SEIZURE DISORDERS

IN CHILDREN
Marietta M. Diaz,
MD,FPPS,FCNSP
 Definition of Terms
Seizure transient occurrence of signs and symptoms
due to an abnormal excessive or synchronous neuronal
activity in the brain

Epilepsy/Seizure Disorder a disease of the brain

defined by any of the ff: 1. at least 2 unprovoked(or reflex
sz) occurring>24 hrs apart 2. 1 unprovoked(or reflex sz)
and a probability of further seizure similar to gen
recurrence risk after 2 unprovoked sz occurring within the
next 10 yrs 3. diagnosis of epilepsy syndrome
Recurrrence Reflex seizure- represents provoked sz
defined as epilepsy;tendency to respond to such stimuli
with sz
 Definition of Terms
Epileptic Syndrome- disorder consisting of cluster of signs and
symptoms customarily occurring together plus its EEG findings.
The syndrome includes type of seizure, etiology, anatomy,
precipitating factors, age of onset, severity, prognosis and
genetic implication

Non-epileptic Paroxysmal Disorders- paroxysmal events that

may mimic seizures

Resolved epilepsy- a person no longer has epilepsy but still

may recur; it is considered when 1. pt who had age dependent
epilepsy syndrome but now past the applicable age 2. pt.
remains sz free for 10 yrs or off AED for 5 yrs
 Mechanism of Seizure Generation
Seizure
Cellular level generation Synaptic level

Cations neurotransmitters

Ca** channels
Na* channels K* channels
(T type Channel)

GABA
Inc. influx of Na Inc. influx of calcium
glutamate
Inc. intracellularly Decrease
Na & water Cell hyperexcitability Increase
concentration
concentration
Neuronal swelling Firing of thalamic and
Hyperexcitable
cortical neurons
state
Increase tissue
excitability

SEIZURE
Causes of Seizures
Classification:
Epilepsy/Seizures
Then Now
1960-1st suggested 2010-Developed methodically
classification and conceptually sound;
meaningful revision to the
1981-1st seizure 1981 and 1989 classification
classification published Based on inputs from
1989 syndrome genetics, neuroimaging,
classification, therapeutics, research
design, adult and pediatric
conceptual epileptology
2001,2006-attempted 2013-on line feedbacks from
updates clinicians and epileptologists-
ILAE stand
International Classification of Epilepsy
1981
1. Generalized seizures-involvement of both hemispheres
1.1 Absence
1.2 Myoclonic
1.3 Clonic
1.4 Tonic
1.5 Tonic clonic
1.6 Atonic

2. Partial seizures
2.1 simple
2.2 complex
2.3 partial seizures evolving to secondarily generalized seizures

3. Unclassified seizures
International Classification of Epilepsies
and Epileptic Syndromes 1989

1. Localization related (focal local partial)

1.1 idiopathic with age related onset
1.2 symptomatic
2. Generalized
2.1 idiopathic with age related onset
2.2 idiopathic /symptomatic in order of age appearance
2.3 symptomatic
3. Epilepsies and syndromes undetermined as to whether they are focal
or generalized
3.1 with both gen and focal seizures
3.2 without unequivocal or focal features
4 . Special syndromes
4.1 situation related seizures
4.2 isolated apparently unprovoked seizures
4.3 epilepsies characterized by specific modes of seizure precipitation
4.4 chronic progressive epilepsia partialis continua
 Classification as to Etiology
Then Now
Idiopathic-presumed Genetic- genetic defect
genetic directly contributes to the
Symptomatic-secondary to epilepsy and seizures are the
core of the disorder-
a known or presumed
channelopathies
disorder of the brain
Structural-metabolic-caused
Cryptogenic-presumed by a structural or metabolic
symptomatic disorder of the brain-
Tuberous sclerosis, cortical
malformation
Unknown-cause is unknown
and might be genetic,
structural or metabolic
Classification as to Mode of Presentation
Then Now
Generalized Sz- Generalized Sz- originates
involves both at some point, bilaterally
hemisphere distributed, cortical and
subcortical
Focal Sz- initiate
Focal Sz-originate from
activation of seizures within networks limited to
limited to one part of one hemisphere; may be
the hemisphere discretely localized or more
Discrete anatomical widely distributed; may
involve contralateral
notion
hemisphere
Separate manifestations
from underlying cause
 Electroclinical Syndromes and
Other Epilepsies Grouped by
Specificity of Diagnosis

As to Age of Onset
Distinctive constellations/surgical syndromes
Nonsyndromic epilepsies
 Electroclinical Syndromes As to Age of Onset

Neonatal period
Benign familial neonatal seizures (BFNS)
Early myoclonic encephalopathy (EME)
Ohtahara syndrome
Infancy
Migrating partial seizures of infancy
West syndrome
Myoclonic epilepsy in infancy (MEI)
Benign infantile seizures
Benign familial infantile seizures
Dravet syndrome
Myoclonic encephalopathy in
nonprogressive disorders
 Electroclinical Syndromes As to Age of Onset

Childhood
Febrile seizures plus (FS+) (can start in infancy)
Early onset benign childhood occipital epilepsy
(Panayiotopoulos type)
Epilepsy with myoclonic atonic (previously astatic) seizures
Benign epilepsy with centrotemporal spikes (BECTS)
Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)
Late onset childhood occipital epilepsy (Gastaut type)
Epilepsy with myoclonic absences
Lennox-Gastaut syndrome
Epileptic encephalopathy with continuous spike-and-wave
during sleep (CSWS)
including: Landau-Kleffner syndrome (LKS)
Childhood absence epilepsy (CAE)
Electroclinical Syndromes As to Age of
Onset
Adolescence - Adult
Juvenile absence epilepsy (JAE)
Juvenile myoclonic epilepsy (JME)
Epilepsy with generalized tonic-clonic
seizures alone
Progressive myoclonus epilepsies (PME)
Autosomal dominant partial epilepsy with
auditory features (ADPEAF)
Other familial temporal lobe epilepsies
 Electroclinical Syndromes
and other epilepsies
Less Specific Age Relationship
Familial focal epilepsy with variable foci
(childhood to adult)
Reflex epilepsies
Distinctive Constellations
Mesial temporal lobe epilepsy with
hippocampal sclerosis (MTLE with HS)
Rasmussen syndrome
Gelastic seizures with hypothalamic
hamartoma
 Electroclinical Syndromes
and other
epilepsies(Nonsyndromic)
Epilepsies attributed to and organized by structural-
metabolic causes
Malformations of Cortical development
(hemimeganencephaly, hetertopias etc)
Neurocutaneous syndromes (Tuberous sclerosis complex,
Sturge-Weber, etc)
Tumor
Infection
Trauma
Angioma
Peri-natal insults
Stroke
Etc.
International Classification of Epilepsy
1981
1. Generalized seizures-involvement of both hemispheres
1.1 Absence
1.2 Myoclonic
1.3 Clonic
1.4 Tonic
1.5 Tonic clonic
1.6 Atonic

2. Partial seizures
2.1 simple
2.2 complex
2.3 partial seizures evolving to secondarily generalized seizures

3. Unclassified seizures
Febrile Seizures

Definition:
seizures with fever in a child 3 months to
5 years of age without evidence of CNS
infection
Types:
simple and complex
Treatment
intermittent
continuous
Febrile Seizures and Generalized
Epilepsy
Febrile Convulsion(Seizure) Syndrome-
confined to early childhood,< 6 yrs and
associated with low overall risk of later
epilepsy( Nelson and Ellenberg 1976,
Commission, 1989)
Febrile Seizure Plus- children with febrile
seizures> 6 yrs with or without associated
afebrile generalized tonic-clonic seizures
 GEFS+(Generalized Epilepsy
with Febrile Seizures Plus)
Genetic syndrome-autosomal dominant gene
Epilepsy prototype
Phenotypic expression comprises a spectrum
of clinical epilepsy prototype- febrile
convulsion syndrome,FS+, FS+ and
absences,FS+ and myoclonic seizures ,FS+
and atonic seizures and Myoclonic Astatic
Epilepsy
Status Epilepticus
Continuous seizure for 30 minutes
Repeated seizures for 30 minutes without recovery of
consciousness
Supportive measures-
a. adequate airway
b. Proper positioning
c. Oxygenation
Specific medications
a. Diazepam
b. Lorazepam
c. Phenobarbital
d. Phenytoin
e. Midazolam
Neurodiagnostic Evaluation in Patients
with Seizures
1. EEG
2. Neuroimaging
3. CSF analysis
4. Video EEG monitoring
5. Skull x-ray
6. Chromosomal analysis
7. Biochemical studies
8. Electrolyte determination
*There are no routine examinations. There are only those
that are indicated by the specific diagnostic problems
presented by the patient
Electroencephalogram
Neuroimaging

1. Cranial ultrasound
2. Cranial Ct scan
3. MRI
4. MRA and Angiography
5. SPECT
Drug Therapy for Epilepsy

Objective: prevent seizure recurrence by

prescribing appropriate anticonvulsant
Guideline questions
1. When is an antiepileptic drug (AED) started?
2. What is the best AED for a patient?
3. If the first AED does not control the seizure,
what will be the next step?
4. How long is the AED given?
5. What are the options if seizures are not
controlled by AED?
When is an AED started?
If a single seizure is followed rapidly by a
second seizure
Definitely
a. with structural lesions- brain tumor,AVM
b. without structural lesion- history of
epilepsy in siblings, EEG with definite pattern
Possibly- unprovoked seizure
Probably not- drug abuse, alcohol withdrawal,
acute illness, certain epilepsy syndromes
 What is the best AED?
Then Now
1857-K Bromide Clobazam 1982
1908- Phenytoin Vigabatrin 1989
Lamotrigine 1991
1912- Phenobarbital Gabapentin 1993
1940- Trimethadione Felbamate 1993
Topiramate 1995
1950- Primidone Tiagabine 1998
1960- Ethosuximide Oxcarbazepine 2000
Levetiracetam 2000
1970- Carbamazepine Pregabalin 2004
1970- Valproic Acid Zonisamide 2005
Rufinamide 2007
1970- Clonazepam Stiripentol 2007
Lacosamide 2008
Eslicarbazepine 2009
Retigabine 2011
Perampanel 2012
Table 1. Clinical uses in common seizure types and syndromes and adverse effects
of antiepileptic drugs.
Drugs Clinical uses Adverse effects

Phenobarbital Partial and generalized Sedation, lethargy, dysarthria,

distractability, hyperkinesia, I

Phenytoin Partial seizures, generalized Ataxia, diplopia, nystagmus,

hirsutism, skin rashes,
agranulocytosis, aplastic anemia,

Ethosuximide Absence seizures GI changes, drowsiness, mood

changes, agranulocytosis

Carbamazepine Partial seizures, generalized Diplopia, dizziness, headache,

agranulocytosis, weight gain,
Benzodiazepines Status epilepticus, partial and
generalized seizures Sedation, lethargy,
behavioral disturbances

Valproic acid Partial and generalized sz Tremor, weight gain,

dyspepsia,
hairloss,thrombocytopenia
Table 1. Clinical uses in common seizure types and syndromes and adverse
effects of antiepileptic drugs.

Drugs Clinical uses Adverse effects

Felbamate severe/refractory epilepsies LGS anorexia,insomnia,ataxia

Gabapentin adjunct partial sz drowsiness,ataxia,hyperactivity

Pregabalin adjunct partial sz weight gain,edema,drowsiness

Lamotrigine adjunct partial sz,LGS dizziness,sedation, rashes

Topiramate adjunct partial/gen sz cognitive problems,weight loss

Tiagabine adjunct partial/gen sz dizziness, emotional changes

Vigabatrin infantile spasms,refractory sz dizziness,ataxia,visual field df

Oxcarbazepine partial/gen sz dizziness,diplopia,skin rash

Table 1. Clinical uses in common seizure types and syndromes and adverse
effects of antiepileptic drugs.

Drugs Clinical uses Adverse effects

Oxcarbazepine partial/gen sz dizziness,diplopia,skin rash, SJS

Zonisamide partial/gen sz sedation,GIstress,rash,agranulocytosis

Levetiracetam adjunct for par/gen sedation,fatigue,leucopenia

Lacosamide Adjunct partial sz nausea,diplopia, blurred vision

Rufinamide Lennox Gastaut Somnolence, vomiting, pyrexia

Stripentol Dravets synd anorexia,drowsiness,ataxia, GI prob

Antiepileptic Drugs
Then Now

Same efficacy Same efficacy

Complex simpler
pharmacokinetics pharmacokinetics
1. Short half life 1. longer half life
2. Minimally or not bound
2. Bound to plasma
to plasma protein
protein
3. No enzyme inducing
3. Enzyme inducing properties
properties Better tolerability
Less tolerability Less teratogenic
Teratogenic potential potential
Cheaper More expensive
If the first AED does not
control the seizures, what next?
Dosage should be increased slowly
until seizures are controlled or
maximum dose is attained or when
side effects ensue
If first AED is not effective, start
a 2nd AED. Slowly taper first drug
once adequate levels of 2nd drug is
attained
How long is the AED given?

Treatment may be stopped after 2

seizure free years
Factors related to successful
withdrawal
single type of seizure
normal NE
normal IQ
normal EEG following treatment
How is an epileptic patient
monitored?

Compliance
Monitoring body weight
Monitoring toxicity
Serum levels of AED
Use individual drugs to its full
potential
Treatment failure on initial drug
Non-Pharmacologic
Treatment:What are the
options if seizures do no
respond to AED?

Dietary
Vagus Nerve Stimulation
Epilepsy Surgery