Epilepsy Syndromes

1. Epilepsy Syndromes Maja Ilic, MD Epileptologist Northeast Regional Epilepsy Group

2. What is seizure and what is epilepsy? • SEIZURE - Physiological: Manifestation of an abnormal and excessive synchronized discharge of a set of neurons - Clinical: Stereotypical, usually unprovoked, disturbance of consciousness, behavior, emotion, motor function or sensation as a result of the cortical neuronal discharge • EPILEPSY: 2 or more seizures

3. Provoked seizures • High fever, febrile seizures • Massive sleep deprivation • Excessive use of stimulants • Withdrawal from sedative drugs or alcohol • Electrolyte disturbance • Hypoxia • Acute neurological illness

4. > 2 million people in US 125,000 new cases per year Cumulative incidence of epilepsy by age 80 = 3.1% Cumulative incidence of seizures by age 80 = 11% Many patients outgrow their epilepsy Epidemiology

5. Historical background: • In an attempt to encompass a broader range of clinical features than is possible in a classification of seizure type – ILAE published a Classifications of Epilepsies and Epileptic Syndromes in 1985 and revised it in 1989

6. Epilepsy syndromes • Syndrome is a cluster of signs and symptoms that occur together but unlike a disease do not have a single known cause or pathology. • Epileptic syndrome integrates all data, seizure type, EEG findings, age of onset, cause, family history, imaging studies, precipitating factors, etc. in order to make a final diagnosis of epilepsy.

7. Most Common Epilepsy Syndromes in Children • Childhood Absence Epilepsy • Juvenile Absence Epilepsy • Juvenile Myoclonic Epilepsy • Benign Epilepsy of Childhood with Centrotemporal Spikes (Benign Rolandic Epilepsy)

8. Childhood Absence Epilepsy

9. Absence Epilepsy • Generalized seizures • Most common in the first decade, particularly ages 5-7 years of age

10. Clinical features • Usual duration – 10 seconds • Ongoing activities cease • Motionless with a fixed blank stare • Attack ends suddenly, activity resumes • Clinical features Occasionally – mild clonic activity of eyelids, corner of mouth • Automatisms – elevation of eyelids, licking, swallowing, scratching movements of hands

11. Absence Epilepsy • Most patients with typical absence have normal development and normal neurological exam • Generalized spikes on EEG • Precipitated by hyperventilation in all untreated patients - Photic stimulation – 15%

12. Absence Epilepsy • 10% family history • Average age when seizures stop is 10 years old • Generally have a good prognosis – resolves in ~ 80 percent of cases

13. Treatment: • Ethosuximide • Depakote Suppress absence in 80% • Lamotrigine

14. Absence Epilepsy Atypical • Complex automatisms • Slower, 2.5 Hz spike-slow wave • Focal and GTC seizures • Developmental delay • Abnormal background EEG Typical • Simple automatisms • 3 Hz spike-slow wave • No other seizure type • Normal exam • Normal background EEG

15. Juvenile Absence Epilepsy

16. Juvenile Absence Epilepsy • Age of onset • Near or after puberty • Between 10-17 years • Normal intelligence & neurological exam

17. Juvenile Absence Epilepsy • Seizures types • Absences • Generalized tonic-clonic seizures- in 80% (often shortly after waking) • Myoclonic seizures- in 15% • GTC and myoclonic seizure more common and most likely to happen with awakening

18. Juvenile Absence Epilepsy • EEG • Normal background • Generalized spike & wave discharges (faster, 4 Hz) • Induced by HV, not photic stimulation • Treatment • Depakote • Lamictal

19. Juvenile Absence Epilepsy • Prognosis • At least 80% of patients can be treated with Depakote alone • Absences and GTC usually respond well to pharmacotherapy • Unlike CAE (in which most patients become seizure free) the long term evolution of JAE has not been properly characterized

20. Juvenile Myoclonic Epilepsy

21. Juvenile Myoclonic Epilepsy • Incidence • 10% of all epilepsies • Age of onset • 12–18 years • Age of onset differs from age of diagnosis

22. Juvenile Myoclonic Epilepsy • Myoclonic jerks, generalized tonic-clonic seizures, and sometimes absence seizures • Myoclonic seizures • Jerks of neck, shoulder, arm or leg extensors • Usually bilaterally symmetric & synchronous • More in upper extremities • Drop objects, interfere in morning activities

23. Juvenile Myoclonic Epilepsy • Usual age at onset: - Absence seizures is 7 -13 years; - Myoclonic jerks, 12- 18 years; - Generalized convulsions, 13 - 20 years

24. Juvenile Myoclonic Epilepsy • More likely to have seizures with sleep deprivation and alcohol ingestion • Risk for seizures is lifelong • Seizures recur when AEDs withdrawn • Photic stimulation often provokes a discharge • Seizures are usually well-controlled (Depakote, Lamictal)

25. Benign Epilepsy of Childhood with Centrotemporal Spikes Benign Rolandic Epilepsy

26. BECT • Age of onset • Range 2 – 13 years • 80% between 5 – 10 years (Peak 9 years) • Typically resolves by age 16 years • Normal intelligence and neurological exam • Seizures usually happen after falling asleep or before awakening (75%)

27. BECT • Most characteristic symptoms • Sensorimotor phenomena of face • Oropharyngeal – Hypersalivation, guttural sounds, contraction of jaw, difficulty moving the tongue etc • Speech arrest • Clonic jerks at corner of mouth • Clonic jerks of one arm • No loss of consciousness • Can have secondarily generalized convulsions

28. BECT • EEG: Spikes in midtemporal and central head region • More spikes in drowsiness and sleep • 30% of cases show spikes only during sleep

29. BECT BECTS spontaneously stop with or without treatment (good prognosis) • If seizures are frequent and/or disturbing to patient and family, treatment with Tegretol or Trileptal (until 14-16, response) • AEDs given in about 50% of cases • Features suggesting risk of repeated seizures • Short interval between 1st & 2nd attacks • Early onset

30. Febrile Seizures • Up to 4% of children • Not epilepsy • Often a family history, 10% (chromosomes 8q, 19p) • Seizures only occur with fever in children age 6 months – 6 years

31. Febrile Seizures • Simple - 1 brief seizure (generalized) • Complex – Prolonged • More than 1 • Focal

32. Febrile seizures • 13% incidence of epilepsy if at least 2 factors: • History of non-febrile seizure • Abnormal neurological exam or development • Prolonged febrile seizure • Focal febrile seizure

33. Febrile seizures • Recurrence risk: • Children with simple FS 30% • Children with complex FS 50% Risk of epilepsy: - With history of simple FS 2-4% - With history of complex FS 6%

34. Febrile Seizures • Increase risk of recurrence if 1st before 18 months or lower temperature • Focal need MRI, EEG • Testing unnecessary with simple • Treatment usually not necessary

35. Epilepsy Prognosis: Depends on seizure type: • Typical Absence – 80% resolve • JME- respond well to treatment but need meds for life Neurologically abnormal often difficult to control seizures

36. Drug Refractoriness of Different Seizure Types • Idiopathic partial 0-2% • Childhood absence 10-30% • Juvenile absence 10-35% • Primary GTCS 20-30% • Secondary GTCS 30-60% • CPS 40-60% • LGS 60-80% • Infantile spasms 60-80%

37. Most patients (>70%) will have excellent seizure control with medications • Some patients will continue to have seizures despite good medical therapy • Ketogenic diet • Vagal nerve stimulator • Epilepsy surgery

38. Treatment Goals • Prevent recurrence of seizures • Avoid side effects from AEDs • Attain “therapeutic levels” • Ensure compliance

39. General Guidelines for Use of AEDs • Select AED specific for seizure type and EEG findings • Start with single drug • Optimize AED • Balance seizure control vs. toxicity • Add second drug if first fails • Anticipate medication interactions

40. When to Treat After Single Seizure? Definitely • With structural lesion • Brain tumor • Arteriovenous malformation • Infection, such as abscess, herpes encephalitis • Without structural lesion • EEG with definite epileptic pattern • History of previous seizure • History of previous brain injury • Status epilepticus at onset Possibly • Unprovoked seizure Probably not (although short-term therapy may be used) • Alcohol withdrawal • Drug abuse • Seizure in context of acute illness • Postimpact seizure • Specific benign epilepsy syndrome • Seizure provoked by excessive sleep deprivation

41. Medications • Trileptal, Tegretol, Keppra, Depakote, Lamictal, Phenobarbital,Topamax, Ethosuximide… • Choice based on type of seizures, EEG findings, side effects, age and sex • 2nd AED may be added if seizures not controlled

42. Newer antiepiletic medications: • Lacosamide (Vimpat) • Vigabatrin (Sabril) • Rufinamide (Banzel) • Perampanel (Fycompa)

43. Conclusion: • Seizure type and diagnosis are only one element of a more comprehensive patient assessment that should result in a precise epilepsy syndrome diagnosis • Only an accurate diagnosis of a specific epilepsy syndrome allows patients and physicians to examine all treatment options

44. www.epilepsyfoundation.org • www.epilepsyadvocate.com • www.paceusa.org • www.epilepsy.com