1. Seizures and Epilepsy
Dr. Khalid El-Salem
American Board of Neurology
American Board of Clinical Neurophysiology
Assistant Prof of Neurology
JUST

2. Concepts
 Seizure: sudden temporary
change in brain function caused
by an abnormal rhythmic
excessive electrical discharge
 Epilepsy: a state of recurrent
seizures

3. Epidemiology of Epilepsy
 Lifetime risk of developing
epilepsy is 3.2%
 10% of population experience
at least one seizure before the
age of 80 years
 Higher prevalence at the
extremes of age

4. Seizure Type Versus
Epileptic Syndrome
 A seizure type is determined by the
patient’s behavior and EEG pattern
during the ictal event
 An epileptic syndrome is defined by
- Seizure type(s)
- Natural history
- EEG (ictal and interictal)
- Response to AEDs
- Etiology

5. Classification of Seizures
 Partial seizures
- Simple partial seizures
- Complex partial seizures
Impaired consciousness at outset
Simple partial evolving to lost consciousness
- Partial seizures evolving to general
tonic-clonic seizures (GTCS)

6. Classification of Seizures
(cont.)
 Generalized seizures
- Absence seizures
- Tonic-clonic seizures
- Myoclonic seizures
- Tonic seizures
- Clonic seizures
- Atonic seizures

7. Classification of Epilepsies
 Partial Epilepsy Syndromes  Generalized Epilepsy Syndromes
- Symptomatic - Symptomatic
•Lennox-Gastaut Syndrome
•Lesional epilepsy
•West’s Syndrome
•Medial Temporal Sclerosis
•Progressive Myoclonic Epilepsy
•Neocortical Epilepsy
- Idiopathic(Genetic)
- Idiopathic(Genetic) •Juvenile myoclonic epilepsy
•Benign Rolandic Epilepsy •Generalized tonic clonic
•Benign occipital Epilepsy seizures upon awakening

8. Absence Seizure
 Simple: abrupt onset and
cessation of motionless stare,
with unresponsiveness and no
post ictal state ( few-30 sec)
 Complex:
typical+clonic/myoclonic activity
or automatism
 Activated by hyperventilation

9. Generalized Tonic Clonic
Seizure
 Prodrome: apathy, fatigue
 No aura
 Tonic phase: 10-15 sec, jaw snap shut,
spasm, cyanosis
 Clonic phase: 1-2 min, rhythmic
generalized muscle contractions apnea,
increased BP
 Terminal phase: coma, pupils react,
breathing resume
 Post-ictal phase: confusion, somnolence

10. Complex Partial Seizures
 Prodrome: Lethargy
 Aura: common
 Oral or motor automatism,
alteration of consciousness, head
and eye deviation, contralateral
twitching or clonic movements,
posturing
 Rt temporal often hypermobile
 Lt temporal often behaviour arrest

11. Frontal lobe seizures
are partial seizures
that can be easily
confused with
psychiatric disease

13. Acquired Epilepsy
 Trauma
 Infection
 Vascular disease
 Metabolic changes
 Tumor
 Age effects on brain

14. Epilepsy Risk Factors
 Structural brain lesions
 Degenerative diseases
 Head trauma
 CNS infections
 Perinatal insults
 Alcohol/drugs
 HIE
 Febrile seizures
 Genetic factors

16. Diagnosing Epilepsy
 History of recurrent seizures
- Differentiate epileptic from non-
epileptic fits
- Classify seizure type
- Determine etiology
Associated clinical features
Diagnostic testing
• EEG
• MRI

17. Epileptiform Discharges

18. Focal Discharges

19. Generalized Discharges

20. Phenytoin
 For partial and generalized Sz
 ^ Pt. bound, hepatic inducer
 Side effects
- Dose related: ataxia, dysarthria,
nystagmus
- Idiosyncratic: hirsutism, gingival
hypertrophy, acne, coarsening
facial features

21. Valproic Acid
 Strong metabolic inhibitor
 For partial and generalized Sz
 Strongly Teratogenic: spina
bifida
 Side effects:
- somnolence, wt gain, tremor, hair
loss
- Pancreatitis, hepatotoxicity, blood
dyscrasias

22. Carbamazepine
 Potent enzyme inducer
 Mainly for partial seizures
 Side effects:
- somnolence, dizziness, blurred
vision, diplopia’ nystagmus
- skin rash, hepatotxicity, blood
dyscrasias

23. Classic Versus Newer
Anticonvulsants
Classic AEDs Newer AEDs
 Phenobarbital  Felbamate (Felbatol®)
 Phenytoin (Dilantin®)  Gabapentin (Neurontin®)
 Lamotrigine (Lamictal®)
 Primidone (Mysoline )
®
 Levetiracetam (Keppra®)
 Carbamazepine  Oxcarbazepine
(Tegretol®) (Trileptal®)
 Valproate  Tiagabine (Gabitril®)
(Depakote®/ Depacon®)  Topiramate (Topamax®)
 Ethosuximide  Vigabitrin (Sabril®)
(Zarontin®)  Zonisamide (Zonegran®)

24. Applications of New AEDs in Epilepsy
Medication Application in Epilepsy
Felbamate Some efficacy in all seizure types
Gabapentin Partial and sec generalized tonic clonic seizures only
Lamotrigine Some efficacy in all seizure types
Levetiracetam Partial and sec generalized tonic clonic seizures
Oxcarbazepine Partial and sec generalized tonic clonic seizures
Tiagabine Partial and sec generalized tonic clonic seizures only
Topiramate Some efficacy in all seizure types
Vigabatrin Infantile spasms, Partial seizures
Zonisamide Some efficacy in all seizure types

25. Choice and Use of Drugs
Partial
Generalized
Simple
Complex
Secondary
generalized
Tonic- Infantile
clonic
Tonic Myoclonic Atonic Spasms
Absence
PHT, CBZ, PB,
GBP, TGB, ACTH
LVT, OCBZ TPM? ESX
TGB?
VGB?
VPA, LTG, TPM, ZNS
FBM

26. Newer ADE Mechanisms of Action
Medication Na Channel GABA R NMDA Channel T Calcium
Channel Channel
Felbamate +/? +/? +/? ?
Gabapentin +/? +/? +/? ?
Lamotrigine ++ -/? +/? -/?
Levetiracetam - - - -
Oxcarbazepine +/? ? - -
Tiagabine - ++ - -
Topiramate +/? ? ? ?
Vigabatrin + - - -
Zonisamide + - - +

27. New AEDs Dosing
Medication Starting dose Incrementation mg Maintenance dose
mg mg
Felbamate 600 tid 600-1200 / wk 1200-1600 tid
Gabapentin 300-400 qd 300-400 / day 600-1200 tid
Lamotrigine 50 qd 100 / wk 100-300 bid
Levetiracetam 500 bid 500 bid / 2 wks 500-1000 bid
Oxcarbazepine 300 bid 300 bid / wk 600-1200 bid
Tiagabine 4 qd 4-8 qd / wk 32-56 in 2-4 doses
Topiramate 50 qd 50 / wk 100-200 bid
Vigabatrin 40/kg/d 80-150 /kg/d
Zonisamide 100 qd-bid 100 / wk 100-300 bid

28. Elimination of classic AEDs
Valproate
Hepatic
Ethosux
Renal
Phenobarb
0 20 40 60 80 100

29. Elimination of Newer AEDs
Zonisamide
Levitiracetam
Oxcarbazepine
Tiagabine
Lamotrigine
hepatic
Felbamate Renal
Topiramate
Vigabatrin
Gabapentin
0 20 40 60 80 100

30. Hepatic Enzyme Effects Of AEDs
Inducers Inhibitors No or Min
Phenytoin
Valproate Gabapentin
Phenobarbital
Felbamate Lamotrigine
Primidone
Topiramate
Carbamazepine
Tiagabine
Oxcarbazepine
Levitiracetam
Zonisamide

31. Drug-Drug Interaction Potential
of AEDs
High Intermediate Minimal-None
Phenytoin Topiramate Gabapentin
Carbamazepine Lamotrigine Ethosuximide
Valproate Tiagabine Levitiracetam
Phenobarbital Oxcarbazepine Vigabatril
Primidone Zonisamide
Felbamate

32. Main Inhibitory Interactions of
AED’s

33. Effect of Inducer AED’s on
Other AED’s

34. Serious Side Effects
Medication Serious side effects
Felbamate Aplastic anemia, Liver failure
Gabapentin None
Lamotrigine Stevens Johnson Syndrome
Levetiracetam None
Oxcarbazepine Hyponatremia
Tiagabine Stupor
Topiramate Nephrolithiasis, glucoma
Vigabatrin Optic nerve demyelination
Zonisamide Renal calculi

35. Cognetive Effects of AEDs
Minimal- some Significant
None
Gabapentin Phenytoin Phenobarbital
Tiagabine Carbamazepine Primidone
Lamotrigine Valproate Topiramate
Oxcarbazepine Zonisamide
Levitiracetam

36. Therapeutic Drug Monitoring for
Newer AEDs
• Not widely practiced
• No generally accepted target
ranges
• A wide range is associated with
clinical efficacy.
• Considerable overlap in drug
concentrations related to
toxicity and non response.

37. Tentative Target Concentration
Ranges
Medication Range
Felbamate 40-100 mic g/ml
Gabapentin >2 mic g/ml
Lamotrigine 1-4 mic g/ml
Levetiracetam 35-120 mic m/L
Oxcarbazepine 4-12 mic g/ ml
Tiagabine 50-250 nmol/L
Topiramate 2-4 mic g/ml
Vigabatrin 6-278 mic m/L
Zonisamide 10-30 mic g/ml

38. AAN Evidence Based Guidelines
Level A or B Recommendations
Newly Diagnosed Epilepsy
Medication Monotherapy for newly Newly diagnosed absence
diagnosed partial/mixed
Felbamate
Gabapentin Yes No
Lamotrigine Yes Yes
Levetiracetam No No
Oxcarbazepine Yes No
Tiagabine No No
Topiramate Yes No
Vigabatrin
Zonisamide No No

39. AAN Evidence Based Guidelines
Level A or B Recommendations
Refractory Epilepsy
Medication Partial Partial Primary Symptomatic Peds
Add on/adult Monotherapy Generalized Generalized Partial
Felbamate
Gabapentin Yes No No No Yes
Lamotrigine Yes Yes No Yes Yes
Levetiracetam Yes No No No No
Oxcarbazepine Yes Yes No No Yes
Tiagabine Yes No No No No
Topiramate Yes Yes Yes Yes Yes
Vigabatrin
Zonisamide Yes No No No No

40. Conclusions
 New AED’s are not more
effective than classical ones
 Classical AEDs remain first line
of treatment
 Pharmacokinetics and dynamics
are more determinent than
efficacy.