Dr Sankalp Mohan DM resident neurology

1. Starting and continuing
treatment in epilepsy
Dr Sankalp Mohan
Resident ,Neurology

2. Epilepsy in India
• About 10 million people with epilepsy
(prevalence of about 1%);
• One fifth of Global figures
• 70-80 % can lead normal lives
• Still 50-70% are receiving No treatment or
inadequate treatment

3. DEFINING EPILEPSY
• Epilepsy is a chronic disorder characterized by
recurrent unprovoked seizures
• An epileptic seizure refers to transient occurrence
of signs and/or symptoms due to abnormally
excessive or synchronous neuronal activity in the
brain may be characterized by sensory, motor or
autonomic phenomena with or without loss of
consciousness.
• Seizures occurring in a setting of an acute illness or
medical condition like high fever, hypoglycemia, etc.
are classified as acute symptomatic seizures.

4. CLASSIFICATION
• ILAE classification of epilepsies
• 1. Localization-related epilepsies are characterized
by seizures that have a focal or partial and
generalized epilepsies are characterized by
generalized onset of seizures.
• 2. Idiopathic epilepsies are those that are inherited or
occur without identifiable pathologic cause.
Symptomatic epilepsies are those associated with a
known or suspected brain disease or lesion.
• 3. Epilepsy syndromes are age specific and may begin
during infancy, childhood or adolescence

5. DIAGNOSIS OF EPILEPSY
•
•
•
•
Detailed History and examination
Clues on Clinical ExaminationPresence of an aura
bilateral tonic clonic movements, sudden
jerking, deviation of eyes and head, alteration or
loss of consciousness, and may be associated
with injuries, tongue bite or incontinence
• Postictally the patient may have confusion,
drowsiness, headache or weakness.

6. ILAE CLASSIFICATION OF SIEZURE

8. SYNCOPE VS SIEZURE

9. SIEZURE AND PSEUDOSIEZURE

10. INVESTIGATIONS FOR FIRST SIEZURE
• Baseline blood counts, liver enzymes and renal
functions, serum electrolytes ,-Metabolic screen
Serum Calcium
If diagnosis of siezure in doubt
- Serum Prolactin – within 10 -20 minutes of the
event .sensitivity for GTC -60 %. CPS -46 %
- Can be false positive in syncope
- Serum Creatine kinase- elevated for hours

11. EEG
• An EEG should be performed only to support a
diagnosis of epilepsy in children and young
people
• Normal variants . False positive in syncope
• Within 24 hrs of siezure • Predicts recurrence
• Nature ,Type of Epilepsy, epilepsy syndrome
• sensitivity – variable ,specificity -99 %

13. 3 Hz spike and wave – absence
siezures

14. Generalised polyspike - JME
2 hz spike and wave –
Lennox Gestaut syndrome

15. VIDEO EEG
• Long term Video EEG is time consuming
• Short term video EEG to distinguish from
psychogenic
• Done for 24 hrs with documentation of 3 or
more events
• Carried in centres with expertise

16. Neuroimaging Studies
•
•
•
•
Neuroimaging in epilepsy is useful in:
• Focal seizures
• Seizures suspected to be symptomatic in origin
• Difficult to control seizures (MRI using special
epilepsy protocol).
• Computed tomography scan should be the initial
investigation in epilepsy patients in India

17. • Advanced epilepsy protocols and newer imaging
modalities [functional magnetic resonance
imaging (fMRI), single photon emission CT
(SPECT), positron emission tomography (PET)

18. Invsestigations in suspected siezure

19. TREATMENT OF EPILEPSY
• Treatment should be initiated following the
occurrence of two or more unprovoked seizures
• Risk of developing a second seizure following a
single unprovoked seizure is about 35- 40%
• Therapy started only after diagnosis of epilepsy
is confirmed.
• Treament after first siezure reduces recurrence
by 50 %..15 % discontinue due to ADR

20. WHEN TO TREAT FIRST SIEZURE ?

21. AED treatment may occasionally be deferred
• Infrequent seizures with extremely long / several
years interval
• Rolandic epilepsy in children

22. Principles of AED treatment
• Treatment should be started with a single
conventional antiepileptic drug-monotherapy
• Start with a low dose and gradually increase the
dose
• If ineffective or poorly tolerated, then
monotherapy using another AED , first drug
slowly tapered
• Combination therapy -considered when two
attempts at monotherapy with AEDs have not
resulted in seizure freedom.

23. CHOICE OF ANTIEPILEPTIC DRUG
• Preferable to use a conventional AED Phenytoin
(PHT), Phenobarbitone (PB), Carbamazepine
(CBZ), Oxcarbazepine (OXC)
• partial seizures -CBZ, OXC, PHT, VPA
• GTC S - VPA, PHT,PB, CBZ, OXC
• Absence seizures –VPA
• myoclonic jerks- VPA and benzodiazepines

24. Partial siezures
• Carbemzepine is more effective for complex partial
siezures
Disadvantages – potent enzyme
inducer,autoinduction –accelerates own metabloism
- Newer AED Topiramate and oxcarbezepine –FDA approved as
monotherapy
oxcarbezepine – weaker enzyme induction, no
autoinduction ,more likely to cause hyponatremia

25. GENERALISED SIEZURES
• Valproate is the AED of choice
• Phenytoin .CBZ and oxcarbazepine may be
considered
• Newer AED – Topiramate is the only FDA
approved for GTC s
Lamotrigine and leviteracetam for adjunctive
therapy

26. SUBSTITUTION MONOTHERAPY
• Choice of substitution depends on reason for
failure of orignal AED (ADR or lack of response)
• Usually a period of adjunctive therapy .
• Any AED can be considered .

27. ADJUNCTIVE THERAPY
DEPENDS ON
• Pharmacokinetic interactions –eg enzyme
inducer with hepatically metabolized drug
• Newer drugs advantageous –less interactions
eg Gabapentin,Leviteractam,Pregabalin
• ADR – sodium channel blockers similar ADR
• Different mechanism of actions
• Synergistic effects – Valproate and Lamotrigine,

28. Newer drugs
- All newer drugs FDA approved for adjunctive
therapy for partial siezures
- Lamotrigine,Topiramate and Leviteracteam –
adjunctive for GTC s
- Leviteracetam FDA approved for adjunctive therapy
in Myoclonic siezures .(lamotrigine,Topiramate and
zonisamide may be considered)
- No FDA approved newer drugs for adjunctive
therapy in absence siezures

29. NEWER ANTIEPILEPTICS
• People who have not benefited from treatment
with the conventional AED
• contraindications to the first line drugs
• If The first line drugs interact with other drugs

30. Specific syndromes
• Benign Rolandic Epilepsy – Treament may not
be necessary . Valproate or Carbamzepine
• Lennox Gestaut syndrome –difficult to control
multiple siezure types . Valproate ,Clonazepam
- FDA approved.Lamotrigine ,topiramate used
- Juvenile Myoclonic Epilepsy – Myoclonic,90% GTC s ,30% absence ..Valproate –DOC
.Leviteracetam –Adjunctive therapy

31. COMMONLY USED DRUGS

33. Adverse reactions
• A.) Acute CNS ADR –
- somonolence ,dizziness ,ataxia ,vertigo,cognitive
dysfunction .
- depends on High initial dose ,rapid escaltion
- phenytoin,CBZ (peak dose dependent)
- cognitive dysfunction- Barbiturates ,BZD
,Topiramate
- Hyponatremia ,water intoxication –OXC ,CBZ
B) Acute CVS – Arrythmias ,hypotension –
CBZ,PHT

34. C) IDIOSYNCRATIC REACTIONS –
• -RASH – Highest with Phenytoin -10% ,CBZ8.7%, LTG -6.2%
• -serious idiosyncratic reactions – SJS ,TEN
• Discontinuation of drug always recommended
,switch to BZD ,LEV – low rash potentialid
avoid switching if cross reacitvity

35. • HEPATOTOXICITY• - Acute hepatitis occurs usually within first 3
months
• Coexisting liver disease ,other enzyme inducing
drugs
• Fulminant liver failure can occur
• ALT,AST poor predictors
• Felbamate ,Lamotrigine

36. • Hematotoxicity
• -Macrocytic Anemia – PHT,CBZ,PHB ,VPA
• Aplastic Anemia – CBZ .5-20 cases per million
• Agranulocytosis – CBZ,PHT
• Mild decrease in leucocyte count – CBZ
• Mild decrease in platelet count –VPA .
-Psychiatric- Vigabatrin ,Topiramate, Leviteracetam
- Paradoxical Aggravation of Siezures-Typical
Absence ,Myoclnic aggravated by PHT,OXC,VGB
- CBZ cause myoclonus ,Absence status

37. • Valproate induce pancreatitis – infrequent
• Poor corelation with amylase.Lipase more
helpful
• Changes in Body weightClinically significant weight gain – 62% seen with
valproate
- BONE HEALTH- Higher risk of Fractures
,Osteoporosis .-PHT,CBZ Barbituartes .Enzyme
inducing drugs

38. Teratogenicity
• Major or minor malformations
• Fetal anticonvulsant syndrome – many drugs share
same effects
• Prenatal exposure is associated with 9% risk of
major malformation (2-4 % in normal population)
• Number of AED used ,First trimester
• Valproate – maximum chance
• Risk lower for CBZ,lamotrigine
• Substitute VPA for lamotrigine
• Newer drugs not extensively studied

39. • Prenatal exposure to AED cognitive slowing in
children
• Phenytoin associated with
lymphoma./pseudolymphoma

40. Drug interactions
• (PHT, PB, CBZ and OXC ) induce hepatic
enzymes and enhance the metabolism of lipid
soluble drugs. Reduced efficacy of drugs like
oral contraceptives and oral anticoagulants.
• VPA inhibits hepatic enzymes . slows down the
metabolism of concomitant AEDs causing
toxicity
• Anti-tubercular drugs (like isoniazid and
rifampicin are enzyme inducers and also
hepatotoxic)

41. Frequency of follow-up
• maintain a seizure diary-prescribed medication
is taken as advised and to detect any adverse
effects of AED.
• The first follow-up -within 2-4 weeks of
initiation of treatment
• Subsequent follow-ups at every 3-6 months,

42. Role of AED level monitoring
• Routine monitoring of AED blood levels is not
recommended
Indications
• Non-compliance
• Suspected toxicity.
• Adjustment of AED dose while managing drug
interactions
• Specific clinical conditions-status epilepticus,
liver or renal disease and pregnancy

43. Failure of initial treatment
• Ascertain the accuracy of the diagnosis of
epilepsy
• The appropriateness of the drug for the
particular seizure type,
• the adequacy of dosage
• compliance of the individual
• should be encouraged to make a record seizure
on a cell phone camera.

45. STATUS EPILEPTICUS
• CONVULSIVE status epilepticus –
continous convulsive siezures lasting %min or
more in which the patient doesn t return to
baseline consiousness
• Non convulsive stutus Epilepticus –
Change in Mental status for at least 30 minutes
associated with ictal discharges on EEG
• Refractory status Epilepticus –Siezure
activity that continues after 1st and 2nd line
drugs have failed

46. TREATMENT OF STATUS EPILEPTICUS

47. Treament of Refractory status
epilepticus

48. Withdrawal of AEDs
• seizure-free period of two to three years.
• Avoided in certain epilepsy syndromes (e.g.,juvenile
myoclonic epilepsy) because of the higher risk of
seizure relapse
• withdrawn gradually over several months (at least 36 months or longer).
• Withdraw one drug at a time in those patients who
are on multiple AEDs
• The tapering may be performed at a slower rate for
benzodiazepines (6 months or longer).
• If seizure recurs during withdrawal person may be
advised to revert to their AED dose

49. Women with Epilepsy
• (WWE) who continue appropriate AEDs under
proper supervision have more than 90% chance of
having a normal pregnancy and children.
• All WWE should be advised to plan their
pregnancies.
• cautioned that some AEDs may make OCPs
ineffective
• All WWE in the reproductive age group should be
started on folic acid (5 mg/day) at the time of
starting AED

50. • The risk of major fetal malformations is
approximately 5% more
• risk is further reduced when the mother is using
monotherapy (a single AED)
• VPA at higher doses carries higher risk for
neural tube defects

51. Siezures in pregnancy
• Seizures may remain unchanged in 50% WWE or
improve (25%) or even worsen (25%) during
pregnancy.
• Antiepileptic drugs should be continued in
pregnancy.
• All pregnant WWE should be advised screening for
fetal malformations by serum alpha fetoprotein at 16
weeks and by detailed ultrasound scanning by an
experienced ultrasonologist at 18 weeks.

52. Recommendations
• All WWE should be given two doses of vitamin K 10 mg intramuscularly
(IM) at 34 and 36 weeks of pregnancy, unless there is a contraindication for
the same.
• All infants born to mothers taking AEDs should be given vitamin K 1 mg IM
at birth.
• If preterm labor is threatened in women taking enzyme-inducing AEDs, 48
mg betamethasone (double the normal dose) should be given over 48 hours.
• Seizures during labor should be terminated as soon as possible using
intravenous (IV) lorazepam (4 mg IV) or diazepam
• All WWE should be encouraged to breast-feed their babies

53. Epilepsy in Children and Neonates
• Subtle manifestations of seizures are common in
neonates and infants and these must be looked
for very carefully
• Febrile Seizures • during fever between 6 months and 5 years of
age in the absence of intracranial infection
• Single FS occur in 3–5% children

54. West Syndrome and Infantile Spasms
• corticotropin or corticosteroids should be used
as first-line treatment.
• benzodiazepines, VPA, vigabatrin and
topiramate are used as second choice

55. EPILEPSY IN ADOLESCENTS
•
•
•
•
Avoiding sleep deprivation,
alcohol and substance abuse,
driving,
potentially risky leisure activities like rock
climbing, horse riding,
• prolonged television (TV) viewing, playing video
games and
• dancing in dark rooms with flickering/flashing
lights (discotheques).

56. COMORBID CONDITIONS
• CARDIAC DISEASE – iv Phenytoin can cause
arrythmias , Hypotension
• In patients with cardiac disease infusion rate <10
mg/min.
• Iv Valproate is safe, Leviteracetam may be safe
• Chronic treatment –CBZ,OXC,PHT should be
avoided in AV conduction defects
• Respiratory disease – iv benzodiazepines ,iv
Phenytoin can cause respiratory depression
• Respiratory rate ,HR to be monitored
• Valproate .Leviteractam safer

57. • LIVER DISEASE – Hepatic metabolism of
drugs may be altered
• - Phenobarbitone ,benzodiazepines can
precipitate Hepatic Encephalopathy
• Valproate C/I due to hepatotoxicity
• Phenytoin highly protein bound
hypoalbuminemia – toxicity
• Leviteracetam,oxcarbazepine,topiramate
• Renal disease- Drugs eliminated by kidneys
require dose reduction .LEV,LTG,OXC,PB,TPM

58. EPILEPSY IN ELDERLY
• Generalized tonic-clonic seizures dominate for metabolic
or toxic etiologies
• Every elderly patient with epilepsy should undergo, at
least a CT scan, though MRI is preferable as
symptomatic epilepsy is common in elderly
• nonconvulsive status epilepticus (NCSE)
• The choice of AEDs in elderly depends on many factors:
changes in liver, kidney, gastrointestinal (GI) system
• Bioavailability of the drug in elderly is altered

59. MEDICALLY INTRACTABLE EPILEPSY
• Those in whom epilepsy is not controlled by two or more
appropriate AEDs used in their optimal dosage
• Adults (16 years or above) who continue to have seizures
even after 2 years of treatment.
• Pediatric epilepsy patients can be labeled as MIE much
earlier (sometime even within weeks of onset of
seizures), if they present with epileptic encephalopathy,
infantile spasms, catastrophic onset of epilepsy, seizure
frequency of more than one per month

60. • 30 -40 % SIEZURES persist despite multiple
AED
• Rule out erroneous diagnosis, non compliance
• Partial/localization related epilepsy(30 -70 %
cure ), MTS (20 -50 % cure), secondary
genralised epilepsy ,Lennox gestaut syndrome

62. SURGERY IN EPILEPSY
• GOOD SURGICAL CANDIDATE • Epileptogenic Area is Clearly Defined ,Amenable
to Rescetion with minimal morbidity
• Presurgical Evaluation –
• High Resolution MRI- Thin Cuts Along
Temporal Lobes – For detection of MTS
• Structural Lesion correspomding to
Epileptogenic Zone

63. • Continuous video EEG- ictal and interictal
record with discontinuation of drug
• 75 % cases Localisation with Scalp Recordings
• Functional Neuroimaging• Ictal or Interictal SPECT- Radioactive isotope –
Technitium 99 – siezure area has highest
Perfusion
• FDG –PET – interictally done to indentify
decreased metabolism

64. • Resective surgery includes
• lesionectomy (resection of the lesion and the
surrounding epileptogenic area),
• amygdalohippocampectomy with or without
temporal lobe resection
• Anterotemporal Lobectomy
• Nonresective surgery includes multiple
subpial transections corpus colostomy and vagus
nerve stimulation (VNS

65. VAGAL NERVE STIMULATION
• Those who are not surgical candidates
• Pacemaker device implanted subcutaneously in
left infraclavicular region
• Efficacy is less in partial epilepsy ..10% of
patients benefit
• Better response in lennox gestaut syndrome

66. Thank you

67. References
• Indian Epilepsy Associationguidelines for the management of epilepsy in
India (GEMIND). -2008
- International League against Epilepsy(ILAE) –
Guidleines 2006
- NICE GUIDELINES
- Seminars in neurology –july 2008
- European journal of epilepsy -review