Clinical Epilepsy American Epilepsy Society CSlide 1 Clinical

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Clinical Epilepsy American Epilepsy Society C-Slide 1

Clinical Epilepsy American Epilepsy Society C-Slide 1

Clinical Epilepsy: Index Hyperlinks can be used in slide-show mode: Click on topics to

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 [Pub. Med] links to view citations in pubmed Definitions and epidemiology Status Epilepticus Evaluation of a first seizure Non-epileptic events Choosing antiepileptic drugs Drug-drug interactions Adverse effects Epilepsy monitoring units Discontinuing antiepileptic drugs Driving Epilepsy comorbidities Pregnancy and epilepsy SUDEP Epilepsy surgery Alternative therapies American Epilepsy Society 2015 Appendix C-Slide 2

Return to index Definitions • Seizure: the manifestation of an abnormal, hypersynchronous discharge of

Return to index Definitions • 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 American Epilepsy Society 2015 C-Slide 3

Return to index Epidemiology of Seizures and Epilepsy • Seizures • Incidence: 80/100, 000

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 2015 C-Slide 4

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial Absence Complex Partial

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial Absence Complex Partial Myoclonic Secondarily Generalized Atonic Tonic ILAE – International League Against Epilepsy American Epilepsy Society 2015 Tonic-Clonic C-Slide 5

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial Complex Partial Secondarily

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial Complex Partial Secondarily Generalized American Epilepsy Society 2015 C-Slide 6

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial With somatosensory or

Return to index ILAE Classification of Seizures Partial Generalized Simple Partial With somatosensory or special sensory symptoms With motor signs With autonomic symptoms or signs With psychic or experiential symptoms American Epilepsy Society 2015 C-Slide 7

Return to index Complex Partial Seizures Impaired consciousness Seizures Clinical manifestations vary with site

Return to index Complex Partial Seizures Impaired consciousness Seizures Clinical manifestations vary with site of origin and degree of spread • Presence and nature of aura • Automatisms Partial Generalized • Other motor activity Duration typically < 2 minutes Complex Partial American Epilepsy Society 2015 C-Slide 8

Secondarily Generalized Seizures Begins focally, with or without focal neurological symptoms Seizures Variable symmetry,

Secondarily Generalized Seizures Begins focally, with or without focal neurological symptoms Seizures Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases Partial Generalized Typical duration 1 -3 minutes Postictal confusion, somnolence, with or without transient focal deficit American Epilepsy Society 2015 Secondarily Generalized C-Slide 9

Return to index EEG: Partial Seizure Right Frontal seizure American Epilepsy Society 2015 C-Slide

Return to index EEG: Partial Seizure Right Frontal seizure American Epilepsy Society 2015 C-Slide 10

Return to index EEG: Partial Seizure Continuation of the same seizure with change in

Return to index EEG: Partial Seizure Continuation of the same seizure with change in amplitude and frequency American Epilepsy Society 2015 C-Slide 11

Return to index EEG: Partial Seizure Continuation of the same seizure with spread to

Return to index EEG: Partial Seizure Continuation of the same seizure with spread to the other hemisphere American Epilepsy Society 2015 C-Slide 12

Return to index EEG: Partial Seizure Continuation of the same seizure with spread to

Return to index EEG: Partial Seizure Continuation of the same seizure with spread to the other hemisphere American Epilepsy Society 2015 C-Slide 13

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

Return to index ILAE Classification of Seizures Partial Generalized Absence Myoclonic Atonic Tonic-Clonic American Epilepsy Society 2015 C-Slide 14

Return to index Typical Absence Seizures Brief staring spells (“petit mal”) with impairment of

Return to index Typical Absence Seizures Brief staring spells (“petit mal”) with impairment of awareness 3 -20 seconds Seizures Sudden onset and sudden resolution Often provoked by hyperventilation Onset typically between 4 and 14 years of age Partial Generalized Often resolve by 18 years of age Normal development and intelligence EEG: Generalized 3 Hz spike-wave discharges American Epilepsy Society 2015 Absence C-Slide 15

Return to index EEG: Typical Absence Seizure 3 Hz spike/slow wave complexes American Epilepsy

Return to index EEG: Typical Absence Seizure 3 Hz spike/slow wave complexes American Epilepsy Society 2015 C-Slide 16

Atypical Absence Seizures Return to index Brief staring spells with variably reduced responsiveness 5

Atypical Absence Seizures Return to index 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 2015 C-Slide 17

Atypical Absence Seizures American Epilepsy Society 2015 Return to index C-Slide 18

Atypical Absence Seizures American Epilepsy Society 2015 Return to index C-Slide 18

Myoclonic Seizures Return to index Seizures Epileptic Myoclonus Brief, shock-like jerk of a muscle

Myoclonic Seizures Return to index 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 American Epilepsy Society 2015 Partial Generalized Myoclonic C-Slide 19

Return to index Myoclonic Seizures Generalized polyspike-slowwave discharges American Epilepsy Society 2015 C-Slide 20

Return to index Myoclonic Seizures Generalized polyspike-slowwave discharges American Epilepsy Society 2015 C-Slide 20

Return to index Tonic and Atonic Seizures Tonic seizures • Symmetric, tonic muscle contraction

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. Seizures Atonic seizures • Sudden loss of postural tone Partial Generalized • When severe often results in falls • When milder produces head nods or jaw drops. • Consciousness usually impaired Tonic • Duration - usually seconds, rarely more than 1 minute • EEG – sudden diffuse attenuation or generalized polyspikewave American Epilepsy Society 2015 Atonic C-Slide 21

Return to index Tonic and Atonic Seizures American Epilepsy Society 2015 C-Slide 22

Return to index Tonic and Atonic Seizures American Epilepsy Society 2015 C-Slide 22

Generalized Tonic-Clonic Seizures Return to index Associated with loss of consciousness and post-ictal confusion/lethargy

Generalized Tonic-Clonic Seizures Return to index Associated with loss of consciousness and post-ictal confusion/lethargy Duration 30 -120 seconds Tonic phase Stiffening and fall Often associated with ictal cry Seizures Partial Generalized Clonic Phase Rhythmic extremity jerking EEG – generalized polyspikes American Epilepsy Society 2015 Tonic Clonic C-Slide 23

Return to index Epilepsy Syndromes Epilepsy Syndrome Grouping of patients that share similar: •

Return to index Epilepsy Syndromes Epilepsy Syndrome Grouping of patients that share similar: • • • American Epilepsy Society 2015 Seizure type(s) Age of onset Natural history/Prognosis EEG patterns Genetics Response to treatment C-Slide 24

Return to index Epilepsy Syndromes Epilepsy Partial Idiopathic American Epilepsy Society 2015 Generalized Symptomatic

Return to index Epilepsy Syndromes Epilepsy Partial Idiopathic American Epilepsy Society 2015 Generalized Symptomatic Idiopathic Symptomatic C-Slide 25

C-Slide 26

C-Slide 26

Return to index Etiology of Seizures and Epilepsy Infancy and childhood • Prenatal or

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 2015 C-Slide 27

Return to index Etiology of Seizures and Epilepsy Adolescence and young adult • Head

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 2015 C-Slide 28

Return to index Questions Raised by a First Seizure or not? Provoked? (ie metabolic

Return to index Questions Raised by a First 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 2015 C-Slide 29

Return to index Evaluation of a First Seizure History, physical Blood tests: CBC, electrolytes,

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) Blood or urine screen for drugs Electroencephalogram (EEG) CT or MR brain scan American Epilepsy Society 2015 C-Slide 30

C-Slide 31

C-Slide 31

Return to index Seizure Precipitants Metabolic and Electrolyte Imbalance Stimulant/other proconvulsant intoxication Sedative or

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 2015 C-Slide 32

Return to index Seizure Precipitants (cont. ) Metabolic and Electrolyte Imbalance Low blood glucose

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 2015 C-Slide 33

Return to index Metabolic abnormalities and seizures Type Comment Hyponatremia Osmotic shifts, disrupted ionic

Return to index Metabolic abnormalities and seizures Type Comment Hyponatremia Osmotic shifts, disrupted ionic balance, in anoxia w/ shutdown of Na-K pump Hypo- or hyperkalemia Rare to cause seizure. Sometimes through hypomagnesemia Hypo- or hypercalcemia Usually other seizures first, such as tetany or altered consciousness Hypoglycemia BS <50, disrupted Na/K pump Hyperthyroidism May exacerbate epilepsy but rarely is de novo cause BS = blood sugar. American Epilepsy Society 2015 34

Return to index Seizure Precipitants (cont. ) Stimulants/Other Pro-convulsant Intoxication IV drug use Cocaine

Return to index Seizure Precipitants (cont. ) Stimulants/Other Pro-convulsant Intoxication IV drug use Cocaine Ephedrine Other herbal remedies Medication reduction American Epilepsy Society 2015 C-Slide 35

Return to index Seizure Precipitants (cont. ) Medications that can lower seizure threshold Antidepressants

Return to index Seizure Precipitants (cont. ) Medications that can lower seizure threshold Antidepressants Bupropion Tricyclics Neuroleptics Phenothiazines Clozapine Isoniazid Penicillins Cyclosporin Meperidine Theophylline American Epilepsy Society 2015 36

Return to index EEG Abnormalities Background abnormalities: significant asymmetries and/or degree of slowing inappropriate

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 2015 C-Slide 37

Return to index EEG Abnormalities Interictal left temporal sharp wave consistent with a diagnosis

Return to index EEG Abnormalities Interictal left temporal sharp wave consistent with a diagnosis of partial epilepsy of left temporal origin American Epilepsy Society 2015 C-Slide 38

Return to index EEG Abnormalities Interictal generalized polyspike-wave complex consistent with a diaganosis of

Return to index EEG Abnormalities Interictal generalized polyspike-wave complex consistent with a diaganosis of idiopathic generalized epilepsy American Epilepsy Society 2015 C-Slide 39

Return to index Medical Treatment of First Seizure Whether to treat first seizure is

Return to index Medical Treatment of First Seizure 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) First Seizure Trial Group. Neurology. 1993; 43: 478– 483. [Pub. Med] Camfield et al. Epilepsia. 2002; 43: 662– 663. [Pub. Med] American Epilepsy Society 2015 C-Slide 40

Return to index Antiepileptic Drug (AED) Choice: Considerations Seizure type Epilepsy syndrome Efficacy Cost

Return to index Antiepileptic Drug (AED) Choice: 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 2015 C-Slide 41

Return to index AED Choice: Attempt Monotherapy Simplifies treatment Reduces adverse effects Conversion to

Return to index AED Choice: Attempt Monotherapy Simplifies treatment Reduces adverse effects Conversion to monotherapy • Eliminate sedative drugs first • Withdraw antiepileptic drugs slowly over several months American Epilepsy Society 2015 C-Slide 42

AED Choice: More Considerations Return to index Limited placebo-controlled trials available, particularly of newer

AED Choice: More Considerations Return to index 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 American Epilepsy Society 2015 C-Slide 43

Return to index AED Choice by Seizure Type Broad-Spectrum Agents Valproate Felbamate Lamotrigine Topiramate

Return to index AED Choice by Seizure Type Broad-Spectrum Agents Valproate Felbamate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide* Narrow-Spectrum Agents Partial onset seizures Phenytoin Carbamazepine Oxcarbazepine Gabapentin Pregabalin Tiagabine Lacosamide* Ezogabine* Absence Ethosuximide Vigabatrin* Clobazam* * New AEDs (approved since 2008) American Epilepsy Society 2015 C-Slide 44

Return to index AED Choice: Focal Onset Seizures Best evidence: Carbamazepine**, phenytoin**, levetiracetam, zonisamide

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 Society 2015 C-Slide 45

C-Slide 46

C-Slide 46

Return to index AED Choice: Generalized. Onset Tonic-Clonic Seizures Best evidence and FDA Indication:

Return to index AED Choice: Generalized. Onset Tonic-Clonic Seizures Best evidence and FDA Indication: Valproate**, topiramate** Also shown to be effective: Zonisamide, levetiracetam, oxcarbazepine Phenytoin**, carbamazepine** (may exacerbate absence and myoclonic sz ) Lamotrigine (may exacerbate myoclonic sz of symptomatic generalized epilepsies) ** FDA approved for monotherapy American Epilepsy Society 2015 C-Slide 47

Return to index AED Choice: Absence Seizures Best evidence: Ethosuximide (limited spectrum, absence only),

Return to index AED Choice: 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 May precipitate or aggravate absence seizures: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, tiagabine, vigabatrin American Epilepsy Society 2015 C-Slide 48

Return to index AED Choice: Myoclonic Seizures Best evidence: Valproate Levetiracetam (FDA indication as

Return to index AED Choice: Myoclonic Seizures 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) American Epilepsy Society 2015 C-Slide 49

Return to index AED Choice: Lennox-Gastaut Syndrome Best evidence/FDA indication*: Topiramate, felbamate, clonazepam, lamotrigine,

Return to index AED Choice: Lennox-Gastaut Syndrome 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 American Epilepsy Society 2015 C-Slide 50

Return to index AED Mechanisms of Action AED Na+ Channel Blockade PHT X CBZ,

Return to index AED Mechanisms of Action AED Na+ Channel Blockade PHT X CBZ, OXC X Ca++ Channel Blockade H-current enhancement Glutamate Receptor Antagonism Carbonic Anhydrase Inhibition X (NMDA glycine) X (CBZ>OXC) barb, benzo X (GABAA) ESM X VPA X X FBM X X GBP X LTG X TPM X X (NMDA) X X (NMDA glycine) X X (kainate) X (AMPA, kainate) TGB X X (reuptake) LEV ZNS GABA Enhancement X (kainate) X PGB X X X LCM X (slow inact. ) RUF X VGB X (metab. ) Modified from White HS and Rho JM, Mechanisms of Action of AEDs, 2010. American Epilepsy Society 2015 P-Slide 51

Return to index AED Interactions: Mechanisms AEDs that may induce metabolism of other drugs:

Return to index AED Interactions: Mechanisms AEDs that may induce metabolism of other drugs: Broad spectrum inducers: carbamazepine, phenytoin, phenobarbital, primidone Selective CYP 3 A (at higher doses): oxcarbazepine, topiramate, felbamate AEDs that inhibit metabolism of other drugs: Valproate Selective CYP 2 C 19: felbamate, topiramate and oxcarbazepine Can concentrations of phenytoin and phenobarbital AEDs that are highly protein bound: Valproate, phenytoin, carbamazepine, tiagabine, ezogabine Other drugs may alter metabolism or protein binding of antiepileptic drugs (especially antibiotics, chemotherapeutic agents and antidepressants) American Epilepsy Society 2015 C-Slide 52

AED Interactions: Anticoagulation Return to index Antiplatelet/ Anticoagulant Potential Clinical Effect Phenytoin (PHT) 1.

AED Interactions: Anticoagulation Return to index Antiplatelet/ Anticoagulant Potential Clinical Effect Phenytoin (PHT) 1. Warfarin 2. Aspirin 1. Increases INR* 2. Increases free PHT Carbamazepine (CBZ) Warfarin Decreases INR Phenobarbital (Pb) Primidone (PRM) Warfarin Decreases INR Valproic acid (VPA) 1. Warfarin 2. Aspirin 1. Slight decrease in INR 2. Increases free VPA AED *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 2015 C-Slide 53

Return to index AED Interactions: Hormonal Contraception Enzyme-inducing AEDs that may decrease the efficacy

Return to index AED Interactions: Hormonal Contraception Enzyme-inducing AEDs that may decrease the efficacy of hormonal contraception: Carbamazepine (Tegretol, Carbatrol) Clobazam (Onfi) Eslicarbazepine (Aptiom) Felbamate (Felbatol) Oxcarbazepine (Trileptal) Perampanel (Fycompa) Phenobarbital (Phenobarbital, Primidone) Phenytoin (Dilantin) Rufinamide (Banzel) Topiramate (Topamax) American Epilepsy Society 2015 IUD is the preferred contraceptive method for women taking enzyme-inducing AEDs. Gaffield ME et al. Contraception 2011; 83: 16– 29. [Pub. Med] C-Slide 54

AED Interactions: Return to index Lamotrigine and oral contraception Lamotrigine clearance is increased significantly

AED Interactions: Return to index Lamotrigine and oral contraception Lamotrigine clearance is increased significantly by estrogen, particularly synthetic estrogens. Oral contraceptive pills can decrease lamotrigine levels by up to 50% Lamotrigine levels may increase significantly during the placebo week IUD is the contraceptive method of choice for women taking lamotrigine Gaffield ME et al. Contraception 2011; 83: 16– 29. [Pub. Med] American Epilepsy Society 2015 C-Slide 55

Return to index AEDs: Serum Concentrations AED serum concentrations are to be used as

Return to index AEDs: Serum Concentrations AED serum concentrations are to be used as a guide, not dictate clinical decision making. Serum concentrations are useful when optimizing AED therapy, assessing compliance, monitoring during pregnancy or oral contraceptive use, or teasing out drug-drug interactions. Individual patients define their own “therapeutic” and “toxic” ranges. Patsalos et al. Epilepsia. 2008; 49: 1239– 1276. [Pub. Med] American Epilepsy Society 2015 C-Slide 56

Return to index AEDs: Common Adverse Effects Typically dose-related: Dizziness , Fatigue , Ataxia,

Return to index AEDs: Common Adverse Effects Typically dose-related: Dizziness , Fatigue , Ataxia, Diplopia all AEDs Irritability, neuropsychiatric side effects Levetiracetam, ezogabine Word-finding difficulty Topiramate Weight loss/anorexia Topiramate, zonisamide, felbamate Weight gain Valproate (also associated with polycystic ovarian syndrome ) Carbamazepine, gabapentin, pregabalin American Epilepsy Society 2015 C-Slide 57

Return to index AEDs: Serious Adverse Effects Typically Idiosyncratic: Renal stones Topiramate, zonisamide Anhydrosis,

Return to index AEDs: Serious Adverse Effects Typically Idiosyncratic: Renal stones Topiramate, zonisamide Anhydrosis, heat stroke Topiramate, Zonisamide Acute closed-angle glaucoma Topiramate Hyponatremia Carbamazepine, oxcarbazepine Urinary Retention Ezogabine American Epilepsy Society 2015 C-Slide 58

Return to index AEDs: Serious Adverse Effects Typically Idiosyncratic: Aplastic anemia Felbamate, zonisamide, valproate,

Return to index AEDs: Serious Adverse Effects Typically Idiosyncratic: Aplastic anemia Felbamate, zonisamide, valproate, carbamazepine Hepatic Failure Valproate, felbamate, lamotrigine, phenobarbital Peripheral vision loss Vigabatrin Rash Phenytoin, lamotrigine, zonisamide, carbamazepine American Epilepsy Society 2015 C-Slide 59

Return to index AEDs: Adverse Effects - Rash 15. 9% patients experienced a rash

Return to index AEDs: Adverse Effects - Rash 15. 9% patients experienced a rash attributed to an AED Average rate of AED-related rash for a given AED 2. 8%, 2. 1% causing AED discontinuation. Predictors significant in multivariate analysis: occurrence of another AED-rash Arif H. et al. Neurology. 2007; 68: 1701– 1709. [Pub. Med] American Epilepsy Society 2015 C-Slide 60

Return to index AED Adverse Effects - Rash Stevens-Johnson Syndrome (SJS) and Toxic Epidermal

Return to index AED Adverse Effects - Rash Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TENS) Severe life threatening allergic reaction Blisters and erosions of the skin, particularly palms/soles and mucous membranes Fever and malaise Rare: severe risk roughly 1 -10/10, 000 for many AEDs Rapid titration of lamotrigine especially in combination with valproate increases risk American Epilepsy Society 2015 C-Slide 61

Return to index AED-related rash in adult patients with epilepsy ▲▲= rash rate significantly

Return to index AED-related rash in adult patients with epilepsy ▲▲= rash rate significantly greater than average of all other AEDs (p<0. 003) ▼▼= rash rate significantly lower than average of all other AEDs (p<0. 003) ▲= trend towards significantly higher than average rash rate of all other AEDs (0. 003<p<0. 05) ▼= trend towards significantly lower than average rash rate of all other AEDs (0. 003<p<0. 05) Arif H. et al. Neurology. 2007; 68: 1701– 1709. [Pub. Med] American Epilepsy Society 2015 C-Slide 62

Return to index AEDs: Adverse Effects - Rash Drugs rarely associated with rash Valproate

Return to index AEDs: Adverse Effects - Rash Drugs rarely associated with rash Valproate Gabapentin Pregabalin Levetiracetam Topiramate American Epilepsy Society 2015 C-Slide 63

AED-related rash in Asian patients FDA alert 12/2007: Risk of “dangerous or even fatal

AED-related rash in Asian patients FDA alert 12/2007: Risk of “dangerous or even fatal skin reactions” such as Steven-Johnson Syndrome and Toxic epidermal necrolysis is increased in patients with HLA-B*1502 allele Return to index Estimated absolute risk for those with the allele: 5% This allele is almost exclusively found in Asians 10 -15% of population in China, Thailand, Malaysia, Indonesia, Phillipines and Taiwan 2 -4% in India <1% in Japan and Korea 59/60 Asian patients w/ SJS/TEN had this allele vs 4% of CBZ tolerant patients Asians “should be screened for the HLA-B*1502 allele before starting treatment with carbamazepine” These patients may also be at risk with other AEDs (phenytoin, oxcarbazepine, lamotrigine) C-Slide www. fda. gov/Drugs/Drug. Safet American Epilepsy Society 2015 64 y/Postmarket. Drug. Safety. Infor

Return to index Possible suicide risk with AEDs Recent FDA alert (1/2008): • Meta-analysis

Return to index Possible suicide risk with AEDs Recent FDA alert (1/2008): • Meta-analysis of 199 placebo-controlled add-on tx trials (44, 000 patients) • Suicidality with adjunct AEDs than adjunct placebo: • 0. 43% vs 0. 22% • Extra 2. 1 patients per 1000 more patients will have suicidality • 4 suicides with AEDs vs 0 with placebo • “generally consistent across the 11 AEDs” Data analysis is controversial and overall difference is very small Further investigation is needed Clinicians should be aware of potential risk and screen for depression/suicidality www. fda. gov/ohrms/dockets/a c/08/slides/2008 -4372 s 1 -06 C-Slide American Epilepsy Society 2015 OPH 1_files/frame. htm 65

Return to index Starting AEDs Discuss likely adverse effects Discuss unlikely but important adverse

Return to index Starting AEDs Discuss likely adverse effects Discuss unlikely but important adverse effects Discuss likelihood of success Discuss recording/reporting seizures, adverse effects, potential precipitants American Epilepsy Society 2015 C-Slide 66

Return to index Discontinuing AEDs Seizure freedom for 2 years implies overall >60% chance

Return to index Discontinuing AEDs Seizure freedom for 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes Favorable factors • • • Control achieved easily on one drug at low dose No previous unsuccessful attempts at withdrawal Normal neurologic exam and EEG Primary generalized seizures except JME “Benign” syndrome Consider relative risks/benefits (e. g. , driving, pregnancy) Practice parameter. Neurology. 1996; 47: 600– 602. [Pub. Med] American Epilepsy Society 2015 C-Slide 67

Return to index Evaluation After Seizure Recurrence Progressive pathology? Avoidable precipitant? If on AED

Return to index Evaluation After Seizure Recurrence Progressive pathology? Avoidable precipitant? If on AED • • Problem with compliance? Pharmacokinetic factor? Increase dose? Change medication? If not on AED • Start therapy? American Epilepsy Society 2015 C-Slide 68

Return to index Medical Comorbidities of Epilepsy § Most medical conditions occur with increased

Return to index Medical Comorbidities of Epilepsy § Most medical conditions occur with increased incidence in patients with epilepsy compared to patients without it § Some of these may be pathophysiologically related (stroke) and some may be less so § Recurrent seizures may be feature of a cryptogenic condition that has myriad downstream manifestations (? auto-immune illness) American Epilepsy Society 2015 C-Slide 69

Return to index Medical/Neuro Comorbidities of Epilepsy (CDC Novmeber 2013) no epilepsy % any

Return to index Medical/Neuro Comorbidities of Epilepsy (CDC Novmeber 2013) no epilepsy % any epilepsy % Heart 11. 3 HTN 29 Stroke 2. 4 Arthritis 21. 4 18. 3 34 4. 3 30. 9 Face Pain 4. 8 14. 2 HA/Migraine 16. 2 34. 7 Ulcer 28. 9 47. 1 American Epilepsy Society 2015 C-Slide 70

Return to index Psychiatric Comorbidities of Epilepsy § Anxiety § Generalized Anxiety Disorder §

Return to index Psychiatric Comorbidities of Epilepsy § Anxiety § Generalized Anxiety Disorder § Panic Attacks § Affective § Unipolar Depression § Bipolar Disorder § Psychosis § Post-ictal § Chronic Interictal/Schizophrenia-like American Epilepsy Society 2015 C-Slide 71

Return to index Anxiety and Epilepsy § With rigorous diagnostic criteria prevalance of anxiety

Return to index Anxiety and Epilepsy § With rigorous diagnostic criteria prevalance of anxiety disorders in epilepsy patients in the community are between 14. 8 - 25% (Edeh ‘ 87 and Jacoby ‘ 96) § Pariente in 1991 reported an incidence of 21% of panic attacks in French Epilepsy patients compared to 3% of controls § Hospital based studies show similar rates as community (Perino ‘ 96, Gureje ‘ 91) § In epilepsy surgery candidates rates have been found as high as 31% (Manchanda ‘ 96) American Epilepsy Society 2015 C-Slide 72

Return to index Affective Disorders and Epilepsy § Major Depression § Bipolar Disorder §

Return to index Affective Disorders and Epilepsy § Major Depression § Bipolar Disorder § Subsyndromal Symptoms American Epilepsy Society 2015 C-Slide 73

Return to index Major Depression and Epilepsy § Conservative estimates state that 20% of

Return to index Major Depression and Epilepsy § Conservative estimates state that 20% of Epilepsy patients will develop Depression § Some estimates as high as 50 - 80% § Women with significantly higher rates § Rates vary regionally § Studies have consistently shown that Depression increases the risk of developing Epilepsy, suggesting a common stem etiology American Epilepsy Society 2015 C-Slide 74

Return to index Bipolar Disorder and Epilepsy § Lifetime prevalence of Bipolar Disorder in

Return to index Bipolar Disorder and Epilepsy § Lifetime prevalence of Bipolar Disorder in Epilepsy patients is 1. 5 - 2% § Much less common than Depression § Notably, post-ictal psychosis can have a bipolar flavor, schizophreniform but with preserved affect and mild hypomania § Many AED’s are mood stabilizers, most notably: Lamictal, Depakote, Tegretol, Trileptal American Epilepsy Society 2015 C-Slide 75

Sub-Syndromal Symptoms Return to index § The most common presentation of Affective Disorders in

Sub-Syndromal Symptoms Return to index § The most common presentation of Affective Disorders in Epilepsy patients is sub-syndromal depression § They don’t meet criteria for Major Depressive Episode but can be significantly symptomatic § Depressive symptoms have been shown to correlate with quality of life consistently, even when seizure frequency, type, etc. have not American Epilepsy Society 2015 C-Slide 76

Return to index Psychosis and Epilepsy § Ictal § Post-Ictal § Interictal American Epilepsy

Return to index Psychosis and Epilepsy § Ictal § Post-Ictal § Interictal American Epilepsy Society 2015 C-Slide 77

Return to index Ictal Psychosis § Can range from a sense of being followed

Return to index Ictal Psychosis § Can range from a sense of being followed over the contralateral shoulder (amygdaloid focus) with mild paranoia to hallucinations of all sorts (auditory, visual, olfactory, tactile) § Can be associated with EEG changes, though not frequently if awareness is unaltered § Fluctuating awareness and paranoia/hallucinations with lability are hallmarks of non-convulsive status epilepticus American Epilepsy Society 2015 C-Slide 78

Return to index Post-Ictal Psychosis § Often after a lucid period of 24 -

Return to index Post-Ictal Psychosis § Often after a lucid period of 24 - 36 hours. § Bizarre in nature often, religious at times, schizophreniform in content § Affect often preserved with irritability or hypomania § Can last hours to days to even weeks § Treating with anti-psychotics for a few weeks limits intensity and duration § RF include, prolonged seizures, seizures with l. o. c. , bitemporal foci, clusters of seizures, GTC’s, family history of mood disorders, and longer duration of epilespy American Epilepsy Society 2015 C-Slide 79

Return to index Interictal Psychosis § Most commonly seen in Temporal Lobe Epilepsy of

Return to index Interictal Psychosis § Most commonly seen in Temporal Lobe Epilepsy of long duration with poor seizure control § Post-Ictal Psychoses increase in frequency and duration and then become chronic interictal psychosis without return to baseline § Very schizophreniform looking with paranoid, bizarre, religious delusional systems § Require chronic anti-psychotic pharmacologic and psychosocial interventions § Can occur de novo after Epilepsy Surgery American Epilepsy Society 2015 C-Slide 80

Return to index Diagnosis of Psychiatric Symptoms in Epilepsy § Every visit with a

Return to index Diagnosis of Psychiatric Symptoms in Epilepsy § Every visit with a provider should include a discussion of psychiatric symptoms with patient and family § Remember that sub-syndromal symptoms can significantly impact quality of life and respond to treatment § Know when to refer to psychiatrist or therapist for ongoing treatment § Depression and Anxiety should always be explored § Screen for post-ictal psychosis American Epilepsy Society 2015 C-Slide 81

Return to index Psychosocial Concerns and Quality of Life in Epilepsy § The most

Return to index Psychosocial Concerns and Quality of Life in Epilepsy § The most common concerns noted by patients with epilepsy: § § § § Driving (70%) Independence Work and Education Social Embarrassment Medication Dependence Mood/Stress Safety § Giliam and Kuzniecky 1997 American Epilepsy Society 2015 C-Slide 82

Return to index Patient Selection for Surgery Epilepsy syndrome not responsive to medical management

Return to index Patient Selection for Surgery Epilepsy syndrome not responsive to medical management • Unacceptable seizure control despite maximum tolerated doses of 2 -3 appropriate drugs as monotherapy Epilepsy syndrome amenable to surgical treatment American Epilepsy Society 2015 C-Slide 83

Return to index Evaluation for Surgery History and Exam: consistency, localization of seizure onset

Return to index Evaluation for Surgery History and Exam: consistency, localization of seizure onset and progression 3 Telsa MRI: 1. 5 mm coronal cuts with sequences sensitive to gray-white differentiation and to gliosis Other neuroimaging options: PET, ictal SPECT EEG: ictal and interictal, special electrodes Magnetoencephalography (MEG): interictal, mapping Neuropsychological battery Psychosocial evaluation Intracarotid amobarbital test (Wada) American Epilepsy Society 2015 C-Slide 84

C-Slide 85

C-Slide 85

Return to index Surgical Treatment Potentially curative • Resection of epileptogenic region (“focus”) avoiding

Return to index Surgical Treatment Potentially curative • Resection of epileptogenic region (“focus”) avoiding significant new neurologic deficit Palliative • Partial resection of epileptogenic region • Disconnection procedure to prevent seizure spread • Callosotomy • Multiple subpial transections American Epilepsy Society 2015 C-Slide 86

Return to index Epilepsy Surgery Outcomes Anterior Temporal Resection Neocortical Resection Seizure Free 66%

Return to index Epilepsy Surgery Outcomes Anterior Temporal Resection Neocortical Resection Seizure Free 66% 49% (except auras) (possibly higher with mesial (63% if lesional) Improved 21% 30% Not improved 14% 21% temporal sclerosis) Engel J, Jr, et al. Neurology. 2003; 60: 538– 547. [Pub. Med] American Epilepsy Society 2015 C-Slide 87

C-Slide 88

C-Slide 88

Return to index Epilepsy Surgery Corpus Callosotomy § Palliative surgery for intractable epilepsies with

Return to index Epilepsy Surgery Corpus Callosotomy § Palliative surgery for intractable epilepsies with drop attacks (i. e. Lennox-Gastaut Syndrome) § Up to 75% have > 75% reduction in atonic seizures § Risk of disconnection syndromes Hemispherectomy § Indicated for catastrophic hemispheric epilepsies, usually presenting in children (i. e. Rasmussen’s encepalitis, hemimegalencephaly) § 43 -79% seizure free (varies by etiology) § “Functional hemispherectomy” (disconnection without removal) now more commonly performed Multiple Subpial Transections § Cuts horizontal cortical-cortical connections § Generally reserved for epileptogenic regions in functional cortex Spencer SS and L Huh. Lancet Neurol. (2008), 525– 537. [Pubmed] American Epilepsy Society 2015 C-Slide 89

Return to index Vagus Nerve Stimulator Intermittent programmed electrical stimulation of left vagus nerve

Return to index Vagus Nerve Stimulator Intermittent programmed electrical stimulation of left vagus nerve Option of magnet activated stimulation Adverse effects local, related to stimulus (hoarseness, throat discomfort, dyspnea) Mechanism unknown Clinical trials show that 35% of patients have a 50% reduction in seizure frequency and 20% experience a 75% reduction after 18 months of therapy. May improve mood and allow AED reduction FDA approved for refractory partial onset seizures and refractory depression American Epilepsy Society 2015 C-Slide 90

Non-Drug Treatment/ Lifestyle Modifications Return to index Adequate sleep Avoidance of alcohol, stimulants, etc.

Non-Drug Treatment/ Lifestyle Modifications Return to index Adequate sleep Avoidance of alcohol, stimulants, etc. Avoidance of known precipitants Stress reduction — specific techniques American Epilepsy Society 2015 C-Slide 91

Non-Drug Treatment/ Ketogenic Diet Return to index Main experience with children, especially with multiple

Non-Drug Treatment/ Ketogenic Diet Return to index Main experience with children, especially with multiple seizure types Likely anti-seizure effect of ketosis (beta hydroxybutyrate), but other mechanisms also may be responsible for beneficial effects Low carbohydrate, adequate protein, high fat 50% with a >50% seizure reduction 30% with >90% reduction Side effects include kidney stones, weight loss, acidosis, dyslipidemia American Epilepsy Society 2015 C-Slide 92

Non-Drug Treatment/ Alternative Diets Return to index Modified Atkins diet • 10 g/day carbohydrates

Non-Drug Treatment/ Alternative Diets Return to index Modified Atkins diet • 10 g/day carbohydrates to start, fats encouraged • No protein, calorie, fluid restriction • 3 reports to date from Johns Hopkins, 1 from South Korea – 47% all children with >50% seizure reduction – Studies underway for adults Low-glycemic index treatment • 40 -60 g/day low-glycemic carbohydrates • Portions generally controlled • Single report from Massachusetts General American Epilepsy Society 2015 C-Slide 93

Return to index Status Epilepticus Definition • More than 5 minutes of continuous clinical

Return to index Status Epilepticus Definition • More than 5 minutes of continuous clinical or electrographic seizure activity or • Two or more sequential seizures without full recovery between seizures American Epilepsy Society 2015 C-Slide 94

Return to index Status Epilepticus (SE) A medical emergency • Adverse consequences can include

Return to index Status Epilepticus (SE) A medical emergency • Adverse consequences can include hypoxia, hypotension, acidosis, hyperthermia, rhabdomyolysis and neuronal injury • Know the recommended sequential protocol for treatment and distribute a written protocol to emergency rooms, ICUs and housestaff. • Goal: stop seizures as soon as possible American Epilepsy Society 2015 C-Slide 95

Return to index Mortality of SE by Age American Epilepsy Society 2015 Towne AR

Return to index Mortality of SE by Age American Epilepsy Society 2015 Towne AR et al. Epilepsia. 1994; 35: 27 -34. C-Slide 96

Return to index Mortality of SE by duration American Epilepsy Society 2015 Towne AR

Return to index Mortality of SE by duration American Epilepsy Society 2015 Towne AR et al. Epilepsia. 1994; 35: 27 -34. C-Slide 97

SE Treatment Algorithm Return to index • • • Check emergency ABC’s Give O

SE Treatment Algorithm Return to index • • • Check emergency ABC’s Give O 2 Obtain IV access Begin EKG monitoring Check fingerstick glucose Draw blood for Chem-7, Magnesium, Calcium, Phosphate, CBC, LFTs, AED levels, ABG, troponin • Toxicology screen (urine and blood). • Thiamine 100 mg IV; 50 ml of D 50 IV unless adequate glucose known. Arif H, Hirsch LJ. Semin Neurol. 2008; 28: 342– 354. [Pub. Med] American Epilepsy Society 2015 C-Slide 98

Return to index Status Epilepticus: First-line Treatment Options Benzodiazepine Route Dosing Maximum Dose Class

Return to index Status Epilepticus: First-line Treatment Options Benzodiazepine Route Dosing Maximum Dose Class & Level of Evidence Class I Level A LORAZEPAM IV 0. 1 mg/kg 4 mg @ 2 mg/min May repeat x 1 in 5 -10 min MIDAZOLAM IM Nasal Buccal 0. 2 mg/kg 10 mg Class I Level A DIAZEPAM PR 0. 2 mg/kg 20 mg Class IIa, Level A Brophy GM et al. Neurocrit. Care 2012; 17: 3– 23 [Pub. Med] American Epilepsy Society 2015 C-Slide 99

Return to index Status Epilepticus: Second-line Treatment Options AED Fosphenytoin Phenytoin Valproate Sodium Rout

Return to index Status Epilepticus: Second-line Treatment Options AED Fosphenytoin Phenytoin Valproate Sodium Rout e IV Dosing Maximum Rate of Infusion Additional Dose Class & Level of Evidence 20 PE/kg 150 PE/min 5 PE/kg , 10 min after loading dose Class IIa Level B Class IIa Level A IV 20 mg/kg 50 mg/min 5 -10 mg/kg, 10 min after loading dose IV 20 -40 mg/kg 3 -6 mg/kg/min 20 mg/kg, 10 min after loading dose Brophy GM et al. Neurocrit. Care 2012; 17: 3– 23 [Pub. Med] American Epilepsy Society 2015 C-Slide 100

Return to index Refractory Status Epilepticus: Treatment Options Infusions Initial Dose Midazolam 0. 2

Return to index Refractory Status Epilepticus: Treatment Options Infusions Initial Dose Midazolam 0. 2 mg/kg @ 2 mg/min Propofol Pentobarbita l 1 -2 mg/kg @ 20 mcg/kg/min 5 -15 mg/kg @ ≤ 50 mg/min American Epilepsy Society 2015 Continuous Infusion Class & Level of Evidence 0. 05 -2 mg/kg/hr Class IIa Level B Respiratory depression Hypotension Class IIb Level B Respiratory Depression Hypotension* Propofol infusion syndrome Renal Failure Class IIb Level B Respiratory depression Hypotension Cardiac depression Paralytic Ileus Prolonged mental status depression C-Slide 30 -200 mcg/kg/min 0. 5 -5 mg/kg/hr Brophy GM et al. Neurocrit. Care 2012; 17: 3– 23 [Pub. Med] Adverse Effects 101

Return to index SE Treatment Algorithm Begin EEG monitoring ASAP if patient does not

Return to index SE Treatment Algorithm Begin EEG monitoring ASAP if patient does not rapidly awaken, or if any CIV treatment is used. ~20% of those patients successfully treated clinical for status will still be seizing on EEG. Treiman et al. N Engl J Med. 1998; 339: 792– 8. [Pub. Med] American Epilepsy Society 2015 C-Slide 102

Return to index Differential Diagnosis of Non-epileptic Events: Physiologic Syncope Cardiac (Arrhythmia) Non-Cardiac Syncope

Return to index Differential Diagnosis of Non-epileptic Events: Physiologic Syncope Cardiac (Arrhythmia) Non-Cardiac Syncope (Vasovagal, Dysautonomic) Metabolic (Hypoglycemia) Migraine Sleep Disorders (Narcolepsy) Movement Disorders (Paroxysmal Dyskinesia) Transient Ischemic Attacks American Epilepsy Society 2015 C-Slide 103

Differential Diagnosis of Return to index Non-epileptic Events: Psychogenic Seizures Malingering Panic Attacks Intermittent

Differential Diagnosis of Return to index Non-epileptic Events: Psychogenic Seizures Malingering Panic Attacks Intermittent Explosive Disorder Breath-holding Spells American Epilepsy Society 2015 C-Slide 104

Return to index Syncope Characteristic warning, usually gradual (except with cardiac arrhythmia) Typical precipitants

Return to index Syncope Characteristic warning, usually gradual (except with cardiac arrhythmia) Typical precipitants (except with cardiac arrhythmia) Minimal to no postictal confusion/somnolence Convulsive syncope — tonic>clonic manifestations, usually < 30 sec; usually from disinhibited brainstem structures (only rarely from cortical hypersynchronous activity) American Epilepsy Society 2015 C-Slide 105

Return to index Syncope vs Seizure: Before Spell Syncope Seizure Trigger (position, emotion, Valsalva)

Return to index Syncope vs Seizure: Before Spell Syncope Seizure Trigger (position, emotion, Valsalva) Common Rare Sweating & nausea Common Rare Common Aura (e. g. déjà vu, smell) or unilateral symptoms Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 106

Return to index Syncope vs Seizure: During Spell Pallor Cyanosis Loss of consciousness Syncope

Return to index Syncope vs Seizure: During Spell Pallor Cyanosis Loss of consciousness Syncope Seizure Common Rare Common <20 secs >60 secs Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 107

Return to index Syncope vs Seizure: During Spell Syncope Seizure Occasional Common Tongue biting,

Return to index Syncope vs Seizure: During Spell Syncope Seizure Occasional Common Tongue biting, lateral Rare Occasional Frothing/hyper-salivation Rare Common Automatisms Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 108

Return to index Syncope vs Seizure: During Spell Syncope Movements Duration Frothing/hypersalivation Seizure Few

Return to index Syncope vs Seizure: During Spell Syncope Movements Duration Frothing/hypersalivation Seizure Few clonic or Prolonged tonic myoclonic jerks or phase » rhythmic brief tonic clonic mvmts posturing < 15 seconds 30 -120 seconds Rare Common Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 109

Syncope vs Seizure: After spell Return to index Confusion/ disorientation Diffuse myalgias Creatine kinase

Syncope vs Seizure: After spell Return to index Confusion/ disorientation Diffuse myalgias Creatine kinase elevation Syncope Seizure Rare; <30 secs Common; several mins or longer Rare, brief, usually shoulders/chest Common, hours-days Rare Common Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 110

Return to index Features That Are Not Helpful in Differentiating Syncope from Seizure Incontinence

Return to index Features That Are Not Helpful in Differentiating Syncope from Seizure Incontinence Prolactin level Dizziness Fear Injury other than lateral tongue biting Eye movements (rolling back) Brief automatisms Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 111

Return to index Migraine aura vs. occipital seizure Migraine Occipital Seizure Duration 5 -20

Return to index Migraine aura vs. occipital seizure Migraine Occipital Seizure Duration 5 -20 min 0. 5 -5 min Typical Content B&W; straight lines; slow spread Color, round, variable spread Laterality Either side Always same side (contralateral) Associated Features Altered awareness, automatisms Hirsch et al, Merritt’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 112

Return to index Psychogenic Non-epileptic Seizures 10 -45% of patients referred for intractable spells

Return to index Psychogenic Non-epileptic Seizures 10 -45% of patients referred for intractable spells Females > males Psychiatric mechanism — dissociation, conversion Common association with physical, emotional, or sexual abuse Spells with non-epileptic etiology No obvious ictal eeg correlation (classically normal awake background during episode of impaired consciousness) Caveats: Diagnosis can be complicated The majority of simple partial seizures have no EEG correlation Frontal lobe seizures may have unusual semiology and no discernable EEG correlation American Epilepsy Society 2015 C-Slide 113

Return to index Psychogenic Non-epileptic Seizures FEATURES SUGGESTIVE OF NONEPILEPTIC PSYCHOGENIC SEIZURES Eye Closure

Return to index Psychogenic Non-epileptic Seizures FEATURES SUGGESTIVE OF NONEPILEPTIC PSYCHOGENIC SEIZURES Eye Closure Pelvic thrusting Opisthotonus Side-to-side head shaking Prolonged duration (>4 minutes) Stopping and starting Suggestibility American Epilepsy Society 2015 C-Slide 114

C-Slide 115

C-Slide 115

Return to index Psychogenic Non-epileptic Seizures Features suggestive of Non-epileptic seizures Important Caveats Thrashing,

Return to index Psychogenic Non-epileptic Seizures Features suggestive of Non-epileptic seizures Important Caveats Thrashing, struggling, crying, pelvic thrusting, side-to-side rolling, wild movements Bizarre complex automatisms can occur with frontal lobe seizures Preserved consciousness with bilateral tonic or clonic mts Frontal lobe seizures may have bilateral convulsive movements without impairment of consciousness Lack of postictal confusion Posti-ictal confusion is often absent after frontal lobe seizures Postictal crying or shouting Aggressive and emotional behavior can occur after epileptic seizures American Epilepsy Society 2015 C-Slide 116

Return to index Psychogenic Non-epileptic Seizures Represents psychiatric disease Once recognized, approximately 50% respond

Return to index Psychogenic Non-epileptic Seizures Represents psychiatric disease Once recognized, approximately 50% respond well to specific psychiatric treatment Epileptic and nonepileptic seizures may co-exist Video-EEG monitoring often required for diagnosis American Epilepsy Society 20105 C-Slide 117

Return to index Utility of epilepsy video/EEG monitoring units Epilepsy Monitoring Unit (EMU): Inpatient

Return to index Utility of epilepsy video/EEG monitoring units Epilepsy Monitoring Unit (EMU): Inpatient unit with specialized personnel Continuous video and EEG recording Utility: Differentiate between epileptic and non-epileptic spells Identification of unrecognized seizures Recording seizures for presurgical evaluation NAEC Guidelines for EMU evaluation: Treatment failure of 1 year Failure of 2 -3 AEDs American Epilepsy Society 2015 C-Slide 118

Return to index Utility of epilepsy video/EEG monitoring units: Non-epileptic spells Study of 213

Return to index Utility of epilepsy video/EEG monitoring units: Non-epileptic spells Study of 213 EMU admissions • 21% had purely nonepileptic events • Treated as if epilepsy for a mean of 9 yrs • Half treated w/ >3 AEDs • EMU yielded definitive diagnosis in 88% Smolowitz et al. American Journal of Medical Quality. 2007; 22(2): 117– 122. [ Pub. Med] American Epilepsy Society 2015 C-Slide 119

Return to index Utility of epilepsy video/EEG monitoring units (EMU): Epilepsy Early Identification of

Return to index Utility of epilepsy video/EEG monitoring units (EMU): Epilepsy Early Identification of Refractory Epilepsy n=525 Kwan P and MJ Brodie. N Engl J Med. 342 (2000), 314 -9. [Pubmed] • 192 (37%) patients were refractory. • Only 11% of patients became seizure-free if the first drug was ineffective. • Suggests need for early pre-surgical evaluation Patient awareness of seizures n=31 Blum DE et al. Neurology. 1996; 47: 260– 4. [Pub. Med] • 30% patients deny all seizures • Only 23% were aware of all seizures American Epilepsy Society 2015 C-Slide 120

Return to index Sudden Unexplained Death in Epilepsy: SUDEP Definition: “Sudden, unexpected, witnessed or

Return to index Sudden Unexplained Death in Epilepsy: SUDEP Definition: “Sudden, unexpected, witnessed or unwitnessed, nontraumatic and nondrowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (seizure duration >30 min or seizures without recovery in between), in which postmortem examination does not reveal a cause of death” Nashef, et al. Epilepsia 2012; 53: 227 [PMID: 22191982] American Epilepsy Society 2015 C-Slide 121

Return to index SUDEP Definitions - Updated • SUDEP definitions updated in 2012 to

Return to index SUDEP Definitions - Updated • SUDEP definitions updated in 2012 to recognized that: • Some cases of sudden death have insufficient information to determine cause of death • Some patients with SUDEP have coexisting conditions that may (in conjunction to seizure) contribute to death (e. g. long QT syndrome) • Recognize the concept of near-SUDEP, a patient resuscitated after a probable SUDEP American Epilepsy Society 2015 C-Slide 122

Return to index Epidemiology of SUDEP • Represents about 2 -18% of deaths among

Return to index Epidemiology of SUDEP • Represents about 2 -18% of deaths among the general population of patients with epilepsy Forsgren et al, Epilepsia 2005; 46 Suppl 11: 18 • Likely most common disease-related cause of death in refractory epilepsy • Risk of sudden death in epilepsy patients 24 X that of general population. Ficker et al, Neurology 1998; 51: 1270 • Epilepsy is a significant risk factor for sudden death in population-based studies. Holst et al, Epilepsia 2013; 29: 1 – 8. American Epilepsy Society 2015 C-Slide 123

Return to index SUDEP Incidence n 100 fold range in SUDEP incidence n Rates

Return to index SUDEP Incidence n 100 fold range in SUDEP incidence n Rates depend on the population studied: • Incidence cohort of newly diagnosed epilepsy: 0. 09 per 1000 person-years • Refractory epilepsy patients: 2. 26. 0 per 1000 p-y • Surgical patients : 6. 3 -9. 3 per 1000 p-y • Low rates in children but higher rates in adults with childhood onset epilepsy Devinsky NEJM 2011 Reviewed in Tomson, et al. Lancet neurol 2008; 7: 1021 [PMID: 18805738], Devinsky N Engl J Med 2011; 365: [PMID: 22070477] American Epilepsy Society 2015

Return to index Sudden Unexplained Death in Epilepsy: SUDEP Witnessed SUDEP Langan Y et

Return to index Sudden Unexplained Death in Epilepsy: SUDEP Witnessed SUDEP Langan Y et al. JNNP 2000; 68: 211– 213. [Pub. Med] • 15/135 SUDEP cases were witnessed. • 12/15 were associated with a convulsive seizure. • One collapse occurred 5 minutes after a GTC seizure and one after an aura. • One patient died in a probable postictal state. • 12/15 were noted to have experienced respiratory difficulties. • Suggests that respiratory dysfunction may be an important contributing factor in SUDEP. • Suggests that positioning or stimulation of respiration may be important in the prevention of SUDEP. American Epilepsy Society 2015 C-Slide 125

Return to index SUDEP Risk Factors associated with increased SUDEP risk Frequent GTCs*** Factors

Return to index SUDEP Risk Factors associated with increased SUDEP risk Frequent GTCs*** Factors associated with decreased SUDEP risk Seizure freedom Symptomatic etiology Nocturnal seizures* Subtherapeutic AED levels AED polytherapy** carbamazepine use lamotrigine use Early age of epilepsy onset/longer duration of epilepsy** Male sex Mental retardation Sharing bedroom/monitoring • Risk factors found in multiple studies Reviewed in Tomson, et al. Lancet neurol 2008; 7: 1021 -31 [PMID: 18805738]; Hesdorffer, et al. Epilepsia 2012; 53: 249 -52 [PMID: 22191685] American Epilepsy Society 2015 C-Slide 126

Return to index SUDEP: Mechanisms n Witnessed, EMU-recorded, and post-mortem studies all support a

Return to index SUDEP: Mechanisms n Witnessed, EMU-recorded, and post-mortem studies all support a seizure, typically GTC, as the terminal event n Three main mechanism emerge from observed cases: • Primary respiratory causes: central or obstructive apnea • Cerebral shutdown: diffuse post-ictal suppression of EEG preceding EKG or respiratory changes • Cardiac arrhythmias/autonomic failure Friedman, et al. JCI 2013; 123: 1415 [PMID: 23524959] American Epilepsy Society 2015 C-Slide 127

Return to index SUDEP Prevention Evidence suggests seizure control reduces SUDEP risk • Meta-analysis

Return to index SUDEP Prevention Evidence suggests seizure control reduces SUDEP risk • Meta-analysis showed subjects randomized to effective dose of an AED had 7 fold reduction in risk of SUDEP during the observation period compared to placebo in add-on studies. Ryvlin et al. Lancet neurol. 2011; PMID: 21937278 Optimize seizure control as promptly as possible • Re-evaluate epilepsy diagnosis and treatment as soon as 2 AEDs have failed, or when GTC szs are frequent despite initial AED treatment • Evaluate for otherapies: surgery, VNS, diet therapy • Maximize adherence to AEDs • Address seizure-provocative lifestyle factors (alcohol use, sleep deprivation) Educate patients and families Seizure alert devices • • Several devices (watches, bed motion detectors) exist to alert caregivers for GTC sz Caution: none are FDA approved or proven to prevent SUDEP or other complications of seizures. American Epilepsy Society 2015 C-Slide 128

First Aid Tonic-Clonic Seizure Return to index After seizure ends, turn person on side

First Aid Tonic-Clonic Seizure Return to index After seizure ends, turn person on side with face turned toward ground to keep airway clear, protect from nearby hazards Transfer to hospital needed for: • Multiple seizures or status epilepticus • Person is pregnant, injured, diabetic • New onset seizures DO NOT put any object in mouth or restrain American Epilepsy Society 2015 C-Slide 129

Return to index Driving and Epilepsy Regulation varies state by state regarding: • Reporting

Return to index Driving and Epilepsy Regulation varies state by state regarding: • Reporting requirements • Required seizure-free period • Favorable/unfavorable modifiers Insurance issues Employment issues Resource: www. epilepsyfoundation. org/living/wellness/transportation/d rivinglaws. cfm American Epilepsy Society 2015 C-Slide 130

Return to index Pregnancy and Epilepsy Guidelines for Management - 50% of pregnancies in

Return to index Pregnancy and Epilepsy Guidelines for Management - 50% of pregnancies in women with epilepsy are unplanned - All women with epilepsy of reproductive age should be counseled about the effects of epilepsy and AEDs on a future pregnancy - Pregnancy planning starts with the first AED prescription for a woman of childbearing age and drug changes should be made a year before conception when possible American Epilepsy Society 2015 C-Slide 131

Return to index Pregnancy and Epilepsy 96% of pregnancies in mothers with epilepsy produce

Return to index Pregnancy and Epilepsy 96% of pregnancies in mothers with epilepsy produce normal children There is an increased rate of fetal malformations associated with antiepileptic drug exposure Seizures during pregnancy may be harmful Tonic-clonic seizures associated with intracranial hemorrhage, fetal bradycardia and lower IQ in children Status associated with increased fetal and maternal mortality in some studies Insufficient data on non-convulsive seizures Harden CL et al. Neurology. 2009 Jul 14; 73(2): 133 -41. [Pub. Med] American Epilepsy Society 2015 C-Slide 132

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs Most available data

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs Most available data on risk of AEDs comes from pregnancy registries Main outcome variable of most registries are major congenital malformations (MCM) MCM = malformation that affects physiologic function or requires surgery. Examples: Neural tube defects Cardiac defects Genitourinary defects Oral clefts Recent prospective studies have also investigated the effects of AEDs on cognitive development of exposed children American Epilepsy Society 2015 C-Slide 133

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs MCMs are more

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs MCMs are more common with AED exposure MCM risk in general population 1. 6 -2. 1% MCM risk with AED monotherapy 4. 5% (OR 2. 6) MCM risk with Polytherapy 8. 6% (OR 5. 1) Polytherapy risk may be related to specific combinations of drugs, particularly combinations with valproic acid MCM risk seems to be dose-related for most drugs Holmes et al. N Engl J Med. 2001; 344: 1132– 1138. [Pub. Med] American Epilepsy Society 2015 C-Slide 134

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs Valproate has been

Pregnancy and Epilepsy: Return to index Major Congenital Malformation and AEDs Valproate has been consistently associated with poorer outcomes MCM rate with valproate monotherapy 6. 2 -16. 3% across 5 registries Most studies show dose- related increase in risk with doses > 750 mg/day Polytherapy regimens including valproate also substantially increased risk of MCM Valproate is associated with lower IQs in exposed children compared with other AEDs (10 pts on average) Valproate is associated with an increased risk of autism and autism spectrum disorder in exposed children American Epilepsy Society 2015 C-Slide 135

Return to index AEDs in Pregnancy n Probably safest AEDs (range of published MCM

Return to index AEDs in Pregnancy n Probably safest AEDs (range of published MCM rates) • • Lamotrigine (2 -5. 2%) Levetiracetam (3%) Carbamazepine (2. 2 -6. 3%) Phenytoin (2. 9 -6. 7%) n Probably have risk lower than valproate (more data needed) • Oxcarbazepine • Zonisamide • Gabapentin n Have significant risk greater than some other AEDs • Topiramate • Phenobarbital • Valproate Adapted from Harden CL: Continuum. 2014; 20: 60– 79 [Pub. Med] American Epilepsy Society 2015 C-Slide 136

Return to index Pregnancy and Epilepsy Guidelines for Management Education • Most women with

Return to index Pregnancy and Epilepsy Guidelines for Management Education • Most women with epilepsy have normal children • Risk of fetal malformations is increased with AED exposure • AED teratogenicity is related to exposure in the first trimester of pregnancy • Effects on cognitive development likely occur throughout pregnancy but particularly in 3 rd trimester • Planning should begin well before pregnancy • Seizures may be deleterious to the fetus • Compliance with AED treatment is important • Prenatal diagnosis of fetal malformations is possible American Epilepsy Society 2015 C-Slide 137

Return to index Pregnancy and Epilepsy Guidelines for Management Before pregnancy • Confirm epilepsy

Return to index Pregnancy and Epilepsy Guidelines for Management Before pregnancy • Confirm epilepsy diagnosis (exclude non-epileptic seizures) • Attempt AED monotherapy with lowest effective dose • Consider switching AEDs prior to pregnancy, particularly if on valproate • Establish baseline therapeutic levels • Folate supplementation • 0. 4 – 5 mg/day American Epilepsy Society 2015 C-Slide 138

Return to index Pregnancy and Epilepsy Guidelines for Management During pregnancy • Continue folate

Return to index Pregnancy and Epilepsy Guidelines for Management During pregnancy • Continue folate supplementation • Recommend level II ultrasound • Monitor AED levels at least monthly and adjust dose accordingly • Lamotrigine clearance increases dramatically over the course of pregnancy • Metabolism also increased for levetiracetam, oxcarbazepine, phenobarbital and phenytoin • Carbamazepine levels may be relatively stable, but depends on the individual patient • Patients need a post-partum dosing plan to avoid toxicity post-partum American Epilepsy Society 2015 C-Slide 139

Return to index Breast Feeding and Epilepsy • Breastfeeding should be encouraged for most

Return to index Breast Feeding and Epilepsy • Breastfeeding should be encouraged for most women with epilepsy • Known benefits of breastfeeding likely outweigh theoretical risks of medication exposure for most drugs • Six-year old breastfed children of mothers taking carbamazepine, lamotrigine, phenytoin or valproic acid monotherapy had higher IQs and verbal abilities than children who were not breastfed. No adverse effects were noted • Some recommendations advise caution with drugs with longer half-lives including ethosuxamide, phenobarbital and zonisamide but concerns are mostly theoretical. More data is needed on these drugs Meador KJ et al JAMA Pediatr. 2014; 168: 729– 736 [Pub. Med] American Epilepsy Society 2015 C-Slide 140

Return to index Appendix: References for Neurologists Epidemiology and classification § Herman ST. Classification

Return to index Appendix: References for Neurologists Epidemiology and classification § Herman ST. Classification of Epileptic Seizures. Continuum Neurol. 2007; 13(4): 13 -47. § Engel J et al. A Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001; 42(6): 796 -803. [Pub. Med] § Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935– 1984. Epilepsia. 1993; 34(3): 453– 468. [Pub. Med] § French, JA and Pedley, TA. Management of Epilepsy. N Engl J Med 2008 359: 166 -176 [Pub. Med] American Epilepsy Society 2015 C-Slide 141

Return to index Appendix: References for Neurologists Evaluation of a first seizure § First

Return to index Appendix: References for Neurologists Evaluation of a first seizure § First Seizure Trial Group. Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonicclonic seizure. Neurology. 1993; 43: 478– 483. [Pub. Med] § Camfield P, Camfield C, Smith S, Dooley J, Smith E. Long-term outcome is unchanged by antiepileptic drug treatment after a first seizure: a 15 -year followup from a randomized trial in childhood. Epilepsia. 2002; 43: 662– 663. [Pub. Med] § Krumholz A, Wiebe S, Gronseth G, et al. Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society. Practice parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review) Neurology. 2007; 69(21): 1996– 2007. [Pub. Med] American Epilepsy Society 2015 C-Slide 142

Return to index Appendix: References for Neurologists Anti-epileptic drugs § French JA, Kanner AM,

Return to index Appendix: References for Neurologists Anti-epileptic drugs § French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs Neurology. 2004 a; 62: 1252– 60. [Pub. Med] 2004 b; 62: 1261– 73. [Pub. Med] § Glauser T, Ben-Menachem, Bourgeois B et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54(3): 551 -563. [Pub. Med] § Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs–best practice guidelines for therapeutic drug monitoring: A position paper by the Subcommission on therapeutic drug monitoring, ILAE Commission on therapeutic strategies. Epilepsia. 2008; 49: 1239– 1276. [Pub. Med] American Epilepsy Society 2015 C-Slide 143

Return to index Appendix: References for Neurologists Anti-epileptic drugs in special populations § Harden

Return to index Appendix: References for Neurologists Anti-epileptic drugs in special populations § Harden CL et al. Practice parameter update: management issues for women with epilepsy. Neurology. 2009 Jul 14; 73(2): 133 -41. [Pub. Med] § Harden CL: Pregnancy and epilepsy. Continuum (Minneap. Minn). 2014; 20: 60– 79 [Pub. Med] § Rowan AJ et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14; 64(11): 1868 -73. [Pub. Med] § Azar NJ and BW Abou-Khalil. Considerations in the Choice of an Antiepileptic Drug in the Treatment of Epilepsy. Seminars in Neurology. 2008; 28(3): 305316. [Pub. Med] American Epilepsy Society 2015 C-Slide 144

Return to index Appendix: References for Neurologists Discontinuing antiepileptic drugs § Berg AT, Shinnar

Return to index Appendix: References for Neurologists Discontinuing antiepileptic drugs § Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994; 44: 601608. [Pub. Med] § Practice parameter: a guideline for discontinuing antiepileptic drugs in seizure-free patients-summary statement. Report of the Quality Standards Subcommittee of the American Academy of Neurology. 1996; 47: 600– 602. [Pub. Med] § Specchio LM et al. Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy. J Neurol Neurosurg Psychiatry 2002 72: 22 -25 [Pub. Med] American Epilepsy Society 2015 C-Slide 145

Return to index Appendix: References for Neurologists Intractable epilepsy and epilepsy surgery § Kwan

Return to index Appendix: References for Neurologists Intractable epilepsy and epilepsy surgery § Kwan P and MJ Brodie. Early Identification of Intractable Epilepsy. N Engl J Med. 342 (2000), 314 -9. [Pubmed] § Wiebe S et al. A randomized, controlled trial of surgery for temporallobe epilepsy, N Engl J Med 345 (2001), 311– 318 [Pubmed] § Engel J et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons, Neurology 60 (2003), 538– 547 [Pubmed] § Spencer SS and L Huh, Outcomes of epilepsy surgery in adults and children. Lancet Neurol. (2008), 525– 537. [Pubmed] C-Slide American Epilepsy Society 2015 146

Return to index Appendix: References for Neurologists Management of status epilepticus § Arif H,

Return to index Appendix: References for Neurologists Management of status epilepticus § Arif H, Hirsch LJ. Treatment of status epilepticus. Semin Neurol. 2008; 28: 342– 354. doi: 10. 1055/s-2008 -1079339. [Pub. Med] § Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ, Shutter L, Sperling MR, Treiman DM, Vespa PM: Guidelines for the evaluation and management of status epilepticus. Neurocrit. Care 2012; 17: 3– 23 [Pub. Med] § Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, Handforth A, Faught E, Callabresi VP, Uthman BM, Ramsay RE, Mamdani MB. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med. 1998; 339: 792– 8. [Pub. Med] § Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O'Neil N, Neuhaus JM, Segal MR, Lowestein DH. A comparison of lorazepam, diazepam and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001; 345: 631– 7. [Pub. Med] American Epilepsy Society 2015 C-Slide 147

Return to index ILAE Summary Guidelines Seizure type or epilepsy syndrome Class III Level

Return to index ILAE Summary Guidelines Seizure type or epilepsy syndrome Class III Level of efficacy and effectiveness evidence (in alphabetic order) Adults with partial-onset seizures 4 1 34 Level A: CBZ, LEV, PHT, ZNS Level B: VPA Level C: GBP, LTG, OXC, PB, TPM, VGB Children with partial-onset Seizures 1 0 19 Level A: OXC Level B: None Level C: CBZ, PB, PHT, TPM, VPA, VGB Elderly adults with partialonset seizures 1 1 3 Level A: GBP, Level B: None Level C: CBZ Adults with generalized onset tonic–clonic seizures 0 0 27 Level A: None Level B: None Level C: CBZ, LTG, OXC, PB, PHT, TPM, VPA Children with generalized onset tonic–clonic seizures 0 0 14 Level A: None Level B: None Level C: CBZ, PB, PHT, TPM, VPA Children with absence Seizures 1 0 7 Level A: ESM, VPA Level B: None Level C: LTG BECTS 0 0 3 Level A: None Level B: None Level C: CBZ, VPA JME 0 0 1 Levels A, B, C: None American Epilepsy Society 2015 LTG Glauser et al. Epilepsia 2013; 54(3): 551 -563. [Pub. Med] C-Slide 148

Return to index Recommendation Levels Level A= Established as useful/predictive or not useful/predictive for

Return to index Recommendation Levels Level A= Established as useful/predictive or not useful/predictive for the given condition in the specified population. Level B= Probably useful/predictive or not useful/predictive for the given condition in the specified population. Level C= Possibly useful/predictive or not useful/predictive for the given condition in the specified population. Level U= Data inadequate or conflicting. Given current knowledge, test, predictor is unproven. French et al. Neurology. 2004 a; 62: 1252– 60. [Pub. Med] 2004 b; 62: 1261– 73. [Pub. Med] American Epilepsy Society 2015 C-Slide 149

Clinical Epilepsy Workgroup n Daniel Friedman, MD (chair) n Elizabeth E. Gerard, MD (past

Clinical Epilepsy Workgroup n Daniel Friedman, MD (chair) n Elizabeth E. Gerard, MD (past chair) n Ed Garcia, MD n Sara Inati, MD n Mirret El-Hagrassy, MD n David Ko, MD n Siddhartha Nadkarni, MD Prior members: Larry Hirsch, MD (past chair) Alan Ettinger, MD American Epilepsy Society 2015 C-Slide 150