EPILEPSYEPILEPSY

Terminology and ClassificationTerminology and Classification SeizureSeizure

Brief disturbance of cerebral dysfunction due to abnormal Brief disturbance of cerebral dysfunction due to abnormal synchronized neuronal electrical dischargesynchronized neuronal electrical discharge

““Provoked or acute symptomatic seizure” Provoked or acute symptomatic seizure” Identifiable temporary or permanent isolated condition that disrupts Identifiable temporary or permanent isolated condition that disrupts

cerebral structure or functioncerebral structure or function Drug (ETOH) withdrawal, acute head trauma, hypoglycemia, CVADrug (ETOH) withdrawal, acute head trauma, hypoglycemia, CVA

“ “Unprovoked seizure”Unprovoked seizure” Cryptogenic: Occult cause other then genetic etiologyCryptogenic: Occult cause other then genetic etiology Idiopathic: no cause other than genetic predispositionIdiopathic: no cause other than genetic predisposition

Epilepsy: recurrent uprovoked seizuresEpilepsy: recurrent uprovoked seizures Epilepsy is considered to have occurred after the 2Epilepsy is considered to have occurred after the 2ndnd unprovoked unprovoked

event.event.

International Classification of International Classification of EpilepsyEpilepsy

Partial seizuresPartial seizures Simple partial seizures (Simple partial seizures (unimpaired consciousnessunimpaired consciousness)) Complex partial seizures (Complex partial seizures (impaired consciousnessimpaired consciousness)) Partial seizure evolving into Secondarily generalizedPartial seizure evolving into Secondarily generalized

Generalized seizuresGeneralized seizures ( (Primary seizure disorderPrimary seizure disorder)) Absence seizuresAbsence seizures Tonic-Clonic seizuresTonic-Clonic seizures Clonic seizuresClonic seizures Tonic seizuresTonic seizures Myoclonic seizuresMyoclonic seizures Atonic seizuresAtonic seizures

Secondary versus Primary Secondary versus Primary Generalized seizuresGeneralized seizures

Hauser et al,Epilepsia 1993;34:453-468

EpidemiologyEpidemiologyIncidence of 1st Incidence of 1st

unprovoked seizuresunprovoked seizuresOverall incidence: 60/100K person-yearsOverall incidence: 60/100K person-years

Hauser et al, Epilepsia 1993;34:453-468

Incidence of EpilepsyIncidence of EpilepsyOverall incidence: 44/100K person-yearsOverall incidence: 44/100K person-years

Hauser et al, Epilepsia 1993

Proportion of all incidence Proportion of all incidence cases of epilepsy by seizure cases of epilepsy by seizure

typetype

Hauser et al, Epilepsia 1993

Proportion of newly diagnosed epilepsy Proportion of newly diagnosed epilepsy cases according to etiologic categories cases according to etiologic categories

within age groupswithin age groups

DeLorenzo et al, JCN 1995;12:316-325

Age-specific distribution of the Age-specific distribution of the incidence of first status epilepticus incidence of first status epilepticus

per year per 100K in Richmond, per year per 100K in Richmond, VAVA

Hauser et al, Epilepsia 1993

Prevalence of EpilepsyPrevalence of Epilepsyage and sex age and sex

DiagnosisDiagnosis Case 1: Case 1: 22 y/o male with 3 episodes of abnormal behavior for 22 y/o male with 3 episodes of abnormal behavior for

the past 3 months witnessed by his wife. With the 1the past 3 months witnessed by his wife. With the 1stst 2 events, he 2 events, he suddenly felt “weird” in his stomach, few seconds later, stopped suddenly felt “weird” in his stomach, few seconds later, stopped talking and was staring. No response when his name was called. talking and was staring. No response when his name was called. He began to make lip smacking, chewing movements and fumbled He began to make lip smacking, chewing movements and fumbled with his shirt for a minute, following which became responsive but with his shirt for a minute, following which became responsive but felt tired. Yesterday, he had similar spell, but after 15 seconds of felt tired. Yesterday, he had similar spell, but after 15 seconds of staring and smacking movements with his mouth, he fell to the staring and smacking movements with his mouth, he fell to the floor and had jerking of his trunk and all limbs. The jerking floor and had jerking of his trunk and all limbs. The jerking continued for 2 minutes; after that he fell into deep sleep.continued for 2 minutes; after that he fell into deep sleep.

What type of seizure does the patient have?What type of seizure does the patient have? Based on the clinical manifestation, where is the Based on the clinical manifestation, where is the

neuroanatomic localization?neuroanatomic localization? Identifying risk factors for epilepsyIdentifying risk factors for epilepsy EvaluationEvaluation

Evaluating a patient with Evaluating a patient with EpilepsyEpilepsy

Risk factors for Risk factors for epilepsyepilepsy Febrile convulsionFebrile convulsion Perinatal insultPerinatal insult CNS infectionCNS infection Mass lesion in the brainMass lesion in the brain Family history of Family history of

epilepsyepilepsy Head injury (LOC Head injury (LOC

>30min)>30min) Developmental delayDevelopmental delay History of CVAHistory of CVA Focal neurological examFocal neurological exam

LaboratoryLaboratory ElectrolytesElectrolytes HypoglycemiaHypoglycemia HepaticHepatic Renal dysfunctionRenal dysfunction DrugsDrugs ToxinsToxins AlcoholAlcohol

CT CT MRI brainMRI brain EEGEEG

Noseworthy, Neuro therapeutics 2003; pg 289

EEG testEEG test Emergent EEG: To rule out NCSEEmergent EEG: To rule out NCSE Support diagnosis and localize seizure focusSupport diagnosis and localize seizure focus Normal EEG during clinical spell suggest non-Normal EEG during clinical spell suggest non-

epileptic event epileptic event

Normal EEG does not rule out epilepsyNormal EEG does not rule out epilepsy ¼ of epileptics have normal EEG¼ of epileptics have normal EEG Deep focus (hippocampus, parasagittal frontal Deep focus (hippocampus, parasagittal frontal

cortex)cortex) Incr diagnostic yield: SD, HV and photic stimulationIncr diagnostic yield: SD, HV and photic stimulation

Focal slowing: Focal brain dysfunctionFocal slowing: Focal brain dysfunction

Luders EEG atlas 1994, page 60

Luders EEG atlas 1994, pg 103

What other diagnosis should be What other diagnosis should be considered when evaluating a considered when evaluating a patient with suspected seizure patient with suspected seizure

disorder?disorder? Non-epileptic Non-epileptic

physiologicalphysiological SyncopeSyncope

ArrhythmiasArrhythmias VasovagalVasovagal Orthostatic hypotensionOrthostatic hypotension Medication-inducedMedication-induced

CerebrovascularCerebrovascular: : TIA/CVATIA/CVA

Classic migrainesClassic migraines Toxic-metabolicToxic-metabolic

ETOH, hypoglycemiaETOH, hypoglycemia

Non-epileptic Non-epileptic psychogenicpsychogenic Conversion disorderConversion disorder Anxiety or panic Anxiety or panic

disorderdisorder

Medical Treatment of EpilepsyMedical Treatment of Epilepsy The patient with a single seizureThe patient with a single seizure

50-70% will not have another seizure50-70% will not have another seizure 50% of untreated patient: 2nd seizure within 5 yrs.50% of untreated patient: 2nd seizure within 5 yrs.

The decision to treat should be based on the The decision to treat should be based on the presence or absence of risk factors associated presence or absence of risk factors associated with recurrencewith recurrence Abnormal NE, abnormal EEGAbnormal NE, abnormal EEG Partial seizure with or without secondary Partial seizure with or without secondary

generalizationgeneralization History of neurologic injury (CVA, hge, tumor)History of neurologic injury (CVA, hge, tumor) Possible consequence of second seizure Possible consequence of second seizure

Risk of injury for patients taking anticoagulationRisk of injury for patients taking anticoagulation Risk of the patient’s job requires driving.Risk of the patient’s job requires driving.

Differentiating Epileptic from non-Differentiating Epileptic from non-epileptic seizuresepileptic seizures

FeatureFeature Epileptic Epileptic Non-Non-epilepticepileptic

OnsetOnset SuddenSudden Maybe Maybe gradualgradual

Retained Retained consciousnessconsciousness

RarelyRarely CommonCommon

Flailing, thrashingFlailing, thrashing RareRare CommonCommon

Rolling movementsRolling movements RareRare CommonCommon

Starting and Starting and stoppingstopping

RareRare CommonCommon

Resistance to Resistance to passive limb passive limb movementsmovements

UnusualUnusual CommonCommon

Induced by Induced by suggestionsuggestion

RareRare OftenOften

Postictal confusionPostictal confusion CommonCommon Often absentOften absent

General Principles of AED General Principles of AED ManagementManagement

MonotherapyMonotherapy is the goalis the goal Selection of AEDSelection of AED is based mainly on the is based mainly on the seizure seizure

typetype In emergent situationsIn emergent situations loading doseloading dose is preferrableis preferrable

(Phenytoin, Valproic acid, PB)(Phenytoin, Valproic acid, PB) ““Start low and go slowStart low and go slow”, ”, when loading dose is when loading dose is

notnot givengiven. . Therapeutic dose is guided by occurrence Therapeutic dose is guided by occurrence of breakthrough seizures or intolerable SEof breakthrough seizures or intolerable SE TTreatreat the patient and not the drug levelthe patient and not the drug level TThe risk ofhe risk of dose-related symptoms dose-related symptoms andand acute acute

idiosyncratic SE idiosyncratic SE is minimized by is minimized by slow and cautious slow and cautious dosedose escalationescalation..

IfIf toxicity toxicity occursoccurs during adjustment of AED, during adjustment of AED, reduce dose by 25%, wait 2 weeks then increase reduce dose by 25%, wait 2 weeks then increase again.again.

Selection of AED based on Selection of AED based on Seizure typeSeizure type

MKSAP 13, pg 52

AED withdrawal/ AED withdrawal/ discontinuationdiscontinuation

Unprovoked seizures caused by neurologic Unprovoked seizures caused by neurologic illness (brain tumor) require continuous drug illness (brain tumor) require continuous drug therapy.therapy.

If seizure-free for >2 years, re-evaluate.If seizure-free for >2 years, re-evaluate. Tapering considered if no factors associated with Tapering considered if no factors associated with

high recurrence risk (structural lesion, abnormal high recurrence risk (structural lesion, abnormal EEG, abnormal NE, severe epilepsy prior to being EEG, abnormal NE, severe epilepsy prior to being controlled).controlled).

Without risk: 25 % risk of having recurrence Without risk: 25 % risk of having recurrence 80% within 4 months, 90% within 1 year after 80% within 4 months, 90% within 1 year after

Driving and potentially dangerous activities Driving and potentially dangerous activities should be prohibited during tapering of AED should be prohibited during tapering of AED for at least 4 months.for at least 4 months.

Status epilepticusStatus epilepticus

Continuous seizure activity for at least 20 Continuous seizure activity for at least 20 minutesminutes (+/-) impairment of consciousness(+/-) impairment of consciousness..

The patient does not completely recover to The patient does not completely recover to baseline neurologic functioning between 2 or baseline neurologic functioning between 2 or more seizuresmore seizures

Approx 12% of epileptics have SE as initial event.Approx 12% of epileptics have SE as initial event.

5 Major subtypes of SE5 Major subtypes of SE GCSE: Overt Generalized Convulsive SE (primary and GCSE: Overt Generalized Convulsive SE (primary and

secondary generalized seizure)secondary generalized seizure) Subclinical or Subtle GCSE (frequently referred as Subclinical or Subtle GCSE (frequently referred as

Myoclonic status)Myoclonic status) CPSE: Complex Partial SECPSE: Complex Partial SE Absence SE (Petit Mal status)Absence SE (Petit Mal status) Simple Partial SE (No impairment of consciousness)Simple Partial SE (No impairment of consciousness)

Treiman et al, NEJM 1998;339:792-798

Comparative Trial of initial IV Comparative Trial of initial IV treatment of GCSEtreatment of GCSE

Neurologic Therapeutics 2003; pg 324

Noseworthy 2003, Neurologic Therapeutics; page 326

Management of Status Management of Status EpilepticusEpilepticus

Special issues in EpilepsySpecial issues in Epilepsy CVACVA is the leading cause of epilepsy >60 y/o is the leading cause of epilepsy >60 y/o

Majority occurs within 3-12 monthsMajority occurs within 3-12 months Risk include cortical involvement, lobar hematomas close to Risk include cortical involvement, lobar hematomas close to

the brain surface.the brain surface.

Women with epilepsy: 30%Women with epilepsy: 30% have increased risk have increased risk seizure frequency during pregnancy.seizure frequency during pregnancy. Seizures poses more danger to the fetus than AED itself. Seizures poses more danger to the fetus than AED itself.

Discourage patients from reducing or stopping AED during Discourage patients from reducing or stopping AED during pregnancy. pregnancy.

90% of epileptic women: Normal pregnancy/ deliver normal 90% of epileptic women: Normal pregnancy/ deliver normal children.children.

Surgical treatmentSurgical treatment is more superior than medical is more superior than medical treatment in medically intractable epilepsy. Referral to treatment in medically intractable epilepsy. Referral to Epilepsy centerEpilepsy center

Ketogenic dietKetogenic diet, high fat, low-protein and low-, high fat, low-protein and low-carbohydrate diet, starve the body, increase ketones, carbohydrate diet, starve the body, increase ketones, increase seizure threshold.increase seizure threshold.

Report seizure patients to Dept ofReport seizure patients to Dept of Health/DMVHealth/DMV. . Advise them not to drive, avoid heights, swimming, weaponry, Advise them not to drive, avoid heights, swimming, weaponry,

equipment that can potentially harm self or othersequipment that can potentially harm self or others