Clinical Epilepsy

1. Clinical Epilepsy American Epilepsy Society

2. Clinical Epilepsy: Index Hyperlinks can be used in slide-show mode: Click on topics to navigate to section. Click on Return to index to return to this page. Click on [PubMed] links to view citations in pubmed • Definitions and epidemiology • Evaluation of a first seizure • Choosing antiepileptic drugs • Drug-drug interactions • Adverse effects • Discontinuing antiepileptic drugs • Epilepsy comorbidities • Epilepsy surgery Alternative therapies Status Epilepticus Non-epileptic events Epilepsy monitoring units SUDEP Driving Pregnancy and epilepsy Appendix American Epilepsy Society2015

3. Return to index Definitions American Epilepsy Society2015 •  Seizure: the manifestation of an abnormal, hypersynchronous discharge of a population of cortical neurons •  Epilepsy: recurrent seizures (two or more) which are not provoked by acute systemic or neurologic insults

4. Return to index Epidemiology of Seizures and Epilepsy American Epilepsy Society2015 •  Seizures • Incidence: 80/100,000 per year • Lifetime incidence: 9% (1/3 febrile convulsions) •  Epilepsy • Incidence: 45/100,000 per year • Point prevalence: 0.5-1% • Cumulative lifetime incidence: 3%

5. Return to index Seizures Partial Generalized Simple Partial Absence Complex Partial Myoclonic Secondarily Generalized Atonic Tonic Tonic-Clonic ILAE Classification of Seizures ILAE – International League Against Epilepsy American Epilepsy Society2015

6. Return to index Seizures Partial Generalized Simple Partial Complex Partial Secondarily Generalized ILAE Classification of Seizures American Epilepsy Society2015

7. Return to index Seizures Partial Generalized Simple Partial With somatosensory or special sensory symptoms With motor signs With autonomic symptoms or signs With psychic or experiential symptoms ILAE Classification of Seizures American Epilepsy Society2015

8. Return to index Complex Partial Seizures Seizures  Impaired consciousness  Clinical manifestations vary with site of origin and degree of spread • Presence and nature of aura • Automatisms • Other motor activity  Duration typically < 2 minutes Partial Generalized Complex Partial American Epilepsy Society2015

9. Secondarily Generalized Seizures Seizures  Begins focally, with or without focal neurological symptoms  Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases  Typical duration 1-3 minutes  Postictal confusion, somnolence, with or without transient focal deficit Partial Generalized Secondarily Generalized American Epilepsy Society2015

10. Return to index EEG: Partial Seizure American Epilepsy Society2015 Right Frontal seizure

11. Return to index EEG: Partial Seizure American Epilepsy Society2015 Continuation of the same seizure with change in amplitude and frequency

12. Return to index EEG: Partial Seizure American Epilepsy Society2015 Continuation of the same seizure with spread to the other hemisphere

13. Return to index EEG: Partial Seizure American Epilepsy Society2015 Continuation of the same seizure with spread to the other hemisphere

14. Return to index Seizures Partial Generalized Absence Myoclonic Atonic Tonic Tonic-Clonic ILAE Classification of Seizures American Epilepsy Society2015

15. Return to index Typical Absence Seizures Seizures  Brief staring spells (“petit mal”) with impairment of awareness • 3-20 seconds • Sudden onset and sudden resolution • Often provoked by hyperventilation • Onset typically between 4 and 14 years of age • Often resolve by 18 years of age  Normal development and intelligence  EEG: Generalized 3 Hz spike-wave discharges Partial Generalized Absence American Epilepsy Society2015

16. Return to index EEG: Typical Absence Seizure 3Hzspike/slow wave complexes American Epilepsy Society2015

17. Return to index Atypical Absence Seizures American Epilepsy Society2015  Brief staring spells with variably reduced responsiveness • 5-30 seconds • Gradual (seconds) onset and resolution • Generally not provoked by hyperventilation • Onset typically after 6 years of age  Often in children with global cognitive impairment  EEG: Generalized slow spike-wave complexes (<2.5 Hz)  Patients often also have Atonic and Tonic seizures

18. Return to index Atypical Absence Seizures American Epilepsy Society2015

19. Return to index Myoclonic Seizures Seizures Epileptic Myoclonus  Brief, shock-like jerk of a muscle or group of muscles  Differentiate from benign, nonepileptic myoclonus (e.g., while falling asleep)  EEG: Generalized 4-6 Hz polyspike-wave discharges Partial Generalized Myoclonic American Epilepsy Society2015

20. Return to index Myoclonic Seizures Generalized polyspike-slow-wave discharges American Epilepsy Society2015

21. Return to index Tonic and Atonic Seizures Tonic seizures • Symmetric, tonic muscle contraction of extremities with tonic flexion of waist and neck • Duration - 2-20 seconds. • EEG – Sudden attenuation with generalized, low-voltage fast activity (most common) or generalized polyspike-wave. Atonic seizures • Sudden loss of postural tone • When severe often results in falls • When milder produces head nods or jaw drops. • Consciousness usually impaired • Duration - usually seconds, rarely more than 1 minute • EEG – sudden diffuse attenuation or generalized polyspike-wave Seizures Partial Generalized Tonic Atonic American Epilepsy Society2015

22. Return to index Tonic and Atonic Seizures American Epilepsy Society2015

23. Return to index Generalized Tonic-Clonic Seizures Seizures • Associated with loss of consciousness and post-ictal confusion/lethargy • Duration 30-120 seconds • Tonic phase • Stiffening and fall • Often associated with ictal cry • Clonic Phase • Rhythmic extremity jerking • EEG – generalized polyspikes Partial Generalized Tonic- Clonic American Epilepsy Society2015

24. Return to index Epilepsy Syndromes American Epilepsy Society2015 Epilepsy Syndrome Grouping of patients that share similar: • Seizure type(s) • Age of onset • Natural history/Prognosis • EEG patterns • Genetics • Response to treatment

25. Return to index Epilepsy Partial Generalized Idiopathic Symptomatic Idiopathic Symptomatic Epilepsy Syndromes American Epilepsy Society2015

27. Return to index Etiology of Seizures and Epilepsy American Epilepsy Society2015  Infancy and childhood • Prenatal or birth injury • Inborn error of metabolism • Congenital malformation  Childhood and adolescence • Idiopathic/genetic syndrome • CNS infection • Trauma

28. Return to index Etiology of Seizures and Epilepsy American Epilepsy Society2015  Adolescence and young adult • Head trauma • Drug intoxication and withdrawal*  Older adult • Stroke • Brain tumor • Acute metabolic disturbances* • Neurodegenerative *causes of acute symptomatic seizures, not epilepsy

29. Return to index Questions Raised by a First Seizure American Epilepsy Society2015 • Seizure or not? • Provoked? (ie metabolic precipitant?) • Seizure type? (focal vs. generalized) • Evidence of interictal CNS dysfunction? • Syndrome type? • Which studies should be obtained? • Should treatment be started? • Which drug should be used?

30. Return to index Evaluation of a First Seizure American Epilepsy Society2015 • History, physical • Blood tests: CBC, electrolytes, glucose, calcium, magnesium, phosphate, hepatic and renal function • Lumbar puncture (only if meningitis or encephalitis suspected and potential for brain herniation is excluded) • Blood or urine screen for drugs • Electroencephalogram (EEG) • CT or MR brain scan

32. Return to index Seizure Precipitants American Epilepsy Society2015  Metabolic and Electrolyte Imbalance  Stimulant/other proconvulsant intoxication  Sedative or ethanol withdrawal  Sleep deprivation  Antiepileptic medication reduction or inadequate AED treatment  Hormonal variations  Stress  Fever or systemic infection  Concussion and/or closed head injury

33. Return to index Seizure Precipitants (cont.) American Epilepsy Society2015 Metabolic and Electrolyte Imbalance • Low blood glucose (or high glucose, esp. w/ hyperosmolar state) • Low sodium • Low calcium • Low magnesium

34. Return to index Metabolic abnormalities and seizures BS = blood sugar. American Epilepsy Society2015

35. Return to index Seizure Precipitants (cont.) American Epilepsy Society2015 Stimulants/Other Pro-convulsant Intoxication  IV drug use  Cocaine  Ephedrine  Other herbal remedies  Medication reduction

36. Return to index Seizure Precipitants (cont.) • Isoniazid • Penicillins • Cyclosporin • Meperidine American Epilepsy Society2015 Medications that can lower seizure threshold • Antidepressants Bupropion Tricyclics • Neuroleptics Phenothiazines Clozapine • Theophylline

37. Return to index EEG Abnormalities American Epilepsy Society2015  Background abnormalities: significant asymmetries and/or degree of slowing inappropriate for clinical state or age  Interictal abnormalities associated with seizures and epilepsy • Spikes • Sharp waves • Spike-wave complexes  May be focal, lateralized, generalized

38. Return to index EEG Abnormalities Interictal left temporal sharp wave consistent with a diagnosis of partial epilepsy of left temporal origin American Epilepsy Society2015

39. Return to index EEG Abnormalities Interictal generalized polyspike-wave complex consistent with a diaganosis of idiopathic generalized epilepsy American Epilepsy Society2015

40. Return to index Medical Treatment of First Seizure First Seizure Trial Group. Neurology. 1993;43:478–483. [PubMed] Camfield et al. Epilepsia. 2002;43:662–663. [PubMed] American Epilepsy Society2015 Whether to treat first seizure is controversial • 16-62% of unprovoked seizures will recur within 5 years • Relapse rate may be reduced by antiepileptic drugs • Relapse rate increased if: • abnormal imaging • abnormal neurological exam • abnormal EEG • family history  Quality of life issues are important (ie driving)

41. Return to index Antiepileptic Drug (AED)Choice: Considerations American Epilepsy Society2015 • Seizure type • Epilepsy syndrome • Efficacy • Cost • Pharmacokinetic profile • Adverse effects • Patient’s related medical conditions (ie beneficial or deleterious effects on co-morbid conditions)

42. Return to index AED Choice: Attempt Monotherapy American Epilepsy Society2015  Simplifies treatment  Reduces adverse effects  Conversion to monotherapy • Eliminate sedative drugs first • Withdraw antiepileptic drugs slowly over several months

43. Return to index AED Choice: More Considerations American Epilepsy Society2015 • Limited placebo-controlled trials available, particularly of newer AEDs • Several drugs are commonly used for indications other than those for which they are officially approved/recommended • Choice of AED for partial epilepsy: • drug side-effect profile and patient’s preference/concerns • Choice of AED for generalized epilepsy: • predominant seizure type(s) • drug side-effect profile and patient’s preference/concerns See appendix for ILAE Summary Guidelines and Summary of AAN evidence-based guidelines

44. Return to index AED Choice by Seizure Type Broad-Spectrum Agents Valproate Felbamate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide* Vigabatrin* Clobazam* Narrow-Spectrum Agents Partial onset seizures Phenytoin Carbamazepine Oxcarbazepine Gabapentin Pregabalin Tiagabine Lacosamide* Ezogabine* Absence Ethosuximide * New AEDs (approved since 2008) American Epilepsy Society2015

45. Return to index AED Choice: Focal Onset Seizures Best evidence: Carbamazepine**, phenytoin**, levetiracetam, zonisamide Also shown to be effective, weaker evidence: Valproate**, lamotrigine**, oxcarbazepine**, topiramate**, phenobarbital**, gabapentin, vigabatrin Limited or no data for monotherapy: Pregabalin, lacosamide, rufinamide, ezogabine ** FDA approval for monotherapy Glauser T, Ben-Menachem E, Bourgeois B et al. In Epilepsia, 54(3):551-563, 2013. American Epilepsy Society2015

47. Return to index AED Choice: Generalized-Onset Tonic-Clonic Seizures American Epilepsy Society2015 Best evidence and FDA Indication: Valproate**, topiramate** Also shown to be effective: Zonisamide, levetiracetam, oxcarbazepine Phenytoin**, carbamazepine** (may exacerbate absence and myoclonicsz ) Lamotrigine(may exacerbate myoclonicsz of symptomatic generalized epilepsies) ** FDA approved for monotherapy

48. Return to index AED Choice: Absence Seizures American Epilepsy Society2015 Best evidence: Ethosuximide (limited spectrum, absence only), valproate Also shown to be effective: Lamotrigine May be considered as second-line: Zonisamide, levetiracetam, topiramate, felbamate, clonazepam May precipitate or aggravate absence seizures: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, tiagabine, vigabatrin

49. Return to index AED Choice: Myoclonic Seizures American Epilepsy Society2015 Best evidence: Valproate Levetiracetam (FDA indication as adjunctive tx) Clonazepam (FDA indication) Possibly effective: Zonisamide, topiramate May Precipitate or Aggravate: Carbamazepine, gabapentin, oxcarbazepine, phenytoin, tiagabine, vigabatrin, and possibly lamotrigine (in JME)

50. Return to index AED Choice:Lennox-Gastaut Syndrome American Epilepsy Society2015 Best evidence/FDA indication*: Topiramate, felbamate, clonazepam, lamotrigine, rufinamide, valproate, clobazam * FDA approval is for adjunctive treatment for all except clonazepam Some evidence of efficacy: Zonisamide, levetiracetam