Epilepsy in children Amira Masri - PowerPoint Presentation

Slide1

Epilepsy in children

Amira Masri Prof of child neurology Faculty of medicine –The university of Jordan

Slide2

Objectives

History

Epidemiology

Definitions : seizure , epilepsy , febrile convulsion , status epilepticus ,epileptic encephalopathy

Classification

Aetiology

Treatment

Outcome

Slide3

History of epilepsy

Epilepsy : comes from the

latin

word

epilepsia

which means : to be ceased , to be attacked by surprise

Hippocrate

400 B.C.: the sacred disease

Ibn

Sina

+Al Tabari :1000 years ago =Al

Saraa

, disease of the brain

Slide4

Epidemiology

incidence rates of epilepsy in childhood :0.5 to 8 per 1,000

0.5 -

1%

: experience

at least one afebrile

seizure by age adolescence.

Of all children,

3 - 5%

will have a

single febrile

seizure

30 %

: will have

additional febrile

seizures

3 – 6%

of those with febrile seizures will develop afebrile seizures or

epilepsy

3.6% risk of experiencing at least one seizure in an 80-year lifespan

focal seizures

(with or without impairment of awareness) are the most common seizure type in all age groups and account for more than 50 percent of all seizures in children

Focal seizures with alterations of awareness are the most common subtype

Uptodate

2019

Slide5

Basic mechanisms

The basic mechanism of neuronal excitability is the

action potential

Action potentials occur due to

depolarization

of the neuronal membrane

Membrane potential thus varies with

1-activation of ligand- gated channels

:conductance is affected by binding to

neurotransmitter

2-

activation of voltage-gated channels

: conductance is affected by changes in transmembrane potential; or with changes in

intracellular ion compartmentalization.

Slide6

various glutamate receptor subtypes and locations

GABA receptors

GABA site

Barbiturate site

Benzodiazepine

site

Slide7

Definitions

Seizure

Epilepsy

Febrile convulsions

Epileptic encephalopathy

Status epilepticus

Slide8

Seizure

Disorder of cerebral function

characterized by sudden brief attacks of: -

loss of consciousness

-motor activity

-sensory phenomena

- inappropriate behavior

Caused by

excessive discharge

of cerebral neurons

.

Slide9

Epilepsy

Slide10

Epilepsy is a disease of the brain defined by any of the following

:

At least

two

unprovoked (or reflex) seizures occurring

> 24 h

apart

2.

One unprovoked

(or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years

3.Diagnosis of an

epilepsy syndrome

Epilepsy is considered to be resolved for the following individuals:

Those who had an

age-dependent epilepsy

syndrome but are now past the applicable age

Those who have remained

seizure-free for the last 10 years

, with no antiseizure medicines for the last

5 years

Slide11

Febrile convulsion

A seizure in association with febrile illness in the absence of CNS or acute electrolyte imbalance in children

>1 month of age

without prior afebrile seizures

Age :6m-6years (peak 18 m )

2-5% of children

Most common form of seizures in children

Simple and complex

Slide12

Epileptic encephalopathy

A condition in which the

epilep

tiform abnormalities themselves are believed to

contribute

to the progressive

disturbance

of cerebral dysfunction.

Slide13

Epileptic

activity itselfcontributes to severe cognitive and behavioral impairment above and beyond that expected from the underlying pathology and that these can worsen over time

Developmental and/or Epileptic encephalopathies

Berg et al 2010

Slide14

Status epilepticus

Emergency room definition :

5 minutes

shortening the required seizure duration from 30 min to

5 min

Why ??????

The longer SE persists:

1-the lower is the likelihood of spontaneous cessation

2-the harder it is to control

3-the higher is the risk of morbidity and mortality

Seizures that do not cease in 5-10min are less likely to terminate without intervention

Slide15

Classification of epilepsy

1- According to the

clinical

picture : generalized ,focal

2 - According to the

aetiology:

genetic , structural , metabolic infections, immune, unknown.

3-According to the epilepsy

syndrome

: age of onset , type of seizures and EEG findings

Slide16

International league against epilepsy website

Slide17

Slide18

Purpose of the new classification 2017: for clinical diagnosis

Transparent language: use words that mean what they say

Slide19

Unknown

Immune

Infectious

Structural

Etiology

Metabolic

Genetic

Co-morbidities

Epilepsy types

Focal

Generalized

Combined

Generalized

& Focal

Unknown

Focal

Epilepsy Syndromes

Seizure types

Generalized onset

Unknown onset

Focal

onset

Slide20

Generalized seizures

O

riginate at some

O

riginate at some point within and rapidly engage bilaterally distributed

networks

Can include cortical and subcortical structures

but not necessarily the entire cortex

Slide21

Originate within net

Originate within networks limited to one hemisphere

May be discretely localized

or more widely distributed.…

Focal seizures

Slide22

Note

When a seizure type begins with ”focal, generalized or absence” then the word “onset” can be presumed

Slide23

Pedalling

grouped in hyperkinetic rather than automatisms (arbitrary)

Cognitive seizures

impaired language

other cognitive domains

positive features

eg

déjà vu, hallucinations, perceptual distortions

Emotional seizures: anxiety, fear, joy,

etc

Slide24

Aetiology

Structural :example porencephalic cyst Genetic :example : absence epilepsy Metabolic : example :penylketonureaInfection :example : meningitis Immune :example :Rasmussen Unknown

Slide25

Etiology

Tuberous Sclerosis

GLUT1 deficiency

Unknown

Immune

Infectious

Structural

Metabolic

Genetic

Seizure types

Generalized onset

Unknown onset

Focal

onset

Slide26

Tuberous sclerosis : 2 genes ( TSC1 and TSC2 )

Slide27

Terms no longer used

Complex partial

Simple partial

Partial

Psychic

Dyscognitive

Secondarily generalized tonic-clonic

Slide28

Genetic versus idiopathic

‘Idiopathic’ = presumed hereditary predisposition

Genetic ≠ inherited

Importance

of de novo

mutations in both

mild and severe epilepsies

Critical problem of stigma in some parts of the world

Slide29

Benign

Many epilepsies not benign

Childhood hood absence epilepsy : psychosocial impact

Benign epilepsy with centrotemporal spikes : learning concerns

Replaced by terms:

Self-limited

Pharmacoresponsive

No longer use

Malignant

Catastrophic

Slide30

Changing Lexicon and Concepts for the Epilepsies

New Terminology

Old Terminology

Person with epilepsy

Epileptic

Epilepsy seizures

Epileptic seizures

Antiseizure medications

Antiepileptic drugs

Focal onset

Partial

Focal dyscognitive

Complex partial

Epileptic spasms

Infantile spasms

Genetic

Idiopathic

Structural-metabolic

Symptomatic

Unknown

Cryptogenic

Slide31

Epilepsy syndromes

Slide32

Epilepsy syndromes by age

NEONATAL

Benign familial neonatal epilepsy

Early myoclonic encephalopathy

Ohtahara syndrome

INFANCY

Epilepsy of infancy with migrating focal seizures

West syndrome (infantile spasms, hypsarrhythmia; to be distinguished from benign myoclonus of early infancy, a nonepilepsy)

Myoclonic epilepsy in infancy (benign Dravet variant)

Benign infantile epilepsy

Benign familial infantile epilepsy

Severe myoclonic epilepsy of infancy (classic Dravet syndrome)

Myoclonic encephalopathy in nonprogressive disorders

Slide33

Epilepsy syndromes by age

CHILDHOOD

Genetic epilepsy with febrile seizures plus (GEFS +; can begin in infancy)

Panayiotopoulos syndrome

Epilepsy with myoclonic atonic (previously astatic) seizures (Doose syndrome)

Benign epilepsy with centrotemporal spikes (BECTS, or benign rolandic epilepsy)

Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)

Late-onset childhood occipital epilepsy (Gastaut syndrome)

Epilepsy with myoclonic absences (Tassinari syndrome)

Lennox–Gastaut syndrome

Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)

Landau–Kleffner syndrome (LKS)

Childhood absence epilepsy (

pyknolepsy

)

Generalized epilepsy with eyelid myoclonia (Jeavons syndrome)

*

ADOLESCENCE–ADULT

Juvenile absence epilepsy (JAE)

Juvenile myoclonic epilepsy (JME)

Epilepsy with generalized tonic-clonic seizures alone

Progressive myoclonus epilepsies (PME)

Autosomal-dominant epilepsy with auditory features

Other familial temporal lobe epilepsies

LESS SPECIFIC AGE RELATIONSHIP

Familial focal epilepsy with variable foci (childhood to adult)

Reflex epilepsies (e.g., photosensitive, audiogenic, or reading-induced seizures; may or may not coexist with spontaneous seizures)

Slide34

https://

www.epilepsydiagnosis.org

Slide35

Slide36

How to confirm the diagnosis

History + examination : most important =

30%

of subjects diagnosed with epilepsy had been

misdiagnosed and do not have epilepsy

Rule out disorders that mimic seizures

Role of neuroimaging : Brain MRI superior to CT scan

EEG:standard

=positivity rate 60%

Sleep =positivity rate 90%

Slide37

Misdiagnosis of epilepsy is common :Rule out epilepsy imitators

False

tendency : think of epilepsy as a

single

disorder

Diagnosis : history , usually no confirmatory test: There is a

large differential diagnosis

Many clinicians charged with diagnosing paroxysmal disorders

do not have sufficient

knowledge

of the clinical features of epileptic and non-epileptic seizure disorders

Abuse of EEG

=overreading

Most clinicians with responsibility for diagnosing epilepsy

do not have easy access

to the full range of appropriate investigations

.

There is a false perception that to miss a diagnosis of epilepsy carries grave risks

Slide38

Differential diagnosis: epilepsy imitators

Huge list >36 disorders

Breath holding spells

GE reflux

cardiogenic syncope

Pseudoseizures

Benign infantile myoclonus

Migraine

Night terrors

Paroxysmal

dyskinesisa

Self gratification

Somnambulism

hyperekplexia

Slide39

When should we start ttt

First seizure

: general rule :do not

ttt

(risk of recurrence

30%

)

First

prolong

seizure (status ) : risk of recurrence

same

( however higher risk of recurrence of prolonged seizures

Multiple

seizures within 24 hours : considered first seizure : recurrence risk

same

Slide40

Recurrence of unprovoked seizures

First

seizure :

40%

will have recurrence

Second

seizure :

80%

will have recurrence

Recurrence usually within the first 6 m (first

2 years )

Recurrence : rare after 2 years

Slide41

Evaluating a first non febrile seizure in children:

Laboratory tests :If suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness. (Option) Toxicology screening :if there is any question of drug exposure or substance abuse (option)LP :if possible meningitis or encephalitis (option)

EEG

: recommended for all :Establish Dx + recurrence risk

If a neuroimaging study is obtained, MRI is the preferred modality

Slide42

Urgent neuroimaging

in any age who exhibits a postictal focal deficit (Todd’s paresis) not quickly resolvingor who has not returned to baseline within several hours after the seizure

in any child with a significant cognitive or motor impairment of unknown etiologyunexplained abnormalities on neurologic examination a seizure of partial (focal) onset with or without secondary generalization.an EEG that does not represent a benign partial epilepsy of childhood or primary generalized epilepsy children under 1 year of age.

Non urgent neuroimaging

Slide43

Principles and goals of treatment

60-70% of children : seizure-free with no treatment or a low-to-moderate dose of monotherapy30–40% : likely to continue to have seizures despite multiple AED

Seizure control with one AED and without adverse events for some no treatment is appropriateequilibrium between maximum seizure control with minimum adverse effects, to ensure the best quality of life

Slide44

Which drug to use

Most likely to be effectiveLeast likely to cause side effects Evidence based approach

type of seizure +

epileptic syndrome

Patient age

Presence of other associated diseases (

eg

:patients with kidney stones avoid topiramate +

zoisamide

, patients with psychiatric disorders avoid

leveteracitam

)

Slide45

Slide46

Slide47

Slide48

Slide49

Slide50

Which is better the old or new

In terms of efficacy : both same

If patient fails to respond to one drug due to lack of efficacy : the success with 2

nd

or 3rd drug is only 11%

Refractory epilepsy :

1/3

of patients

Slide51

Refractory epilepsy : what to do ?

Other

non pharmacological

modalities

Ketogenic diet

Epilepsy surgery

Brain stem stimulation

Slide52

Ketogenic diet

Available since 1920

High fat (80%), low carbohydrate , adequate protein (20%)=results in ketosisSupplemented with vitamins + calciumNeeds admission for few days to hospital : to induce ketosis

Common SE: non compliance , acidosis, constipation, failure to gain weight, increase cholesterol

Successful control of seizures :equal or surpasses that of AED

Children who become seizure free will continue to be seizure free even when diet is discontinued

Slide53

Epilepsy surgery

Lesionectomy

Lobectomy

Corpus

callosotomy

Hemispherectomy

Multilobar

resection

Multiple subpial transection

Slide54

Vagal nerve stimulation

First implantation in humans :1988FDA approved : 1997

Tech. : pacemaker behind left carotid ( electrode for regulation of stimulation)=transmit intermittent electrical stimulation to an electrode wrapped around the left vagus nerve

Slide55

Mech.: stimulation with high frequency : desynchronisation of EEG ( anticonvulsant effect ), increase GABA , decrease excitatory a.a

Indication : pharmacoresistant epilepsy that is not candidate for surgeryRarely causes seizures to remit completelyDecrease seizure frequency : 25-30%Adjunctive ttt to AED

Slide56

Deep brain stem stimulation

Slide57

Prognosis of epilepsy in children

50% will outgrow their epilepsy and stop treatmentSyndromic approach to discontinuation of ttt.

Depends on epileptic syndrome In general : 2 years seizure free

When to stop treatment

Slide58

Thank you

Thank you for supporting epilepsy