Epilepsy: Challenges & Epilepsy: Challenges & TherapiesTherapies
Orrin Devinsky, M.D.NYU Epilepsy Center
Diagnostic ChallengesDiagnostic Challenges
Define epilepsy syndrome Video-EEG monitoring
Understand the cause of epilepsy High resolution MRI Genetic studies (GEFS+, Chromosomal microarrays)
Define factors that provoke seizures FAILURE
Identify long-term effects of epilepsy &s its treatment
Therapeutic ChallengesTherapeutic Challenges
No seizures, no side effects If patients had their choice:
No doctors, No Medicines In general, would rather see doctor than take medication
Therapeutic ChallengesTherapeutic Challenges
Ongoing assessment: consequences of seizures and therapy
How aggressive to pursue seizure control?
Do we treat interictal EEG? ? Benign rolandic epilepsy
How to assess effects of long-term therapies?
Alternative Therapies for Alternative Therapies for EpilepsyEpilepsy
Diverse group Osteopathy, chiropractic, homeopathy, herbs, EEG feedback (neurotherapy), stress reduction, magnetic stimulation, carbon dioxide therapy, fatty acids
We need data!
Common Errors that Common Errors that Doctors MakeDoctors Make
Misdiagnosis Is it epilepsy? Which epilepsy syndrome? Not noticing change
Incorrect medication choice AEDs can exacerbate seizures
Failure to reassess orconsider VNS or surgery
Mistakes I’ve Made Mistakes I’ve Made
Relying on prior diagnosis Becoming “invested” in a course of action
Not listening to the information Not challenging one’s own conclusion Finding information that supports Explaining information that doesn’t fit
Physician Issues in Physician Issues in Selecting AED Selecting AED
AED relative efficacy:toxicity Knowledge
Published studies Randomized v. open-label Dose range, methodology Statistical v. clinical significance
Information from colleagues Personal experience Belief, Bias, & Comfort Zone
Quality of Life: Quality of Life: The Traditional ViewThe Traditional View
Medical Education - MD perspective Medical literature, clinical experience
Disorders - signs & symptoms Evaluation - history, PE, Lab Therapy - studies of medical outcome
QOL: QOL: A Different ViewA Different View
QOL - Defined by patient not MD Should patient’s perspective be filtered through “objective medical lens”? - NO
QOL is about listening, changing perspective, and using the patients’ view as the ultimate measure of outcome
QOL: QOL: Relevance to Relevance to Epilepsy?Epilepsy?
QOL issues most relevant to chronic disorders, problems beyond disease symptoms
Epilepsy is the paradigm of such a disorder
Seizures are infrequent,AED effects & psychosocial problems are chronic
A Case StudyA Case Study
29 y.o. woman monthly CPS, rare GTCs Routine 6 mo. Checkup: complains of some tiredness, blurred vision, nausea
Exam - mild nystagmus, tremor Labs - slightly elevated LFTs
MD’s perspective - doing great Woman’s perspective - doing poorly; not driving, underemployed, fearful of seizures, troubled by AEs
Cognitive & Cognitive & Behavioral Changes Behavioral Changes
in Epilepsyin Epilepsy Must diagnose to treat Cognitive-behavioral disorders are often overlooked - “under appreciated” Not spontaneously reported Not asked about by MD/RN Noted, but considered minor Noted, but considered untreatable
Seizure Burden: Seizure Burden: The Great LieThe Great Lie
Are complex partial seizures bad? Memory - long-term consequences Personality changes Affective changes Psychosis
Are tonic-clonic seizures bad? You bet!
PGE and Behavior:Absence Epilepsy (Wirrell et al, 1997)
56 absence epilepsy v. 61 JRA patient Pts with absence epilepsy had more academic, personal, and behavioral disorders (p<.001)
Those with ongoing seizures had worse outcomes
Epilepsy: Epilepsy: Progressive Progressive
Cognitive DeclineCognitive Decline Tuberous Sclerosis (Gomez)
Relation of Seizure and MR Of 140 pts with Szs - 89 MR Of 19 pts w/o Szs - none MR Age of seizure onset and MR related:
MR in 72/79 with seizures before age 1y MR in 6/25 with seizures after age 4 y
? Role of CNS pathology vs. Seizures ? Younger brain protected or at risk
Issues with AED Issues with AED SafetySafety
Idiosyncratic AE’s Dose-related AE’s
Cognitive Behavioral Quality of life
Chronic AE’s Teratogenic AE’s Drug interactions
Uncommon Side Uncommon Side EffectsEffects
Increased frequency of urination - lamotrigine
High blood pressure, migraines - carbamazepine
Aggressiveness - phenobarb, ethosuximide, levetiracetam
Severe sedation, coma - valproic acid Movement disorders - phenytoin, carbamazepine
Kidney stones - topiramate, zonisamide, acetazolamide
Getting Off AEDsGetting Off AEDs Everyone’s goal Must balance risk - benefit
Lifestyle factors such as driving Potential side effects How long do you wait for seizure freedom Do you ever try when EEG has spikes or sharp waves, or if auras/minor seizures persist
Middle road is often reasonable - gradual taper over months or often years
Chronic Adverse Chronic Adverse Effects: Effects:
Bone DisordersBone Disorders Decrease Ca/Vit D levels
CBZ (?OXC), PRM, PB, PHT, VPA New AEDs appear safer, but ?
Risk factors Dose, polytherapy, & duration
Diagnosis Suspicion; bone densitomety
Treatment - Vit D/Ca, sun, alendrodate, estrogen supp after menopause
Rapist RoostersRapist RoostersGrandin - Animals in Grandin - Animals in
TranslationTranslation Observed chicken pecked to death
Chicken farmer - we see this; roosters rape and murder, lots of them
Breeding for single traits Large breasts & rapid growth Roosters lost their mating dance
We get used to abnormal, and think its normal
Long Term Side Long Term Side Effects: Effects:
? Drugs v. Disease ? Drugs v. Disease v. Person v. Person
After several years, hard to determine if something really exists - ? personality/person versus disease process versus AED
Can be impossible to determine Reducing or changing drugs may be only way to answer, but may be dangerous
Young woman, PB, and memory
DepressionDepression
Common Underdiagnosed Undertreated
Doctors and patients are at fault Major factor in reducing quality of life
Polycystic ovarian syndrome
Depression and QOL in Epilepsy
Beck Depression Inventory Score
4035302520151050-5
QO
LIE
-89
Tot
al S
core
100
80
60
40
20
0
Depression (SCL-90-R)
90807060504030
Tot
al Q
OL
IE-8
9
70
60
50
40
30
20
Johnson et al.,2004
Gilliamet al., 2002
Crameret al, 2003
CES-D
706050403020100
QO
LIE
-31
100
80
60
40
20
00
10
20
30
40
50
60
70
80
90
100
-5 0 5 10 15 20
25 30 35 40 45 50
Depression (BDI)
Qua
lity
of L
ife (
QO
LIE
-31)
Boylan et al., 2004
Sudden Unexplained Sudden Unexplained Death in Epilepsy Death in Epilepsy
(SUDEP)(SUDEP) SUDEP incidence increases with epilepsy severity Community sample -- 0.35/1000 pt-yrs
24X general populate rate Epilepsy centers -- 1.0/1000 pt-yrs
AED/VNS trials -- 3.75/1000 pt-yrs
0 25 50 75 100 125 150 175 200
Annual incidence per 10,000 population
Sudden Unexplained Sudden Unexplained Death Death in Epilepsy (SUDEP)in Epilepsy (SUDEP)General population (2–3)
Epilepsy incidence population (5)
Epilepsy prevalence population (7)
Patients in clinical trials (30–50)
Patients undergoing vagus nerve stimulation (41)
Patients referred to epilepsy centers (50–60)
Surgical candidates (90)
Surgical failures (150)
Developmental Developmental Disabilities & Disabilities &
EpilepsyEpilepsy Never lose sight of the person behind the frail frame or cognitive impairment
Put yourself in their shoes We relate to those like us Teachers favor good looking students, what of doctors?
Lower expectations Don’t tolerate side effects, seizures, lower QOL
Neurologic disorders close doors of normality, but open new ones
New Therapies in New Therapies in Epilepsy:Epilepsy:
AED PipelineAED Pipeline Novel mechanisms
Potassium channels - retigabine, Functionalized amino acid (glycine; NMDA antagonist)
- lacosamide GABAA receptor modifiers - neuroctive steroid
(ganaxalone) New Relatives of known drugs
Synaptic vesical 2A ligands (levetericetam relatives)
Sodium channel - oxcarbazepine relative Valproate relatives - valrocamide, isovaleramide Felbamate relative - flourofelbamate
Nasal midazolam - new rescue medication! More rapid onset, quicker offset than rectal
diazepam
Closing ThoughtsClosing Thoughts Health care is a partnership
Knowldege is power Communication is essential QOL is yours
Never accept seizures and side effects
The future has never been better
