1. Pediatric Epilepsy: An Overview and Update on Treatment Options
Mitzi Payne, MD
Pediatric Neurology
Marshall University 1

2. Approach to a patient with “spells”
Paroxysmal events
Obtain thorough history:
Before event
Description of event
After the event
Do descriptions vary event to event?
Are the events epileptic? 2

3. If the “spells” appear to be epileptic…
What type of epileptic seizures?
What is the cause of the seizure?
Is there a syndrome associated with the seizure type? 3

4. “Fits, faints, and funny turns”1
Differential Diagnosis of “spells”
Syncope
Migraine
Sleep disorders
Pseudoseizures (nonepileptic seizures) 4

5. Helpful tools for diagnosis
Accurate history and description of events
Ask family member to “act out” event
Ask family to videotape event
Provoking factors
Electroencephalogram 5

6. Some important points Classification(s)
seizure type an ictal event believed to represent a unique pathophysiological mechanism and anatomic substrate
epilepsy syndrome a complex of signs and symptoms that define a unique epilepsy condition
Etiological categories of syndromes
idiopathic no underlying structural brain disease, presumed genetic
symptomatic seizures are the result of lesional or metabolic disease of the brain
probably symptomatic (cryptogenic) believed symptomatic but no etiology established 6

7. Seizures: focal vs. generalized
Generalized seizure
a seizure whose initial semiology indicates, or is consistent with, more than minimal involvement of both hemispheres
Focal seizure (partial, localization-related)
a seizure whose initial semiology indicates, or is consistent with, initial activation of only part of one cerebral hemisphere 7

8. Generalized seizure types
Myoclonic
Sudden, <100 ms involuntary contraction of muscle(s) or muscle groups
Clonic
Repetitive, rhythmic myoclonus at 2-3 Hz
Tonic
Sustained muscle contraction for seconds to minutes
Generalized tonic-clonic
Bilateral symmetrical tonic contraction, then bilateral clonic contractions
Atonic
Sudden, brief, 1–2 s decrease in tone without preceding myoclonic or tonic event
Astatic
Loss of posture (=drop) due to atonic, myoclonic, or tonic event
Spasm
Axial contraction, may be asymmetric 8

9. Generalized epilepsies
Idiopathic generalized epilepsies
Benign myoclonic epilepsy in infancy
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absence seizures
Childhood absence epilepsy
IGE with variable phenotypes Juvenile absence, JME, epilepsy with GTC only
Generalized epilepsies with febrile seizures plus
Epileptic encephalopathies
Syndromes of infancy Early myoclonic encephalopathy; Ohtahara, Dravet, West syndromes
Lennox-Gastaut syndrome
Landau-Kleffner syndrome
Epilepsy with continuous spike waves in SW sleep 9

10. Focal seizure types Focal sensory Focal motor
with elementary sensory symptoms
with experiential sensory symptoms
Focal motor
with elementary clonic motor signs
with symmetric tonic motor signs
with automatisms
Secondarily generalized seizures 10

11. EEG Activating Procedures: Hyperventilation
Deep and regular respirations at a rate of 20 / minute for 2 to 4 minutes
Drop in plasma CO2 by 4-7 ml%
Normal response (and best seen in children) is high amplitude slow activity 11

12. EEG Activating Procedures: Hyperventilation
Hyperventilation may induce diffuse sharp waves or spike-wave complexes
Patients with generalized epilepsies are most likely to have these findings
Actual seizures can be induced by hyperventilation
Absence (petit mal)
Temporal lobe seizures 12

13. EEG Activating Procedures: Intermittent Photic Stimulation
Strobe light flashes (1-30 Hz)
Photic driving
Rhythmic activity over the posterior head regions
Photomyoclonic response
Repetitive muscle spikes over the anterior regions of the head
Photoconvulsive (-paroxysmal) response
Generalized spike and wave complexes
15-20 Hz
May have jerking or impairment of consciousness
Photosensitive epilepsies 13

15. EEG Activating Procedures
Somatosensory stimulation
Electrical stimulation of peripheral nerves
Epileptiform discharges in contralateral hemisphere
Reenactment of a trigger
Visual stimulation of geometric patterns
Auditory stimulation
Reading
Hypoglycemia 15

16. Common Childhood Epilepsy Syndromes16

17. Infantile spasms West syndrome
Onset ages 3-12 months
Brief axial contractions
usually bilateral, may be asymmetrical
typically flexor, may be extensor
usually in clusters, less likely random
typically on awakening, or when drowsy
EEG shows hypsarrhythmia
multifocal spikes
high voltage, chaotic background 17

18. Flexor spasm 18

19. 19

20. 20

21. Infantile spasms Often “cryptogenic” “Symptomatic” cases
no definite cause established but child is delayed
Rarely “idiopathic”
no cause established and child is normal
“Symptomatic” cases
congenital infections
CNS malformations
metabolic disorders
genetic syndromes
tuberous sclerosis
perinatal asphyxia
postnatal trauma
acquired infections
immunizations 21

22. Infantile spasms Short term treatment to stop spasms, improve EEG
ACTH effective, dose not established
oral steroids not proven effective
Vigabatrin, especially in tuberous sclerosis
not available in US,
potential retinal toxicity
Data insufficient to show early treatment or any treatment changes long term outcome 22

23. West Syndrome Infantile Spasms Hypsarrhythmia on EEG
Developmental regression that begins concurrently with the onset of spasms 23

24. Prognosis of West Syndrome2
Series of 150 patients with West Syndrome between 1954 and 1970
Idiopathic (n = 44)
Symptomatic (n = 106)
Outcomes measured by school type or residence (home or hospital) 24

25. Outcome Idiopathic cases: Normal school 37% Death 6%
Other seizure types 43%
Neurologic abnormality 31% 25

26. Outcome Symptomatic cases: Normal school - none Death 37%
Other seizure types 59%
Neurological abnormality 65%
Large number progress to develop Lennox Gastaut Syndrome 26

27. Rolandic epilepsy Onset ages 2-12 yrs, peak 5-10 yrs
Characteristic seizures
Infrequent simple partial seizures
tingling in mouth, on face, speech arrest
rare GTCS in sleep
Resolve by puberty
Characteristic EEG
high voltage centrotemporal spikes
usually bilateral
Imaging normal
Considered an idiopathic focal epilepsy
some evidence for genetic basis
Treatment
may not be necessary
may respond to many drugs 27

28. Centrotemporal spikes in Benign Rolandic Epilepsy28

29. Presentation of “staring spells”
Complex partial seizures
Absence seizures
Behavior staring

30. Complex Partial Seizures
Commonly temporal lobe focus
Begins in one area, then spreads enough to impair consciousness, but not to evoke a generalized tonic-clonic seizure
Staring is often part of the initial spread
Also can see automatisms…

31. Automatisms Coordinated involuntary movements Consciousness impaired
Patient does not recall activity
Simple
Lip smacking, chewing, uttering sounds, picking, tapping, walking straight or in circles
Complex (behavior involved)
Undressing, chewing inedible objects, wandering, aggression

32. Complex Partial Seizure

33. Complex Partial Seizure

34. Complex Partial Seizure

35. Treatment of complex partial seizures
Use medications for focal onset seizures
Levetiracetam (Keppra)
Oxcarbamazepine (Trileptal)
Carbamazepine (Tegretol/ Carbatrol)
Lamotrigine (Lamictal)
Topiramate (Topamax)
Zonisimide (Zonegran)
Phenobarbital
Valproic Acid (Depakote)
Lacosamide (Vimpat)

36. Absence epilepsy

37. Childhood absence (petit mal) epilepsy
Peak onset age 4-6 years
Many seizures daily
Seizures last seconds
70+% have associated automatisms
eyelid flutter
simple vocalizations
picking movements
Typical EEG with 3 Hz spike wave
Majority resolve by adolescence

38. slightly irregular
3 per second spike wave ▼

39. Absence Seizure

40. Absence Seizure

41. Absence Seizure

42. Pathophysiology of Absence Seizures
Generalized discharges occur from abnormal oscillatory rhythm in thalamocortical circuits
High density of T-type calcium channels in thalamus, thought to be involved

43. Treating absence seizures
Ethosuximide (Zarontin)
Valproic Acid (Depakote)
Lamotrigine (Lamictal)
Levetiracetam (Keppra)

44. Absence v. Complex Partial Sz
< 30 sec
Non-convulsive status epilepticus
Frequent (100’s a day)
Sudden onset, sudden termination
No post-ictal state
Hyperventilation a trigger
EEG: 3-4 Hz spike and wave
Rare interictal abnormalities
Complex Partial
> 1 minute
Rare non-convulsive epilepticus
Occur ≤ daily
Frequent simple, complex automatisms
Evolve to other sz manifestations
Post-ictal state
EEG: Interictal focal abnormalities

45. Behavioral Staring Most commonly seen in children with ADD, PDD, MR
Occurs when “bored” or over-stimulated
Does not typically make the patient fall or stop an activity abruptly
Can be stopped with close contact / stimulation
Also can be seen in children with epilepsy!

46. Evaluation of a 1st unprovoked seizure
Good evidence recommends EEG
EEG can help diagnose the event
EEG can identify a specific syndrome
EEG can help with prognosis
timing of EEG not determined
immediate EEG may show abnormality or post ictal slowing
abnormal EEG best predictor of recurrence in neurologically normal children
abnormal neuro exam also strong predictor of recurrence
Generalized burst
Benign focal spike 46

47. Evaluation of a 1st unprovoked seizure
Insufficient evidence for routine labs, LP, imaging
consider emergent imaging
if postictal focal deficit, or not at baseline in several hours
consider nonurgent MRI
with significant neuro abnormalities of unknown etiology
a seizure of focal onset
in children under 1 year of age
consider LP
in the very young child (<6 months)
in the patient who fails to return to baseline
in any patient with meningeal signs
if increased ICP suspected, image before LP 47

48. How likely is a 2nd seizure?
Evidence from multiple Class III studies
Recurrence ranged from 14%-65%
Most recurrences early (in 1st year)
Factors increasing recurrence risk
abnormal EEG
etiology
remote symptomatic seizure recurrence >50%
idiopathic seizure recurrence 30-50% 48

49. Summary of evidence: Treatment of 1st unprovoked seizure
Most children with a 1st seizure have few or no recurrences
10% will have many seizures regardless of initial Rx
Rx after 1st vs. 2nd seizure does not affect long term prognosis
Rx in adults and children leads to decreased recurrences 49

50. Recommendations: Treatment of a 1st Seizure
Anticonvulsant treatment after a 1st seizure must be individualized
treatment is not indicated for prevention of epilepsy
treatment may be considered if risks of recurrent seizure out weigh risks of Rx
Treatment must take into account patient and family preferences 50

51. Febrile seizures The most common seizures in childhood
In US affect 2-4% of children < age 5 yrs
8% Japan, 14% Guam
1/3 have at least 1 recurrence
Risk factors for recurrence
first febrile seizure < 1 year of age
low degree of fever at first febrile seizure
family history of febrile seizures
brief duration between fever onset and febrile seizure
4 risk factors = 70% recurrence
No risk factors = 20% recurrence 51

52. Febrile seizures Simple Complex generalized
and <15 minutes duration
Complex
focal
or >15 minutes
or recurrent within 24 hours 52

53. Evaluation of the child with simple febrile seizures
Lumbar puncture
if meningeal signs
in infants < 12 months
with prior antibiotic Rx
Blood studies not needed routinely
Imaging not necessary
EEG not necessary in simple febrile seizures 53

54. Treatment of the child with simple febrile seizures
Effective in reducing recurrences but with potential toxicities
continuous phenobarbital or valproic acid
intermittent diazepam 54

55. Treatment options for pharmacoresistant epilepsy
Ketogenic diet
Vagus nerve stimulation
Surgery 55

56. Ketogenic diet Very high fat, very low CHO, minimum RDA protein
Vitamins, mineral supplements necessary
Rigid compliance essential
Effective in 1/3-1/2 cases
all seizure types
all ages, but easiest to maintain in children
breakfast
lunch 56

57. Ketogenic diet formulations
Formulated in fat:CHO ratios
generally between 4:1 and 3:1
Atkins diet is about 2.2:1
Traditional diet
uses 40% cream, fatty foods
MCT diet
adds oils to “normal foods”
Tube feeding diet
CHO-free formula + microlipids or cooking oil 57

58. Surgical treatment of epilepsy
Lobectomy
anterior temporal lobectomy most frequent procedure
70% of selected patients become seizure-free
Extratemporal resection
nature and extent of pathology determine results
Hemispherectomy, multilobar resections
done in cases with extensive pathology
Corpus callosotomy
rarely performed as sole procedure
Multiple subpial transections
Palliative, done when focus is in “eloquent cortex” 58

59. Epilepsy surgery evaluation (for example)
Record seizures
MRI, MRA, SPECT, PET
Speech and memory tests
Wada test
neuropsych testing
fMRI
Electrocorticography, intracranial monitoring
Brain mapping
VideoEEG
SPECT
Intracranial grid 59

60. Vagus nerve stimulation (VNS)
FDA approved 1997
adjunctive treatment pharmacoresistant partial- onset epilepsy
ages 12 and older
Over 25,000 implanted
5,000 in children <12 60

61. Vagus nerve stimulation
Mild electrical pulses sent to L vagus
Automatic, intermittent stimulation
On-demand stimulation with magnet
In-office programming
Compliance assured
Programming
Magnet activation 61

62. VNS pulse generator and lead
>25,000 patients worldwide
Model 102 (June 2002)
single pin lead
6.9 mm thick
weight 25 grams
6-11 year battery life
Outpatient implantation
1 hour surgery
device test in OR, activated later 62

63. Seizure-response dogs
How do they do it?
Trained by several organizations 63

64. Diastat 64

65. Rectal diazepam - Given for seizures lasting longer than 5 minutes - Diastat is a safe way to give rescue seizure medication in the home or school environment - Dose varies by age and weight - If seizure continues 5 minutes after Diastat given, then EMS should be contacted - Some children have seizures that consistently are prolonged; in the case Diastat may be prescribed to be given at onset of seizure, instead of waiting 5 minutes. - Not FDA approved in children less than 2 years of age 65

66. Other Rescue Medication Options - Nasal midazolam - children refractory to Diastat - Oral lorazepam - seizure clusters - Routine seizure medications are NOT given as rescue medications - If a child routinely requires rescue medications on a consistent basis, then routine scheduled seizure medications need to be changed 66

68. Thank you!