Epilepsy SyndromesEpilepsy Syndromes

Maja Ilic, MDMaja Ilic, MD

EpileptologistEpileptologistNortheast Regional Epilepsy GroupNortheast Regional Epilepsy Group

What is seizure and what is What is seizure and what is epilepsy?epilepsy?

• SEIZURESEIZURE

- Physiological: Manifestation of an abnormal - Physiological: Manifestation of an abnormal and excessive synchronized discharge of a set and excessive synchronized discharge of a set of neuronsof neurons

- Clinical: Stereotypical, usually unprovoked, - Clinical: Stereotypical, usually unprovoked, disturbance of consciousness, behavior, disturbance of consciousness, behavior, emotion, motor function or sensation as a emotion, motor function or sensation as a result of the cortical neuronal dischargeresult of the cortical neuronal discharge

• EPILEPSY:EPILEPSY: 2 or more seizures 2 or more seizures

Provoked seizuresProvoked seizures

• High fever, febrile seizuresHigh fever, febrile seizures• Massive sleep deprivationMassive sleep deprivation• Excessive use of stimulantsExcessive use of stimulants• Withdrawal from sedative drugs or alcoholWithdrawal from sedative drugs or alcohol• Electrolyte disturbanceElectrolyte disturbance• HypoxiaHypoxia• Acute neurological illnessAcute neurological illness

EpidemiologyEpidemiology > 2 million people in US> 2 million people in US

125,000 new cases per 125,000 new cases per yearyear

Cumulative incidence of Cumulative incidence of epilepsy by age 80 = 3.1%epilepsy by age 80 = 3.1%

Cumulative incidence of Cumulative incidence of seizures by age 80 = 11%seizures by age 80 = 11%

Many patients outgrow Many patients outgrow their epilepsytheir epilepsy

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20

30

40

50

60

70

80

90

0-9 10--19

20-39

40-59

60+

Age group (years)

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Historical background:Historical background:

In an attempt to encompass a broader In an attempt to encompass a broader range of clinical features than is possible range of clinical features than is possible in a classification of seizure type – in a classification of seizure type –

ILAE published a Classifications of ILAE published a Classifications of Epilepsies and Epileptic Syndromes in Epilepsies and Epileptic Syndromes in 1985 and revised it in 19891985 and revised it in 1989

Epilepsy syndromesEpilepsy syndromes

SyndromeSyndrome is a cluster of signs and symptoms that is a cluster of signs and symptoms that occur together but unlike a disease do not have a occur together but unlike a disease do not have a single known cause or pathology.single known cause or pathology.

Epileptic syndromeEpileptic syndrome integrates all data, seizure integrates all data, seizure type, EEG findings, age of onset, cause, family type, EEG findings, age of onset, cause, family history, imaging studies, precipitating factors, etc. history, imaging studies, precipitating factors, etc. in order to make a final diagnosis of epilepsy.in order to make a final diagnosis of epilepsy.

Most Common Epilepsy Syndromes in Most Common Epilepsy Syndromes in ChildrenChildren

Childhood Absence EpilepsyChildhood Absence Epilepsy

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

Juvenile Myoclonic EpilepsyJuvenile Myoclonic Epilepsy

Benign Epilepsy of Childhood with Centrotemporal Benign Epilepsy of Childhood with Centrotemporal SpikesSpikes

(Benign Rolandic Epilepsy)(Benign Rolandic Epilepsy)

Childhood Absence Childhood Absence EpilepsyEpilepsy

Absence EpilepsyAbsence Epilepsy

Generalized seizuresGeneralized seizures

Most common in the first decade, Most common in the first decade, particularly ages 5-7 years of ageparticularly ages 5-7 years of age

Clinical featuresClinical features• Usual duration – 10 secondsUsual duration – 10 seconds• Ongoing activities ceaseOngoing activities cease• Motionless with a fixed blank stareMotionless with a fixed blank stare• Attack ends suddenly, activity resumesAttack ends suddenly, activity resumes

Clinical features Clinical features Occasionally – mild clonic activity of eyelids, corner of mouthOccasionally – mild clonic activity of eyelids, corner of mouth

• Automatisms – elevation of eyelids, licking, swallowing, scratching Automatisms – elevation of eyelids, licking, swallowing, scratching movements of handsmovements of hands

Absence EpilepsyAbsence Epilepsy

Most patients with typical absence have normal Most patients with typical absence have normal development and normal neurological exam development and normal neurological exam

Generalized spikes on EEG Generalized spikes on EEG

- Precipitated by hyperventilation in all untreated Precipitated by hyperventilation in all untreated patientspatients

- Photic stimulation – 15%- Photic stimulation – 15%

Absence EpilepsyAbsence Epilepsy

10% family history 10% family history

Average age when seizures stop is 10 years oldAverage age when seizures stop is 10 years old

Generally have a good prognosis – Generally have a good prognosis –

resolves in ~ 80 percent of casesresolves in ~ 80 percent of cases

Treatment:Treatment:

• EthosuximideEthosuximide• DepakoteDepakote

Suppress absence in 80%Suppress absence in 80%

• LamotrigineLamotrigine

Absence EpilepsyAbsence Epilepsy

Atypical

Complex automatisms

Slower, 2.5 Hz spike-slow wave

Focal and GTC seizures

Developmental delay

Abnormal background EEG

Typical

Simple automatisms

3 Hz spike-slow wave

No other seizure type

Normal exam

Normal background EEG

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

Age of onsetAge of onset

Near or after pubertyNear or after puberty

Between 10-17 yearsBetween 10-17 years

Normal intelligence & neurological examNormal intelligence & neurological exam

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

Seizures typesSeizures types AbsencesAbsences

Generalized tonic-clonic seizures- in 80%Generalized tonic-clonic seizures- in 80% (often shortly after waking)(often shortly after waking)

Myoclonic seizures- in 15%Myoclonic seizures- in 15%

GTC and myoclonic seizure more common and most likely to GTC and myoclonic seizure more common and most likely to happen with awakeninghappen with awakening

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

EEGEEG Normal backgroundNormal background Generalized spike & wave discharges (faster, 4 Hz)Generalized spike & wave discharges (faster, 4 Hz) Induced by HV, not photic stimulationInduced by HV, not photic stimulation

TreatmentTreatment DepakoteDepakote LamictalLamictal

Juvenile Absence EpilepsyJuvenile Absence Epilepsy

PrognosisPrognosis At least 80% of patients can be treated with At least 80% of patients can be treated with

Depakote aloneDepakote alone

Absences and GTC usually respond well to Absences and GTC usually respond well to pharmacotherapypharmacotherapy

Unlike CAE (in which most patients become Unlike CAE (in which most patients become seizure free) the long term evolution of JAE has seizure free) the long term evolution of JAE has not been properly characterizednot been properly characterized

Juvenile Myoclonic Juvenile Myoclonic EpilepsyEpilepsy

Juvenile Myoclonic EpilepsyJuvenile Myoclonic Epilepsy

IncidenceIncidence• 10% of all epilepsies10% of all epilepsies

Age of onsetAge of onset• 12–18 years12–18 years• Age of onset differs from age of diagnosisAge of onset differs from age of diagnosis

Juvenile Myoclonic EpilepsyJuvenile Myoclonic Epilepsy

Myoclonic jerks, generalized tonic-clonic Myoclonic jerks, generalized tonic-clonic seizures, and sometimes absence seizures seizures, and sometimes absence seizures

• Myoclonic seizures Myoclonic seizures Jerks of neck, shoulder, arm or leg extensorsJerks of neck, shoulder, arm or leg extensors Usually bilaterally symmetric & synchronousUsually bilaterally symmetric & synchronous More in upper extremitiesMore in upper extremities Drop objects, interfere in morning activitiesDrop objects, interfere in morning activities

Juvenile Myoclonic EpilepsyJuvenile Myoclonic Epilepsy

Usual age at onset:Usual age at onset:

- Absence seizures is 7 -13 years; - Absence seizures is 7 -13 years;

- Myoclonic jerks, 12- 18 years; - Myoclonic jerks, 12- 18 years;

- Generalized convulsions, 13 - 20 years- Generalized convulsions, 13 - 20 years

Juvenile Myoclonic EpilepsyJuvenile Myoclonic Epilepsy More likely to have seizures with sleep deprivation and More likely to have seizures with sleep deprivation and

alcohol ingestionalcohol ingestion

Risk for seizures is lifelongRisk for seizures is lifelong Seizures recur when AEDs withdrawnSeizures recur when AEDs withdrawn

Photic stimulation often provokes a dischargePhotic stimulation often provokes a discharge

Seizures are usually well-controlled (Depakote, Lamictal)Seizures are usually well-controlled (Depakote, Lamictal)

Benign Epilepsy of Childhood with Centrotemporal Spikes Benign Epilepsy of Childhood with Centrotemporal Spikes

Benign Rolandic Epilepsy Benign Rolandic Epilepsy

BECTBECT

Age of onsetAge of onset• Range 2 – 13 yearsRange 2 – 13 years• 80% between 5 – 10 years (Peak 9 years)80% between 5 – 10 years (Peak 9 years)

Typically resolves by age 16 yearsTypically resolves by age 16 years

Normal intelligence and neurological examNormal intelligence and neurological exam

Seizures usually happen after falling asleep or Seizures usually happen after falling asleep or before awakening (75%)before awakening (75%)

BECTBECT

Most characteristic symptomsMost characteristic symptoms• Sensorimotor phenomena of faceSensorimotor phenomena of face

Oropharyngeal – Hypersalivation, guttural sounds, Oropharyngeal – Hypersalivation, guttural sounds, contraction of jaw, difficulty moving the tongue etccontraction of jaw, difficulty moving the tongue etc

Speech arrestSpeech arrest Clonic jerks at corner of mouthClonic jerks at corner of mouth Clonic jerks of one armClonic jerks of one arm

No loss of consciousnessNo loss of consciousness

Can have secondarily generalized convulsionsCan have secondarily generalized convulsions

BECTBECT

EEG: Spikes in midtemporal and central head EEG: Spikes in midtemporal and central head regionregion

More spikes in drowsiness and sleep More spikes in drowsiness and sleep

30% of cases show spikes only during sleep30% of cases show spikes only during sleep

BECTBECT

BECTS spontaneously stop with or without treatment (good BECTS spontaneously stop with or without treatment (good prognosis)prognosis)

If seizures are frequent and/or disturbing to patient and If seizures are frequent and/or disturbing to patient and family, treatment with Tegretol or Trileptal (until 14-16, family, treatment with Tegretol or Trileptal (until 14-16, response)response)• AEDs given in about 50% of casesAEDs given in about 50% of cases

• Features suggesting risk of repeated seizuresFeatures suggesting risk of repeated seizures Short interval between 1Short interval between 1stst & 2 & 2ndnd attacks attacks Early onsetEarly onset

Febrile SeizuresFebrile Seizures Up to 4% of childrenUp to 4% of children

Not epilepsyNot epilepsy

Often a family history, 10% Often a family history, 10% (chromosomes 8q, 19p)(chromosomes 8q, 19p)

Seizures only occur with fever in children age 6 Seizures only occur with fever in children age 6 months – 6 yearsmonths – 6 years

Febrile SeizuresFebrile Seizures

SimpleSimple

- 1 brief seizure (generalized)- 1 brief seizure (generalized)

ComplexComplex

– – ProlongedProlonged- More than 1More than 1- FocalFocal

Febrile seizuresFebrile seizures

13% incidence of epilepsy if at least 2 factors:13% incidence of epilepsy if at least 2 factors:

- History of non-febrile seizureHistory of non-febrile seizure- Abnormal neurological exam or developmentAbnormal neurological exam or development- Prolonged febrile seizure Prolonged febrile seizure - Focal febrile seizure Focal febrile seizure

Febrile seizuresFebrile seizures

Recurrence risk:Recurrence risk:- Children with simple FS 30%Children with simple FS 30%- Children with complex FS 50%Children with complex FS 50%

Risk of epilepsy:Risk of epilepsy:

- With history of simple FS 2-4%- With history of simple FS 2-4%

- With history of complex FS 6%- With history of complex FS 6%

Febrile SeizuresFebrile Seizures

Increase risk of recurrence if 1Increase risk of recurrence if 1stst before 18 months before 18 months or lower temperatureor lower temperature

Focal need MRI, EEGFocal need MRI, EEG

Testing unnecessary with simpleTesting unnecessary with simple Treatment usually not necessaryTreatment usually not necessary

Epilepsy Prognosis:Epilepsy Prognosis:

Depends on seizure type:Depends on seizure type:

Typical Absence – 80% resolveTypical Absence – 80% resolve

JME- respond well to treatment but need JME- respond well to treatment but need meds for lifemeds for life

Neurologically abnormal often difficult to control seizuresNeurologically abnormal often difficult to control seizures

Drug Refractoriness of Different Seizure TypesDrug Refractoriness of Different Seizure Types

Idiopathic partial 0-2%Idiopathic partial 0-2% Childhood absence Childhood absence 10-30%10-30% Juvenile absence Juvenile absence 10-35%10-35% Primary GTCS Primary GTCS 20-30%20-30% Secondary GTCS Secondary GTCS 30-60%30-60% CPS 40-60%CPS 40-60% LGS LGS 60-80%60-80% Infantile spasms 60-80%Infantile spasms 60-80%

Most patients (>70%) will have excellent seizure Most patients (>70%) will have excellent seizure control with medicationscontrol with medications

Some patients will continue to have seizures Some patients will continue to have seizures despite good medical therapydespite good medical therapy

• Ketogenic dietKetogenic diet• Vagal nerve stimulatorVagal nerve stimulator• Epilepsy surgeryEpilepsy surgery

Treatment GoalsTreatment Goals

Prevent recurrence of seizuresPrevent recurrence of seizures Avoid side effects from AEDsAvoid side effects from AEDs Attain “therapeutic levels”Attain “therapeutic levels” Ensure complianceEnsure compliance

General Guidelines for Use of AEDsGeneral Guidelines for Use of AEDs

Select AED specific for seizure type and EEG Select AED specific for seizure type and EEG findingsfindings

Start with single drugStart with single drug

Optimize AEDOptimize AED• Balance seizure control vs. toxicityBalance seizure control vs. toxicity

Add second drug if first failsAdd second drug if first fails

Anticipate medication interactionsAnticipate medication interactions

When to Treat After Single Seizure?When to Treat After Single Seizure?

DefinitelyDefinitely With structural lesionWith structural lesion

• Brain tumorBrain tumor• Arteriovenous Arteriovenous

malformationmalformation• Infection, such as abscess, Infection, such as abscess,

herpes encephalitisherpes encephalitis

Without structural lesionWithout structural lesion• EEG with definite epileptic EEG with definite epileptic

patternpattern• History of previous seizure History of previous seizure • History of previous brain History of previous brain

injuryinjury• Status epilepticus at onsetStatus epilepticus at onset

PossiblyPossibly Unprovoked seizureUnprovoked seizure

Probably notProbably not (although short- (although short-term therapy may be used)term therapy may be used)

Alcohol withdrawalAlcohol withdrawal Drug abuseDrug abuse Seizure in context of acute Seizure in context of acute

illness illness Postimpact seizure Postimpact seizure Specific benign epilepsy Specific benign epilepsy

syndromesyndrome Seizure provoked by Seizure provoked by

excessive sleep deprivationexcessive sleep deprivation

MedicationsMedications

Trileptal, Tegretol, Keppra, Depakote, Trileptal, Tegretol, Keppra, Depakote,

Lamictal, Phenobarbital,Topamax, Lamictal, Phenobarbital,Topamax, Ethosuximide…Ethosuximide…

Choice based on type of seizures, EEG Choice based on type of seizures, EEG findings, side effects, age and sexfindings, side effects, age and sex

22ndnd AED may be added if seizures not AED may be added if seizures not controlledcontrolled

Newer antiepiletic medications:Newer antiepiletic medications:

Lacosamide (Vimpat)Lacosamide (Vimpat)

Vigabatrin (Sabril)Vigabatrin (Sabril)

Rufinamide (Banzel)Rufinamide (Banzel)

Perampanel (Fycompa)Perampanel (Fycompa)

Conclusion:Conclusion:

Seizure type and diagnosis are only one element Seizure type and diagnosis are only one element of a more comprehensive patient assessment of a more comprehensive patient assessment that should result in a precise epilepsy syndrome that should result in a precise epilepsy syndrome diagnosisdiagnosis

Only an accurate diagnosis of a specific epilepsy Only an accurate diagnosis of a specific epilepsy syndrome allows patients and physicians to syndrome allows patients and physicians to examine all treatment optionsexamine all treatment options

www.epilepsyfoundation.orgwww.epilepsyfoundation.org www.epilepsyadvocate.comwww.epilepsyadvocate.com www.paceusa.orgwww.paceusa.org www.epilepsy.comwww.epilepsy.com