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EpilepsyEpilepsy

Hyunmi Choi, M.D., M.S.Hyunmi Choi, M.D., M.S.Columbia Comprehensive EpilepsyColumbia Comprehensive Epilepsy

CenterCenterThe Neurological InstituteThe Neurological Institute

SeizureSeizure SymptomSymptom Transient eventTransient event ParoxysmalParoxysmal Temporary physiologic dysfunctionTemporary physiologic dysfunction Caused by self-limited, abnormal,Caused by self-limited, abnormal,

hypersynchronous hypersynchronous electrical discharge ofelectrical discharge ofcortical neuronscortical neurons

May occur only during course of an acuteMay occur only during course of an acutemedical or medical or neurologic neurologic illness (notillness (notpersisting after resolution of acute illness)persisting after resolution of acute illness)

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EpilepsyEpilepsy

Chronic disorderChronic disorder Recurrence of seizureRecurrence of seizure Unprovoked and unpredictableUnprovoked and unpredictable Distinct form with own naturalDistinct form with own natural

history and response to treatmenthistory and response to treatment Seizure type(s) in a ptSeizure type(s) in a pt

•• stereotypedstereotyped

EpidemiologyEpidemiology

PrevalencePrevalence•• 1-2% of population1-2% of population

IncidenceIncidence•• Age-adjusted annual incidence rateAge-adjusted annual incidence rate

31 to 57 per 100,00031 to 57 per 100,000

Incidence rates highest amongIncidence rates highest amongyoung children and elderlyyoung children and elderly

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EpidemiologyEpidemiology

60-70% achieve control of seizures60-70% achieve control of seizureswith antiepileptic medicationswith antiepileptic medications

30-40% refractory to medication30-40% refractory to medication MortalityMortality

•• Risk incurred by underlying diseaseRisk incurred by underlying disease•• Accidental deathsAccidental deaths•• Sudden unexplained death is 25 timesSudden unexplained death is 25 times

more common in epilepsy pts than inmore common in epilepsy pts than ingeneral populationgeneral population

ClassificationClassification

Developing a rational plan of investigationDeveloping a rational plan of investigation Making sound decisions aboutMaking sound decisions about

•• When and how long to treatWhen and how long to treat•• Choosing appropriate antiepileptic drugChoosing appropriate antiepileptic drug•• Considering surgical treatmentConsidering surgical treatment

Providing prognosisProviding prognosis International League Against EpilepsyInternational League Against Epilepsy

(1981 &1987)(1981 &1987)

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Simple partial seizureSimple partial seizure(partial onset epilepsy)(partial onset epilepsy)

Pts interact normally with environmentPts interact normally with environment Discharge occurs in limited andDischarge occurs in limited and

circumbscribedcircumbscribed area of cortex area of cortex SymptomSymptom

•• Subjective (Subjective (““AuraAura””)) Déjà vu, Déjà vu, jamaisjamais vu, vu, epigatricepigatric rising sensation, fear, rising sensation, fear,

feeling of unreality or detachment, olfactory hallucinationfeeling of unreality or detachment, olfactory hallucination Unilateral sensory disturbanceUnilateral sensory disturbance

•• Observable manifestationObservable manifestation Focal motorFocal motor ““JacksonianJacksonian march march””

Video

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Complex partialComplex partial(Partial onset epilepsy)(Partial onset epilepsy)

Impaired consciousnessImpaired consciousness AutomatismAutomatism

•• Repetitive, complex, purposeless motor activityRepetitive, complex, purposeless motor activity•• Lip-smacking, repeated swallowing, chewing,Lip-smacking, repeated swallowing, chewing,

picking motions with handspicking motions with hands StaringStaring Post-ictally Post-ictally –– pts confused and disoriented for pts confused and disoriented for

several minutesseveral minutes 70-80% of complex partial seizures arise from70-80% of complex partial seizures arise from

temporal lobestemporal lobes Remainder arise from frontal and occipital lobesRemainder arise from frontal and occipital lobes

Video

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Secondarily generalized tonicSecondarily generalized tonicclonic clonic seizureseizure

(partial onset epilepsy)(partial onset epilepsy)

ContralateralContralateral•• Head deviationHead deviation•• Gaze deviationGaze deviation•• Arm elevationArm elevation•• Followed by bilateral extension (tonic)Followed by bilateral extension (tonic)•• Bilateral Bilateral clonicclonic activity ( activity (clonicclonic))•• Post-Post-ictalictal lethargy lethargy

Video

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Absence seizureAbsence seizure(Generalized epilepsy)(Generalized epilepsy)

Momentary lapses in awarenessMomentary lapses in awareness Motionless staringMotionless staring Arrest of ongoing activityArrest of ongoing activity No warningNo warning No No postictal postictal periodperiod Characteristic EEG finding during seizureCharacteristic EEG finding during seizure

•• 3 Hz generalized spike wave3 Hz generalized spike wave

EthosuximideEthosuximide Seizure can be induced withSeizure can be induced with

hyperventilation in officehyperventilation in office

Generalized tonic Generalized tonic clonicclonic(Generalized epilepsy)(Generalized epilepsy)

Abrupt loss of consciousnessAbrupt loss of consciousness Loud vocalization as air forced acrossLoud vocalization as air forced across

contracted vocal cords (contracted vocal cords (ictalictal cry) cry) Bilateral tonic extension of trunk andBilateral tonic extension of trunk and

limbs (tonic)limbs (tonic) Synchronous muscle jerking (Synchronous muscle jerking (clonicclonic)) Post-Post-ictallyictally

•• UnarousableUnarousable, then lethargic and, then lethargic andconfusedconfused

•• Prefer to sleepPrefer to sleep

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Other generalized seizure typesOther generalized seizure types MyoclonicMyoclonic seizure seizure

•• Rapid brief muscle jerkRapid brief muscle jerk•• Bilaterally, synchronouslyBilaterally, synchronously•• Asynchronously, unilaterallyAsynchronously, unilaterally•• MyoclonicMyoclonic jerks range from isolated small jerks range from isolated small

movements of face, arm or leg tomovements of face, arm or leg tomassive bilaterally jerksmassive bilaterally jerks

AtonicAtonic seizure seizure•• Drop attacksDrop attacks•• Sudden loss of muscle tone resulting inSudden loss of muscle tone resulting in

fallsfalls

Video

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Temporal lobe epilepsyTemporal lobe epilepsy Age of onset: 7-20Age of onset: 7-20 History of febrile seizure as infantHistory of febrile seizure as infant Seizure types:Seizure types:

•• Simple partial (Simple partial (““AuraAura””))•• Complex partialComplex partial•• Secondarily generalized tonic Secondarily generalized tonic clonicclonic

Characteristic EEG findingCharacteristic EEG finding•• Focal spike waves over temporal lobeFocal spike waves over temporal lobe

Structural abnormality on MRIStructural abnormality on MRI•• Mesial Mesial temporal lobe sclerosistemporal lobe sclerosis

Often refractory to medicationOften refractory to medication

Juvenile Juvenile Myoclonic Myoclonic EpilepsyEpilepsy Idiopathic generalized epilepsyIdiopathic generalized epilepsy Age of onset: 12-20Age of onset: 12-20 Neurologically and intellectually normalNeurologically and intellectually normal Seizure types:Seizure types:

•• Generalized tonic Generalized tonic clonicclonic seizures seizures•• MyoclonicMyoclonic seizures seizures

Sensitivity to sleep deprivation and alcoholSensitivity to sleep deprivation and alcohol Characteristic EEG findingCharacteristic EEG finding

•• 4-5 Hz generalized spike wave discharges4-5 Hz generalized spike wave discharges ValproateValproate, , lamotriginelamotrigine Avoid drugs like Avoid drugs like carbamazepinecarbamazepine or or phenytoinphenytoin Usually lifelongUsually lifelong

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Childhood Absence EpilepsyChildhood Absence Epilepsy Idiopathic generalized epilepsyIdiopathic generalized epilepsy Age of onset: 4-12 yearsAge of onset: 4-12 years Neurologically and intellectually normalNeurologically and intellectually normal Recurrent absence seizuresRecurrent absence seizures If untreated, absence seizures can occurIf untreated, absence seizures can occur

hundreds of times a dayhundreds of times a day EEG during absence characteristic 3-HzEEG during absence characteristic 3-Hz

generalized spike wavegeneralized spike wave Ethosuximide Ethosuximide and and valproatevalproate 60% terminal remission60% terminal remission

Identifiable cause of epilepsy asIdentifiable cause of epilepsy asa function of agea function of age

InfectionsInfectionsMetabolicMetabolicdefectdefect

InfectionInfection

SystemicSystemicmetabolicmetabolicderangementderangement

InfectionInfectionCongenitalCongenitalmalformatiomalformationn

CongenitalCongenitalmalformationmalformation

TraumaTraumaVascularVasculardiseasedisease

TraumaTraumaMetabolicMetabolicdefectsdefects

BrainsBrainstumorstumors

TraumaTraumaInfectionsInfectionsPerinatalPerinatalInjuryInjury

VascularVasculardiseasedisease

Brain tumorsBrain tumorsGeneticGeneticpredispositipredispositionon

PrenatalPrenatalInjuryInjury

Over 60 yrOver 60 yr20-60 yr20-60 yr3-20 yr3-20 yrNeonate to 3Neonate to 3yryr

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Metabolic causes of acuteMetabolic causes of acute(symptomatic) seizure(symptomatic) seizure

Low calciumLow calcium Low sodiumLow sodium Low glucoseLow glucose Liver failureLiver failure Renal failureRenal failure AnoxiaAnoxia NonketoticNonketotic hyperglycemic state hyperglycemic state

Medical TreatmentMedical Treatment

Acute symptomatic seizuresAcute symptomatic seizures•• Childhood febrile seizureChildhood febrile seizure•• Metabolic or toxic encephalopathyMetabolic or toxic encephalopathy•• If conditions resolve without permanentIf conditions resolve without permanent

brain damage, seizures usually self-brain damage, seizures usually self-limitedlimited

Single unprovoked seizureSingle unprovoked seizure•• Only 25% later develop epilepsyOnly 25% later develop epilepsy

EpilepsyEpilepsy

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OutlineOutline

Surgically remediable epilepsiesSurgically remediable epilepsies Criteria for surgical candidacyCriteria for surgical candidacy Surgical evaluationSurgical evaluation Goals of surgeryGoals of surgery Types of surgeryTypes of surgery Surgical OutcomesSurgical Outcomes

MesialMesial temporal lobe epilepsy temporal lobe epilepsy

Most common and widely recognizedMost common and widely recognized H/o febrile seizuresH/o febrile seizures CPS begins in 1CPS begins in 1stst or 2 or 2ndnd decade decade Ant or Ant or midtemporalmidtemporal spike on EEG spike on EEG HippocampalHippocampal atrophy and inc signal atrophy and inc signal

on MRIon MRI <20% undergo spontaneous<20% undergo spontaneous

remission of remission of szsz

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MesialMesial temporal lobe sclerosis temporal lobe sclerosis

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LesionalLesional neocortical epilepsy neocortical epilepsy

Discrete neocortical lesionDiscrete neocortical lesion Examples: tumor, vascularExamples: tumor, vascular

malformation, focal cortical malformation, focal cortical dysplasiadysplasia Surrounding cortex Surrounding cortex ––occult pathology andoccult pathology and

be be epileptogenicepileptogenic

Cavernous Cavernous AngiomaAngioma

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Cortical Cortical dysplasiadysplasia

TassiTassi, L et al. Brain 2002, L et al. Brain 2002

““NonlesionalNonlesional”” neocortical neocorticalepilepsyepilepsy

Most challengingMost challenging Temporal vs. Temporal vs. extratemporalextratemporal Phase II evaluation tailored toPhase II evaluation tailored to

patientspatients Microscopic pathologyMicroscopic pathology Relationship to eloquent cortexRelationship to eloquent cortex

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Goals of surgeryGoals of surgery

Identify discrete and localized area ofIdentify discrete and localized area ofseizure focusseizure focus

Establish lack of vital functionEstablish lack of vital function CurativeCurative

•• Eradicates seizures and need for medEradicates seizures and need for med

PalliativePalliative•• Lessens seizure severity and frequencyLessens seizure severity and frequency

Criteria for surgical candidacyCriteria for surgical candidacy

Medical IntractabilityMedical Intractability Surgically remediable syndromeSurgically remediable syndrome ContraindicationsContraindications

•• Underlying degenerative or metabolic disordersUnderlying degenerative or metabolic disorders•• Primary generalized epilepsy syndromePrimary generalized epilepsy syndrome•• Benign epilepsy syndromes with potential forBenign epilepsy syndromes with potential for

spontaneous remissionspontaneous remission•• Medication noncomplianceMedication noncompliance•• InterictalInterictal psychosis psychosis•• Severely dysfunction family dynamicsSeverely dysfunction family dynamics

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Tests important in pre-surgicalTests important in pre-surgicalevaluationevaluation

Video-EEG, including recording typicalVideo-EEG, including recording typicalseizuresseizures

MRIMRI Neuropsychological testingNeuropsychological testing Wada testWada test PETPET IctalIctal SPECT SPECT Functional MRIFunctional MRI Intracranial EEGIntracranial EEG

Video-EEG MonitoringVideo-EEG Monitoring

To record seizures, and interictalTo record seizures, and interictal(between seizures) EEG activity(between seizures) EEG activity

24 hr monitoring, ~7 days.24 hr monitoring, ~7 days. Withdraw medicationsWithdraw medications Activation (HV, photic, sleepActivation (HV, photic, sleep

deprivation)deprivation)

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Magnetic Resonance ImagingMagnetic Resonance Imaging

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Wada testWada test

To identify language and memoryTo identify language and memoryfunction in each hemispherefunction in each hemisphereseparatelyseparately

Helps predict risks of surgeryHelps predict risks of surgery•• memorymemory•• languagelanguage

Helps predict success of surgeryHelps predict success of surgery Same day procedureSame day procedure

Other testOther test

PETPET SPECTSPECT Neuropsychological testNeuropsychological test

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Invasive MonitoringInvasive Monitoring

Negative non-invasive testsNegative non-invasive tests A discrete lesion located near regionA discrete lesion located near region

of seizure onsetof seizure onset If non-If non-lesionallesional, estimate and place, estimate and place

intracranial electrodes based on allintracranial electrodes based on allnon-invasive test resultsnon-invasive test results

Invasive monitoringInvasive monitoring

EEG electrodeEEG electrodeplacementplacement(intracranial(intracranialmonitoring)monitoring)

Record seizure withRecord seizure withvideo/EEG in Epilepsyvideo/EEG in EpilepsyMonitoring UnitMonitoring Unit

When area of seizureWhen area of seizureonset is not preciselyonset is not preciselydefined during phase Idefined during phase Ievaluationevaluation

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Epilepsy surgeryEpilepsy surgery

History of Brain surgery for epilepsyHistory of Brain surgery for epilepsy•• >100 years old>100 years old

The most common operationThe most common operation•• resection of the anterior portion of either theresection of the anterior portion of either the

right or left temporal loberight or left temporal lobe

The restThe rest•• resections of portions of the frontal, parietal orresections of portions of the frontal, parietal or

occipital lobes, and section of the anterior two-occipital lobes, and section of the anterior two-thirds of the corpus thirds of the corpus callosumcallosum

Surgical OutcomeSurgical Outcome

Dependent on syndrome andDependent on syndrome andconcordance of findingsconcordance of findings

Anterior temp resection Anterior temp resection 70-90%70-90% LesionectomyLesionectomy 75%75% Non-Non-lesionallesional resection resection <50%<50% ~~5% complication rate in temporal5% complication rate in temporal

lobectomylobectomy, most temporary; ~1%, most temporary; ~1%permanent complicationpermanent complication

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What options exist for patients withWhat options exist for patients withpatients who are not surgicalpatients who are not surgical

candidates?candidates?

Multiple regions of seizure onsetMultiple regions of seizure onset Seizure starts in a region withSeizure starts in a region with

intact functioningintact functioning Cannot undergo surgery safelyCannot undergo surgery safely

because of multiple factors such asbecause of multiple factors such asage, concurrent medical problemsage, concurrent medical problems

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Vagus Nerve Stimulation (VNS)Vagus Nerve Stimulation (VNS)

First done 1988, FDA approved 1997First done 1988, FDA approved 1997 Surgical implantationSurgical implantation Periodic adjustments of stimulationPeriodic adjustments of stimulation

to maximize benefit and minimizeto maximize benefit and minimizeside effectsside effects

Magnet allows self-activationMagnet allows self-activation Being studied for depression as wellBeing studied for depression as well

VagalVagal Nerve Stimulator Nerve Stimulator

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ExperiementalExperiemental: Current clinical: Current clinicaltrialstrials

Brain Stimulation with implantedBrain Stimulation with implanteddevicedevice•• Responsive Responsive NeurostimulatorNeurostimulator

Detects seizuresDetects seizures At seizure focusAt seizure focus

•• Deep brain stimulationDeep brain stimulation Bilateral anterior nuclei of ThalamusBilateral anterior nuclei of Thalamus

Responsive Responsive NeurostimulatorNeurostimulator

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Responsive Responsive NeurostimulatorNeurostimulator

Stimulation of the Anterior Nucleus ofStimulation of the Anterior Nucleus ofthe Thalamus for Epilepsythe Thalamus for Epilepsy

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Example: AFExample: AF Presented age 21, college studentPresented age 21, college student seizure onset age 10seizure onset age 10 feeling of feeling of ““disorientationdisorientation””, inability to, inability to

speak, preservation of consciousness, oralspeak, preservation of consciousness, oralautomatisms, presently 4-7/weekautomatisms, presently 4-7/week

febrile seizure @ 10 mo; normal examfebrile seizure @ 10 mo; normal exam EEG rare left sharp waves, MRI normalEEG rare left sharp waves, MRI normal had failed had failed phenytoinphenytoin, , carbamazepinecarbamazepine

Neuropsychological testNeuropsychological test

FSIQ 101; VIQ 101; PIQ 102FSIQ 101; VIQ 101; PIQ 102 mild left dysfunction on specificmild left dysfunction on specific

language taskslanguage tasks

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WadaWada

left language dominanceleft language dominance left injection: 7/8 recallleft injection: 7/8 recall right injection: 6/10 recallright injection: 6/10 recall

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SummarySummary

temporal appearing seizures,temporal appearing seizures,intractableintractable

concordant concordant ictalictal EEG EEG no MRI abnormalityno MRI abnormality minimal minimal interictalinterictal spikes spikes Wada suggestive of left Wada suggestive of left mesialmesial

dysfunctiondysfunction unclear whether unclear whether mesialmesial or neocortical or neocortical

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Follow-upFollow-up

standard left temporal standard left temporal lobectomylobectomy 1- 1-20-9920-99

no further seizuresno further seizures mild decline in verbal memory,mild decline in verbal memory,

improvement in naming, receptiveimprovement in naming, receptivelanguage, arithmeticlanguage, arithmetic

carbamazepinecarbamazepine discontinued 2-99 discontinued 2-99 gabapentingabapentin discontinued 2-00 discontinued 2-00 working as financial analystworking as financial analyst

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ConclusionConclusion

Epilepsy surgery is an underutilizedEpilepsy surgery is an underutilizedprocedureprocedure

Surgically remediable syndrome andSurgically remediable syndrome andmedically refractorymedically refractory

Noninvasive evaluation shouldNoninvasive evaluation shouldconsidered early in diseaseconsidered early in disease