Seizure- a paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy- Recurrent seizure due to chronic underlying process.

1. Advances in Management of
Seizure Disorder
Speaker- Dr. Shadab Ahmad

2. Seizure- a paroxysmal event due to abnormal
excessive or synchronous neuronal activity
in the brain.
Epilepsy- Recurrent seizure due to chronic
underlying process.
 A person with a single seizure or recurrent seizures due to
correctable or avoidable circumstances does not necessary have
epilepsy

3. Common causes of seizure
Trauma
CNS infection
Intracranial hemorrhage
Metabolic disturbances
• Hypoglycemia
• Hyperglycemia
• Hypocalcemia
• Hypomagnesemia
• Uremia
• Hepatic failure
Fever
Hypoxia
Brain tumor
Alcohol withdrawal
Drug withdrawal
Illicit drug use
Developmental disorders
Genetic disorders
Idiopathic

4. Causes of Seizure
Neonates
(<1 month)
Perinatal hypoxia and ischemia
Intracranial hemorrhage and trauma
Acute CNS infection
Metabolic disturbances(hypoglycemia, hypocalcemia, hypomagnesemia, pyridoxine deficiency)
Drug withdrawal
Developmental disorders
Genetic disorders
Infant and children
(>1 month and <12 years)
Febrile seizures
Genetic disorders (metabolic, degenerative, primary epilepsy syndrome)
CNS infection
Developmental disorders
Trauma
Idiopathic
Adolescents
(12-18 years)
Trauma
Genetic disorders
Infections
Brain tumor
Illicit drug use
Idiopathic
Young adults
(18-35 years)
Trauma
Alcohol withdrawal
Illicit drug use
Brain tumor
Idiopathic
Older adults
(>35 years)
Cerebrovascular disease
Brain tumor
Alcohol withdrawal
Metabolic disorders(uremia, hepatic failure, electrolyte abnormalities, hypoglycemia,
hyperglycemia)

5. Classification of Seizures
Focal seizures Motor
Sensory
Autonomic
Cognitive
Other
Generalized seizures Absence
• Typical
• Atypical
Tonic-clonic
Clonic
Tonic
Atonic
Myoclonic
Focal, generalized, or unclear Epileptic spasm

6. Provocative or Precipitating factors
Intrinsic physiologic process
• Psychological or physical stress
• Sleep deprivation
• Hormonal changes associated with menstrual cycle
Exogenous factors
• Exposure to toxic substance
• Certain medications
Epileptogenic factors
• Penetrating head trauma
• Stroke
• Infections
• Abnormalities of CNS development

7. Basic mechanism of seizure & AEDs

8. Diagnosis & Treatment of Seizure
•

9. History and Examination
The first goal is to determine whether the event was truly a seizure.
• Question should focus on symptoms before, during and after the episode in order to
differentiate a seizure from other paroxysmal events.
History should also focus on risk factors and predisposing factors.
• H/o febrile seizures, earlier auras and family history of seizures
• Epileptogenic factors such as prior head trauma, stroke, tumor or infection of CNS
should be identified
• Presipitating factors such as sleep deprivation, systemic disease,
electrolyte/metabolic derangements, alcohol or illicit drug use should also be
identified.
General physical examination includes
• Search for signs of infection or systemic illness
• Signs of neurocutaneous disorders such as tuberous sclerosis, neurofibromatosis
• Organomegaly may indicate a metabolic storage disease
• Auscultation of heart and carotid may identify cerebrovascular disease.

10. Laboratory studies
• Routine blood studies
• Urine examination
• CSF examination

11. Electrophysiological examination
EEG
• All patients who have a possible seizure disorder should
be evaluated with an EEG as soon as possible.
• The presence of electrographic seizure activity (i.e. abnormal, repetitive,
rhythmic activity having a discrete onset and termination) clearly establish the
diagnosis, however
• The absence of electrographic seizure activity does not exclude a seizure disorder.
• Even in an individual who is known to have epilepsy, the initial routine intertctal
EEG may be normal up to 60% of the time.
 The EEG can not establish the diagnosis of epilepsy in many cases but, it may be
used to assess the prognosis of seizure disorders (i.e. normal EEG implies a better
prognosis)

12. MEG (Magnetoencephalography)
• It is an another way of looking noninvasively at
cortical activity.
• It measures the small magnetic fields that are
generated by electrical activity of brain.
• It uses a verity of mathematical techniques to generate a magnetic
source image (MSI) that can be used to localize potential seizure foci.

13. MRI
• Almost all patient with new onset seizures should have a brain
imaging study to determine underlying structural abnormality that is
responsible.
 MRI is superior to CT for detection of cerebral lesions associated
with epilepsy.
• In patient with suspected CNS infection or mass lesions, CT scan
should be performed emergently when MRI is not immediately
available.

14. Other Functional imaging procedures
PET (Positron emission tomography)- a biologically active molecule incorporated with tracers
fluorodeoxyglucose (FDG), which is an analogue of glucose is used to
detect metabolically active tissue.
-system detects a pair of gamma rays emitted indirectly by a positron
emitting radionuclide (tracer)
- widely used in detection of CNS tumors
SPECT (Single-photon emission computed tomography)- gamma emitting tracers, Tc-HMPAO is used to
assess brain metabolism regionally.
- More widely available and less expensive than PET
- produce less spatial resolution images than PET
fMRI (Functional magnetic resonance imaging)- based on the fact that cerebral blood flow and neuronal
activation are coupled i.e. when an area of brain is in use,
blood flow to that region is also increases.
- uses the change in magnetization between oxygen rich and
oxygen poor blood

15. Antiepileptic Drugs
Classical
• Phenobarbitone
• Phenytoin
• Primidone
• Carbamazepine
• Ethosuxamide
• Valproic acid
• Clonazepam
• Diazepam
• Lorazepam
• Clobazam
Newer drugs
• Lamotrigine
• Gabapentin
• Topiramate
• Zonisamide
• Levetiracetam
• Vigabatrin
• Tiagabin
• Lacosamide
• Rufinamide

16. Mechanism of AEDs
• Inhibition of Na+ dependent action potentials in a frequency dependent
manner
Eg.
Phenytoin
Carbamazepine
Lamotrizine
Topiramate
Zonisamide
Lacosamide
Rufinamide

17. • Inhibition of voltage gated Ca2+ channels
Eg.
Phenytoin
Gabapentin
Pregabalin

18. • Attenuation of glutamate activity
Eg.
Lamotrigine
Topiramate
Felbamate

19. • Potentiation of GABA receptor function
Eg.
Benzodiazepins
• Clonazepam
• Diazepam
• Lorazepam
• Clobazam
Barbiturates
• Phenobarbiton

20. • Increase in availability of GABA
Eg.
Valproic acid
Gabapentin
Tiagabin

21. • Modulation of release of synaptic vesicles
Eg.
Levetiracetam
• Inhibition of T-type Ca2+ channels
Eg.
Ethosuxcimide
Valproic acid

22. Dosage and Adverse effects of AEDs
Name Principal uses Dose Half life Adverse effects
Phenytoin
(Eptoin, Dilantin)
Tonic clonic
Focal onset
300-400 mg/d
(3-6 mg/kg adult,
4-8 mg/kg child)
24 hour Diplopia, ataxia,
gum hypertrophy,
hirsutism,
osteomalacia
Valproic acid
(Encorate, Valtec)
Tonic clonic
Absence
Myoclonic
Focal onset
Atonic
750-2000 mg/d
(20-60 mg/kg)
15 hour Ataxia, tremor,
hepatotoxicity,
thrombocytopenia,
weight gain,
GI irritation
Carbamazepine
(Tegrital)
Tonic clonic
Focal onset
600-1800 mg/d
(15-35 mg/kg)
10-17 hour Ataxia, diplopia,
vertigo, aplastic
anemia, leukopenia,
hepatotoxicity,
hyponatremia
Ethosuximide Absence 750-1250 mg/d
(20-40 mg/kg)
60 hour, adult
30 hour, child
Ataxia, lethargy,
headache, Gi
irritation, bone
marrow supression

23. Cont.
Name Principal uses Dose Half life Adverse effects
Phenobarbital
(Gardenal, Phenobarb)
Tonic clonic 60-180 mg/d 90 hours Sedation, ataxia,
depression,
decreased libido
Primidone
(Mysoline)
Tonic clonic 750-1000 mg/d 8-15 hours Sedation, ataxia,
depression,
decreased libido
Clonazepam
(Clonafit)
Absence
Atypical
absence
Myoclonic
1-2 mg/d 24-48 hours Ataxia, sedation,
lethargy, anorexia
Oxcarbazepine
(Trioptal)
Focal onset
Tonic colic
900-2400 mg/d
(30-45 mg/kg,
child)
10-17 hours Fatigue, ataxia,
diplopia, vertigo,
aplastic anemia,
leukopenia,
hepatotoxicity,
hyponatremia

24. Newer AEDs
Name Principal uses Dose Half life Adverse effects
Lamotrigine
(Lamepil)
Focal onset
Tonic clonic
Atypical absence
Myoclonic
Lennox Gastaut
syndrome
150-1250 mg/d 25 hours Dizziness, diplopia,
ataxia, headache,
Stevens-Johnson
syndrome
Gabapentin
(Neurontin)
Focal onset 900-2400 mg/d 5-9 hours Sedation, dizziness,
ataxia, GI irritation,
weight gain, edema
Topiramate
(Topamate)
Focal onset
Tonic clonic
Lennox- Gastaut
syndrome
200-400 mg/d 20-30 hours Psychomotor slowing,
speech/language
problem, paresthesia,
renal stone,
glaucoma, weight
loss, hypohidrosis
Tiagabin Focal onset 32-56 mg/d 7-9 hours Confusion, psychosis,
depression,
speech/language
problem, paresthesia

25. Cont…
Name Principal uses Dose Half life Adverse effects
Levetiracetam
(Levepsy)
Focal onset 1000-3000 mg/d 6-8 hours Sedation, fatigue,
mood changes,
anemia, leucopenia
Felbamate Focal onset
Lennox-Gastaut
syndrome
Tonic clonic
2400-3600 mg/d 16-22 hours Insomnia, sedation,
aplastic anemia,
hepatic failure,
weight loss, GI
irritation
Zonisamide
(Zonicare)
Focal onset
Tonic clonic
200-400 mg/d 50-68 hours Sedation, psychosis,
anorexia, renal
stone, hypohidrosis
Lacosamide
(Lacopsy)
Focal onset 200-400 mg/d 13 hours Dizziness, ataxia,
diplopia, vertigo, GI
irritation, PR
prolongation
Rufinamide Lannox-Gastaut
syndrome
3200 mg/d
(45 mg/kg, child)
6-10 hours Sedation, fatigue,
ataxia, diplopia, GI
irritation,leukopenia
,QT prolongation

26. Other Newer AEDs are….
• Retigabine - it opens voltage gated KCNQ2/3 and KCNQ3/5 potassium
channels leading to cellular membrane hyperpolarization.
- developed as an adjunctive treatment for partial epilepsy
• Brivaracetam- an analogue of levetiracetam
- useful in treatment of photosensitive epilepsy and
- adjunctive treatment in refractory partial onset epilepsy
• Ganoxolone- a synthetic analogue of allopregnenolone, a neurosteroid
which is an allosteric modulator of GABA-A receptor complex.
- useful in treatment of refractory infantile spasm and
catamenial seizures.

27. Cont..
• Eslicarbazepine – Structurally related to carbamazepine and
oxcarbazepine
- used as adjunctive therapy for partial seizures.
• Perampanel – a selective, non-competitive antagonist of AMPA type
glutamate receptors.
- used as adjunctive therapy for the treatment of
refractory partial onset seizures

28. When to initiate Antiepileptic drug therapy ?
1. AEDs should be started in any patient with recurrent seizure of unknown
etiology or known case that can not be reversed.
2. Patient with a single seizure due to an identified lesion (eg. CNS tumor,
infection or trauma) in which there is strong evidence that the lesion is
epileptogenic.
3. Patients with risk factors for recurrent seizure.
Risk factors are-
1. Abnormal neurological examination
2. Status epilepticus
3. Postictal Todd’s paralysis
4. Strong family history of seizure
5. Abnormal EEG
 Monotherapy should be goal whenever possible.

29. Monitoring of Therapy
• In the initiation of therapy, determination of optimal dose is often a matter
of trial and error.
• So, starting doses should be lowest value, subsequent increase should be
made only after achieving a steady state with previous dose (i.e. after an
interval of five or more half-lives).
• Patients with decreased level of serum proteins may have subtherapeutic
drug level, but the dose should be changed only if seizures remain
uncontrolled, not just to achieve a therapeutic level.
• So, monitoring of serum antiepileptic drug levels are useful during-
• Initiation of therapy
• Modification of therapy
• Documentation of compliance

30. When to discontinue therapy ?
AEDs can be discontinued –
Patients profile-
1. Complete medical control of seizure for 1-5 years
2. Single seizure type, either focal or generalized
3. Normal neurological examination
4. Normal EEG
 It is reasonable to attempt withdrawal of therapy after 2 years in a patient who
meets all of the above criteria.
• It is preferable to reduce dose of the drug gradually over 2-3 months

31. Treatment of refractory epilepsy
There are currently no clear guidelines for rational polypharmacy, although a
combination of drugs with different mechanism of action may be most
useful.
• In most cases initial combination therapy combines first line drugs (i.e.
carbamazepine, oxcarbazepine, lamotrigine valproic acid and phenytoin)
• If these drugs are unsuccessful, then addition of newer drug is indicated
such as levetiracetam, topiramate, zonisamide.
• If there is no improvement , a third drug can be added while the first two
are maintained.
• If there is a response, the less effective or less well tolerated of the first
two drugs should be gradually withdrawn.

32. Status Epilepticus
Status epilepticus refers to continuous seizures or
repetitive, discrete seizures with impaired consciousness
in the interictal period.
• The duration of seizure activity sufficient to meet the definition is
specified as 15-30 minutes however,
 For practical definition status epilepticus should be considered when
seizures last beyond 5 minutes.

33. Types of Status Epilepticus
Generalized convulsive status
epilepticus (GCSE)
Eg.
• Persistent
• Generalized electrographic
seizures
• Coma
• Tonic- clonic movements
Nonconvulsive status epilepticus
Eg.
• Persistent absence seizure
• Focal seizures
• Confusion or partially impaired
consciousness
• Minimal motor abnormalities

34. Common causes of GCSE
• Anticonvulsant withdrawal
• Noncompliance to medication
• Metabolic disturbances
• Drug toxicity
• CNS infection
• CNS tumors
• Refractory epilepsy
• Head trauma

35. Consequences of GCSE
• Cardiorespiratory dysfunction
• Hyperthermia
• Metabolic derangement

36. Management of Status Epilepticus
GCSE is an emergency and must be treated immediately
• Lorazepam- Inj. Ativan (2 mg/ml)
• Fosphenytoin- Inj. Fosolin (75 mg/ml)
• Phenytoin- Inj. Eptoin (50 mg/ml)
• Valproate- Inj. Encorate (100 mg/ml)
• Phenobarbital- Inj. Gardenal (200mg/ml)
• Propofol- inj. Propovan (10 mg/ml)
• Midazolam- Inj. Mezolam (1 mg/ml)

37. THANK YOU