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Adult Epilepsy Update

J. Layne Moore, MD, MPHAssociate Professor

Department of Neurology and PharmacyDirector, Division of Epilepsy

The Ohio State University

Epilepsy• Affects 1 to 2% of US Population• Chronic Condition• Multiple Drug Therapies• Issues

Patients• Compliance• Drug Interactions• Education• Social and Behavioral

Used by permission Health Press Oxford

Annual Incidence

“the spontaneous cessation of the disease

is an event too rare to be reasonably

anticipated in any give case.”

Gowers 1881

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Refractory Epilepsy• What is refractory epilepsy?

Uncontrolled with multiple medicationsIntolerable side-effects to achieve control• How to fight back?

Newly Diagnosed (n=470)

Seizure-free 47%(n=222)

Uncontrolled 53%(n=248)

Seizure-free 13%(n=61)

Uncontrolled 40%(n=187)

Seizure-free 4%(n=18)

Uncontrolled 36%(n=169)

Kwan & Brodie NEJM 2000

1st drug

2nd drug

3rd drug

Which patients respond?

• Early response in key • Response to the 1st drug

11% response to 2nd drug if 1st was ineffective41% for SE55% idiosyncratic reaction

Kwan and Brodie

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Seeking a Cause• For most persons with epilepsy or

seizures no cause is found

• People without a clear cause have the best prognosis.

Risk Ratios for Selected Causes

1

29

4

1.5

20

7.3

2

16

10

0 5 10 15 20 25 30 35

Baseline

Severe HI

Moderate HI

Mild HI

Stroke

HTN LVH

Aseptic Meningitis

Encephalitis

Alzheimers

Risk Ratio

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Diagnostic Pitfalls• Is the diagnosis correct?

• Does the patient have epilepsy?

• SyncopeOften prominent autonomic symptoms

• Seizure• An “aura” is a seizure

symptoms may be positive, negative, or mixed• pSychogenic spell

Almost anything goes• other Stuff

cataplexymigraineTIA

Our Differential Diagnoses

Seizure or Spell Evaluation

• Careful history hopefully with collateral history

Past Medical History• Risk factors

• Neurological examination• EEG• Neuroimaging

Seizure Evaluation• EEG

Awake and asleep increase sensitivityLooking for evidence of epilepsy*Less than 2% of normal people have

epileptiform discharges• Evidence of focal-onset vs.

generalized-onset seizure• This will dictate our choice of AEDs

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• Awake• Stage I• Stage II• Stage III• Stage IV• REM

Most InterictalsSeizures

Sleep Stages

Seizure Evaluation

• NeuroimagingMRI with thin coronal cuts through hippocampusCT scan is only indicated if:• Patient has contraindications to MRI• It is emergent to look for a bleed or

mass effect

MTS

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Strategies for Management of Epilepsy

• MedicationPartialGeneralized

• Resective Surgery• Vagal Nerve Stimulator• Ketogenic Diet/ Atkins Diet• Stimulators

Antiepileptic Drug (AED) Therapy

Long-Term ManagementStrategies for Epilepsy

1900 1920 1940 1960 1980 2000

PB PHT CBZ VPA FBMGBP

LTGFOS

TPMTGB

PGB

1st Generation 2nd Generation

OCBZLVT

ZNS

• Dilantin (Phenytoin) PHT• Phenobarbital• Tegretol, Carbatrol (Carbamazepine) CBZ• Depakote, Depakene (Valproic Acid) VPA

Bones loss• Aging population, post-menopausal

womenHormonal birth control failure (except VPA)• And may decrease the levels of other AEDs

High protein binding displacing drugs like coumadin and synthroid

Older Drugs

• Neurontin (Gabapentin)• Felbatol (Felbamate)• Lamictal (Lamotrigine)• Topamaz (Topiramate)• Gabitril (Tiagabine)

No enzyme inductionLow protein binding

Less interference with other drugs

2nd Generation Drugs

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3rd Generation Drugs• Trileptal (Oxcarbazepine)• Zonegran (Zonisamide)• Keppra (Leviteracitam)• Lyrica (Pregabalin)

Little interaction with other drugsRenal excretion

Kwan & Brodie NEJM 2000

Newly Diagnosed (n=470)

Seizure-free 47%(n=222)

Uncontrolled 53%(n=248)

Seizure-free 13%(n=61)

Uncontrolled 40%(n=187)

Seizure-free 4%(n=18)

Uncontrolled 36%(n=169)

3rd drug

2nd drug

1st drug

The End

Pediatric EpilepsyJorge Vidaurre M.D.Director Epilepsy Center

Nationwide Children’s Hospital- OSU

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Epilepsy• Convulsive disorders are among the

most frequently occurring neurological condition in children

Incidence• Incidence of seizures is higher in

childhood, especially the first year of life (100/100,000) and in older patients

Epilepsy: Incidence/100,000

200

150

100

50

00 20 40 60 80 100

AgeHauser, Epilepsia 33:1992

181,000 new Cases Per year

Causes of Childhood-Acquired Epilepsy

TraumaTumors

Prematurity

Poison

MetabolicDisturbances

Birth injury

45%-55%

Fever

45%-55%

Infection

Genetic oridiopathic

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Definitions• Seizure: Clinical manifestation of an

abnormal, excessive activity of a set of cortical neurons

• Epilepsy: Chronic brain disorder of various etiologies characterized by recurrent, unprovoked seizures

• Epilepsy syndromes: Grouping of similar patients according to seizure type EEG, ageof onset, familial episodes, prognosis, and other clinical signs

Was the Event a Seizure?

• Syncope • Breath-holding spells• Movement disorders (tics)• Sleep disorders (parasomnias, night

terrors, sleep walking)• Day dreaming, inattentiveness &

distractibility• Self stimulatory behavior • Gastroesophageal reflux• Psychogenic

Non-epileptic paroxysmal events in childhood

Breath Holding Event Video

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Seizure Classification• Partial seizures: originating in a focal area

of the brain.

Simple: Do not impair consciousness

Complex: Impairment of consciousness

• Generalized seizures

Absences, clonic, tonic, tonic-clonic, atonic and myoclonic

Benign Partial Epilepsies of

Childhood

Benign Rolandic Epilepsy (BRE)

• One of the most frequent syndromes, occurring in up to 24% of all epileptic seizures in children between ages 5 and 14

• Age of presentation: 3- 13 year

• Remission rate almost 100% at age 16.

• Seizures are usually infrequent.

Benign Rolandic Epilepsy (BRE)

• Seizures usually occur during sleep

• Partial sensorimotor: hemi facial twitching, drooling, arrest of speech, numbness of tongue, lips.

• GTC in 20-30% of cases

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BRE Video

Idiopathic Generalized Epilepsies

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Childhood Absence Epilepsy(Pyknolepsy, Petit Mal Epilepsy)

• “Very frequent (several to many per day) absence seizures”

• Brief in duration (usually 5-30 seconds)

• Sudden behavioral arrest, with staring and quick return to normal baseline activities

• “Otherwise normal child”

Childhood Absence Epilepsy(Pyknolepsy, Petit Mal Epilepsy)

• Often precipitated by hyperventilation

• An EEG demonstrating “bilateral, synchronous spike-waves, usually 3 HZ, on a normal background activity”

Absence Video

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Commonly used Medications

• Ethosuxamide

• Valproic acid

• Lamotrigine

• Age of onset: 8-24 years. Peak between 12-18 years

• The characteristic seizure type is “myoclonus”, usually affecting shoulders

• GTC seizures appear usually more than 3 years after myoclonus.

• Absences occur in up to 30% of patients.

Juvenile MyoclonicEpilepsy(JME)

Juvenile MyoclonicEpilepsy(JME)

• Seizures are precipitated by sleep deprivation, alcohol, stress.

• Photosensitivity

• Intelligence remain normal

Myoclonus videoChild during sleep

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Photic Induced Seizure

Medications used for JME

• Broad spectrum medications:• Valproic Acid• Lamotrigine• Topiramate• Levetiracetam• Medications that can worsen seizures:• Phenytoin, carbamazepine

Symptomatic Generalized Epilepsies

• Infantile spasms

• Lennox Gastaut syndrome

• Age of onset: 4-6 months • Types: flexor (Jackknife, salaam attacks) ,

extensor or mixed.• Usually occur in cluster, during awakening

or falling sleep• Usual EEG shows hypsarrhythmia

interictaly. Most frequent ictalmanifestation: ”electrodecrementalresponse”

Infantile Spasms

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• Infantile spasms

• Hypsarrhythmia

• Mental retardation

West Syndrome

Hypsarrhythmia-Wakefulness

Hypsarrhythmia Sleep

Ictal Event: IS