S A B A H M A D , M D

EPILEPSY SYNDROMES

EPILEPSY CLASSIFICATION

• International League Against Epilepsy (ILAE) 2010 revised the classification scheme• Seizures are classified by ONSET in the brain and

the cause of the seizures

ONSET IN THE BRAIN (EEG)

• Generalized• Absence• Myolconic• Tonic• Clonic• Atonic• Generalized tonic-

clonic

• Focal• Seizure semiology is

critical• Secondary

generalization• Epileptic spasms• Unknown • All other seizure

type/not categorized

ETIOLOGY

• Genetic (or presumed genetic)-SPECIFIC EPILEPSY GENES, where EPILEPSY is the primary manifestation like SCN1A, ADNFLE (this category does not include many SYNDROMES like TS, or some genetic causes of cortical malformations)• Structural/Metabolic-tubers (caused by TS), cortical

malformations (possibly caused by a genetic disorder), strokes, abscess, tumors, etc• Unknown cause• COMMON EPILEPSY SYNDROMES are NOT insisted

upon by the official classifications (but they are still clinically very useful

GENERALIZED SEIZURES

• On EEG-these start in the WHOLE BRAIN all at once• Examples-Childhood absence epilepsy, Juvenile

myoclonic epilepsy• Sometimes there are features on EEG to help

distinguish epilepsy syndromes

FOCAL SEIZURES

• On EEG, seizures CLEARLY start in one part of the brain • Seizures can stay focal or spread• Sometimes there is secondary generalization

CHILDHOOD ABSENCE EPILEPSY (CAE)

• GENERALIZED EPILEPSY• Onset between 4-10 years (peak onset 5-7 years)• Frequent typical absence seizures: short staring spells

(less than 20 seconds), occasionally with other features: automatisms of hands or mouth, eye fluttering

• Neurological development is normal• More prevalent in girls (60-70% affected patients are

girls)• Onset of seizures often accompanies a decline in school

performance• Seizures brought out by hyperventilation

EEG CHARACTERISTICS: VERY REGULAR 3 HERTZ SPIKE-SLOW WAVE DISCHARGES

TREATMENT OF CAE

• Ethosuximide (only useful in this disorder)• Lamotrigine• Valproic acidThese are considered equivalent (pick your side effect profile)

• Can try in refractory cases: clobazam, levetiracetam, topiramate, zonisamide

PROGNOSIS OF CAE

• Generally good. Seizures remit in up to 95% of cases• Increased risk of other epilepsies• Children can have learning/cognitive difficulties

even after seizure remission occurs

JUVENILE MYOCLONIC EPILEPSY (JME)

• GENERALIZED EPILEPSY• 3 seizure types: ***myoclonic jerks (cardinal

symptom), absences, convulsions• Myoclonic jerks are more typical in the morning• Onset between 8-24 years (peak onset 12-18)• Patients are very sensitive to sleep deprivation

and alcohol consumption

EEG IN JME-IRREGULARLY GENERALIZED POLY-SPIKE SLOW WAVE

TREATMENT OF JME

• First line: • Valprioc acid• Lamotrigine (may make myoclonus worse)

Other agents: Levetiracetam is useful of convulsions and myoclonus, Topirmate and zonisamide are useful for convulsions, clobazam is good for everything

PROGNOSIS OF JME

• Usually people are on medication lifelong• Occasionally seizures do remit, but most people

elect to stay on medications• If seizures are poorly controlled, it can cause

cognitive impairments, but if well controlled, many people can live normal lives• Advise against sleep deprivation/alcohol

A WORD ABOUT JUVENILE ABSENCE EPILEPSY (JAE)

• GENERLIZED EPILEPSY• Typical absences, like CAE• Onset after age 10• Higher risk for evolving into JME like picture

EEG IN JAE

BENIGN EPILEPSY WITH CENTRO-TEMPORAL SPIKES (BECTS), FORMERLY KNOWN AS BENIGN ROLANIDIC

EPILEPSY

• FOCAL EPILEPSY• Onset between 2-13 years (peak onset 5-10

years)• Seizures occur around sleep (falling asleep or

waking up)• Typical seizure: face pulling/drooling, inability to

speak, sometimes ipsilateral hand involvement, sometimes secondary generalization• At onset of seizure, children typical have

preserved awareness

EEG IN BECTS: BILATERAL CENTRO-TEMPORAL SPIKES THAT INCREASE WITH SLEEP

PROGNOSIS

• These seizures may not need treatment (some patients only have 1-2 seizures in their life separated by many years)• Treat when seizures are recurrent (greater than

2), prolonged, or if thy generalize to convulsions• Benign is a misnomer: even though the seizures

remit, there can be long term learning/cognitive issues

PANAYIOTOPOULOS SYNDROME

• FOCAL EPILEPSY• Childhood onset (between 1-14, median onset 5 years)• Autonomic seizures, 2/3 of them out of sleep• Common clinical features: emesis with eye deviation.

At onset children can have preserved awareness• Can secondarily generalize• Can have other autonomic features: pallor/flushing,

cyanosis, mydriasis or miosis, hypersalivation, incontinence, penile erection

• Events can be long: 10-30 minutes• Interictal eeg can be normal

EEG IN PANAYIOTOPOULOS SYNDROME

PROGNOSIS

• Generally good• Treatement is not typically needed, especially if

events are rare• Treat if there are convulsions or cardiorespiratory

instability

AUTOSOMAL DOMINANT NOCTURNAL FRONTAL LOBE EPILEPSY (ADNFLE)

• FOCAL EPILEPSY• Onset between 1-64 (median onset 14)• Frontal lobe seizures out of sleep• Nocturnal arousals out of non-REM sleep with

bizarre behavior, wanderings, dystonia• Some well described genetic associations with

incomplete penetrance• Video EEG is very useful to help distinguish from

REM sleep behaviors disorder, sleep waling, etc

PROGNOSIS OF ADNFLE

• Very treatable• Early recognition improves outcomes

DOOSE’S SYNDROME (MYOCLONIC-ASTATIC EPILEPSY OR MAE)

• GENERALIZED EPILEPSY• Clinical hallmark is myoclonic-astatic seizures (or

myoclonic atonic seizures)• Can also have absences, convulsions• Onset between ages 2-4• Normal development up to the age of onset, then

during the active phase of seizures-regression can occur• Differential includes Dravet’s syndrome or

Lennox-Gastaut syndrome

TREATMENT/PROGNOSIS

• Lamotrigine, valproic acid, the ketogenic diet• Prognosis can actually be good, when the

seizures go into remission-many children have an improvement in development

DRAVET’S SYNDROME (SEVERE MYOCLONIC EPILEPSY OF INFANCY OR SMEI)

• MIXED EPILEPSY (both focal and generalized features)• Seizures begin in the first year of life• There severe encephalopathy with developmental

regression or plateau with onset of seizures• Seizures can be myoclonic, clonic, focal,

convulsive• Well described genetic associations

TREATMENT/PROGNOSIS

• Typically refractory seizures/medication resistant. Due to mixed epilepsy type: broad spectrum agents (valprioc acid, lamotrigine, topiramate) indicated. Avoid carbemazepine/oxcarbazepine• Stiripentol, has orphan drug approval to treat

Dravet’s in the EU• Severe long term encephalopathies• Cannabidiol oil??? Research is ongoing

INFANTILE SPASMS/WEST SYNDROME (IS)

• Has its own classification• Epileptic encephalopathy• Clinical triad of clinical spasms (myoclonic tonic),

hypsarrhythmia on EEG, developmental regression• Can be idiopathic or caused by

structural/metabolic defect: TS, perinatal stroke, Sturge Weber, cortical migration abnormalities• Typical age of onset 3-18 months (peak incidence

6-9 months)

EEG IN IS

ELECTRODECREMENT

TREATMENT/PROGNOSIS

• ACTH, Vigabitrin (first line in TS), topirmate (if there are focal seizures as well), clobazam• Most children have long term

neurodevelopmental problems, which are worse the longer it takes to initiate treatment• Some evolve to a Lennox-Gastaut picture as they

get older

OHTAHARA SYNDROME

• Catastrophic form of an early epileptic encephalopathy• Onset between birth and 3 months• Various structural and genetic causes• Very poor psychomotor outcome

LENNOX-GASTAUT SYNDROME (LGS)

• MIXED EPILEPSY• Often severe epileptic encephalopathy• Multiple seizure types: tonic, myoclonic, atonic,

atypical absence, focal seizures that can generalize• EEG hallmark: “slow” generalized spike-wave 2

hertz-usually at onset of disease, EEG can evolve over time, can also have other focality• Many children with LGS have evolved to that from

IS

LGS EEG

TREATMENT/PROGNOSIS

• Can be medication resistant• Broad spectrum agents preferred: lamotrigine,

valproic acid, topiramate, clobazam, runfinamide• Long term neuro-developmental

problems/encephalopathy