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The Evaluation and Management of Seizures

Elizabeth Waterhouse, M.D.Associate ProfessorDepartment of NeurologyVirginia Commonwealth University School of Medicine

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Introduction

• Evaluating a single seizure• The epidemiology of epilepsy• Seizure classification• Treatment options

– traditional antiepileptic drugs (AEDs)– newer AEDs

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Historical Overview: Epilepsy Prevention and Cure

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Definitions

• Seizure: – the clinical manifestation of an abnormal and

excessive excitation of a population of cortical neurons

• Epilepsy: – recurrent unprovoked seizures

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Diagnosis/Etiology: When in Doubt, Check it Out• Does the patient have epilepsy? Differentiate:

– Epileptic seizure: stereotyped and nonprovoked

– Syncope: visual change, pallor, diaphoresis, slump, rapid recovery unless convulsive syncope

– Psychogenic event: nonstereotyped, bilateral convulsions without loss of consciousness, pauses, normal EEG

• may represent 20 to 30% of referrals to epilepsy clinics

• Are seizures due to active brain disorder?– tumor– infection– metabolic disease 6

Questions Raised by a First Seizure

• Seizure or not?• Focal onset?• Evidence of CNS dysfunction?• Identifiable precipitant?• Seizure type? Syndrome type?• Studies?• Start antiepileptic drug (AED)?

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Diagnosis of Seizures

Annegers JF. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md:Williams & Wilkins; 1997:165-172.

Potential diagnosisof seizures

Seizures Reject (syncope, breath holding,loss of consciousness [LOC])

Acute cause?

Yes No

Acute symptomatic

Febrile convulsions

Unprovoked

Only one

Solitaryseizure

Morethan one

Epilepsy

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Evaluating a spell

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Ask

• Tell me what happened from start to finish• Was there weakness? Numbness? Trouble

speaking? Alteration of consciousness?• Did anyone else see it? What did they see?• What were the warning symptoms?• Did you pass out?• If so, were you confused when you came to?• How long did it last? • Was there incontinence or tongue biting?

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• Has anything like this ever happened before?• Have you ever had a seizure? A stroke?• Associated with the spell, did you have chest

discomfort? Racing or irregular heartbeat? Nausea? Diaphoresis?

Ask (con’t)

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Don’t forget to ask about…

• Alcohol• Diabetes• Family history• History of trauma• Stress/psychological factors• Any other factors the patient feels may have

contributed to the event

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• As you listen, try to figure out if it sounds more like: – A seizure– A TIA or stroke– A cardiac arrhythmia– A panic attack– Vasovagal syncope– A provoked spell due to alcohol, hypoglycemia, etc.

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Exam

• Do the whole neuro exam• Listen to heart and lungs• Listen for carotid bruits• If you suspect vasovagal event, check lying & standing

pulse rates

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Plan for suspected seizures…

• Blood tests– electrolytes, CBC– toxic screen, alcohol screen– medication levels– Possible ABG or O2 sat

• EEG• Brain imaging– MRI is preferred• If there is any suspicion of infection, consider LP• If seizure was provoked, address underlying provoking

factors.• If seizures are unprovoked and recur, consider treatment

with an antiepileptic drug• No driving!

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Seizures That May Not Require Treatment

• Single seizure• Febrile seizure• Idiopathic localization-related seizures of childhood• Benign familial seizures of childhood• Simple partial seizure• Post-traumatic impact seizures

– occurring within minutes of trauma• Provoked seizures

– alcohol withdrawal

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Risk Factors for Seizure Recurrence After First Seizure• If idiopathic—only 17% had recurrence at 20 months

– 26% by 36 months• If idiopathic with spike-wave on EEG—risk 50% at 18

months• If idiopathic with sibling with seizure—risk 35% at 4

months• Age at first seizure and onset with status epilepticus

are not risk factors

Adapted with permission from Hauser WA, et al N Engl J Med 1982; 307(9):522-528.

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Factors That Increase Risk for Seizure Recurrence• Prior neurologic insult most powerful predictor• Abnormal EEG• Prior seizures, including complex febrile seizure• Postictal paralysis• Partial seizure

Adapted with permission from Hauser WA, et al N Engl J Med 1982; 307(9):522-528.18

Epidemiology

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Prevalence and Incidence in the United States• 2.5 million persons with epilepsy• 70,000-128,000 new cases annually• Cumulative adjusted lifetime risk: 1.3%-3.1%

Hauser WA, Hesdorffer DC. Epilepsy: Frequency, Causes, and Consequences. New York, NY: Demos; 1991:1. 20

Consequences of Epilepsy and Its Treatment: Injury and Death• Risk of injury is increased in people with epilespy-5% annual

rate of Emergency Dept. care due to seizure related injuries– burns– head injuries– falls– drownings– fractures– may be amplified by medications causing ataxia,

drowsiness, or dizziness• Increased risk of death• Sudden unexplained death

– higher in patients with seizures– related to poor seizure control

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Epilepsy-Related Financial Cost

• Average treatment-related costs of each new diagnosis (1995 dollars)– during first 3 months $ 2,642 – during year 6 $ 329– total over 6 years $ 6,429

• High cost at onset due to diagnosis and initial treatment

• Decline in cost partly due to remission and AED discontinuation

• Highest costs for patients with intractable epilepsyBegley CE, et al. Epilepsia. 2000;41:342-351.

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Epilepsy Incidence: 1935 – 1984

Adapted with permission from Hauser WA, et al. Epilepsia. 1993;34:453-468.

0

50

100

150

200

806040200

Inci

denc

e (p

er 1

00,0

00 P

erso

n-Ye

ars)

Age (y)

MaleFemaleTotal

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Etiology of EpilepsyInfection

3%Stroke 8%

Degenerative – 4%Other – 1%

Mental retardation/Cerebral palsy

15%

Trauma – 4%Tumor – 3%

Unknowns62%

Adapted with permission from Olafsson E, et al. Epilepsia, 1999; 40(11):1529-1534 24

Common Etiologies of Seizures Change With Age• Children

– febrile seizures– congenital causes– metabolic causes

• Young adults– trauma– tumor

• Elderly– stroke– degenerative changes

Adapted with permission from Hauser WA, et al. Epilepsia. 1993;33(suppl 4):S6-S14.

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Classification of Seizure Types

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Seizure Types

• Syncope• Migraine• Psychogenic• Toxic• Cerebrovascular• Metabolic

Single

Nonepileptic

Recurrent

Epileptic

Generalized Partial

Simple Complex

SecondarilyGeneralized

• Absence• Tonic-clonic• Tonic • Clonic• Myoclonic• Atonic

Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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International League Against Epilepsy: Seizure Classification (1981)• Currently used seizure classification scheme based

upon mode of seizure onset– partial: starts in one region of a hemisphere– generalized: starts in both hemispheres

simultaneously• Distinction between partial and generalized seizures

– clinical phenomena– ictal and interictal electroencephalograms

Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981; 22(4):489-501. 28

International League Against Epilepsy:Revised Classification of Epileptic Seizures (1981)• Partial (focal, local) seizures

– simple: motor, autonomic, psychological, somatosensory or special sensory—no alteration in awareness

– complex:± automatisms—has alteration in awareness– secondarily generalized tonic-clonic-also called grand mal or

convulsive seizure• Generalized seizures

– absence: ± clonic, atonic, tonic, autonomic, automatic– atypical absence: changes in postural tone– clonic– tonic-clonic– myoclonic– atonic

Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981; 22(4):489-501.

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Diagnosis of Seizure Type(s)

• Grand mal and petit mal seizures– these are old terms and may no longer be useful for

classification• Patient has seizures with blank stare

– complex partial versus absence• Patient has generalized convulsive activity

– primary generalized tonic-clonic versus partial onset with secondary generalization

• Patient has tonic-clonic seizures with myoclonic jerks– consider juvenile myoclonic epilepsy

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EEG in New-Onset Seizures

• May be normal in up to 50% of patientsa

• Simple partial seizures may not induce a change in scalp-recorded EEG activityb

• Activation procedures used includec

– Hyperventilation– Intermittent photic stimulation– Sleep/sleep deprivation

aSchachter SC. Neurol Clin. 2001;19:57-78.bLowenstein DH. In: Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998:2311-2325.

cDrury I. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams &Wilkins; 1997:251-263.

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Normal Brain Waves

Gibbs FA, et al. Atlas of Electroencephalography, Vol 2. Epilepsy 3rd ed. 1952.32

Simple Partial Seizures

• Locus – One site or lobe

• Manifestations – duration: ~30 seconds– involuntary muscle jerks, sensory (tastes or smells),

psychic or emotional (fear)– olfactory sensation, metallic taste, light-headedness,

bright light, rising sensation in stomach• Consciousness

– patient retains consciousness

Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Simple Partial Seizure

Gibbs FA, et al. Atlas of Electroencephalography, Vol 2. Epilepsy 3rd ed. 1952.34

Complex Partial Seizures• Locus

– One or multiple sites or lobes, commonly bilateral mesial temporal lobes

• Manifestations – Duration: 1-3 minutes– Automatisms (picking at clothes, smacking lips,

wandering, repeating words)– May begin as a smell (olfactory aura), metallic taste,

light-headedness, bright light, rising sensation in stomach

– May begin as simple partial seizures• Consciousness

– Patient has alteration of awarenessAdapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Complex Partial Seizure

Gibbs FA, Gibbs EL. Atlas of Electroencephalography, Vol 2. Epilepsy. 3rd ed. 1952.36

Complex Partial Seizures With Secondary Generalization

• Locus – Locally initiated, then spreads to both hemispheres

• Manifestations – Duration: ~2 minutes– Muscles rigid (tonic) – person falls down, rhythmic

muscle contractions (clonic), shallow breathing, incontinence, postictal drowsiness

– Partial seizure may be the beginning of a secondarily generalized seizure

• Consciousness– Patient loses consciousness

Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Primary Generalized Tonic-Clonic Seizures

• Locus – Both hemispheres affected from onset

• Manifestations – Duration: ~2 minutes– Muscles rigid (tonic) – person falls down,

rhythmic muscle contractions (clonic), shallow breathing, incontinence, postictal drowsiness

– Usually no aura or warning• Consciousness

– Patient loses consciousness Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Tonic-Clonic Seizure

Gibbs FA, Gibbs EL. Atlas of Electroencephalography, Vol 2. Epilepsy. 3rd ed. 1952.

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Absence Seizures• Occur primarily in children• Locus

– Both hemispheres • Manifestations

– Duration: 2-15 seconds– Staring or blinking, upward rotation of eyes,

no motor activity– Atypical absence seizures may involve automatisms and

muscle twitching– Abrupt onset; usually no aura or warning

• Consciousness– Patient loses consciousness briefly

but does not fallAdapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Absence Seizure

Gibbs FA, Gibbs EL. Atlas of Electroencephalography, Vol 2. Epilepsy. 3rd ed. 1952.

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Myoclonic Seizures

• Locus – usually both hemispheres

• Manifestations – rapid jerks of one or both arms or legs– may precede tonic-clonic seizures

• Consciousness– patient may or may not lose consciousness

Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501. 42

Myoclonic Seizure

Gibbs FA, et al. Atlas of Electroencephalography, Vol 2. Epilepsy 3rd ed. 1952.

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Atonic Seizures (Drop Attacks)

• Locus – Both hemispheres

• Manifestations – Duration: 1-60 seconds– Sudden loss of muscle control – patient may fall to

floor, head drops down, jaw slackens– Frequent injuries occur– Usually no aura or warning

• Consciousness– Patient may lose consciousness

Adapted from International League Against Epilepsy. Epilepsia. 1981:22:489-501.

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Lennox Gastaut Syndrome

Gibbs FA, et al. Atlas of Electroencephalography, Vol 2. Epilepsy 3rd ed. 1952.

Approaches to Epilepsy Management

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Epilepsy and Quality of Life Issues• Patients who are seizure-free report levels of QOL similar to

those of the general populationa

• QOL in people with epilepsy is significantly impaired compared with the general populationa,b

– High levels of anxiety and depression– Poor self-esteem– Problems with social interaction

• Number of adverse effects is a significant predictor of QOLc

• Driving is a major issue that must be addressed

aLeidy NK, Elixhauser A, Vickrey B, et al. Neurology. 1999;53:162-166.bJacoby A. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia, Pa: Lippincott-Raven; 1997:1121-1129. cGrudzinski AN, Hakim Z, Coons SJ, Labiner DM. J Epilepsy. 1999;11:34-47.

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Epilepsy-Related Comorbid Conditions

• Cognitive impairment• Depression• Injury• Endocrine dysfunction• Migraine• Sleep disorders

Blum D. BNI Quarterly. 1999;15:42-48.

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Goals of Pharmacotherapy

• Complete control of seizuresa-c

• No adverse eventsa-c

• No drug-drug interactions• Improved quality of lifec

• Optimize growth and development in pediatric patientsa

aDulac O, Leppik IE. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia, Pa: Lippincott-Raven; 1997:1237-1246. bBrodie MJ, French JA. Lancet. 2000;356:323-329.cDam M. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia, Pa: Lippincott-Raven; 1997:1103-1105.

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Initiating Therapy• Monotherapy is preferable whenever possible• Start at low dose of chosen antiepileptic drug (AED)

and titrate to therapeutically effective dose – May be difficult to assess in patients with

infrequent seizures• If seizures persist, consider an alternative drug as

monotherapy• If a second drug must be added, dose of the first drug

may need to be adjusted due to interactions• If patient becomes seizure-free, dose of the initial

drug may be reduced

Karceski S, et al. Epilepsy Behav. 2001;2:A1-A50.

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Risk of Adverse Reactions With AED Polypharmacy

50

40

30

20

10

0

% R

isk

One Drug Two Drugs Three Drugs

Adapted with permission from Collaborative Group for Epidemiology of Epilepsy. Epilepsia. 1986; 27(4):323-330.

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AEDs Through the Years

1900 1920 1940 1960 1980 2000

phenobarb phenytoinethosuximide

carbamazepinevalproate

felbamate

lamotriginegabapentin

topiramatetiagabine

oxcarbazepinezonisamidelevetiracetam

Graves N. Am J Managed Care. 1998;4:S463-S474.52

Selecting an AED

• Choose the AED most suited to the individual patient – seizure/epilepsy type– ease of use– cost– side effects– patient profile (eg, sex, age)

• Balance efficacy, tolerability, and safety • Epilepsy may be a life-long diagnosis

Dam M. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia, Pa: Lippincott-Raven; 1997:1103-1105.

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Selecting an AED: Efficacy Issues

• Old drugs– VA trials – blinded comparator monotherapy– no placebo– CBZ, PHT, PB, primidone, VPA

• New drugs – placebo-controlled FDA registration trials– few direct comparative trials– most drugs produce 30%-40% reductions of

seizures in refractory patients

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Seizure type and choice of AED

• For localization related epilepsy (simple partial, complex partial, or secondarily generalized seizures)– Carbamazepine, phenytoin, valproate, phenobarbital,

primdone– Lamotrigine, topiramate, zonisamide, gabapentin,

oxcarbazepine, levetiracetam, tiagabine, felbamate• For primary generalized seizures

– Valproate, lamotrigine, topiramate– Zonisamide, levetiracetam

• For absence seizures– Ethosuximide or valproate

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Selecting an AED: Tolerability Issues

Side Effects• Dose-related• Idiosyncratic

– eg, rash, hepatic, anemia• CNS toxicity

– eg, drowsiness, dizziness, ataxia, tremor• Some may only be apparent after long-term use

– eg, neuropathies, cosmetic effects, bone effects• Teratogenic

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Newly Diagnosed Epilepsy:Seizure Freedom With Monotherapy*

64%Total seizure-free3%Duotherapy1%Third-drug monotherapy13%Second-drug montherarpy47%First-drug monotherapy% Patients

*Single center retrospective analysis.

Adapted with permission from Kwan P, et al. N Engl J Med. 200; 342:314-319.

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Traditional Antiepileptic Drugs: Efficacy and Tolerability Issues

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Traditional AEDs for Partial and Generalized Tonic-Clonic Seizures

1983 (in US)Valproate1972Carbamazepine1952Primidone1938Phenytoin1912PhenobarbitalYear IntroducedAgent

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Traditional AEDs: Seizure Free Percentages in Partial and Generalized Tonic-Clonic Seizures*

39424048Heller 1995

--6663Ramsay 1983

--74-Reynolds 1976

PhenobarbitalValproatePhenytoinCarbamazepine

*Studies pooling these seizure types

Adapted with permission from Reynolds EH, et al. Lancet. 1976;1(7966):923-926; Ramsay RE, et al. Neurology.1983;33(7):904-910; Heller AJ, et al. J Neurol Neurosurg Psychiatry. 1995;58(1):44-50.

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Traditional AEDs: Seizure-Free Percentages in Generalized Tonic-Clonic Seizures

-7356-Turnbull 1985

-597339Callaghan 1985 (1O GTC)

43-4348Mattson 1985 (2o GTC)

-46-59Mattson 1992 (2o GTC)

-8276-Wilder 1983

PhenobarbitalValproatePhenytoinCarbamazepine

Adapted with permission from Mattson RH, et al. N Engl J Med. 1985;313(3):145-151; Mattson RH, et al. N Engl J Med. 1992;327(11):756-771; Turnbull DM, et al. Br Med J (Clin Res Ed). 1985;290(6471):815-819; Wilder BJ, et al. Neurology. 1983;33(11):1474-1476.

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Seizure-Free Percentages in Partial Seizures

-272958

Valproate

--29-Turnbull 1985---45Mattson 1992

22183244Mattson 1985

---42Loiseau 1984

PrimidonePhenobarbitalPhenytoinCarbamazepine

Adapted with permission from Loiseau P, et al. Rev Neurol (Paris), 1984; 140(6-7)434-443; Mattson RH, et al. N ENgl J Med. 1985;313(3)145-151; Mattson RH, et al. N Engl J Med. 1992;327(11):765-771; Turnbull DM, et al. Br Med J (Clin Res Ed). 1985; 290(6471)815-819.

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Traditional AEDs: Aspects and Side Effects

Tremor, lethargy, weight gain

Sedation, depressionAtaxia

Diplopia,dizziness

Dose-limiting side effects*

GI effectSedationSedation,dizziness

Sedation, dizziness

Initial side effects*

-19%16%12%Discon-tinuation rate, toxicity1

PhenobarbitalValproatePhenytoinCarbamazepine

*Typical side effects, not comprehensible list.

Adapted with permission from “Mattson RH, et al. Neurology. 1983:33(suppl 1):14-25.

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Traditional AEDs: Cognitive Effects

• All traditional AEDs can produce cognitive side effects, especially at higher doses

• Effects at usual doses are most often mild or absent• Phenobarbital has a high incidence of cognitive and

behavioral adverse effects, especially in children – 60% vs 4% to 9% for valproate, carbamazepine,

and phenytoin1

• Phenytoin and carbamazepine are comparable2,3

Adapted with permission from 1deSilva et al. Lancet. 1996;347:709-713; 2Meador et al. Neurology. 1990;40(3 pt 1):391-394; 3Dodrill CB, et al. Neurology. 1991;41(1):141-143. 64

Clinical Application of Traditional AEDs: Summary• Carbamazepine

– Best documented efficacy against complex partial seizures– Traditional AED of choice for partial seizures

• Phenytoin– Second-choice traditional AED for partial seizures but

difficult to use• Valproate

– Traditional AED of choice for primary generalized seizuresEthosuximide may be used for absence seizures alone

• Barbituates– Avoid, if possible

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Traditional AEDs: Summary

• Only ~30% to 60% of patients achieve seizure freedom– 50% of patients achieve seizure freedom with

partial seizures• Inducers or inhibitors of cytochrome P450

– potential for drug failure or interactions• Adverse reaction rate increases with polypharmacy• Significant cognitive side effects may be seen• Mechanism of action addresses GABA and voltage-

gated Na channel

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Perspectives on the Newer Antiepileptic Drugs

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Pattern of AED Use

Alternative monotherapy

Adjunctive therapy as bridge to alternative

monotherapy

Failure of initial monotherapy

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The Newer Antiepileptic Drugs: 2003

2000Zonisamide (Zonegran)1999Oxcarbazepine (Trileptal)1999Levetiracetam (Keppra)1998Gabapentin (Neurotin)1997Tiagabine (Gabitril)1996Topiramate (Topamax)1994Lamotrigine (Lamictal)1993Felbamate (Felbatol)Year IntroducedAgent

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Potential Advantages of Newer AEDs

• Most are broad spectrum– work in multiple seizure types

• Improved safety• Better tolerability• Effective• Fewer interactions• Better for female patients

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The Newer AEDs:Spectrum of Activity

???++Felbamate

?---+Oxcarbazepine

?---+Tiagabine

??+?+?+Levetiracetam

?+

?+

-

?+

Juvenile MyoclonicEpiepsy

??+++Lamotrigine

?--+Gabapentin

??++Topiramate

??+?++Zonisamide

Generalized Tonic-ClonicSeizuresAbsence

Lennox-GastautPartial

+=randomized controlled trials; ?+= case reports or open-label trials only; ?=no data; - =any negative data or evidence of worsening

Adapted with permission from Brodie MJ, et al. Lancet. 2000;356:323-329

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Tolerability of the Newer AEDs:Most Common Adverse Events in Adults

Somnolence, anorexia, dizziness, headache, nausea, and agitation/irritability, weight loss

Zonisamide

Somnolence, dizziness, ataxia, speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesias, diplopia, and weight loss

Topiramate

Dizziness, ataxia, somnolence, headache, diplopia, blurred vision, vomiting, and rash (some severe)

Lamotrigine

Somnolence, dizziness, ataxia, fatigue, and nystagmus

GabapentinAnorexia, Vomiting, insomnia, nausea, and headacheFelbamateAdverse EventsAED

Physicians’ Desk Reference. 56th ed. Montvale, NJ: Medical Economics Co; 2002.72

Tolerability of the Newer AEDs:Most Common Adverse Evenets in Adults (con’t)

Dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, and abnormal gait

Oxcarbazepine

Somnolence, asthenia, infection, and dizzinesLevetiracetam

Dizziness/light-headedness, asthenia/lack of energy, somnolence, nausea, nervousness,/irritability, tremor, abdominal pain, and thinking abnormal/difficulty with concentration or attenetion

TiagabineAdverse EventsAED

Physicians’ Desk Reference. 56th ed. Montvale, NJ: Medical Economics Co; 2002.

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The Newer AEDs: Summary

• The 8 newer AEDs may represent advances over older AEDs with respect to pharmacokinetics and side effects

• Overall, the newer AEDs:– have broader spectrum of activity– are safer (with the exception of felbamate– are well tolerated (with the exception of felbamate– are as efficacious as the traditional AEDs– have fewer interactions– are better for women

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Summary

• Evaluation of a seizures involves assessing provoking factors, and risk of recurrence

• EEG is helpful for prognosis and seizure classification• If treatment is warranted, selection of AED depends

on seizure type, patient profile, and drug characteristics, especially tolerability

• Seizure freedom, if possible, is the goal of treatment• With traditional AEDs 30-60% of patients achieve

seizure freedom.

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Summary (continued)

• Traditional AEDs interact with cytochrome P450, with potential for drug interactions; all have cognitive side effects

• Newer AEDs are generally better tolerated, have fewer idiosyncratic reactions, fewer drug-drug interactions, a broader spectrum of activity, and may be safer for women, children, and the elderly

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Future Directions

• Imaging--better visualization of seizure focus• Increased understanding of cellular mechanisms of

AEDs will lead to more intelligent use of polypharmacy• Understanding of the genetic basis of epilepsy

syndromes will allow the opportunity for early intervention

• Surgery will become an increasingly utilized option for selected patients