMAD ULLAH
RESIDENT ,PHASE-B
NEUROLOGY,DMCH

2. INTRODUCTION
• Epilepsy is a chronic noncommunicable disease of the brain that
affects people of all ages,genders and races.
• In developed countries, 0.8% people develop epilepsy during
their lifetime. The risk is higher in resource-poor countries.
• More than 50 millions people worldwide have epilepsy, making it
one of the most common neurological diseases globally.
• Nearly 80% of people with epilepsy live in low- and middle-
income countries.

3. INTRODUCTION
• It is estimated that 70% of people living with epilepsy
could live seizure- free if properly diagnosed and treated.
• About three quarters of people with epilepsy living in
low- and middle- income countries do not get/seek the
treatment they need.
• In many parts of the world, people with epilepsy and
their families suffer from stigma and discrimination.

4. Historical Background
•Epilepsy derived from a Greek term Epilambanei -
to posses, to take hold of, to grab or to seize.
•Hippocrates 400 BC: ‘This is not a sacred disease rather
disorder of brain’ . He stated it is an incurable chronic
illness.
•Ibn Sina 980 AC: described epilepsy as a brain
disease

5. Historical Background
• 1873 H. Jackson: Neurologist of London,
described relationship of electrochemical
discharge of brain and seizure.
• 1920 H. Berger: German Psychiatrist developed
EEG to measure brain waves and its application
in the field of epilepsy.

6. Historical Background
• 1909: Formation of International league against epilepsy (ILAE).
• 1912: Use Phenobarbitone as AED.
• 1938: Use Phenytoin as AED.
• 1950-1970: Developed many AED.
• 1981: ILAE classified epilepsy.
• 1997: ILAE, WHO jointly established Global campaign against
epilepsy

7. SEIZURE
• The word seizure derived from the Latin word –
sacire which means to take possession of.
• Seizure :Transient occurrence of sign and /or
symptom due to abnormal excessive or
synchronous neuronal activity in brain.
• Convulsion: Motor manifestation of seizure.

8. Definition of epilepsy
•According to ILAE(2014):
1. After at least 2 unprovoked seizures >24 hours apart; or
2. After one unprovoked (or reflex) seizure when there is >60%
chance of seizure recurrence(similar to that after two unprovoked
seizures) over next 10 years; or
3. When an epilepsy syndrome can be identified.

9. Salient features of epilepsy:
• Attacks of neurological dysfunction, which are:-
• Recurrent and transient
• Occur any time and anywhere e.g. during sleep
• Commonly becomes unconscious but eyes remain open
• Usually has motor features
• Motor features last shorter period than that of unconsciousness
• Frequently there is injury and incontinence
• There is post-ictal features(Headache,confusion,unconsciousness).

11. When to start antiseizure drug therapy ?
• First time unprovoked seizure: The term unprovoked
seizure refers to a seizure of unknown etiology as well as
one that occurs in relation to preexisting brain lesion or
progressive nervous system disorder. (Provoked seizure:
acute conditions such as toxic or metabolic disturbance,
head trauma or acute stroke)
• The decision of whether or not to start antiseizure drug
therapy at the time of first unprovoked seizure in an adult
should be individualized.

12. CONTINUED
The main factors to consider in making the decision are:
1.The risk for recurrence.
2.The approximate benefit of early vs deffered treatment.
3.The side effect profile vs patient benefit.
4.Patient values and preference with regard to the social
consequencesof a recurrent seizure(driving and
employment.

13. Risk of seizure recurrence
• Symptomatic cause , as identified by clinical history or
neuroimaging(eg , brain tumor, brain malformation, head
injury with LOC etc ).
• Abnormal neurological examination, including MR.
• Epileptiform discharge on EEG.
• First seizure that occurs in sleep.

14. Second unprovoked seizure
•Patients presenting a second unprovoked
seizure have 73% chances of recurrence in
next 4 years.
•So antiseizure drug should be started.

15. Selection of antiseizure drugs
• There is no single AED that is ideal for all patients.
• About 50% patients become seizure free on first AED on
low to moderate dose.
• Second generation AEDs are no more effective than
older argents, but some offer fewer drug interactions and
tolerability.

16. Selection of antiseizure drugs
• The standard vs New Antiepileptic Drug(SANAD)
trial found Lamotrigine was slightly better than
Carbamazepine due to fewer patients discontinuing
treatment because of adverse effect in focal onset
seizure

17. Selection of antiseizure drugs
• Others head to head trail have not shown substantial
difference between controlled released Carbamazepine
and others second generation AEDs,;that is
Levetiracetam, Zonasimide and Lacosamade.
• A separate arm of SANAD study found Valproic acid to
be more effective than Lamotrigine and Topiramate for
generalised and unclassified epilepsies.

18. • The superiority of Valproic acid was more pronounce in
the subgroups of genetic generalized epilepsies(CAE,
JAE, JME, GTCS)
• However , current guidelines recommended avoiding
Valproic acid in women of childbearing age whenever
possible due to high risk of anatomical teratogenesis
eg. neural tube defect, and behavioral teratogenesis eg.
cognitive impairment and Autism.

20. Pharmacogenomics
• There has been major progress in identifying genomic predictors
of idiosyncratic AED reactions. In Han Chinese and other South
Asian populations, HLA-B*1502 is strongly associated with the
risk of carbamazepine-induced Steven-Johnson syndrome and
toxic epidermal necrolysis. HLA-B*1502 screening is highly
recommended in high risk individuals before commencing
carbamazepine (eg, Chinese, Thai, Indian, Malay, Filipino and
Indonesian populations).

21. Pharmacogenomics
HLA-A*3101 is also associated with an increased risk of
carbamazepine-induced cutaneous reactions; including
maculopapular exanthema, Steven-Johnsons syndrome,
toxic epidermal necrolysis and drug reaction with
eosinophilia and systemic symptoms .As opposed to HLA-
B*1502;HLA-A*3101 is common in most ethnic groups,
including European and Asian populations.

22. Drug resistant epilepsy
• According to ILAE : Failure of adequate trail of two
tolerated, appropriately chosen and used AED
schedule(whether monotherapy or in combinations) to
achieve sustained seizure- freedom.
• Overall, fewer than15% of patients who continue to have
seizures after two appropriate AEDs trails become seizure-
free with subsequent AEDs.

23. Drug resistant epilepsy
•As soon as a patient has failed two AEDs, the
feasibility of epilepsy surgery should be
considered.
•For patients who are not surgical candidates,
alternative AEDs or VNS may tried .

24. Epileptic surgery
• Five main types of surgical approach:
1.Focal resection for hippoccampal sclerosis and other
lesions in mesial temporal lobe.
2.Focal resections dor others lesion.
3.Non lesional focal resections(lesions found on functional
method).

25. Epileptic surgery
4.Hemispherectomy,hemispherotomy and other
large multilobar resections.
5.Functional procedures-corpus callosotomy ,
focal ablation ,vagus nerve stimulation.

26. Special situations : Pregnancy
• Seizure frequency during pregnancy remain unchanged
50%, decreased 20% and increased 30% .
• Seizures particularly convulsive seizures, are believed to be
harmful to foetus.
• The overall incidence of foetal abnormalities in born to
mothrs with epilepsy is 5-6% compared to 2-3% in healthy
women.

27. Pregnancy
• While no antiseizure drug has been shown to be safe in
pregnancy, the evidence linking Valproic acid is strongly
associated increased risk of adverse fetal outcome.
• In Pregnancy marked effects on pharmacokinetics of
antiepileptic drugs particularly in last trimester.
• The greatest problems seems to arise with Lamotrigine,
with level falling in some patients by 60%

28. Pregnancy
• Carbamazepine levels decline less than others AEDs and this is
another reasons for choosing this drug during pregnancy
• Serum level fall 40% of phenytoin ,phenobarbital, levetiracetam,
oxcarbazepine .So dose SHOULD be adjudged.
• Screening for foetal malformations with high quality USG
should be taken at 10,18 and 24 weeks
• Measurements of alpha fetoprotein and amniocentesis may be
done

29. Hormonal contraception
• Some AEDs induce hepatic enzymes that metabolize synthetic
hormones, increasing the risk of contraceptive failure. This is
most marked with carbamazepine, phenytoin and barbiturates,
but clinically significant effects can be seen with lamotrigine
and topiramate. If the AED cannot be changed, this can be
overcome by giving higher-dose preparations of the oral
contraceptive. Sodium valproate and Levetiracetam have no
interaction with hormonal contraception.
• Combined hormonal contraception increase metabolism of
Lamotrigine. So dose should be adjusted.

30. Hepatic disease
• Some antiseizure drugs are associated with hepatotoxicity
and should be avoided in pre-existing liver disease. These
include valproate and felbamate and to a lesser extent
phenytoin, Carbamazepine.
• Levetiracetam,gabapenrin,pregabalin and vigabatrin don’t
undergo hepatic metabolism and less problematic for use
in patients with chronic liver disease.

31. Renal disease
• Renal failure is associated with decrease protein binding of
phenytoin and valproate.
• The clearance of gabapentin ,pregabalin , levetiracetam ,vigabatrin
will be reduced in severe renal failure ,necessitating dose
adjustment.
• Topiramate and zonisamide are associated with nephrolithiasis and
should be avoided in patients with H/Oor prone to this condition.

32. Diabetes
•Because of its association with weight gain , insulin
resistance, and POCS, use of valproate in individual
with diabetes and obesity should be reconsidered.
•Carbamazepine, gabapentin and pregabalin are also,
but less frequently, associated with weight gain.

33. Cardiovascular disease
• There is potential drug interactions between enzymes
inducing antiseizure drugs and statin, CCB, warfarin etc.
• Carbamazepine has been associated with heart block and
others bradyarrythmia in susceptible individuals.
• Non enzyme inducing antiseizure drugs levetiracetam or
Lamotrigine may be used in that case.

34. PROGNOSIS
• Generalized seizures are more readily controlled
than partial seizures.
• Childhood onset epilepsy (particularly classical
absence seizures) carries the best prognosis for
successful drug withdrawal.
• The presence of a structural lesion makes
complete control of epilepsy less likely.

35. PROGNOSIS
• Epilepsy outcome: After 20 years
• 50% seizure-free, without drugs, for last 5 years
• 20% seizure-free, continue to take medication, for
last 5 years
• 30% seizures continue in spite of adequate dose of
AEDs