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Clinical Epilepsy

Clinical Epilepsy. American Epilepsy Society. 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

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Clinical Epilepsy

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  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 Epilepsy comorbidities Discontinuing antiepileptic drugs Alternative therapies Epilepsy surgery Status Epilepticus Non-epileptic events Physiologic Psychogenic Epilepsy monitoring units Epilepsy safety SUDEP Pregnancy and epilepsy Pediatric epilepsy and seizures Appendix for nurses Appendix for neurologists American Epilepsy Society 2010

  3. Return to index Definitions • Seizure: the clinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons • Epilepsy: recurrent seizures (two or more) which are not provoked by systemic or acute neurologic insults American Epilepsy Society 2010

  4. Return to index Epidemiology of Seizures and Epilepsy • 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% American Epilepsy Society 2010

  5. Return to index Seizures Partial Generalized Simple Partial Absence Myoclonic Complex Partial Secondarily Generalized Atonic Tonic Tonic-Clonic ILAE Classification of Seizures ILAE – International League Against Epilepsy American Epilepsy Society 2010

  6. Return to index Seizures Partial Generalized Simple Partial Complex Partial Secondarily Generalized ILAE Classification of Seizures American Epilepsy Society 2010

  7. Return to index Seizures Generalized Partial 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 Society 2010

  8.  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 Return to index Seizures Partial Generalized Complex Partial Complex Partial Seizures

  9.  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 Return to index Seizures Partial Generalized Secondarily Generalized Secondarily Generalized Seizures American Epilepsy Society 2010

  10. Return to index EEG: Partial Seizure RightFrontal seizure

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

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

  13. Return to index EEG: Partial Seizure 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 Society 2010

  15.  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 Return to index Seizures Partial Generalized Absence Typical Absence Seizures American Epilepsy Society 2010

  16. Return to index EEG: Typical Absence Seizure American Epilepsy Society 2010

  17. Return to index Atypical Absence Seizures  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 American Epilepsy Society 2010

  18. Return to index Atypical Absence Seizures

  19. 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 Return to index Seizures Partial Generalized Myoclonic Myoclonic Seizures American Epilepsy Society 2010

  20. Return to index Myoclonic Seizures American Epilepsy Society 2010

  21. 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 Return to index Seizures Partial Generalized Tonic Atonic Tonic and Atonic Seizures

  22. Return to index Tonic and Atonic Seizures American Epilepsy Society 2010

  23. 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 Return to index Seizures Partial Generalized Tonic- Clonic Generalized Tonic-Clonic Seizures American Epilepsy Society 2010

  24. Return to index Epilepsy Syndromes Epilepsy Syndrome Grouping of patients that share similar: • Seizure type(s) • Age of onset • Natural history/Prognosis • EEG patterns • Genetics • Response to treatment American Epilepsy Society 2010

  25. Return to index Epilepsy Partial Generalized Idiopathic Symptomatic Idiopathic Symptomatic Epilepsy Syndromes American Epilepsy Society 2010

  26. Return to index Etiology of Seizures and Epilepsy  Infancy and childhood • Prenatal or birth injury • Inborn error of metabolism • Congenital malformation  Childhood and adolescence • Idiopathic/genetic syndrome • CNS infection • Trauma American Epilepsy Society 2010

  27. Return to index Etiology of Seizures and Epilepsy  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 American Epilepsy Society 2010

  28. Return to index Questions Raised by a First Seizure • 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? American Epilepsy Society 2010

  29. Return to index Evaluation of a First Seizure • 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) Continued on next slide American Epilepsy Society 2010

  30. Evaluation of a First Seizure, Con’t • Blood or urine screen for drugs • Electroencephalogram (EEG) • CT or MR brain scan

  31. Return to index Seizure Precipitants  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 American Epilepsy Society 2010

  32. Return to index Seizure Precipitants (cont.) Metabolic and Electrolyte Imbalance • Low blood glucose (or high glucose, esp. w/ hyperosmolar state) • Low sodium • Low calcium • Low magnesium American Epilepsy Society 2010

  33. Return to index Metabolic abnormalities and seizures BS = blood sugar. American Epilepsy Society 2010

  34. Return to index Seizure Precipitants (cont.) Stimulants/Other Pro-convulsant Intoxication  IV drug use  Cocaine  Ephedrine  Other herbal remedies  Medication reduction American Epilepsy Society 2010

  35. Return to index Seizure Precipitants (cont.) Medications that can lower seizure threshold • Antidepressants: Bupropion Tricyclics • Neuroleptics Phenothiazines Clozapine • Theophylline • Isoniazid • Penicillins • Cyclosporin • Meperidine American Epilepsy Society 2010

  36. Return to index EEG Abnormalities  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 American Epilepsy Society 2010

  37. Return to index EEG Abnormalities Interictal left temporal sharp wave consistent with a diagnosis of partial epilepsy of left temporal origin American Epilepsy Society 2010

  38. Return to index EEG Abnormalities Interictal generalized polyspike-wave complex consistent with a diaganosis of idiopathic generalized epilepsy American Epilepsy Society 2010

  39. 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] 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) American Epilepsy Society 2010

  40. Return to index Choosing Antiepileptic Drugs Considerations: • Seizure type • Epilepsy syndrome • Efficacy • Cost • Pharmacokinetic profile • Adverse effects • Patient’s related medical conditions (ie beneficial or deleterious effects on co-morbid conditions) American Epilepsy Society 2010

  41. Return to index Choosing Antiepileptic Drugs • 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 depends largely on drug side-effect profile and patient’s preference/concerns • Choice of AED for generalized epilepsy depends on predominant seizure type(s) as well as drug side-effect profile and patient’s preference/concerns See appendix for ILAE Summary Guidelines and Summary of AAN evidence-based guidelines American Epilepsy Society 2010

  42. Return to index Choosing Antiepileptic Drugs Broad-Spectrum Agents Valproate Felbamate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide* Vigabatrin Narrow-Spectrum Agents Partial onset seizures Phenytoin Carbamazepine Oxcarbazepine Gabapentin Pregabalin Tiagabine Lacosamide* Absence Ethosuximide * New AEDs (approved 2008) categorization may change American Epilepsy Society 2010

  43. Return to index Choosing Antiepileptic Drugs (cont.) Monotherapy for Partial Seizures Best evidence and FDA indication: Carbamazepine, Oxcarbazepine, Phenytoin, Topiramate Similar efficacy, likely better tolerated: Lamotrigine, Gabapentin, Levetiracetam Also shown to be effective: Valproate, Phenobarbital, Felbamate, Lacosamide Limited data but commonly used: Zonisamide, Pregabalin Azar NJ and BW Abou-Khalil. Seminars in Neurology. 2008; 28(3): 305-316. [PubMed] American Epilepsy Society 2010

  44. Return to index Choosing Antiepileptic Drugs (cont.) Monotherapy for Generalized-Onset Tonic-Clonic Seizures Best evidence and FDA Indication: Valproate, Topiramate Also shown to be effective: Zonisamide, Levetiracetam Phenytoin, Carbamazepine (may exacerbate absence and myoclonicsz ) Lamotrigine (may exacerbate myoclonicsz of symptomatic generalized epilepsies) American Epilepsy Society 2010

  45. Return to index Choosing Antiepileptic Drugs (cont.) Absence seizures 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 American Epilepsy Society 2010

  46. Return to index Choosing Antiepileptic Drugs (cont.) Myoclonic Seizures Best evidence: Valproate Levetiracetam (FDA indication as adjunctive tx) Clonazepam (FDA indication) Possibly effective: Zonisamide, Topiramate American Epilepsy Society 2010

  47. Return to index Choosing Antiepileptic Drugs (cont.) Lennox-Gastaut Syndrome Best evidence/FDA indication*: Topiramate, Felbamate, Clonazepam, Lamotrigine, Rufinamide, Valproate * FDA approval is for adjunctive treatment for all except clonazepam Some evidence of efficacy: Zonisamide, Levetiracetam

  48. Return to index Antiepileptic Drug Monotherapy  Simplifies treatment  Reduces adverse effects  Conversion to monotherapy • Eliminate sedative drugs first • Withdraw antiepileptic drugs slowly over several months American Epilepsy Society 2010

  49. Return to index Antiepileptic Drug Interactions • AEDs that mayinduce metabolism of other drugs: • carbamazepine, phenytoin, phenobarbital, primidone • AEDs that inhibitmetabolism of other drugs: • valproate, felbamate • AEDs that are highly protein bound: • valproate, phenytoin, tiagabine • carbamazepine, oxcarbazepine • topiramate is moderately protein bound • Other drugs may alter metabolism or protein binding of antiepileptic drugs (especially antibiotics, chemotherapeutic agents and antidepressants)

  50. Return to index AEDs and INR *AEDs increase metabolism of warfarin, but warfarin is 99% protein bound, and PHT and VPA increase warfarin’s free fraction. INR = international normalized ratio. Boggs J. In: Ettinger AB, Devinsky O, eds. Managing Epilepsy and Co-Existing Disorders. Boston: Butterworth-Heinemann; 2002:39-47. American Epilepsy Society 2010

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