Epilepsy Syndromes Maja Ilic, MD Epileptologist Northeast Regional Epilepsy Group

What is seizure and what is epilepsy? SEIZURESEIZURE - Physiological: Manifestation of an abnormal and excessive synchronized discharge of a set of neurons - Clinical: Stereotypical, usually unprovoked, disturbance of consciousness, behavior, emotion, motor function or sensation as a result of the cortical neuronal discharge EPILEPSY: 2 or more seizuresEPILEPSY: 2 or more seizures

Provoked seizures Provoked 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

Epidemiology > 2 million people in US > 2 million people in US 125,000 new cases per year 125,000 new cases per year Cumulative incidence of epilepsy by age 80 = 3.1% Cumulative incidence of epilepsy by age 80 = 3.1% Cumulative incidence of seizures by age 80 = 11% Cumulative incidence of seizures by age 80 = 11% Many patients outgrow their epilepsy Many patients outgrow their epilepsy

Historical background: In an attempt to encompass a broader range of clinical features than is possible in a classification of seizure type – In an attempt to encompass a broader range of clinical features than is possible in a classification of seizure type – ILAE published a Classifications of Epilepsies and Epileptic Syndromes in 1985 and revised it in 1989 ILAE published a Classifications of Epilepsies and Epileptic Syndromes in 1985 and revised it in 1989

Epilepsy syndromes Syndrome is a cluster of signs and symptoms that occur together but unlike a disease do not have a single known cause or pathology. Syndrome is a cluster of signs and symptoms that occur together but unlike a disease do not have a single known cause or pathology. Epileptic syndrome integrates all data, seizure type, EEG findings, age of onset, cause, family history, imaging studies, precipitating factors, etc. in order to make a final diagnosis of epilepsy. Epileptic syndrome integrates all data, seizure type, EEG findings, age of onset, cause, family history, imaging studies, precipitating factors, etc. in order to make a final diagnosis of epilepsy.

Most Common Epilepsy Syndromes in Children Childhood Absence Epilepsy Childhood Absence Epilepsy Juvenile Absence Epilepsy Juvenile Absence Epilepsy Juvenile Myoclonic Epilepsy Juvenile Myoclonic Epilepsy Benign Epilepsy of Childhood with Centrotemporal Spikes Benign Epilepsy of Childhood with Centrotemporal Spikes (Benign Rolandic Epilepsy) (Benign Rolandic Epilepsy)

Childhood Absence Epilepsy

Absence Epilepsy Generalized seizures Generalized seizures Most common in the first decade, particularly ages 5-7 years of age Most common in the first decade, particularly ages 5-7 years of age

Clinical features Clinical 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 mouth Occasionally – mild clonic activity of eyelids, corner of mouth Automatisms – elevation of eyelids, licking, swallowing, scratching movements of handsAutomatisms – elevation of eyelids, licking, swallowing, scratching movements of hands

Absence Epilepsy Most patients with typical absence have normal development and normal neurological exam Most patients with typical absence have normal development and normal neurological exam Generalized spikes on EEG Generalized spikes on EEG - Precipitated by hyperventilation in all untreated patients - Photic stimulation – 15%

Absence Epilepsy 10% family history 10% family history Average age when seizures stop is 10 years old Average age when seizures stop is 10 years old Generally have a good prognosis – Generally have a good prognosis – resolves in ~ 80 percent of cases resolves in ~ 80 percent of cases

Treatment: Treatment: EthosuximideEthosuximide DepakoteDepakote Suppress absence in 80% LamotrigineLamotrigine

Absence 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 Epilepsy

 Age of onset  Near or after puberty  Between years  Normal intelligence & neurological exam

Juvenile Absence Epilepsy  Seizures types  Absences  Generalized tonic-clonic seizures- in 80% (often shortly after waking) (often shortly after waking)  Myoclonic seizures- in 15% GTC and myoclonic seizure more common and most likely to happen with awakening GTC and myoclonic seizure more common and most likely to happen with awakening

Juvenile Absence Epilepsy  EEG  Normal background  Generalized spike & wave discharges (faster, 4 Hz)  Induced by HV, not photic stimulation  Treatment  Depakote  Lamictal

Juvenile Absence Epilepsy  Prognosis  At least 80% of patients can be treated with Depakote alone  Absences and GTC usually respond well to pharmacotherapy  Unlike CAE (in which most patients become seizure free) the long term evolution of JAE has not been properly characterized

Juvenile Myoclonic Epilepsy

Incidence Incidence 10% of all epilepsies10% of all epilepsies Age of onset Age of onset 12–18 years12–18 years Age of onset differs from age of diagnosisAge of onset differs from age of diagnosis

Juvenile Myoclonic Epilepsy Myoclonic jerks, generalized tonic-clonic seizures, and sometimes absence seizures Myoclonic jerks, generalized tonic-clonic seizures, and sometimes absence seizures Myoclonic seizuresMyoclonic seizures Jerks of neck, shoulder, arm or leg extensors Jerks of neck, shoulder, arm or leg extensors Usually bilaterally symmetric & synchronous Usually bilaterally symmetric & synchronous More in upper extremities More in upper extremities Drop objects, interfere in morning activities Drop objects, interfere in morning activities

Juvenile Myoclonic Epilepsy Usual age at onset: Usual age at onset: - Absence seizures is years; - Absence seizures is years; - Myoclonic jerks, years; - Myoclonic jerks, years; - Generalized convulsions, years - Generalized convulsions, years

Juvenile Myoclonic Epilepsy More likely to have seizures with sleep deprivation and alcohol ingestion More likely to have seizures with sleep deprivation and alcohol ingestion Risk for seizures is lifelong Risk for seizures is lifelong Seizures recur when AEDs withdrawn Seizures recur when AEDs withdrawn Photic stimulation often provokes a discharge Photic 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 Rolandic Epilepsy

BECT Age of onset Age 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 years Typically resolves by age 16 years Normal intelligence and neurological exam Normal intelligence and neurological exam Seizures usually happen after falling asleep or before awakening (75%) Seizures usually happen after falling asleep or before awakening (75%)

BECT Most characteristic symptoms Most characteristic symptoms Sensorimotor phenomena of faceSensorimotor phenomena of face Oropharyngeal – Hypersalivation, guttural sounds, contraction of jaw, difficulty moving the tongue etc Oropharyngeal – Hypersalivation, guttural sounds, contraction of jaw, difficulty moving the tongue etc Speech arrest Speech arrest Clonic jerks at corner of mouth Clonic jerks at corner of mouth Clonic jerks of one arm Clonic jerks of one arm No loss of consciousness No loss of consciousness Can have secondarily generalized convulsions Can have secondarily generalized convulsions

BECT EEG: Spikes in midtemporal and central head region EEG: Spikes in midtemporal and central head region More spikes in drowsiness and sleep More spikes in drowsiness and sleep 30% of cases show spikes only during sleep 30% of cases show spikes only during sleep

BECT BECTS spontaneously stop with or without treatment (good prognosis) If seizures are frequent and/or disturbing to patient and family, treatment with Tegretol or Trileptal (until 14-16, response) If seizures are frequent and/or disturbing to patient and family, treatment with Tegretol or Trileptal (until 14-16, 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 1 st & 2 nd attacks Short interval between 1 st & 2 nd attacks Early onset Early onset

Febrile Seizures Up to 4% of children Up to 4% of children Not epilepsy Not 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 months – 6 years Seizures only occur with fever in children age 6 months – 6 years

Febrile Seizures Simple Simple - 1 brief seizure (generalized) Complex Complex – Prolonged - More than 1 - Focal

Febrile seizures 13% incidence of epilepsy if at least 2 factors: 13% incidence of epilepsy if at least 2 factors: - History of non-febrile seizure - Abnormal neurological exam or development - Prolonged febrile seizure - Focal febrile seizure

Febrile seizures Recurrence risk: Recurrence risk: - Children with simple FS 30% - 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 Seizures Increase risk of recurrence if 1 st before 18 months or lower temperature Increase risk of recurrence if 1 st before 18 months or lower temperature Focal need MRI, EEG Focal need MRI, EEG Testing unnecessary with simple Testing unnecessary with simple Treatment usually not necessary Treatment usually not necessary

Epilepsy Prognosis: Depends on seizure type: Typical Absence – 80% resolve Typical Absence – 80% resolve JME- respond well to treatment but need meds for life JME- respond well to treatment but need meds for life Neurologically abnormal often difficult to control seizures

Drug Refractoriness of Different Seizure Types Idiopathic partial 0-2% Idiopathic partial 0-2% Childhood absence 10-30% Childhood absence 10-30% Juvenile absence 10-35% Juvenile absence 10-35% Primary GTCS 20-30% Primary GTCS 20-30% Secondary GTCS 30-60% Secondary GTCS 30-60% CPS 40-60% CPS 40-60% LGS 60-80% LGS 60-80% Infantile spasms 60-80% Infantile spasms 60-80%

Most patients (>70%) will have excellent seizure control with medications Most patients (>70%) will have excellent seizure control with medications Some patients will continue to have seizures despite good medical therapy Some patients will continue to have seizures despite good medical therapy Ketogenic dietKetogenic diet Vagal nerve stimulatorVagal nerve stimulator Epilepsy surgeryEpilepsy surgery

Treatment Goals Prevent recurrence of seizures Prevent recurrence of seizures Avoid side effects from AEDs Avoid side effects from AEDs Attain “therapeutic levels” Attain “therapeutic levels” Ensure compliance Ensure compliance

General Guidelines for Use of AEDs Select AED specific for seizure type and EEG findings Select AED specific for seizure type and EEG findings Start with single drug Start with single drug Optimize AED Optimize AED Balance seizure control vs. toxicityBalance seizure control vs. toxicity Add second drug if first fails Add second drug if first fails Anticipate medication interactions Anticipate medication interactions

When to Treat After Single Seizure? Definitely With structural lesion With structural lesion Brain tumorBrain tumor Arteriovenous malformationArteriovenous malformation Infection, such as abscess, herpes encephalitisInfection, such as abscess, herpes encephalitis Without structural lesion Without structural lesion EEG with definite epileptic patternEEG with definite epileptic pattern History of previous seizureHistory of previous seizure History of previous brain injuryHistory of previous brain injury Status epilepticus at onsetStatus epilepticus at onset Possibly Unprovoked seizure Unprovoked seizure Probably not (although short- term therapy may be used) Alcohol withdrawal Alcohol withdrawal Drug abuse Drug abuse Seizure in context of acute illness Seizure in context of acute illness Postimpact seizure Postimpact seizure Specific benign epilepsy syndrome Specific benign epilepsy syndrome Seizure provoked by excessive sleep deprivation Seizure provoked by excessive sleep deprivation

Medications Trileptal, Tegretol, Keppra, Depakote, Lamictal, Phenobarbital,Topamax, Ethosuximide… Trileptal, Tegretol, Keppra, Depakote, Lamictal, Phenobarbital,Topamax, Ethosuximide… Choice based on type of seizures, EEG findings, side effects, age and sex Choice based on type of seizures, EEG findings, side effects, age and sex 2 nd AED may be added if seizures not controlled 2 nd AED may be added if seizures not controlled

Newer antiepiletic medications: Lacosamide (Vimpat) Lacosamide (Vimpat) Vigabatrin (Sabril) Vigabatrin (Sabril) Rufinamide (Banzel) Rufinamide (Banzel) Perampanel (Fycompa) Perampanel (Fycompa)

Conclusion: Seizure type and diagnosis are only one element of a more comprehensive patient assessment that should result in a precise epilepsy syndrome diagnosis Seizure type and diagnosis are only one element of a more comprehensive patient assessment that should result in a precise epilepsy syndrome diagnosis Only an accurate diagnosis of a specific epilepsy syndrome allows patients and physicians to examine all treatment options Only an accurate diagnosis of a specific epilepsy syndrome allows patients and physicians to examine all treatment options