this presentation was delivered to pediatricians at Royal Taj hotel Hyderabad Pakistan

1. Epilepsy and children
By
Dr.Shahnawaz M.K Dal
M.B.B.S, D.P.M
Consultant Neuropsychiatrist
Sir Cowasjee Institute of Psychiatry Hyderabad
M.K Hospital Hyderabad
shahnawazbest74@gmail.com

2. One of the
oldest known
conditions
Epilepsy & its
management

3. What is epilepsy ?
An epileptic seizure is a
transient occurrence of
signs and or symptoms
due to abnormal
excessive or
synchronous neuronal
activity in the brain.
Epilepsy is a disorder of
the brain characterized
by an enduring
predisposition to
generate epileptic
seizures and by the
neurobiologic, cognitive,
psychological, and social
consequences of this
condition.

4. Facts about epilepsy
At least two animals still have epilepsy for
this reason:
Mexican Waltzing Mouse
Papio Papio baboon

5. History
The word ‘EPILEPSY’
derived from Greek
words meaning “ To
seize upon ” or
“Taking held of ”.
In 1870,British
neurologist
HUGHLINGS
JACKSON defined
word EPILEPSY “An
excessive &
disorderly discharge
of cerebral nervous
tissue on muscles.”
This discharge may
be in the form of
loss of
consciousness,
altered
psychological
functions,
disturbance of
sensations,
convulsive
movements or some
combination there
of.
So the terminology
‘CONVULSION’ is
not proper as it only
involves intense
paroxysm of
involuntary muscle
contractions which
is improper because
this disorder may
involve only
alteration of the
sensorium or
consciousness.
So the SEIZURE is
the proper
terminology for
that.

6. Burden of Epilepsy
Persistent
stigma
Cognitive
problems
Psychiatric
disturbances
Long term
effects of
AEDs
Low quality of
life
Accidents
Sudden
death

7. The goals of the treatment
Seizure
freedom
Keep the
patient safe
Keep the
patient
functional
Keep the
patient
autonomous
Seizure control and the
adverse effects are
pharmacodynamic
measures of a drug
effect on the body.

8. A seizure is a paroxysmal event due to excessive , hyper synchronous ,
abnormal discharge from the aggregate of the central nervous system.
Definitions
A sudden, brief disruption of the normal functioning of neurons in the
brain
A neurological condition causing the tendency for repeated seizures of primary
cerebral origin
Epilepsy is not contagious, it is not a mental illness or a cognitive
disability.
“Paroxysmal excessive neuronal discharge from the cortical or sub-cortical
areas”

9. CLASSIFICATION
Classification of epilepsy are based on various points….
- Idiopathic(primary) or symptomatic(secondary)
- Generalized or focal
- Isolated ,cyclic or repetitive
GASTAUT in 1970 has refined a definition of epilepsy with the help of
ILAE(international league against epilepsy)
By this classification epilepsy has been broadly classified in two major groups
based on EEG features & it is accepted world wide.

10. EPILEPSY:PREVELNCE
• There are over 50 million sufferers in the world today, 85% of whom live in
developing countries.1
• At least 50% of cases begin at childhood or adolescence.1
• High prevalence 3.38/1000 was found in children from Government run
educational institutions.2
12/2/2015

11. BARRIERS TO EDUCATION
• Embarrassment about having seizures in front of peers can lead to children feeling
uncomfortable in the school environment.
• Stigma – feelings of being different to peers – may lead to emotional problems,
worry, stress and anxiety.
• Bullying and reluctance to attend school as a result can lead to school refusal.
• Frustration concerning the inability of school staff to understand epilepsy can
impact on some young people.
12/2/2015

12. BARRIERS TO EDUCATION
• Impact on self-esteem through negative school experiences can lead to loss of
confidence and self-doubt.
• Fear of seizures can impact on willingness to take part in activities.
• Stressful experiences at school can trigger seizures.
• Fear of Sudden Unexpected Death in Epilepsy (SUDEP) can have a negative impact
12/2/2015

13. Epilepsy and Related Conditions
• One of the most prominent cognitive changes that occurs in people
• with epilepsy is a memory problem (Zemen et al. 2012)
• Epilepsy may be impacting on sleep if children are experiencing seizure activity at
night and this may lead to tiredness during the day and impact on learning.
• Anti-epileptic drugs (AEDs) and side effects may be impacting on learning.
• Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD)
will be impacting on some of the pediatric epilepsy population.
• Anxiety and depression will be impacting on some of the paediatric epilepsy
population.
12/2/2015

14. Types of Epilepsy
Two major
categories, namely
1.partial
2. generalised
seizures.
Partial seizures

15. Epilepsy - Pathogenesis
A. Result of complex genetic mutations and environmental factors can
cause
• 1. Abnormal brain wiring AND/OR
• 2. Chemical (neurotransmitter) imbalances AND/OR
• 3. Abnormal connections made when attempting to repair an injury
B. Hypersensitive neurons may exhibit a sudden or violent
depolarization
• 1. epileptogenic (able to cause epilepsy)
• 2. Easily activated by hyperthermia,
• hypoxia, hypoglycemia, hyponatremia,
sensory stimulation, certain sleep phases

16. Clinical Manifestations
Often manifests as
strange sensations,
emotions & behaviors
(including convulsions)
Many may experience
the same seizure
events over and over,
while some have many
different types of
seizures that cause
different symptoms
each time.
Patients should be
evaluated thoroughly
after an initial seizure
(complete history)
The type of seizure
a person has
depends on a
variety of things
The area of the
brain affected
Underlying cause
of
seizure
• Partial or generalized
•Time of day of the event
•Occurred during
wakefulness or sleep
Known triggers
• flickering light ,severe
sleep deprivation

17. Tx
Medications used to treat patients with
epilepsy are called anticonvulsants.
These drugs each have a different mechanism of action, but all
serve to reduce the frequency of epileptic seizures. Monotherapy,
treatment with a single agent, is the goal. Many seizures will
stop without pharmacological intervention.

18. Status epilepticus & febrile convulsions.
Status epilepticus
is a life-
threatening
condition in which
seizure activity is
uninterrupted.
Febrile convulsion is associated with
temperatures101 in a child under age of 6 years .

20. Simple Partial Seizure
Rhythmic movements - isolated twitching of arms, face, legs
Sensory symptoms - tingling, weakness, sounds, smells, tastes ,
feeling of upset stomach, visual distortions
Psychic symptoms - déjà vu, hallucinations, feelings of fear or
anxiety
Usually last less than one minute
May precede a generalized seizure

21. Primary generalized
(absence)seizures
Secondarily
generalized (spread)
Partial (focal)
Difference between

22. SIMPLE PARTIAL SEIZURES

23. Complex Partial Seizure
Characterized by altered awareness
Confusion, inability to respond
Automatic, purposeless behaviors such as picking at clothes, chewing or mumbling.
Emotional outbursts
May be confused with:Drunkenness or drug use
Willful belligerence, aggressiveness

24. COMPLEX PARTIAL SEIZURES

25. Myoclonus A single abrupt shock like
extensor movement of a limb.
Petit Mal Used to describe absence seizures
as well as atypical absence.
Tonic Sustained contraction of one or more
muscle groups, independent of position (i.e.
can be flexed, extended, or opisthotonic).
Aura A generic term for a warning. A
colloquial term for simplepartial seizure.
Convulsion Tonic, clonic or tonic-clonic
seizure
Generalized Seizures INTERNATIONAL CLASSIFICATION OF
EPILEPTIC SEIZURES (abridged version)
Absence seizures
Atypical absence
Myoclonic seizures, Myoclonic jerks (simple or
multiple)
Clonic seizures
Tonic seizures
Tonic-clonic seizures
Atonic seizures (astatic)

26. GENERALIZED TONIC- CLONIC SEIZURE

27. Grand mal epilepsy Petit mal epilepsy

28. Myoclonic seizure Atonic seizure

29. Status epilepticus Febrile convulsions

30. Between
Seizures:
• Normal
Appearance
During
Seizure:
• Vacant stare
• Eyes roll
upward
• Lack of
response
ABSENCE SEIZURE

31. Includes all seizures that cannot be
classified because of inadequate or
incomplete data and some that defy
classification in described categories. This
includes some neonatal seizures, e.g.,
rhythmic eye movements, chewing, and
swimming movements.
UNCLASSIFIED EPILEPTIC SEIZURES

32. TREATMENT PRIORITIES
No AEDs until diagnosis is confirmed
If uncertainty then period of observation will clarify
the epilepsy syndrome
Two seizures
May be started after single seizure in certain
circumstances

33. What Is the Difference Between Epilepsy & Seizures?
A seizure is a
symptom of
epilepsy

35. The Brain Is the Source of Epilepsy
A seizure occurs when too many
nerve cells in the brain “fire” too
quickly causing an “electrical storm”

36. Classifying Epilepsy and Seizures
Seizure types:
• Partial Generalized • Simple Absence
• Complex
Consciousness
is maintained
Consciousness
is lost or
impaired
Altered
awareness
Characterized by
muscle
contractions
with or without
loss
of consciousness

37. Everything
you do, you
do with
your brain!

38. Different parts have different functions, and different
seizures!

39. Seizure Triggers
Missed medication (#1 reason)
Stress, anxiety
Hormonal changes, Menses
Dehydration
Lack of sleep, extreme fatigue
Photosensitivity
Illicit Drug, alcohol use
Certain Medications
Fever in Some Children

40. Treatment Goals in Epilepsy
Help person with epilepsy
lead full and productive
life
Eliminate seizures
without producing side
effects
Tailor treatment to needs
of individuals/special
populations :
• Women, Children, Elderly,
Hepatic or renal failure and
other diseases

41. What if not treated?
Seizures can be potentially life threatening with brain
failure, heart and lung failure, trauma, accidents
Sudden Unexpected Death in Epilepsy (SUDEP)
Even subtle seizures can cause small damage in brain
Long Term problems: fall in IQ, depression, suicide, Social
Problems, Quality of Life

42. Considerations in Epilepsy Management
Age and
Gender
Seizure
Frequency
Underlying
Pathology
Comorbidities
Medication
Side Effects
Syndrome
vs.
Seizure Type

43. Factors That Affect the Choice of Drug
Seizure type/
Epilepsy syndrome
Side effects & safety
Patient age
Ease of Use
Lifestyle
Age, Sex, Childbearing
potential
Other medications

44. New AEDs offer
Alternative as an
add-on
Alternative in case
of adverse effects
Less AED-AED
interactions
Less drug-drug
interactions in
specific conditions
Better tolerability

45. Consistent use
Inadequate dosage or ineffective medication
Drug factors
Disease
Factors That Influence Response to Medication

46. History of Antiepileptic Drug Therapy
1857 - Bromides
1912 - Phenobarbitone
1937 - Phenytoin
1944 - Trimethadione
1954 - Primidone
1960 - Ethosuximide

47. History of AED therapy
1974 – Carbamazepine
1975 - Clonazepam
1978 - Valproate
1990 - Oxcarbazepine
1993 - Felbamate, Gabapentin
1995 – Lamotrigine, Levetiracetam
1997 - Topiramate, Tiagabine

48. Choice of AED
age
Life style
comorbidity
Adverse effects
tolerability
Efficacygender
interactions
cost

49. Principles of AED Selection
Correct diagnosis of the type of epilepsy influences treatment,
prognosis and genetic counseling.
One best drug to fit the fit, fit the patient; Sequential
monotherapy
Use the least expensive AED (all things being equal, like efficacy).
Prefer AEDs which can be taken od over bid / tid.
AEDs almost never need qid dosing

50. Start with one AED and push the dose
to clinical toxicity or seizure control.
Withdraw AEDs that are not effective.
Never have a patient on more than
three (3) AED's.
Principles of AED Selection…cont.

51. Principles of AED Selection… cont.
Don't use combination medications (e.g., phenytoin with
phenobarbital).
No proof that multiple AEDs are synergistic in the treatment
of epilepsy.
Polypharmacy is expensive, increases side effects and
increases the complexity of adjusting AEDs in the refractory
patient.

52. Antiepileptic drug (AED) - Limitations
A drug which decreases the frequency and /or severity of seizures
in people with epilepsy.
Treats the symptom of seizures, not the underlying epileptic
condition.
Improves quality of life by minimizing seizures.

54. Seizure Management
Pharmacologic Treatment
Partial seizures
• Oxcarbazepine
• Carbamazepine
• Phenytoin
• Phenobarbital
• Levetiracetam
• Lamotrigine
• Topiramate
• Lacosamide
• Zonisamide
Absence seizures
• Ethosuaximide
• Valproic acid
• Lamotrigine

55. Seizure Management
Pharmacologic Treatment
Tonic-Clonic Seizures
• Phenytoin
• Valproic acid
• Carbamazepine
• Topiramate
• Levetiracetam
• Lamotrigine
• Zonisamide
Myoclonic and Atonic
Seizures
• Clonazepam
• Lamotrigine
• Levetiracetam
• Infantile Spasms
• ACTH
• Topamax
• Zonisamide
• Valproic acid

56. Antiepileptic
drugs – “newer
drugs” since
1990
• Felbamate
• Gabapentin
• Lamotrigine
• Topiramate
• Vigabatrin
• Oxcarbazepine
• Zonisamide
• Leveteracetam
• Pregabalin
• Rufinamide
• Lacosamide

57. Choosing the right
treatment;
balancing efficacy
and tolerability

58. New AEDs offer
Alternative as an
add-on
Alternative in case
of adverse effects
Less AED-AED
interactions
Less drug-drug
interactions in
specific conditions
Better tolerability

59. Broad Spectrum
anti epileptic,
used to treat
refractory
epilepsy
Levetiracetam:

60. TRADITIONAL ANTI-EPILEPTIC CONCERNS
• Memory impairment & Impaired attention is associated
with traditional Anti-Epileptics.
• Liver failure resulting in death has occurred in patients
receiving Divalproex Sodium.
• laboratory monitoring needed /LFTs Requires
12/2/2015

61. 12/2/2015
An Ideal Anti-epileptic Drug
• Broad spectrum of efficacy
• Goal of Epilepsy Management - Seizure freedom
• Sustained efficacy
• Optimal therapy with no known clinically
significant drug interactions
• Improved quality of life
• Dosage convenience

62. 12/2/2015
1. Levetiracetam is a new antiepileptic drug, structurally and
mechanistically dissimilar to other marketed antiepileptic drugs.
2. Levetiracetam is an anticonvulsant medication used to treat epilepsy. It is the S-
enantiomer of etiracetam, structurally similar to the
prototypical nootropic drug piracetam.
3. It is effective in reducing partial seizures in patients with epilepsy,
both as adjunctive treatment and as monotherapy.
4. Having favorable pharmacokinetic characteristics (good
bioavailability, linear pharmacokinetics, insignificant protein binding,
lack of hepatic metabolism, and rapid achievement of steady-state
concentrations) and a low potential for drug interaction.

63. 12/2/2015
MECHANISM OF ACTION
• The exact mechanism by which Levetiracetam acts to treat
epilepsy is unknown. However, the drug binds to a synaptic
vesicle protein, , which is believed to impede nerve
conduction across synapses.
• appear to be important for the availability of calcium-
dependent neurotransmitter vesicles ready to release their
content. The lack of results in decreased action potential-
dependent neurotransmission, while action potential-
independent neurotransmission remains normal.

64. 12/2/2015

65. 12/2/2015
INDICATIONS
• Monotherapy in the treatment of partial onset seizures
with or without secondary generalization in patients
from 16 years of age with newly diagnosed epilepsy.
• Adjunctive therapy in the treatment of partial onset
seizures with or without secondary generalization in
adults and children from 4 years of age with epilepsy.
• Adjunctive therapy in the treatment of myoclonic seizures
in adults and adolescents from 12 years of age.

66. 12/2/2015
Dosage

67. EPICETAM-Features
• Broad spectrum of potential efficacy
• No hepatic induction
• Well tolerated in most; good cognitive profile
• Excellent safety profile
• No laboratory monitoring needed

68. • Levetiracetam pharmacology
• LEV is rapidly and almost completely absorbed after oral
intake, with peak plasma concentrations approximately one
hour after oral administration. Food reduces the peak
plasma concentration by 20% and delays it by 1.5 hours, but
does not reduce LEV bioavailability (Patsalos 2000, 2003).
There is a linear relationship between LEV dose and LEV
serum level over a dose range of 500–5000 mg (Radtke
2001). LEV protein binding, at less than 10%, is not clinically
relevant. LEV metabolism is not dependent on the liver
cytochrome P450 enzyme system. LEV is predominantly
excreted unchanged through the kidneys, with only about
27% metabolized.

69. Mechanism of action
• The exact mechanism by which levetiracetam
acts to treat epilepsy is unknown. However,
the drug binds to a synaptic vesicle
glycoprotein, and inhibits presynaptic calcium
channels reducing neurotransmitter release
and acting as a neuromodulator. This is
believed to impede impulse conduction across
synapses

70. Lamotrigine
Oxcarbazepine
Topiramate
Levetiracetam
Licensed to Monotherapy
ILAE Treatment Guideline (Glauser T, et al.2006 )
NICE (National Institue for Clinical Excellence 2004) guidance on newer drugs for epilepsy in adults
SIGN (Scottish Intercollegiate Guideline Network, 2005)
SANAD (standard and new antiepileptic drug trial (Marson et al.2007)
BESET (Belgian Study on Epilepsy treatment, Legros B, et al. 2007))

71. SIGN(Scottish Intercollegiate Guideline Network)
All AEDs are
equivalent in
new onset
epilepsy
First drugs to
introduce in
new onset
epilepsy is
standart AEDs
and LTG, OXC

72. • Hirsutismus Alopecia
• Gingiva hyperplasia Coarse face
Cosmetic side effects
• Hyperandrogenism Ovulatory disorders
• PCOS Sperm quality, number
Reproductive health
• 20-30% W, 50% M; Reduced libido
• Anorgasmia
Sexual dysfunction
Bone health
• total, free thyroxine↓
Thyroid functions
Peripheral neuropathies
Cerebellar atrophy

73. CBZ VPA PB ESM PHT
Somnolence *
GIS * * **
Liver *
Depression * * *
Blood * * * * *
Cognition * ** *
Osteoporosis (*) (*) * *
Side effects-I

74. Side effects-II
LTG OXC TPM LEV GBP PGB
Somnolence
* ** * * *
GIS
* * **
Liver
Blood
Cognitive
*
Osteoporosis
Depression
Engel J, Pedley TA, Epilepsy, 2008

75. Idiosyncratic side effects
Vigabatrin
Felbamate
Lamotrigine
Topiramate
Topiramate
Oxcarbazepine
Visual field
defects
Aplastic
anemia
Rash
Renal stones
Glaucoma
Hyponatremia

76. Weight and AEDs
Weight gain Weight loss No effect
VPA
GBP
PGB
VGB
TPM
ZNS
FBM
OXC
LTG
PHT
LEV*

77. Enzyme inducers vs non-inducer AEDs
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Felbamate
Lamotrigine
Oxcarbazepine
Topiramate
Ethosuximide
Gabapentin
Levetiracetam
Pregabalin
Tiagabin
Valproat*
Vigabatrin
Zonisamide
Narrow-
spectrum
inducers
Non-
inducers
Inducers

78. We love our children