Pediatric Epilepsies This is only for UAMS neurology internal use. - PowerPoint Presentation

Slide1

Pediatric Epilepsies

This is only for UAMS neurology internal use. Slide2

Questions taken fromSlide3

At what age do human beings attain the predominant alpha frequency that is seen in adults?

A. 6-8 years

B. 8-10 years

C. 10-12 yearsD. 12-14 yearsE. 14-16 yearsSlide4

Basic EEG

Normal pediatric EEG activity has more variation than adult EEG

EEG varies greatly by age

Alpha rhythmNot present at birth5-6Hz by 12 months in 70% of children8Hz by age 3 in 80% of children

Sleep

Sleep spindles by 2 months of age; synchronous by 2 years

Vertex waves by 5 months

Hyperventilation

Diffuse slowing but in young children can be maximum in posterior region

Done to provoke absence epilepsy

Photic stimulation

Photoconvulsive

/

photoparoxysmal

response

Tends to outlast photic stimulation

Suggestive of primary generalized epilepsiesSlide5

Syndrome with Onset in InfancySlide6

Newborn with seizures characterized by apneic spells associated with unilateral or bilateral

clonic

movements that started on day 5 of life.

Interictal EEG normal. Examine otherwise normal. Most likely diagnosis?A. West SyndromeB. Benign neonatal seizuresC. Aicardi syndromeD.

Ohtahara

Syndrome

E. Benign Myoclonic Epilepsy of InfancySlide7

Benign Neonatal Convulsions

Begins on

days 2-7 of life

(5th day fits)2-7% of neonatal seizuresFrequent brief focal tonic or clonic seizures

usually resolve within 2 weeks

Diagnosis of exclusion

Normal neurological examination before seizure onset and during

interictal

periods

Etiology unknown

Some infants have de novo mutations in the KCNQ2 gene(voltage dependent potassium channel)Slide8

2.5 year old started having seizures at 8mo described as brief generalized myoclonic seizures associated with fast (>3Hz) spike and

polyspike

and wave discharged.

Interictal EEG is normal. Seizures are well controlled on treatment and development remains normal. Most likely diagnosis?A. Dravet syndromeB.

Ohtahara

syndrome

C. Benign myoclonic epilepsy of infancy

D. Generalized epilepsy with febrile seizures plus

E. Myoclonic astatic epilepsySlide9

Benign myoclonic epilepsy of infancy

Starts between 4mo-3 years

Characterized by

brief myoclonic seizures that are easily treatableMore prominent in drowsiness, photostimulation and external stimulationInterictal EEG normal; ictal EEG shows generalized spike and

polyspike

wave discharges

Good prognosis

with easy to treat seizures and most with spontaneous resolution of seizures in less than a yearSlide10

You see a 15 day old neonate with severe

hypotonia

and frequent tonic spasms occurring in clusters of more than 100/day. EEG shows burst suppression present in wakefulness and sleep. Most likely diagnosis?

A. Dravet syndromeB. Ohtahara syndromeC. Benign myoclonic epilepsy of infancy

D. Generalized epilepsy with febrile seizures plus

E. Myoclonic astatic epilepsySlide11

Early Infantile Epileptic Encephalopathy

Also known as

Ohtahara

SyndromeEtiology typically associated with structural brain abnormalitiesInborn errors of metabolism are rareSome genes identified including KCNQ2, SLC25A22, etc

Onset is within the first 3 months of life

Abnormal neurological examination at onset (dev delay, spasticity)

Predominant seizure type is

tonic spasms

EEG shows

burst suppression pattern

seen across all sleep-wake cycles

Prognosis is poor with ~50% passing away in infancySlide12

Early Myoclonic Encephalopathy

Most often associated with inborn errors of metabolism

nonketotic

hyperglycemia, pyridoxine dependency, etcCongenital brain anomalies are uncommon etiology for EMENeurological examination is abnormal at onset with encephalopathic

infant

Segmental erratic

myoclonic seizures

are earliest seizures typically seen but focal

clonic

seizures and repetitive tonic spasms can develop later on

EEG:

burst suppression

pattern mainly in sleep but can be present in all stages

Prognosis is poor with ~50% passing away in the first year of lifeSlide13

6mo old brought in by parents for sudden episodes of tonic flexion of limbs and body occurring in clusters after wakening. EEG is as below. Diagnosis?

A. juvenile myoclonic epilepsy

B. Infantile spasms

C. myoclonic epilepsyD. BECTSE. Absence epilepsySlide14

Which of the following is the most accepted treatment of this disorder?

A. lamotrigine

B. phenytoin

C. phenobarbitalD. ACTHE. carbamazepineSlide15

Epileptic Spasms

Age on onset usually less than 1 year of age (range 1 day-4.5 years)

Seizures consist of usually

symmetric and synchronous contractions of one or more muscle groups followed by a longer tonic phaseCan see flexor, extensor or mixed flexor-extensor spasmsMost often occur in

clusters

Occur more frequently in waking state and arousal than during sleep

Developmental regression usually begins with onset of spasms

EEG:

hypsarrhythmia

(very high voltage chaotic slow wave and spikes diffusely)

Treatment:

ACTH,

Vigabatrin

Overall prognosis is poor

50-90% develop other seizure types

85% develop developmental retardationSlide16

A 9mo old girl has blindness, infantile spasms and abnormal retinal examination. Brain MRI shows agenesis of the corpus callosum. Which of the following is the most likely diagnosis?

A. West Syndrome

B.

Ohtahara SyndromeC. Dravet SyndromeD. Aicardi SyndromeE. Myoclonic-astatic epilepsySlide17

Mutations in which gene is most commonly associated with generalized epilepsy with febrile seizures plus (GEFS+)?

A. SCN1A

B. SCN1C

C. SCN1BD. SCN2AE. GABRDSlide18

2 year old with a history of developmental delays and a prolonged FS at the age of 1 is now admitted with frequent seizures of multiple types including myoclonic, absence, focal and generalized tonic

clonic

seizures. Most likely diagnosis?

A. Dravet SyndromeB. Ohtahara syndromeC. Benign myoclonic epilepsy of infancy

D. Landau-

Kleffner

Syndrome

E. Myoclonic-Astatic epilepsySlide19

Dravet

Sydrome

Early onset epileptic encephalopathy characterized by

refractory epilepsy and neurodevelopmental declinesPatients typically present in 1st year of life with prolonged, often febrile, seizures

with normal development prior to onset of seizures

Have multiple types of seizures that are often refractory with associated cognitive and behavioral impairment. Can have gait and posterior abnormalities

70-80% have mutation in

SCN1A mutation

Avoid Na channel blocking medications such as phenytoinSlide20

Epilepsies in children and adolescentsSlide21

7 year old boy has recurrent nocturnal events where parents witness him shaking uncontrollably. Some events have only involved facial and arm twitching. EEG is most suggestive of what diagnosis?

A. Juvenile myoclonic epilepsy

B. Metabolic encephalopathy

C. Myoclonic epilepsyD. BECTSE. Periodic lateralized epileptiform dischargesSlide22

Given previous diagnosis, what is the antiepileptic of choice, given no contraindications?

A. phenytoin

B.

valproic acidC. topiramate

D. carbamazepine

E.

ethosuximideSlide23

BECTS

Benign Epilepsy of Childhood with

Centrotemporal

spikes (BECTS)Previously known as Benign Rolandic Epilepsy25% of all childhood epilepsiesOnset between 4-10 yearsRemission in

midteens

Semiology initially consists of unilateral

paresthesias

of tongue, lips and cheek and/or unilateral

clonic

activity of facial muscles, at times with secondary generalization

70% only in sleep

, 15% only awake, 15% both

EEG: independent

bihemispheric

centrotemporal

spike

s that increase with sleep; ~1/3 only have discharges during sleep

Prognosis: Very good

; AEDs can generally be stopped after adolescence Slide24

Which of the following is true about oxcarbazepine in comparison to carbamazepine?

A. is not a hepatic enzyme inducer

B. no risk of hyponatremia

C. is not metabolized to an epoxideD. indicated in both partial and generalized epilepsyE. No risk of rashSlide25

11 year old brought to EMU for possible

pseudoseizures

. Spells mainly at

ight with violent like movements. Awake EEG normal. Overnight, a seizure is captured during non-REM sleep. Diagnosis?A. Electrical SE during slow wave sleep (ESES)B. Lennox-Gastaut syndromeC. Landau-

Kleffner

syndrome

D. AD nocturnal frontal lobe epilepsy

E. Panayiotopoulos syndromeSlide26

AD Nocturnal Frontal Lobe Epilepsy

Autosomal Dominant

Presents in childhood or adolescence (mean age: 14years) with clusters of usually

brief nocturnal seizures arising in non-REM sleepInterictal EEG often normalCognition and neurological examination usually normalMost cases are non-

lesional

Genetic forms: most related to

neuronal nicotinic acetylcholine receptor

CHRNA4, CHRNA2, CHRNB2

Prognosis: spontaneous remission is rare and up to 1/3 will have drug resistant epilepsySlide27

4 year old wit episodes of visual phenomena, which he cannot describe, followed by eye deviation and vomiting. He has had 3 episodes total. EEG shows normal background with high-voltage occipital spikes which disappear with eye opening. Most likely diagnosis?

A.

Ohtahara

syndromeB. Late onset or Gastaut type childhood occipital epilepsyC. Early onset or Panayiotopoulos type childhood occipital epilepsy

D.

Dravet

Syndrome

E.

Doose’s

syndromeSlide28

Childhood Epilepsy with Occipital Paroxysms

Childhood Epilepsy with Occipital Paroxysms

Early Onset (Panayiotopoulos Syndrome)

Peak age of onset: 4-6 yearsSemiology: variety of

autonomic symptoms

such as feeling sick, nausea, vomiting, tonic eye deviation lasting 5-10 minutes

Partial or generalized tonic

clonic

seizures can occur during sleep

Nearly all patients become seizure free by age 12

Late Onset (

Gastaut

type)

Peak age of onset:

7-9 years

Semiology: visual symptoms lasting seconds; ½ of patients complain of

severe headache

with nausea and vomiting

Prognosis is variable but most patients have a benign course

EEG is the same in both with high amplitude

occipital spikes

which can be bilaterally independent; increases with sleep; disappears with eye opening and reappear with eye closureSlide29

Patient with inattentiveness at school has the following EEG which is characteristic of what type of epilepsy?

A. Juvenile Myoclonic Epilepsy

B. Absence Epilepsy

C. Myoclonic EpilepsyD. BECTSE. Lennox-Gastaut EpilepsySlide30

Absence Epilepsy

Childhood Absence Epilepsy

Onset of seizures between

3-12 yearsJuvenile Absence EpilepsyOnset between 10-12 years

More likely to develop GTC and myoclonic seizures

Less likely to remit

EEG: Generalized

3cps spike and wave discharges

Initial complex may have

polyspike

pattern

Hyperventilation precipitates bursts in 50-80% of patients

20-40% will show OIRDA

Pathophysiology: generated through thalamus with the low threshold (T-type Ca channels of thalamic neurons playing a central role in

thalamocortical

interactions

Mutations: Ca channel, Chloride channel (CLCN2),

GABAa

receptor (GABRG2, GABRA1)

Treatment:

Ethosuximide

(acts via T-type calcium channel inhibition), VPA, LamotrigineSlide31

Which of the following best describes the interaction between

valproic

acid and lamotrigine?

A. Lamotrigine significantly incrases the half life of valproic acid.B. Valproic acid significantly decreases the half life of lamotrigine

C.

Valproic

acid significantly increases the half life of lamotrigine

D. Lamotrigine significantly decreases the half life of

valproic

acid

E. Lamotrigine and

valproic

acid do not have any significant interactionsSlide32

In a patient with absence epilepsy, which of the following AEDs is least likely to precipitate absence status epilepticus?

A. Phenytoin

B.

TopiramateC. CarbamazepineD. LamotrigineE. GabapentinSlide33

12 year old boy with complaints of early morning falls, clumsiness and dropping objects presents with GTC seizure. EEG is most consistent with which diagnosis?

A. Juvenile myoclonic epilepsy

B. Absence epilepsy

C. Myoclonic epilepsyD. BECTSE. Lennox-Gastaut epilepsySlide34

When necessary, what is the

antiepiletic

of choice for this condition, given no contraindications?

A. phenytoinB. valproic acidC. topiramateD. carbamazepineE. phenobarbitalSlide35

JME

Juvenile Myoclonic Epilepsy

Onset between 12-18 years

Both myoclonic and GTC convulsions tend to occur within 1-2 hours of awakeningHistory of absence seizures coexists with or preceded myoclonic seizures in ~1/2 patientsSeizure triggers include sleep deprivation and alcohol consumption

EEG:

4-6Hz spike and

polyspike

and wave discharges; photosensitivity in 20-40%

Mutations:

GABAa

, Ca channel, Cl channel

Tx

:

Levetiracetam

, VPA

Initially thought to be life long epilepsy but recent studies suggest some patients might outgrow this. Slide36

4 year old boy with normal cognitive development is brought in after a GTC seizure. Recently he has been having increased falls. Mother reports he loses tone, causing him to fall. He can also have episodes of jerk-like movements that cause him to fall. EEG shows bilateral synchronous irregular 2-3Hz spike and wave complexes as well as parietal rhythmic theta activity. Most likely diagnosis?

A.

Dravet

SyndromeB. Ohtahara syndrome

C. Benign myoclonic epilepsy of infancy

D. Generalized epilepsy with febrile seizures +

E. Myoclonic-astatic epilepsy (

Doose’s

syndrome)Slide37

Epilepsy of

Doose

(Myoclonic-Astatic Epilepsy)

Typical onset between 1-5 yearsChildren are normal prior to onset of seizures and many continue to have normal development; however, some have severe developmental delay and intractable seizuresMain seizures are myoclonic or astaticCan have other types of generalized seizures

EEG can show

interictal

bilateral synchronous irregular 2-3Hz spike and wave complexes as well as rhythmic parietal theta activitySlide38

3 year old with cognitive and developmental delay. He began having seizures involving drop attacks one year ago but progressively developed multiple seizure types. Multiple AEDs tried with mild improvement but he still has multiple seizures per day. EEG shows 2cps spike-wave discharges. Diagnosis?

A. Panayiotopoulos syndrome

B. West syndrome

C. Landau-Kleffner SyndromeD. Lennox-Gastaut

Syndrome

E. seizures associated with mesial temporal sclerosisSlide39

Lennox-Gastaut

Syndrome

Most commonly present between 3-5 years of age

Often evolve from other syndromes such as infantile spasmsCharacterized by:Multiple seizure typesSlow <2.5cps spike wave pattern

Mental retardation (90%)

Prognosis is poor with low likelihood of seizure controlSlide40

Parents of 5 year old report he has been more withdrawn over the past several months. One year ago he began having seizures, initially myoclonic and recently GTC. About 9 months ago he was having problems understanding verbal communication and now appears aphasic. EEG shows multifocal spikes. Diagnosis?

/a. Panayiotopoulos syndrome

B. West syndrome

C. Landau-Kleffner syndromeD. Lennox-Gastaut

syndrome

E. Seizures associated with mesial temporal sclerosisSlide41

Landau Kleffner

Syndrome

Patients develop normally until approximately 3-6 years of age

Begins with auditory verbal agnosia (children behave as if they were deaf) and ultimately develop expressive language difficulties75% will have clinical seizures of various typesEEG:

bilateral independent temporal or

temporoparietal

spikes; eventually near continuous spike and wave during non-REM sleep

Epileptiform process appears to originate in the

language cortex

of the dominant temporal lobe and secondarily spreads

Prognosis: many have persistent seizures and residual language dysfunctionSlide42

Epileptic Encephalopathy with Continuous Spikes and Waves during Sleep (CSWS)

Epileptic encephalopathy characterized by:

Seizures

Developmental regressions in at least two domainsEEG pattern of ESES

Etiology unknown in many cases but often structural causes or mutations such as in the GRIN2A gene have been found

Typically normal or only mild cognitive difficulties until seizures start around 2-4 years of age

Unlike LKS, regression is seen across many domains

EEG: during wakefulness shows focal or multifocal spikes with continuous bilateral slow spike and waves during at least 85% of

nonREM

sleep.

Prognosis usually poor with severe neurocognitive regression and outcomesSlide43

13 year old is being evaluated for

epilesia

partialis continua. Rasmussen’s syndrome is suspected. What would be the most common finding on brain MRI in Rasmussen’s syndrome?A. LissencephalyB. Schizencephaly

C. Cortical atrophy

D.

Pachygyria

E.

PorencephalySlide44

Rasmussen’s Syndrome

Rasmussen’s syndrome is characterized by progressive

unilateral hemispheric atrophy,

associated progressive neurologic dysfunction and intractable focal seizuresUncertain pathogenesis but thought to be immune-mediatedUsually presents between 14mo-14 yearsBest treatment for those with intractable seizures is

hemispherectomy

http://

www.radiologyassistant.nl

/

en

/p4f53597deae16/role-of-mri-in-epilepsy.html#i4f53a33401a10Slide45

14 year old with progressive cognitive decline and ataxia has a history of myoclonic epilepsy ad multiple seizure types. EEG shows spikes and waves with predominance in the occipital region. Skin biopsy shows periodic-acid-Schiff-positive intracellular inclusions. Most likely diagnosis?

A.

Lafora

body diseaseB. Unverricht-Lundborg SyndromeC. Sialidosis

D. Juvenile myoclonic epilepsy

E. Neuronal Ceroid

LipofuscinosisSlide46

Progressive Myoclonic Epilepsies

Lafora

body disease: AR; mutations in EPM2A encoding

Laforin; presents between 12-17 years; various seizures, dysarthria, ataxia, dementia; most patients die within 10 years of onset and treatment is palliativeUnverricht-Lundborg Syndrome:AR

; presents between 6-15 years with stimulus sensitive myoclonus but eventually develops multiple seizure types; patients may worsen progressively but in some cases the disease stabilizes over time

Sialidosis

: AR; Type 1 is caused by deficiency of alpha-

neuroaminidase

and presents in adolescents with action myoclonus and slowly progressive ataxia, tonic-

clonic

seizures and vision loss. Cherry red spot. Do not have cognitive deterioration

NCL: AR; progressive psychomotor retardation, seizures and blindness; mutations in several genes have been described (CLN1-CLN10); can present in infantile, late infantile, juvenile and adult forms

Photoparoxysmal

responses are common in patients with

Lafora

disease,

Unverricht-Lundborg

disease, and Batten disease. In Batten disease, single or low-frequency intermittent photic stimulation characteristically produces prominent spike discharges at occipital electrodes with a one-to-one relationship with the light flash Slide47

The other stuff…

.Slide48

In a patient who has suffered a febrile seizure, which of the following choices is least likely predictor of developing subsequent epilepsy?

A. Family history of febrile seizures

B. Complex febrile seizure

C. Developmental delayD. Family history of epilepsyE. Neurologic AbnormalitySlide49

Febrile Seizures

6 months-6 years of age

90% of seizures occur in first 3 years of life

Up to 5% of children have at least one febrile convulsionsOccurs in the setting of a feverSimpleOnly one in 24 hours

Less than 15 minutes in duration

Generalized

Complex

More than one in 24 hours

Greater than 15 minutes

Focal semiology or deficitSlide50

Febrile Seizures

For simple febrile seizure, EEG and MRI are not indicated

Recurrence risk after a single febrile seizure

Simple: 30% (1/3 will have another febrile seizure)Complex: 50%Risk of Epilepsy in children after febrile seizures<5% risk of epilepsy after simple febrile seizureIncreased risk of epilepsy if: developmental delay, abnormal neurologic examination, complex febrile seizures and family history of epilepsy

Treatment: supportive (AAP does not recommend continuous or intermittent anticonvulsant therapy in children with simple febrile seizures)Slide51

Non-Epileptic Paroxysmal Events in Pediatrics

Infants

Benign neonatal myoclonus

Repetitive myoclonic jerks of extremities during sleepTends to have migratory myoclonusGoes away when infant wakes upTends to resolve around 3 months of ageReflux/Sandifer Syndrome

Intermittent spells of stiffening and posturing

Associated with feedings

Benign myoclonus of early infancy

Brief contractions involving axial muscles

Can occur in clusters

Resolves by age 2Slide52

Non-Epileptic Paroxysmal Events in Pediatrics

Infants

Spasmus

NutansHead nodding, head tilt, nystagmus4-12 months of ageMRI to rule out mass lesion of optic chiasm or 3rd

ventricle based on examination

Shuddering Attacks

Precipitated by emotions (fear, frustration)

Can see family history of essential tremor

Self gratification

Rocking pelvis, rubbing of thighs together

Sweating, flushing of face

distractibleSlide53

Non-Epileptic Paroxysmal Events in Pediatrics

Older Children

Breath Holding Spells

6mo-6 years with peak around 2-3 yearsCyanoticProvocation—cries—holds breath in expiration—cyanosisPallidInduced by mild trauma—stops breathing, pale—loss of consciousness

Can do iron deficiency screening

Movement disorders

Paroxysmal

kinesiogenic

dyskinesia

Repetitive attacks of dystonia or

choreoathetosis

precipitated by movement

Chromosome 16p11.2Slide54

Non-Epileptic Paroxysmal Events in Pediatrics

Parasomnias

Night terrors (typical onset age 4), Narcolepsy

Migraine HeadachesConfusional migrainesAlice in WonderlandDistortions of perception, change in size and shape of surroundingsSyncope

Nonepileptic

eventsSlide55

Non-Epileptic Paroxysmal Events in Pediatrics

Nonepileptic

Events

5-10% but higher rate in those admitted to EMUsUp to 10% of those with PNES have comorbid epileptic seizures Men: Woman= 1:3 Risk factorsYounger agePoor social economic status

Female

Psychosocial stressors

Psychiatric comorbiditySlide56

Non-Epileptic Paroxysmal Events in Pediatrics

Nonepileptic

events

PNES symptoms in history:Not responding to AEDsUnusual presentationSigns on exam:Eye flutterClosed eyes

Fluctuating course

Pelvic thrusting

Ictal weeping

Flapping hand movements

Asynchronous movements

Recall of apparent unconsciousnessSlide57

Questions?