1
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
2
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
3
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
4
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
5
• 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
6
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
7
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
8
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
9
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
10
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
11
BRE Video
Idiopathic Generalized Epilepsies
12
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
13
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
14
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
15
• Infantile spasms
• Hypsarrhythmia
• Mental retardation
West Syndrome
Hypsarrhythmia-Wakefulness
Hypsarrhythmia Sleep
Ictal Event: IS