David Lee Gordon, MD, FAHA Update in Stroke 2007
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ASSESSMENT & TREATMENT OF SEIZURES
2016
Jeanne Ann King, MDClinical Associate Professor
Department of NeurologyThe University of Oklahoma Health Sciences Center
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ASSESSMENT & TREATMENT OF SEIZURES
Under Accreditation Council for Continuing Medical Education guidelines disclosure must be made regarding relevant financial
relationships with commercial interests within the last 12 months.
Jeanne Ann King, MD
I have no relevant financial relationships or affiliations with commercial interests to disclose.
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Learning Objectives
n1. List the different types of seizuresn2. Correlate partial seizure symptoms &
neuro-anatomic localizationn3. Describe the differential diagnosis for
seizuresn4. Describe the principles of selection &
implementation of antiepileptic drug therapy
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US EPILEPSY STATISTICS
n 2.2 million people in the United States with epilepsy
n 10,000 people in Oklahoma alone
n 4-7/1000 people/year (.5-1%)
n 150,000 new cases/year
nSingle seizure: 9%
PREVALENCE: INCIDENCE:
>65 million people worldwide
Statistics from Institute of Medicine Report 3/2012
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THE LIFE OF AN EPILEPTICn I’ve had seizures all of my life, so it’s been an
adventure, to balance the living of today, and fear of the future.
n It effects every aspect of living; your career, fun, and even raising children; from holding a baby to driving a car, you learn that nothing is for certain.
nWorking is often difficult, your life is like a yo-yo, no matter how good of a worker you are, a few seizures and they let you go.
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THE LIFE OF AN EPILEPTIC (Cont.)
nMy friends have helped a lot, by learning about me, the person; they accept the individual, without any reservation.
nIf we could educate the world, give them the chance to know, epileptics are ordinary people; good friends and happy lives are our goals.
David Lee Gordon, MD, FAHA Update in Stroke 2007
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OVERVIEW
nDefinitionsnDiagnosisnClassificationnTreatment
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DEFINITIONS
nA seizure is a sign or symptom of cerebral paroxysmal discharge.
nEpilepsy is a tendency to have recurrent seizures.
nThe Epilepsies are syndromes or diseases characterized by a tendency to have recurrent seizures along with other clinical characteristics.
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Old Definition of Epilepsy
nA disorder of the brain characterized by an enduring tendency to have epileptic seizures and by the neurobiologic, cognitive, psychologic, and social consequences
nDiagnosis based on at least 2 unprovoked seizures more than 24 hours apart
ILAE 2005
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ILAE (International League Against Epilepsy) Definition
Epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.
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WHAT HAPPENED?
Credit to John DeToledo, MD
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Clinical question #1: Was it a seizure?
nCareful history is the most importantØ The patient may be the least helpful in some
casesØEye-witness if at all possible ØPrior spells?
nConditions That Can Mimic Epileptic SeizuresØHyperventilation, syncopeØMigraine, TIA (transient ischemic attack)ØPanic attack, psychogenic seizures
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DISORDERS THAT MAY MIMIC EPILEPSY
n Gastroesophageal Refluxn Breath-holding n Migraine
Ø ConfusionalØ BasilarØ With recurrent abdominal
pain and cyclic vomitingn Sleep disorders
(especially parasomnias)n Cerebrovascular events
Ø Pallid infantile syncopeØ Vasovagal attacksØ Vasomotor syncopeØ Cardiac arrhythmias
n Movement disordersØ Stuttering attacksØ Paroxysmal
choreoathetosisØ Nonepileptic myoclonusØ Tics and habit spasms
n Psychological disordersØ Panic disorderØ Hyperventilation Ø RageØ Pseudoseizures
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Clinical question #2: Does the patient have epilepsy?
nPrecipitated seizuresØMetabolic: Uremia, hypoglycemia,
hyperglycemia, hepatic failureØToxic: Drug overdose or withdrawalØInfectious: Meningitis/encephalitis
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Seizure vs Epilepsy
Seizures
CardiovascularDrug relatedSyncopalMetabolicToxicPoisonInfectiousFebrilePseudosz
Nonepilepsy (precipitated) Epilepsy(recurrent sz)
Idiopathic(primary)
Symptomatic(secondary)
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SEIZURE DIAGNOSIS
nPhysical/Neurological Exam
nEEGØPhotic stimulationØHyperventilationØSleep deprivation
nAnatomic studiesØCTØMRI
nSpecial studiesØSPECTØPET
n Intensive CCTV/EEG monitoring
K.Penry 1992
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Laboratory Evaluation of Patients with Seizures
nGlucose, oxygennElectrolytes, BUNnCalcium, magnesiumnDrug screennLumbar puncturenScreen for inborn errors (<5 years)
nEKG
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Electroencephalography (EEG)
nEpileptiform EEG patterns (such as spikes and sharp waves) can substantiate the diagnosis and classify focal or generalized.
nNeither a normal EEG nor interictal abnormalities alone refute or confirm the diagnosis.
n If EEG is normal, repeat with sleep-deprivation.
nVideo EEG monitoring if there is a concern about nonepileptic events or seizures do not respond to medication.
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Guideline: Management of an unprovoked first seizure in adults
nClarifies when a person’s risk for another seizure warrants medication.
nNearly 50 studies reviewednAfter a first seizure, risk for another is
greatest within the first 2 yearsnRisk varies from 21-45%
Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology2015;84:1705-1713.
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Greatest risk of another seizure
nStrong evidence in those withØPrevious brain injury: stroke, brain tumor, head
traumaØEpileptiform discharges on EEG
nModerate evidence in those withØA significant abnormality on brain imagingØNocturnal seizures
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Early Treatment
nAbout half of patients who have a first seizure will never have another seizure.
nEarly treatment lowers the risk of another seizure by 35% within the first 2 years.
nEarly treatment rather than waiting for another seizure is unlikely to increase or decrease the likelihood of remaining seizure free.
n 31% will experience a drug side effect (usually mild and reversible)
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Conclusions
nThere is no black-and-white recommendation about early treatment
nIndividual circumstances, balance of risks and benefits, and personal preferences should be taken into account and the patient should participate in the decision-making process.
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Classification
Treatment
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Seizure Classification
The International Classification of Epileptic Seizures
Clinical Observation+
EEG Findings
Partial Sz Generalized Sz
Focal orlocalization related
Bilateral initially
Widespread cerebralinvolvement
ILAE 1981
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CLASSIFICATION
nPartial seizuresØSimpleØComplex
(dyscognitive)
nGeneralized seizuresØAbsenceØMyoclonicØ Tonic-clonicØAtonic
Continual seizures: Status epilepticus
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Partial Seizure
Simple Complex
Secondarilygeneralized
consciousnessImpaired +
automatisms
consciousnesspreserved
Consciousnessimpaired
+Bilateral cerebral
involvement
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Simple Partial Seizure Features
nConsciousness intactnSigns/symptoms variable
-Motor-Somatosensory-Autonomic-Psychic
nMay have focal EEG abnormality
“Focal Motor Sz”/”Focal Sensory Sz”
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Simple Partial Seizures
K473-0208
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Complex Partial Seizure Features
nImpaired consciousnessnIctus duration, 1 min.nBlank starenAutomatismsnAmnesia for ictal eventnFocal EEG abnormality
“Temporal Lobe Sz”/”Psychomotor Sz”
AV Deigo-Escueta, 1992 (per RE Ramsay)
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Left-sided Focal Spike
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Complex Partial Seizures
K473-0208
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MRI-detected hippocampal atrophy;the most common surgically remediable epilepsy
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Types of Generalized Seizures
nTonic-clonicnClonic-tonic-clonicnClonicnTonicnAbsence (typical, atypical)nMyoclonicnAtonic
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Generalized Tonic-Clonic Seizure
nOccurs in all age groupsnInvolves complete loss of consciousnessnPreviously referred to as a “grand mal” seizure
K473-0208
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Absence Seizure
nMost common in childrennInvolves a brief disruption of consciousnessnPreviously referred to as a “petit mal” seizure
Between Seizures:
• Normal appearance
During Seizure:
• Vacant stare • Eyes roll upward• Lack of response
K473-0208
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Absence Seizure Features
nChildhood onsetnBrief loss of consciousness (10-20 sec)nStaring spellnNo post-ictal periodnSubtle myoclonic movementnSimple automatismsnEEG 3 cps spike and wave
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Generalized Spike & Wave
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Myoclonic Seizure (minor motor)
nBrief, shock-like muscle contractions (jerks)- Head- Upper extremities
nUsually bilaterally symmetricalnConsciousness preservednPrecipitated by awakening or falling asleepnMay progress into clonic or clonic-tonic
seizures
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Atonic Seizure (drop attacks)
nImpaired consciousnessnLoss of muscle tonenHead dropnFallnBrief durationnInjury common
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Treatment
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REMEDIES FOR EPILEPSYfrom Owsai Temkin, The Falling Sickness
nBlood of the tortoise.nTesticles of the hippopotamus.nFeces of the land crocodile.nRoot of strychnos gathered at the time of the
waning of the moon, put into a piece of linen, and hung around the neck.
nScrapings from the selenite stone found by night at the waxing of the moon.
nFilings of iron sharpened on whetstone from Naxos.
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ANTIEPILEPTIC DRUGS (OLDEST)
n 1857 Bromidesn 1912 phenobarbital Luminaln 1935 mephobarbital Mebaraln 1938 phenytoin Dilantinn 1946 trimethadione Tridionen 1947 mephenytoin Mesantoinn 1949 paramethadione Paradionen 1951 phenacemide Phenuronen 1952 metharbital Gemoniln 1953 phensuximide Milontinn 1954 primidone Mysoline
Ferrendeli
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1ST GENERATION ANTIEPILEPTIC DRUGS (OLD)
n 1957 methsuximide Celontinn 1957 ethotoin Peganonen 1960 ethosuximide Zarontinn 1968 diazepam Valiumn 1974 carbamazepine Tegretoln 1975 clonazepam Klonopinn 1978 valproic acid Depakenen 1981 clorazepate Tranxenen 1982 divalproex Depakote
Ferrendeli
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2ND GENERATION AEDS
n 1993 felbamate Felbatoln 1993 gabapentin Neurontinn 1994 lamotrigine Lamictaln 1996 topiramate Topamaxn 1997 tiagabine Gabitriln 1999 levetiracetam Keppran 2000 oxcarbazepine Trileptaln 2000 zonisamide Zonegrann 2005 pregabalin Lyrica
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Newer AEDs
n2008 lacosamide Vimpatn2009 rufinamide Banzeln2009 vigabatrin Sabriln2010 clobazam Onfin2011 ezogabine (retigabine) Potigan2012 perampanel Fycompan2013 eslicarbazepine Aptiomn2016 brivaracetam Briviact
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POTENTIAL ADVANTAGES OF NEW AEDS
nDifferent mechanisms of actionn Improved pharmacokinetics with less need for
therapeutic drug monitoringnFewer drug interactionsn Improved therapeutic ratiosnFewer adverse eventsn Improved tolerability in special populationsn Long-acting formulations available
Willmore LJ. Clinical pharmacology of new antiepileptic drugs. Neurology 2000;55(suppl3):S17-24.
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Considerations in the Selection of AED Therapy
§ Efficacy for seizure type§ epilepsy syndrome§ Etiology§ Side effect profile§ Safety§ Mechanism of action§ Drug interactions§ Route of elimination
§ Pharmacokinetics § Need for laboratory
monitoring§ Dosing
requirements/drugformulations
§ Speed, ease of initiation
§ Co-morbidities§ *Cost
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Female patients
nConsider effects onØOCP (oral contraceptive pills) Øteratogenicity
nPrescribe folic acid 1-4 mg (milligrams)
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Initiating Treatment
nBroad-spectrum AEDs (antiepileptic drugs) are appropriate for all seizure typesØlevetiracetam (Keppra), valproate (Depakote,
lamotrigine (Lamictal) , topiramate (Topamax)nFocal onset seizures: any AED except
ethosuximide (Zarontin) may be effectivenChoice may depend on comorbidities,
adverse events and cost (GoodRX.com)
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BROAD SPECTRUM AEDS
nVPA (valproate, Depakote)nFBM (felbamate, Felbatol)nLTG (lamictal, Lamotrigine)nTPM (topiramate, Topamax)nLVT (levetiracetam, Keppra)nZNS (zonisamide, Zonegran)nRFD (rufinamide, Banzel)nVGB (vigabatrin, Sabril)nCLB (clobazam, Onfi)nBRV (brivaracetam, Briviact)
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LIMITED SPECTRUM AEDS
nPB (phenobarbital) nPHT (phenytoin, Dilantin)nCBZ (carbamazepine, Tegretol)nGBP (gabapentin, Neurontin)nTGB (tiagabine, Gabitril)nOXC (oxcarbazepine, Trileptal)nPGB (pregabalin, Lyrica)nLCS (lacosamide, Vimpat)nPER (perampanel, Fycompa)nESL (eslicarbazepine, Aptiom)
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INDIVIDUALIZING THERAPY
nUse drug most appropriate for patient’s seizure disorder
nTitrate to effective levelnIn case of treatment failure or toxicity,
substitute an alternative agentnIf necessary, combine two nonsedating
agents (avoid phenobarbital and BZD)
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Guidelines for Combination Therapy
nAvoid combining AEDs with similar or additive side effects
nAED blood levels are available even for the new drugs
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Counseling
n Until seizure free (in most states for > 6 months):ØNo driving car (or operating high risk power
equipment)ØNo swimming alone or bathing in a closed-drain tubØNo climbing on ladders (or other high places)
n Avoid sleep deprivation & alcoholn Avoid alcoholn Mood
ØHigh rates of depression & suicidal thoughtsØAEDs sometimes can contribute
n Urge compliance with AEDØDaily schedule, pill boxØExpected side effects
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EMERGING AEDS (NONAPPROVED)
n stiripentoln talampanel n losigamonen remacemiden SGB-017 (ADCI)n PNU-151774E (or NW-
1015)n fluorofelbamaten JZP-4n propyl-
isopropylacetamide (PID)
n M-TMCDn VX-765
n valrocemiden ganaxolone (CCD 1042)n carisbamaten YP3089n 2-deoxyglucose (2DG)n NAX-5055n huperzinen T-2000n tonabersatn sulthiamen ICA-105665n seletracetamn *everolimus
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NON-MEDICATION OPTIONS
nSurgerynVagus Nerve StimulationnDeep Brain Stimulation
ØNeuropace
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Referral to neurologist
nWhen the diagnosis is in questionnWhen the patient has failed to respond to
two seizure medications (drug resistant)nIf you are uncomfortable for any reason
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