1. Pediatric Epilepsy Syndromes
Stefanie Jean-Baptiste Berry, MD
Pediatric Neurologist/Epileptologist
Northeast Regional Epilepsy Group

2. Introduction Most Recent ILAE Definition April 2014:
(1) At least two unprovoked (or reflex) seizures occurring >24 h apart
(2) One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
(3) Diagnosis of an epilepsy syndrome

3. Introduction
Term Epilepsy Syndrome has been used by ILAE to refer to “a complex of signs and symptoms that define a unique epileptic condition.”
Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, other characteristic clinical features such as age at onset, course of epilepsy, associated neurologic and neuropsychological findings, and underlying pathophysiologic or genetic mechanisms.

4. Introduction
Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome.
Idiopathic (primary) – presumed etiology is genetic
Symptomatic (secondary) types – underlying etiology is known or presumed based on other evidence of brain dysfunction, such as developmental delay.
Generalized seizures vs. Localization-related seizures.

6. Benign Familial Neonatal Seizures
Typically present during the first few weeks of life
Focal, multifocal, or generalized seizures
Seizures are brief but occur 20 – 30 times per day
Seizures may be difficult to control

7. Benign Familial Neonatal Seizures
Normal neurologic exam
No specific EEG features
Family history of similar neonatal seizures is important for diagnosis
Autosomal dominant with 85% penetrance
Linked to voltage gate potassium channels KCNQ2 and KCNQ3 on chromosomes 20q and 8q

8. Benign Familial Neonatal Seizures
Outcome generally favorable
Resolution of seizures typically in early to midinfancy
Normal neurodevelopment
8-16% of patients will later develop epilepsy as adults

9. Benign Idiopathic Neonatal Seizures
Healthy, neurologically normal term neonates
Seizures typically begin on the fifth day of life or “fifth day fits”
Partial clonic seizures that migrate, increase in frequency and culminate in status epilepticus

10. Benign Idiopathic Neonatal Seizures
No specific EEG features
There is no family history of seizures
Seizures typically resolve after 24 hours
Children have normal neurodevelopment
No increased risk of seizure recurrence

11. Generalized (Genetic) Epilepsy with Febrile Seizures Plus
Characterized by febrile and afebrile seizures
Febrile seizures continue beyond the typical age of remittance, 6 years
Afebrile seizures are infrequent, brief, and include generalized tonic-clonic, myoclonic, complex partial and atonic seizures.

12. Generalized (Genetic) Epilepsy with Febrile Seizures Plus
Seizures start 4 months and 10 years, with mean onset of 2 years
Prior to onset of afebrile seizures, GEFS+ can be difficult to distinguish from febrile seizure
Careful family history is important

13. Generalized (Genetic) Epilepsy with Febrile Seizures Plus
Interictal EEG may be normal or demonstrate generalized epileptiform discharges
Genetically heterogenous autosomal dominant with 60-80% penetrance
Within families multiple phenotypes with variable severity exist

14. Generalized (Genetic) Epilepsy with Febrile Seizures Plus
Multiple gene mutations linked to GEFS+ including 19q13.1 (SCN1B gene), 2q (SCN1A gene) and 5q
Excellent prognosis in most children
Seizures typically spontaneously remit by age 11 years
Up to 30% may have more severe epilepsy

15. Myoclonic Astatic Epilepsy of Doose
Rare, affecting 1:10,000
Presents in previously neurologically healthy preschool-aged children
Multiple seizure types including generalized tonic clonic, myoclonic, absence, atonic, myoclonic, myoclonic atonic
Myoclonic atonic seizures most prominent

16. Myoclonic Astatic Epilepsy of Doose
Outcome and course are variable – complete remission to intractable epilepsy with poor cognitive outcome
EEG demonstrates 2-3Hz spike and wave discharges
Up to 32% of children have a family history of epilepsy
Inheritance pattern is unknown

17. Childhood Absence Epilepsy
Comprises 2-15% of childhood epilepsy
Onset is usually 4 and 10 years of age
Girls 2-5 times more likely to have absence
Most patients with childhood absence have normal neurological exams and normal intelligence scores

18. Childhood Absence Epilepsy
Inherited in autosomal dominant pattern with incomplete penetrance chromosomes 20q, 16p13.3, and 8q24.3
Caused by abnormalities in T-type calcium channels, which are responsible for rhythmic depolarizing activity in the thalamic neurons

19. Childhood Absence Epilepsy
Generalized type of seizure
Characterized by sudden discontinuation of activity with loss of awareness, responsiveness, and memory, with an abrupt recovery
Automatisms, brief clonic jerks, and loss of postural tone can also be seen

20. Childhood Absence Epilepsy
Usually lasts 5 to 10 seconds
Up to hundreds of seizures per day
Seizures can be provoked by hyperventilation in approximately 90% of children

21. Childhood Absence Epilepsy
Classic EEG finding in typical absence seizures is the sudden onset of 3-Hz generalized symmetrical spike and wave complexes
Interictal EEG background is normal

22. Childhood Absence Epilepsy
Normal EEG

23. Childhood Absence Epilepsy
Absence Seizure

24. Childhood Absence Epilepsy
Most children only experience absence seizures
3% will experience generalized tonic-clonic seizures

25. Childhood Absence Epilepsy
With typical absence seizures, if consistent EEG, normal intelligence, and normal neuro exam, no further work up is necessary
Primary drugs of choice are ethosuximide (Zarontin), valproic acid (Depakote), and lamotrogine (Lamictal)
Most clinicians start with ethosuximide (T-type calcium channel blocker) because of fewer incidence of side effects 25

26. Childhood Absence Epilepsy
Valproic acid is the drug of choice in patients with both absence and generalized tonic-clonic seizures
Lamictal is a safer choice for female teens
Duration of therapy is variable, although general rule is to taper off therapy after 2 seizure free years

27. Childhood Absence Epilepsy
Absence status epilepticus is characterized by sustained impairment of consciousness associated with generalized 3-Hz spike and wave
Patients often exhibit facial twitching, eye blinking, staring and automatisms
Treatment is usually with IV lorazepam or Depakote (not Dilantin)
Dilantin is contraindicated – may worsen 27

28. Childhood Absence Epilepsy
Children with early onset (mean age 6) have the best prognosis with complete remission 2 to 6 years after onset
Onset of absence seizures before age 3 years is associated with increased likelihood of neurodevelopmental abnormalities

29. Childhood Absence Epilepsy
Average age of cessation is 10 years old
Typical absence seizures generally have a favorable prognosis with remission rates of approximately 80 percent
Can precede juvenile myoclonic epilepsy in 11-18% of cases

30. Childhood Absence Epilepsy
Risk factors for intractability: myoclonic or atonic component to seizure, generalized tonic clonic seizures occur at onset and photosensitivity on EEG

31. Juvenile Absence Epilepsy
Onset is typically between ages 10 and 16
Clinical seizures similar to CAE
Seizures occur less frequently and may be longer duration
More likely to experience generalized tonic clonic seizures
Interictal EEG, 3.5-4Hz spike and polyspike and wave
Response to treatment good, but may be lifelong

32. Juvenile Myoclonic Epilepsy
Affects 4 to 10% of all patients with epilepsy and up to 26% of patients with idiopathic generalized epilepsy
Seizures typically present between 12 and 18 years
Inheritance is complex
Classic form is likely autosomal dominant and inherited and linked to 6p12-11

33. Juvenile Myoclonic Epilepsy
Commonly 1st seizure noted is a GTC in setting of sleep deprivation
Careful questioning will reveal a history of myoclonic seizures and possible absence seizures in the preceding months
Occurs in both genders with equal frequency

34. Juvenile Myoclonic Epilepsy
Seizure types include generalized tonic-clonic, myoclonic, and absence
100% have myoclonic seizures, 96% have GTC, and only 20% with absence
Generalized tonic-clonic and myoclonic seizures tend to occur in morning upon awakening
Seizures are precipitated by sleep deprivation, alcohol ingestion and in women, menstruation

35. Juvenile Myoclonic Epilepsy
Myoclonic seizures are brief and bilateral, flexor jerks of the arms, which may be repetitive
Jerks sometimes affect the legs, causing the patient to fall
Consciousness is not impaired during myoclonic seizures

36. Juvenile Myoclonic Epilepsy
Delays in diagnosis are common, often until a generalized tonic-clonic seizure brings the child to medical attention
Interictal EEG in JME consists of generalized spike and polyspike-and-wave discharges of 4 to 6 Hz, usually maximal in the frontocentral regions
Photic stimulation often provokes a discharge (30 to 90%)

37. Juvenile Myoclonic Epilepsy
Generalized Polyspike and Wave Discharge

38. Juvenile Myoclonic Epilepsy
Traditional treatment was valproic acid with 85%-90% response but many side effects
Newer effective drugs include levetiracetam, lamotrogine, topiramate and zonisamide
Carbamazepine, phenytoin and gabapentin may exacerbate seizures
Response to treatment is excellent but treatment is lifelong

39. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
Most common form of idiopathic partial epilepsy
Accounts for 13%-23% of all childhood epilepsies
Although it is clearly familial, its mode of inheritance is unclear
Onset is between 4 and 10 years
Peak age of onset is 7-8 years
Children are neurologically and cognitively normal

40. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
Nocturnal seizure, usually occurring after falling asleep or before awakening is typical
Seizures described as unilateral paresthesias of the face, unilateral clonic or tonic activity involving the face, speech arrest, drooling with preserved consciousness
Can have secondarily generalized tonic-clonic seizures

41. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
EEG background is normal
Spikes are present at the midtemporal and central (centrotemporal) head region
Marked activation of spikes in drowsiness and sleep is characteristic, and 30% of cases show spikes only during sleep

42. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
EEG Findings BCECTS

43. EEG Findings BCECTS

44. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
If typical history, normal neuro exam, and characteristic EEG findings, an MRI is not necessary
No treatment is necessary in patients with infrequent, nocturnal, partial seizures
If seizures are frequent (20%)and disturbing to patient and family, treatment with Tegretol or Trileptal is usually successful 44

45. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
Excellent prognosis
Spontaneous remission occurs by age 15 to 17, often much earlier
Some children may develop language, cognitive or behavioral deficits which improve after remission

46. Panayiotopoulos Syndrome
Early-onset benign childhood epilepsy with occipital paroxysms
Average age of 3-6 years
Normal development
Characterized by nocturnal seizures in two-thirds, with tonic eye deviation, vomiting (autonomic) and impaired consciousness
Hemiconvulsions and GTC seizures are common
Prominent autonomic features include: tachycardia, incontinence and color change

47. Panayiotopoulos Syndrome
Interictal EEG shows normal background with high-amplitude occipital spike-wave complexes on eye closure
Seizures are infrequent and one third of patients will only have a single seizure
Paradoxically, seizures are frequently prolonged (status epilepticus)
Excellent prognosis –seizures usually cease within 2 years onset
Treatment with medication is not necessary

48. Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Rare condition
Ages 6-12 years, average 8 years
21-37% of cases have family history of epilepsy.

49. Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Seizures characterized by visual hallucinations or ictal blindness often with gaze deviation or eyelid fluttering
Often followed by postictal headache
Focal seizures often evolve into hemiconvulsions or GTC seizures
Seizures more frequent but shorter duration

50. Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
EEG –normal background, interictal occipital high amplitude spike wave with attenuation on eye opening
Ictal recordings show fast occipital spikes

51. EEG Findings Childhood Epilepsy with Occipital Paroxysms

52. Late-Onset Childhood Epilepsy with Occipital Paroxysms - Gastaut Syndrome
Brain MRI is normal (neuroimaging is recommended)
Seizures respond well to carbamazepine
50-60% have seizure remission within 2-4 years

53. Infantile Spasms
Occurs almost exclusively in infants younger than 1 year of age
Incidence is 1 in 4,000 to 6,000 births
Spasm onset is usually within the first 4-8 months of life
Familial occurrence is rare

54. Infantile Spasms
Seizures typically described as brief, symmetrical contractions of the neck trunk, and extremities
Flexor or extensor muscles can be involved
Asymmetrical infantile spasms are rare
Spasms frequently occur immediately upon, or soon after, arousal
80% of spasms occur in clusters
Delay in diagnosis is often considerable; parents and pediatricians think movements are due to colic; cry after spasms 54

55. Infantile Spasms
Interictal EEG is characterized hypsarrhythmia defined as high voltage slow waves and multifocal spikes
In a small number of infants, the background activity may appear normal
Most common ictal pattern is characterized by generalized slow wave transient followed by attenuation of background activity
Hypsarrythmia seen in the beginning but will resolve. 55

56. Infantile Spasms
Hypsarrhythmia

57. Infantile Spasms
Etiologies of infantile spasms can be determined in 60%-90% of cases
Tuberous sclerosis is a major cause of infantile spasms (up to 25%)
Other etiologies include: lissencephaly, Sturge-Weber, HIE, meningitis, and inborn errors of metabolism
A minority of infants have idiopathic infantile spasms

58. Infantile Spasms First line is ACTH but has many side effects
Vigabatrin, Prednisone, and Topamax are also effective drugs
A challenge with a 100mg of IV pyridoxine should be considered in idiopathic cases
Pyridoxine deficiency; usually respond within 15 minutes; response to steroids is either complete or not at all 58

59. Infantile Spasms
Overall prognosis is poor, with only 5% of the total patient population having normal outcomes
Severe or very severe impairment was observed in 67% of patients
Only factor that seems to effect long-term outcome is whether the patient is classified as cryptogenic (unknown) or symptomatic

60. Lennox Gastaut Syndrome
Classic Triad:
Multiple seizure types (tonic, atonic, and atypical absence)
EEG pattern of slow spike and wave discharges
Cognitive Impairment

61. Lennox Gastaut Syndrome
Onset usually between 1 and 8 years
Most cases between 2 and 5 years
Onset rare after 10 years
Males > females
10% of childhood epilepsies
Prenatal, perinatal and postnatal disorders; cyptogenic usually begins with drop attacks
1/3 cryptogenic; injuries from violent drops associated with atonic and tonic seizures 61

62. Lennox Gastaut Syndrome
Neurological symptoms may be absent initially
9-39% preceded by infantile spasms
High seizure frequency
At least 1 episode of status in 50%-75%

63. Lennox Gastaut Syndrome
No single cause
2/3 symptomatic (cortical dysplasias, TS, metabolic, prenatal/perinatal)
Cryptogenic (unknown cause) LGS with normal brain MRI accounts for 1/3 cases

64. Lennox Gastaut Syndrome
Tonic Seizures:
Most characteristic – prerequisite
Flexor movement of the head and trunk with apnea preceded by brief cry (axial)
Abduction, elevation of limbs, usually arms with clenching of the fists (axorhizomelic)
Sustained contraction involving most
muscles, including distal (global)

65. Lennox Gastaut Syndrome
Atypical Absence:
Second most common type
Brief loss/lapse of consciousness
Difficult to identify
Difficult to identify brief lapse that are already significantly impaired; parental recognition may be as low as 27% 65

66. Lennox Gastaut Syndrome
Atonic Seizures:
“Drop attacks”
Particularly hazardous
56% of patients
Other types:
Focal
GTC
Unilateral Clonic

67. Lennox Gastaut Syndrome
EEG Findings in LGS:
Slow background
Diffuse slow-spike and wave, Hz
Paroxysmal Fast Activity
Focal or multifocal discharges in 14%-18%
75% of electroclinical persists to adult
Enhanced in NREM sleep; In sleep, fragmentation of SSW pseudoperiodic, burst suppression 67

68. Lennox Gastaut Syndrome
Slow Spike and Wave

69. Lennox Gastaut Syndrome
Paroxysmal Fast Activity 69

70. Lennox Gastaut Syndrome
Seizures resistant to therapy
Drugs used in combination, mostly guided by anecdotal evidence or personal experience
AED may help control one seizure type while worsening another
First line AEDs are Valproic Acid and Benzodiazepines
Rufinamide and Felbamate

71. Lennox Gastaut Syndrome
Overall, unfavorable prognosis
Worse prognosis:
Symptomatic
Infantile spasms
Early onset seizures
Higher seizure frequency
Constant background slowing

72. Dravet Syndrome Rare Incidence of 1 in 20,000 to 40,000
Approximately 80% of cases have mutation in SCN1A (sodium channel)
Vast majority of mutations are sporadic
Close relatives have a higher rate of seizures (GEFS+)
Likely underrecognized

73. Dravet Syndrome
Begins in the first year of life in previously well infant
Generalized or focal clonic seizure is often prolonged
Onset frequently triggered by fever, infection, vaccination or warm bath
Progression to further recurrent prolonged focal seizures with and without fever

74. Dravet Syndrome
End of second year through age 5, myoclonic jerks appear
Atypical absence and complex partial seizures with autonomic symptoms occur in 50% in preschool years
Tonic seizures are rare

75. Dravet Syndrome Initial EEG is typically normal
Over time, background slows
Multifocal and generalized polyspike and wave discharges appear
Epileptiform discharges activated by drowsiness and photic stimulation
MRI normal early, later shows atrophy

76. Dravet Syndrome Infants are developmentally normal at onset
Regression or lack of progression is seen between 1 and 4 years, stabilization after at lower level
Visuomotor skills more affected than language

77. Dravet Syndrome Seizures are medically refractory
Valproic Acid and clobazam are first line
Second line AEDs include topiramate, levetiracetam and zonisamide
Lamotrigine and carbamazepine should be avoided – can aggravate seizures
Mortality rate 16-18% (status, SUDEP, drowning)

78. References
Wirrell, Elaine and Nickels, Katherine C. Pediatric Epilepsy Syndromes. Continuum Lifelong Learning Neurology 2010; 16(3)
Ebersole and Pedley, Current Practice Of Clinical Electroencephalography. Third Edition 2003.
Menke, Sarnat and Maria. Child Neurology. Seventh Edition. 2006
Pellock, Dodson and Bourgeois. Pediatric Epilepsy: Diagnosis and Therapy. Second Edition. 2001