Pediatric Epilepsy: An Overview and Update on Treatment Options

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 8

9. Generalized epilepsies 9

10. Focal seizure types 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) • Absence (petit mal) • 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 Syndromes 16

17. Infantile spasmsWest 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” • 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 Epilepsy 28

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 • Absence • < 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