1. Childhood Epilepsies Dr. Anuruddha Padeniya Eisenhower Fellow 2012
Consultant Paediatric Neurologist
Lady Ridgeway Hospital for Children, Colombo
Academic Head, Faculty of Medicine, Rajarata

2. Objectives Definitions Epilepsies vs. Epilepsy
Approach to childhood epilepsy
Treating childhood epilepsy

3. Are all seizures epileptic?
Epileptic seizures
Transient clinical events which result from abnormal and excessive activity of synchronised populations of cerebral neurons...
Epilepsy
Recurrent epileptic seizures
All seizures are NOT epilepsy!

4. Prevalence 350/100,000 (Gortmaker and Sappenfield, 1984).
However, 3-5% of children will have one or more seizures (Haslem, 2000)

5. Incidence of epilepsy (new cases per year)
Developed Countries
Resource Poor Countries
40-70 per 100,000 /year (Holmes, 1992)
per 100,000 /year
75% of people developing epilepsy are doing so prior to 20 years of age (Holmes, 1992)
No significant difference in incidence between boys and girls was found (Freitag et al. Epilepsia 2001)

6. Significance 35% diagnosed at less than 16 years old
Partial > Generalised
Associated with many disabilities
Risk of sudden death

7. Causes Idiopathic Symptomatic Cryptogenic
(47%; incidence rate, 29/100,000)
Symptomatic
Cryptogenic
(50%; incidence rate, 30/100,000)

8. Mortality rates in childhood onset epilepsies are three times more than the general population as shown in long term prospective studies.
Sillanpää M. NEJM 2010
Many unmet needs and co morbidities lead to more suffering in these children
Perera H. et al CMJ 2004

9. Evolution Approach to childhood epilepsy Seizure classification
Epilepsy syndromes

10. Why do we use a syndrome based classification?

11. Purpose of seizure classification & syndromes
Simple
Easy to use
Communication
Therapeutic guidance
Prognostic information

12. Seizure Classification (1981)
Generalised -Absence -Tonic -Clonic -Tonic-clonic -Myoclonic -Atonic
Partial
- Simple
-Complex

13. Generalized Partial Complex Simple
Involves BOTH hemispheres of the brain
May have aura
No impaired consciousness
Always involves loss of consciousness
Involves motor* or autonomic# symptoms with altered level of consciousness
Can involve motor,* autonomic# or somatosensory+ symptoms
Types:
Tonic or clonic movements or combination (grand mal)
Absence (petit mal)
Myoclonic
Atonic (e.g., drop attacks)
Infantile spasms
May generalize

14. Classification of epilepsies (1989)?
Localisation related
Symptomatic, Cryptogenic, Idiopathic
Generalised
Indeterminate
LGS, SME
Special syndromes
FC, Status epilepticus

15. Epilepsy vs. Epilepsies
Syndromic Diagnosis
5 Axis EEG Diagnosis (DESSCRIBE)

16. The Axis Principle (2001) A Diagnostic Scheme
Axis 1: Describe semiology Axis 2: Define seizure type Axis 3: Define epilepsy syndrome Axis 4: Identify underlying aetiology Axis 5: Characterise additional impairments

17. Get an accurate description of the signs and symptoms.
Axis 1
Describe semiology
Get an accurate description of the signs and symptoms.

18. Axis 2 Define seizure type Eg: Myotonic Clonic Tonic-Clonic Absence
Atonic

19. Define epilepsy syndrome
Axis 3
Define epilepsy syndrome
Try to achieve a comprehensive classification under Idiopathic, Syndromic and cryogenic

20. Identify underlying aetiology
Axis 4
Identify underlying aetiology
For optimum care under guidelines

21. Characterise additional impairments
Axis 5
Characterise additional impairments
Eg : Learning difficulties Behavioural changes

22. ILAE Revised Terminology and Concepts (2010)
Not a new classification scheme
Brought in several lines of developments in the field.
But, was it enough?

23. Practical Approach

24. DESSCRIBE Description Epileptic or not Seizure type Syndrome Cause
Relevant
Intelligence
Behavior
Education

25. Most important part of the history is the early phase
Epileptic or not ?
Most important part of the history is the early phase
How it begins…
Context
Premonitory symptoms
Pallor etc.

26. Non epileptic Breath holding attacks Benign sleep myoclonus Syncope
Pseudo-seizures (NEAD)
Non epileptic myoclonus of infancy

27. Epilepsy in Children 1% children have epilepsy (US )
Focal epilepsy is more common
Some epilepsy syndromes are unique in children

28. Challenge Of Differentiating Epileptic Seizures
Provoked
Febrile seizures
Reflex anoxic seizures
HIE
Hypoglycemia
Hypocalcaemia
Metabolic derangements
Infections
Trauma

29. Febrile Seizures
Most common seizure disorder in childhood, affecting 2 - 5% of children between the ages of 6 months and 5 years
Benign
May be either simple or complex type seizure
Seizure accompanied by fever (before, during or after) without any
Central nervous system infection
Metabolic disturbance
History of previous seizure disorder

30. Epilepsy management is NOT only the control of seizures.
Diagnosis (Complete)
Investigations
Treatment of seizures
Management of other aspects

31. Investigations Analysis of event – Video of the event
EEG – Digital EEG, video EEG
Imaging
Blood investigations – Sugar, Electrolytes, Metabolic

32. Digital EEG Technology

34. Value of Digital EEG Low cost Longer duration of recording time
Multiple montages
Facilitates synchronized (real-time) recording
Facilitates seizure classification and symptomatic diagnosis
Use of more EEG leads (Up to 80)
Easy storing and sharing, in digital form

35. Treatment of Seizures Avoidance of provoking factors Medications
Ketogenic diet
Vagal nerve stimulation
Epilepsy surgery

36. 60 - 70% respond to a single AED
% of childhood onset epilepsies remain drug resistant from beginning.
Sillanpää M. Brain 2006

37. Available Medications
Sodium Valproate
Carbamazepine
Phenobarbital
Phenytoin
Ethosuximide
Gabapentine
Lamotrigine
Topiramate
Vigabatrin

38. Common Paediatric Epilepsy Syndromes

39. Neonatal Period Benign Neonatal Epilepsy
Benign Familial Neonatal Epilepsy
Otahara Syndrome
Early Myoclonic Encephalopathy (EME)

40. Infancy Benign Myoclonic Epilepsy of Infancy
Infantile Spasms/ WEST Syndrome
Severe Myoclonic Epilepsy of Infancy

41. Childhood Childhood Absence Seizures Epilepsy With Myoclonic Absence
Benign Epilepsy With Centro-Temporal Spikes (Rolandic)
Some Progressive Myoclonic Epilepsies
Lennox-Gastuat Syndrome
Epilepsy With Myoclonic-astatic Seizures
Landu-Kleffner Syndrome

42. Adolescent Juvenile Absence Seizures Juvenile Myoclonic Epilepsy
Epilepsy with GTC on awakening

43. Neonatal Epilepsy

44. Benign Neonatal Epilepsy
Age of onset days of life, usually day 5
Prevalence - rare
Seizure type - focal clonic seizures or subtle neonatal seizures, usually unilateral, may occur in clusters
Milestones - normal or minor delay
EEG - Rolandic bursts of theta rhythms, localized spikes or slow waves
Neuroimaging - normal

45. Aetiology - idiopathic
Medical treatment – none
Phenobarbitone
Phenytoin
Benzodiazepines
Prognosis - excellent

46. Benign Familial Neonatal Epilepsy
Age of onset - Day 2-3 after birth, occasionally up to 3 months
Prevalence - rare
Seizure type - generalized clonic or tonic clonic
Milestones - normal
Family history of epilepsy - AD inheritance
EEG - brief flattening followed by asymmetrical spike waves
Neuroimaging - normal

47. Aetiology - idiopathic
Medical treatment - none
Phenobarbitone
Valporate
Prognosis - generally good
seizures cease by age of 6 months
10% develop other syndromes

48. Video

49. Case 1
2month old girl was referred to Paediatric Neurology Unit with medically intractable seizures that started from second day of life. Birth history and antenatal history were unremarkable.
She was treated with phenobarbitone and did not have seizures for one week but seizures recurred and became increasingly frequent.

50. Examination revealed well developed girl having frequent brief extensor tonic spasms in awake and in sleep status.
Physical examination Normal
Neurological Examination-
appeared awake
did not fix and follow
vacant appearance
brachycephaly
diffusely hypotonic hyporeflexic
An EEG was performed

51. EEG

52. Ohtahara’s Syndrome Age of onset - First month of life
Prevalence - rare
Seizure type - brief tonic spasms
Milestones - delayed
Family history of epilepsy - not usually, some have family history of febrile seizures
EEG - burst suppressions
Neuroimaging - abnormal

53. Aetiology - major brain malformations
Medical treatment - usually ineffective
but corticosteroids, Valporate, Vigabatrin & Benzodiazepines tried
Prognosis - poor
frequent evolution in to West syndrome and Lennox-Gastaut syndrome

54. Case 2
A girl born at term to non consanguineous parents with normal birth parameters after normal pregnancy, hospitalized at day 11 due to poor sucking.
During hospitalization, seizures were noted for the first time and initially phenobarbital was administrated.
These seizures were reported as typical ‘erratic myoclonic seizures'.
In addition, she had two generalized tonic–clonic convulsions during fever.
The first EEG performed at day 15 was reported normal. However, in the following days and weeks, the EEG's changed, showing a pattern of suppression bursts initially more accentuating during sleep, but later also during wakefulness.
Despite treatment, the frequency of seizures increased dramatically during the following months.
Her development was severely delayed with pronounced hypotonia, absent eye contact, limited spontaneous movements, no speech development and progressive microcephaly.
The therapy-resistant seizures led to her being admitted, at the age of 18 months, to an epilepsy center for children.

56. Early Myoclonic Encephalopathy
Age of onset - Neonatal period
Prevalence - rare
Seizure type - polymyoclonus, generalized myoclonus, evolving in to infantile spasm after several months
Milestones - delayed
Family history of epilepsy - often present
EEG - burst suppressions
Neuroimaging - normal initially or abnormal

57. Aetiology - genetic and metabolic disorders
non ketotic hyperglycinaemia
Medical treatment - usually ineffective
but corticosteroids, Valporate, Vigabatrin,benzodiazepines tried
Prognosis – poor
50% die within a year
may transiently evolve in to West Syndrome

58. Benign Myoclonic Epilepsy Of Infancy
Age of onset - 4 months to 3 years
Prevalence - rare
Seizure type - generalized myoclonus, often when falling asleep
Milestones - normal
Family history of epilepsy - present in 30% patients
EEG - generalize spike waves and poly spikes
Neuroimaging - normal

59. Aetiology - idiopathic
Medical treatment – Valproate
Benzodiazepines
Prognosis - good

60. Infentile Spasm

61. West Syndrome Syndrome classification - Infantile spasm
- Hypsarrhythmia on EEG
- Arrest of psychomotor development
Age of onset months
Prevalence - uncommon
Seizure type - spasms, some times subtle with head nods in clusters, usually when awakening
Milestones - severely affected
Family history of epilepsy - unusual
EEG - Hypsarrhythmia
Neuroimaging - normal or abnormal according to aeitiology

62. Aetiology - Perinatal Hypoxic Ischaemic Encephalopathy,
Malformations (particularly tuberous sclerosis)
Pre and post natal infections
Metabolic disorders (phenylketoneuria)
Medical treatment -
- 1st line- Vigabatrin and corticosteroids
- Valporate, Nitrazepam , immunoglobulin, pyridoxine are being tried
- ketogenic diet
Prognosis -
poor
development delay 85%, 50-60%
develop in to other epilepsy syndromes- Lennox-Gastaut syndrome

63. Infantile Spasms

64. Severe Myoclonic Epilepsy In Infancy
Age of onset months
Prevalence - 6% of epilepsies starting before the age of 3
Seizure type –
initially (before 1 year of age) febrile seizures- prolonged
second year- generalized or segmental myoclonic seizures
40-60% have additional absence seizures and focal motor seizures
Milestones - initially normal but psychomotor delay in 2years
Family history of epilepsy - present in 15-25% patients
EEG - initially normal in 1st year of life , later diffuse and multifocal abnormalities
Neuroimaging - normal or abnormal (largely diffuse atropy)

65. Aetiology - most often due to sporadic sodium channel mutations
Medical treatment - Valproate
Benzodiazepines
Stripentol
Topiramate
Prognosis - poor

67. Progressive Myoclonic Epilepsies
Age of onset - usually between 8-14 years
Prevalence - rare
Seizure type - generalized myoclonus
Milestones - delayed
Family history of epilepsy - often but not always
EEG - sharp spikes or poly spike and waves
Neuroimaging - normal or abnormal

68. Aetiology - neurodegenerative and genetic metabolic diseases
Medical treatment - limited efficacy
Prognosis - very variable, often poor

70. Childhood Absence Epilepsy
Age of onset years, peak at 5-7 years
Prevalence - common
Male: female= 1:2.5
Seizure type - typical absences
Milestones - normal
Family history of epilepsy - frequent
EEG - generalized spike and waves
Neuroimaging - normal

71. Aetiology - idiopathic
Medical treatment- Valporate Ethosuximide
Lamotrigine
Prognosis – good

72. Rolandic Epilepsy Age of onset - 3-13 years
Prevalence - Most common epilepsy syndrome in childhood
Seizure type - focal sensory or motor seizures
Milestones - normal
Family history of epilepsy - frequent
EEG - Rolandic focal or bilateral spike and waves
Neuroimaging - normal

73. Aetiology - idiopathic
Medical treatment - Carbamazepine
Sultiame
Prognosis - usually excellent
remits spontaneously at puberty

74. Lennox-Gastaut Syndrome
Syndrome definition –
tonic, atonic, atypical, absence seizures
EEG generalizes slow spike waves while awake
developmental delay
learning disability
Age of onset years
Prevalence - uncommon
Seizure type - tonic, atonic, atypical absences
Milestones - severely delayed
Family history of epilepsy - low but depends on aetiology
EEG - generalized slow spike waves while awake
Neuroimaging - normal or abnormal

75. Aetiology - unknown
West Syndrome
diffuse cerebral atrophy
Medical treatment - not very effective
Prognosis - poor

77. Landau-Kleffner Syndrome
Syndrome definition –
acquired aphasia
seizures
behavioral difficulties
continuous status epilepticus during slow wave sleep
Age of onset years
Prevalence - rare, possibly under diagnosed
Seizure type - tonic, clonic or focal motor seizures
Milestones - mainly verbal deficits until adolescence
Family history of epilepsy - 12%
EEG: awake EEG - normal or multifocal discharges
sleep EEG - continuous generalized spike and wave activity
Neuroimaging - normal

78. Aetiology - unknown
Medical treatment -
initial short trial with corticosteroids Benzodiazepines
Valproate
Lamotrigine
Prognosis - good for seizure control
poor for language recovery

79. Juvenile Absence Epilepsy
Age of onset years, peak 9-13 years
Prevalence - common
Seizure type - typical absence and tonic clonic on awakening
Milestones - normal
Family history of epilepsy %
EEG - generalized spike and waves
Neuroimaging - normal

80. Aetiology - idiopathic
Medical treatment –
Valproate
Ethosuximide
Lamotrigine
Prognosis - treatment less effective than absence epilepsy in childhood

81. Juvenile Myoclonic Epilepsy
Age of onset years, peak years
Prevalence - most common epilepsy syndrome in onset of adolescence
Seizure type - myoclonic seizures
Milestones - normal
Family history of epilepsy - frequent
EEG - generalized poly spike and waves activated by sleep
Neuroimaging - normal

82. Aetiology - idiopathic
genetic
Medical treatment -
Valporate is the most effective
Topiramate
Lamotrigine
Levetiracetam
Prognosis - good

83. THANK YOU