Epilepsy in Children.pptx

• Dr.C.S.N.Vittal
Seizure
Disorders
in
Children

Seizure
(Latin sacire, “to take possession of”)
A transient occurrence of signs
and/or symptoms resulting
from abnormal excessive or
synchronous neuronal activity
in the brain.

Epilepsy
Epilepsy is a disorder
characterized by two or more
unprovoked seizures occurring
more than 24 hours apart
beyond neonatal period.

• A seizure is the event
Seizure vs Epilepsy
• Epilepsy is the disease
associated with spontaneously
recurring seizures

Convulsion
A convulsion is any seizure
(not necessarily epileptic)
characterized by excessive,
abnormal muscle
contractions, which are
usually bilateral.

Epilepsy – new definition
Epilepsy is a disease of the brain defined by any of the following:
1. A 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
• Robert S fisher et al; A practical clinical definition of epilepsy: Epilepsia, 55($):475-482, 2014

Risk of epilepsy after 2 seizures
• Hauser et al. Risk of recurrent seizures after two unprovoked seizures. NEJM 1998;338:429.

Seizures
Focal
The first clinical and
electroencephalographic
(EEG)
changes suggest initial
activation of a system of
neurons limited to part
of one cerebral hemisphere
The first clinical and EEG
changes indicate
synchronous
involvement of all
of both
hemispheres
Generalized

Some terminology
• Dr Neeta Naik, Guidelines for Diagnosis and Management of Childhood Epilepsy; Expert Committee On Pediatric Epilepsy, IAP; Ind Ped, Vol 46 Aug 17, 2009:
681-698

Status Epilepsy (>100 / 100000 population)
• Recurrent epileptic seizures continuing for more than 30 minutes without
full recovery of consciousness before the next seizure begins, or continu-
ous clinical and/or electrical seizure activity lasting for more than 30
minutes whether or not consciousness is impaired’
Clinical Definition
New Operational Definition (children > 5 yrs)
• “Greater than or equal to 5 minutes of continuous seizures or two or
more discrete seizures between which there is incomplete recovery of
consciousness.”
• A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of
Status Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121

Time definition for CSE for
treatment purposes
(Operational definition)
Key
time
periods
in
natural
history
of
seizure
0 5 15 30
Interval within
which most
seizures
spontaneously
stop
Optimum interval
for initiation of
rescue therapy
Time definition for CSE for
epidemiological,
pathophysiological and
outcome purposes

Status Epilepsy - ILAE
A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status
Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121
Tonic-Clonic Focal with
impaired
consciousness
Absences
Point 1 (t1)
the earliest time when treatment
should be started.
5 min 10-15 min 15 min
Point 2 (t2)
when long-term consequences,
such as neuronal injury, neuronal
death
30 min > 60 min Unknown

Convulsive
Status epilepticus Complex partial, absence, myoclonic
status, epilepsia partialis continua, and
neonatal status epilepticus, confusional
state, hyperactivity with behavioral
problems, fluctuating impairment of
consciousness with at times unsteady
sitting or walking, fluctuating mental
status, confusional state, hallucinations,
paranoia, aggressiveness catatonia, and
or psychotic symptoms.
Non-convulsive Status epilepticus
Status Epilepticus
Generalized
tonic, clonic, or
tonic–clonic

Mechanisms which Underlie Seizure Generation
• Abnormalities at the cell membrane level (ion channels and receptors) and in
neuronal circuits
• 3 main classes of voltage gated ion channels have been described: Na+, Ca2+, K+.
• Sodium currents are involved in the generation of action potentials.
• Potassium currents cause hyperpolarization and hence stabilize the neuronal
membrane.
• Both calcium and sodium currents are involved in the generation of burst
discharges, generated by certain classes of neurones when excited.
• Gamma amino butyric acid (GABA) and glycine are inhibitory neurotransmitters
while glutamate and aspartate are excitatory neurotransmitters.
• A useful, though simplistic model of epilepsy is that it involves an imbalance of
excitatory and inhibitory neurotransmitter systems within the CNS.

Mechanisms which Underlie Seizure Generation
2. Involves an imbalance of excitatory (glutamate and
aspartate) and inhibitory (Gamma amino butyric acid and
glycine ) neurotransmitter systems within the CNS.
1. Abnormalities at the cell membrane level (ion channels
and receptors) and in neuronal circuits

The 2017 ILAE Classification of Seizures
Robert S. Fisher, MD, PhD
Maslah Saul MD Professor of Neurology Director, Stanford Epilepsy Center
In 2017, the ILAE released a new classification of seizure types,
largely based upon the existing classification formulated in 1981.

Motor
Tonic-clonic
Other motor
Non-Motor (Absence)
Unknown Onset
Motor
Non-Motor
focal to bilateral tonic-clonic
Generalized Onset
Focal Onset
Motor
Tonic-clonic
Other motor
Non-Motor
ILAE 2017 Classification of Seizure Types Basic Version 1
Unclassified 2
Aware
Impaired
Awareness
From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia
doi: 10.1111/epi.13671
1 Definitions, other seizure types and descriptors are listed in the accompanying paper & glossary of terms
2 Due to inadequate information or inability to place in other categories

Motor
tonic-clonic
clonic
tonic
myoclonic
myoclonic-tonic-clonic
myoclonic-atonic
atonic
epileptic spasms2
Non-Motor (absence)
typical
atypical
myoclonic
eyelid myoclonia
Unknown Onset
Motor Onset
automatisms
atonic2
clonic
epileptic spasms2
hyperkinetic
myoclonic
tonic
Non-Motor Onset
autonomic
behavior arrest
cognitive
emotional
sensory
focal to bilateral tonic-clonic
Generalized Onset
Focal Onset
Aware
Impaired
Awareness
Motor
tonic-clonic
epileptic spasms
Non-Motor
behavior arrest
ILAE 2017 Classification of Seizure Types Expanded Version
Unclassified3
2 These could be focal or generalized, with or without alteration of awareness
3 Due to inadequate information or inability to place in other categories
From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671

focal onset
aware impaired awareness
motor onset
(seizures with
physical
movement)
automatisms
atonic
clonic
epileptic spasms
hyperkinetic
myoclonic
tonic
non-motor onset
(seizures without
physical
movement)
autonomic
behaviour arrest
congnitive
emotional
sensory
motor onset
(seizures with
physical
movement)
automatisms
atonic
clonic
epileptic spasms
hyperkinetic
myoclonic
tonic
non-motor onset
(seizures without
physical
movement)
autonomic
behaviour arrest
congnitive
emotional
sensory
focal to bilateral tonic clonic seizure (sec generalized seizures)
seizures start in, and affect
one part of the brain
focal aware seizures
(simple partial seizures)
focal impaired awareness seizures
(complex partial seizures)

generalized onset
seizures start in, and affect
both sides of the brain at once
and
happen without warning
motor
(with physical movement)
non-motor (absence)
(without any physical movement)
Motor
tonic-clonic
clonic
tonic
myoclonic
myoclonic-tonic-clonic
myoclonic-atonic
atonic
epileptic spasms2
Non-Motor (absence)
typical (3 Hz spike & slow wave )
atypical (1-2 Hz spike & slow wave
with head atonia and myoclonus)
myoclonic
eyelid myoclonia

unknown onset
(cryptogenic epilepsy) unclassified
motor
(with physical movement)
non-motor
(without any physical
movement)
if doctors are not sure
where in the brain the seizure starts If there is not enough
information available about
the person’s seizure or because of the
nature of the seizure.

Etiology of Seizures – Neonatal Period
• Birth asphyxia or trauma
• Intracranial hemorrhage
• Hypoglycemia
• Hypocalcaemia or
hypomagnesemia
• Infections: meningitis, septicemia,
tetanus neonatorum
• Inborne errors of metabolism
• Pyridoxin dependent seizures
• Maternal withdrawal of
medications
• Accidental injection of local

Text
Text
Etiology of Seizures – Beyond Neonatal Period
• Vascular: hemorrhage , AV
malformations, intracranial
thrombosis
• Cerebral malformation:
neurocutaneous syndromes,
neuronal migration disorders
• Drugs/Poisons: Phenothiazines,
lead salicylates, phenytoin, CO,
strychnine
• Miscellaneous: Hypertensive
encephalopathy, gray matter
degeneration, storage disorders
• Simple febrile convulsions
• Epilepsy syndromes
• Infections: meningitis,
encephalitis, Reye syndrome,
cerebral malaria
• Metabolic causes:
Dyselectrolytemia,
hypocalcemiam
hypomagnesemia, IEM
• Space occupying lesions:
Neoplasm, brain abscess,
tuberculoma, cysticercosis
• Trauma:

Febrile Seizures
FS is a seizure occurring in childhood after one month of age, associated with a febrile
illness that is not caused by an infection of the central nervous system
ILAE Definition:
Febrile seizures are seizures that occur between the ages of 6 and 60 mo (peak
12-18 mo) with a temperature of 38°C (100.4°F) or higher, that are not the result
of CNS infection or any metabolic imbalance, and that occur in the absence of a
history of prior afebrile seizures
Nelson Text Book Definition:

Febrile Seizures – Types
Simple
• Primary generalized,
• usually tonic–clonic,
• attack associated with fever
• Lasting for a maximum of 15
min
• Do not recurrent within a 24-
hr period
• Do not have an increased risk
of mortality
Complex
• Focal
• Prolonged (>15 min)
• Recurs within 24 hours
• 2-fold long-term increase in
mortality rates, as compared
with the general population,
over the subsequent 2 yr,
probably sec to a coexisting
pathology

Febrile status epilepticus
… is defined as one lasting over 30 minutes.
Febrile seizure plus
When the febrile seizures continue after age 5 or other types of
seizure develop. FS+ usually end in early adolescence. ...
• Febrile infection–related epilepsy (FIRES): In children >5 yr) usually male
children and associated with an encephalitis-like illness but without an
identifiable infectious agent. Children with FIRES were previously normal but
subsequently develop difficult-to-treat epilepsy.
• Generalised epilepsy with febrile seizures plus (GEFS+): Children may go on to
have febrile seizures well beyond 6 yrs age, even into adult life. They may also
develop other seizure types not associated with a high temperature. An
epileptic syndrome.

Risk factors for Recurrence
No risk factors 12%
1 risk factor 25-50%
2 risk factors 50-59%
3 or more risk factors 73-100%
Febrile Seizures – Risk Factors
MAJOR
• Age < 1 yr
• Duration of fever < 24 hr
• Fever > 38-390C
(100.4 – 102.20F)
MINOR
• Family history of febrile seizure
• Family history of epilepsy
• Complex febrile seizure
• Daycare
• Male gender
• Lower serum sodium at time
of presentation
• Nelson Textbook of Pediatrics, 21E

Epilepsy Syndromes Male, 2-13 yrs
Mostly nocturnal
Motor & somatosensory – older children
Hemiclonic / GTCS – younger children
Most AEDs effective, Recovery before 15-16 yrs
Commonest generalized epilepsy in 5-16 yrs olds GTCSs
3-6 Hz generalized polyspikes and waves in EEG
Improve after 4th decade
3-10 %, Genetic pre disposistion
Male preponderance, Onset 1-8 yrs
Poor prognosis
Hypsarrhythmia , Tuberous sclerosis
Typically in 3-5 yrs age group
Severe, Complex epilepsy
Multiple concurrent seizure types
Cognitive dysfunction
Benign Rolandic Epilepsy
Juvenile Myoclonic Epilepsy
West Syndrome
(Infantile Spasms)
Lenox Gestaut Syndrome

Benign epilepsy with occipital spikes
• headaches that occur independently or postictally
(epilepsy–migraine sequence)
Panayiotopoulos
type
•Occur in early
childhood
•Manifests with
focal seizures
•Impaired
awareness
•Ictal vomiting
Gastaut type
•appear in later
childhood
•focal seizures
with
•impaired
awareness
•Visual auras, and
•migraine

Seizure
Evaluation
on
First Visit
1 Seizure / seizure mimic ?
2 Is it unprovoked / provoked seizure?
3 Generalized / focal seizure?
4 Etiology?
5 Any associated comorbidities?
6 Treatment received till now?

Role of Imaging
• MRI is the imaging modality of choice!
But not urgent
• Significant cognitive or motor
impairment of unknown etiology
• Unexplained abnormalities on
neurologic examination
• Focal seizure with or without
secondary generalization
• EEG that does not represent a benign
partial epilepsy or primary
generalized epilepsy
• Seizure in children under 1 year of
age
• If MRI can not be done, better don’t do imaging!! - Epilepsia, 50(9): 2147-2153, 2009

Quietly sitting, relaxed,
eyes closed 20-60 mV
Most common waves.
During mental thought &
activity
2-20 mV
20-100 mV
Common in children.
Displeasure,
pleasure, and drowsiness
Very irregular &slow
waves. Deep sleep in most
people
20-200 mV
Gamma ( g )
36-44 Hz
3-5 mV
With sudden sensory
stimuli

Role of EEG
• EEG when abnormal can suggest the nature of the seizure tendency as focal or
generalized, but does not determine whether or not a spell was a seizure or whether
or not to treat,.
• 50% of patients with partial seizures show focal spikes (or slowing), up to 75% after
repeat studies or sleep deprivation.
• 90% of patients with generalized seizures show generalized spikes, more with sleep
deprivation, hyperventilation, or photic stimulation.
• A normal EEG would favor partial onset seizures in a patient with epilepsy.
• 1-2% of nonepileptics have spikes on their EEGs.
• 20% of patients with spikes on the EEG do not have epilepsy.

Role of EEG in Office practice
Supports the clinical diagnosis of epilepsy
1
To classify epilepsy : Focal vs Generalized epilepsy
2
To identify epilepsy syndromes
3
3
To predict recurrence risk and to prognosticate
4
4
Unexplained GDD/worsening/autistic regression
5
• K.M.Pearce, H.R. Cock, Seizure 2006

A. Onset of a tonic seizure showing generalized repetitive sharp
activity with synchronous onset over both hemispheres.
B. Burst of repetitive spikes occurring with sudden onset in the
right temporal region during a clinical spell characterized by
transient impairment of external awareness.
C. Generalized 3-Hz spike-wave activity occurring synchronously over
both hemispheres during an absence (petit mal) attack. Horizontal
calibration:
• MJ Aminoff [ed]: Aminoff’s Electrodiagnosis in Clinical Neurology, 6th ed. Oxford, Elsevier Saunders, 2012.)

EEG interpretation – in general
Finding Likely Diagnosis
Spike followed by slow waves Interictal pattern of epilepsy
3 Hz spike and wave discharges; provoked by
hyperventilation
Absence epilepsy
Chaotic high voltage of poyspikes with photosensitivity West syndrome
Spike wave complexes in Rolandic areas Juvenile myoclonic epilepsy
Brief bursts of polyspikes with photosensitity Benign epilepsy with centrotemporal spikes
Generalized periodic epileptiform discharges Subacute sclerosing panencephalitis
Lateralized periodic epileptiform discharges Herpes simplex encephalitis

Febrile seizures (typical/atypical)
Autism with only staring episodes
To differentiate - ? Seizure ? Non-epileptic event
Established epilepsy – periodic EEG monitoring
EEG – No role

Step 6
Switch to another
monotherapy or
addon
Management Strategies
Step 1
Step 4
Select AED
Step 3
Evaluate need for Tt
Step 2
Establish seizure type/syndrome
Confirm Diagnosis
Step 5
Start monotherapy

Management Strategies
First Seizure
Generalized
No deficits
normal EEG
Wait and
watch
No deficits
High rec risk
AED trial
Focal deficit
Neuroimaging
treat
accordingly

Principles of drug therapy in epilepsy
1. Start with a single AED
2. Start with low dose and increase gradually
3. Ensure compliance
4. Increase dose gradually to maximum tolerate
“As much as needed BUT as little as possible”
Self evident but often forgotten
5. A seizure diary should be kept by the parents
6. AED is withdrawn after 2 year of seizure freedom.

AED of Choice
Seizure First Choice Second Choice
Focal seizure Oxcarbamazepine: Carbamazepine Valproate, Phenytoin
Idiopathic Generalized
Epilepsy
• BOYS: Valproate, Phenytoin
• GIRLS: Levetiracetam, Lamotrigine
• Levetiracetam, Lamotrigine, Zonisamide
• Valproate, Zonisamide
Absence Valproate, Lamotrigine, Ethosuximide Levetiracetam, Topiramate, Zonisamide
Epileptic spasms ACTH, Steroids Vigabatrine
Myoclonic Valproate Levetiracetam, Topiramate, Zonisamide
Tonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide
Atonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide
Neonatal seizures Phenobarbitone, Phenytoin Levetiracetam
Benign Rolandic Epilepsy None Valproate, Cobazam

Refractory Epilepsy
• Epilepsy which is uncontrolled despite adequate trials of three first
line AEDs and when it disrupts developmental progress or normal
childhood activity

Surgical Remedies
Hemispheric epilepsies – hemispherecomy/hemispherotomy
Neocortical resection, multilobar resection
Mesial temporal lobe epilepsy caused often by hippocampal sclerosis
Drop attacks with injuries respond well to corpus callosotomy
Sterotactic ablation
Multiple subpial transction

Antiepileptic Drugs - Classification
• Sodium channel blockers:
• Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine, Zonisamide,
• Slow Channel : Lacosamide, Eslicarbazepine
• Calcium channel blockers:
• Low Voltage :Ethosuximide, Valpoate, Zonisamide
• High Voltage:Ethosuximide, Valpoate, Zonisamide
• GABA Modulators:
• GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital, Primidone, Benzodiazepines, Phenobarbitone, Felbamate,
Levetiracetam
• GABA Reuptake inhibitors: Tiagabine
• GABA Transaminase Inhibitors : Vigabatrin
• Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate (enhance glutamic acid decarboxylase (GAD))
• Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel, Levetiracetam(AMPA), Valproate (NMDA)
• Carbonic anhydrase inhibitors : Topiramate and Zonisamide
• SV2A-binding agents: Levetiracetam, brivaracetam
• Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol
• Neuronal Potassium Channel Openers :Ezogabine, Retigabine

Summary of Role of AEDs
• Broad spectrum AEDs
• CLB, LGT, TPM, ZNS – used in generalized and focal epilepsies
• CLOBAZAM: Most common and effective add-on AED in many
situations
• LAMOTRIGENE:
• Titrate slowly, otherwise bad skin rashes including SJ syndrome
• Effective add-on for IGE, Absence and Focal epilepsy
• TOPIRAMATE:
• Effective in focal epilepsy including in infants
• Can be titrated quickly
• Beware of speech, memory and cognitive side effects
• ZONISAMIDE: Effective in drop attacks, refractory spasms

Dose Adjustments with Weight Gain
Significant Wt Gain
Sz free
Occasional sz only
AED ceiling dose reached
Continue
same dose
Regular Seizures
AED ceiling dose reached
Yes
Add on AED
No
Increase the dose

Management of Status Epilepticus
Time / Phase Treatment
0-5 min
(Stabilization Phase)
Ensure adequate ventilation/O2, vitals monitoring,
IV line with NS, rapid assessment, blood draw
5 - 20 min
(Initial Therapy Phase)
• Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or
• Rectal diazepam / Intranasal midazolam / buccal midazolam
20 - 40 min
(Second Therapy Phase)
• IV - Fosphenytoin or Phenytoin (20 mg/kg) or Valproic acid (40 mg/kg) or Levetiracetam (60 mg/kg)
single dose
• IV phenobarbital (15 mg/kg) single dose
40 - 60 min
(Third Therapy Phase)
• ?? Repeat of 2nd line therapy; Anaesthetic doses of Thiopental, midazolam, phenobarbital or
propofol with continuous EEG monitoring

Take Home Message
• Approach a child with seizures systematically
• Seizures and epilepsy are clinical diagnoses
• Well reported good EEG supports the clinical diagnosis
• Use neuroimaging judiciously; avoid CT scans
• Treat the patient and NOT the EEG report
• Epilepsy treatment is tailor made

Role of EEG
 EEG when abnormal can suggest the nature of the seizure tendency
as focal or generalized, but does not determine whether or not a
spell was a seizure or whether or not to treat,.
 50% of patients with partial seizures show focal spikes (or slowing),
up to 75% after repeat studies or sleep deprivation.
 90% of patients with generalized seizures show generalized spikes,
more with sleep deprivation, hyperventilation, or photic stimulation.
 A normal EEG would favor partial onset seizures in a patient with
epilepsy.
 1-2% of nonepileptics have spikes on their EEGs.
 20% of patients with spikes on the EEG do not have epilepsy.

Disorders mimicking seizures...
• Jitteriness in newborn
• Breath holding spells in toddlers
• Shuddering attacks
• Syncopal attacks
• Night terror
• Pseudo seizures
• Migraine

Nonepileptic Paroxysms
Age Group Seizure Mimics
Neonates • Jitteriness
• Benign Sleep Myoclonus
• Hyperekplexia
Infants • Breath-holding spells
• Infantile self-stimulation
• Shuddering episodes
• Infantile Tremor
Syndrome
• Sandifer Syndrome
Age
Group
Seizure Mimics
Children • Tics
• Hypnic Jerks
• Syncope – vasovagal, Long QT,
etc.
• Parasomnias
• Psychogenic non-epileptic
episodes
• Migraine associated disorders
• Narcolepsy-cataplexy

• Sodium channel blockers:
• Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine,
Zonisamide,
• Slow Channel : Lacosamide, Eslicarbazepine
• Calcium channel blockers:
• Low Voltage :Ethosuximide, Valpoate, Zonisamide
• High Voltage :Ethosuximide, Valpoate, Zonisamide
• GABA Modulators:
• GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital,
Primidone, Benzodiazepines, Phenobarbitone, Felbamate, Levetiracetam
• GABA Reuptake inhibitors: Tiagabine
• GABA Transaminase Inhibitors : Vigabatrin
• Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate
(enhance glutamic acid decarboxylase (GAD))

• Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel,
Levetiracetam(AMPA), Valproate (NMDA)
• Carbonic anhydrase inhibitors : Topiramate and Zonisamide
• SV2A-binding agents: Levetiracetam, brivaracetam
• Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol
• Neuronal Potassium Channel Openers :Ezogabine, Retigabine

NICE guidelines on AEDs based on seizure types
Seizure
Type
First-Line AEDs Adjunctive AEDs
GTCS Carbamazepine
Lamotrigine
Oxcarbazepine
Sodium valproate
Topiramate
Clobazam
Levetiracetam
Tonic or
atonic
Sodium valproate Lamotrigine
Absene Ethosuximide
Lamotrigene
Sodium valproate
Seizure
Type
First-Line AEDs Adjunctive AEDs
Myoclonic Levetiracetam
Sodium
valproate
Topiramate
Focal Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Sodium
valproate
Clobazam
Gabapentine
Topiramate

Phenytoin
• Causes voltage-dependent block
of voltage gated sodium
channels possibly by promoting sodium
efflux from neurons, phenytoin tends to
stabilize the threshold against
hyperexcitability caused by excessive
stimulation or environmental changes
capable of reducing membrane sodium
gradient.
• The primary site of action appears to be
the motor cortex where spread of
seizure activity is inhibited.
• Phenytoin reduces the maximal activity
of brain stem centers responsible for the
tonic phase of generalized tonic-clonic
seizures

Phenytoin
• Anticonvulsant effect: 10–20 µg/mL;
• Medical uses
• Prophylactic management of tonic-
clonic seizures with complex
symptomatology (psychomotor
seizures
• Effective in controlling partial seizures
with autonomic symptoms.
• Status epilepsy
• Digoxin toxicity, atrial tachycardia
• Trigeminal neuralgia
• Not recommended
• Pregnancy : craniofacial deformities,
lethal fetal hydantoin syndrome
• Side Effects
• swelling and bleeding of the gums
• Hypertrichosis, SJ syndrome
• Hypotension
• Nystagmus, diplopia
• Cerebellar atrophy
• Peripheral neuritis
• Contraindications
• Liver disease
• Not recommend breast feeding because
low concentrations of phenytoin are
excreted in breast milk.
• Sinus bradycardia, AV blocks – IV adm
not recommended
• Pregnancy : craniofacial deformities,
lethal fetal hydantoin syndrome

Newer AEDs
• Felbamate 1993
• Gabapentin 1993
• Lamotrigine 1994
• Topiramate 1996
• Tiagabine 1998
• Levetiracetam 1999
• Oxcarbazepine 2000
• Zonisamide 2000
• Pregabalin 2005
• Lacosamide 2008
• Eslicarbazepine 2009
• Retigabine 2011

a amino hydroxy methyl isoxazole propionic acid

FELBAMATE
• Mechanism of action –
• Sodium channel blockade,
• potentiation of GABA a mediated inhibition and antagonism of NMDA mediated
responses.
• Indications –
• Not indicated as a First line agent.
• Add-on treatment of Lennox-Gestaut Syndrome and partial and secondary
generalised seizure refractory to other agents.
• Dosage:
• 15mg/kg (children)
• Significant drug interactions:
• increases Phenytoin, valproate levels
• lowers carbamazepine and steroid levels
• valproate decreases rate of Felbamate elimination
• Highly effective in severe refractory
cases, but use limited by hepatic and
haematological toxicity.

GABAPENTIN
• Modulates neurotransmitter release by binding to α2-δ subunit of voltage gated
Ca channels. This closes N and P/Q pre-synaptic calcium channels, diminishing
excessive neuronal activity and neurotransmitter release
• Indications –
• Adjunctive therapy or monotherapy of partial or secondary generalized seizures.
• also used in Neuropathic Pain, postherpetic neuralgia and diabetic neuropathy.
• Dosage:
• Antacid can reduce absorption by abt 20%.
• Adverse effects –
• Drowsiness (24.4%), dizziness (20.3%), ataxia (17%), headache (15%), tremor,
diplopia, nausea, vomiting, non-pitting pedal edema, weight gain
• Effective in focal epilepsy but may
aggravate generalized epilepsy.
• Spectrum of efficacy restricted to
partial epilepsies

LAMOTRIGINE
• Blockade of voltage dependent sodium and calcium channels.
• Indications –
• Adjunctive therapy and monotherapy of partial seizures (with or without
secondary generalization), other generalized epilepsy syndromes, including
Lennox-Gastaut Syndrome
• Dosage:
• Serum Lamotrigine levels are increased by Valproic acid as Valproate reduces
rate of Lamotrigine elimination
• adverse effects –
• Dizziness, diplopia, ataxia, blurred vision, somnolence, insomnia, headache,
nausea, asthenia, skin rash
• Useful drug which can be used as 1st or 2nd line monotherapy, or as
adjunctive therapy in treatment of partial seizures and occasionally
in generalised epilepsy syndromes.
• Main disadvantage is need for slow-dose escalation.

TOPIRAMATE
• Blockade of voltage dependent na and ca channels
• Potentiation of GABA mediated inhibition at GABA A receptors,
• Reduction of excitatory action of glutamate via AMPA receptors, -
• Inhibition of carbonic anhydrase.
• Indications –
• Adjunctive therapy or monotherapy of partial and secondary GTCS. Also useful for Lennox-
Gastaut Syndrome and primary
• Dosage:
• Serum Topiramate levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine,
phenobarbital).
• Topiramate may increase serum Phenytoin levels.
• Dizziness, ataxia, somnolence, paraesthesia, tremor, somnolence, cognitive dysfunction,
confusion, agitation, amnesia, depression, headache, nausea, diarrhoea, diplopia, weight loss.
A very useful drug with relatively broad spectrum efficacy.
- Safe in pregnancy.
- Main advantage is high responder rates.
- Main disadvantage is CNS adverse effects. - Dose reduction required in
renal diseases.

LEVETIRACETAM
• Binds to Synaptic Vesicle 2A (SV2A) protein. Precise mechanism by which this binding acts is
unknown but is likely to involve inhibition of neurotransmitter release from nerve end terminals.
• Indications –
• First- line and adjunctive therapy of partial-onset seizures.
• Adjunctive and, possibly, first line therapy of GTCS and Myoclonic seizures associated with
idiopathic generalized epilepsies.
• Dosage:
• 20-60 mg/kg/day. Tt may be started with 10-20 mg/kg/day and adjusted according to response ,
by increments of 10-20 mg/kg/day every 2 weeks
• Serum Levetiracetam levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine,
phenobarbital) by about 20-30 %.
• Dizziness, ataxia, somnolence (10%), asthenia, infection, nervousness, irritability, behavioural
and Psychiatric disorders (12.9% vs 6.2% of placebo patients), suicidal behaviour
• Main advantage is Relatively broad spectrum activity, good tolerability,
and lack of clinically significant drug interactions.
• Main disadvantage is efficacy in some generalized seizure types and
epilepsy syndrome unproven. Behavioural and psychiatric adverse effects

OXCARBAZEPINE
• Blockade of voltage gated Na channels and N and P type calcium channels.
• Indications –
• Adjunctive therapy or monotherapy for partial and secondary generalized seizures.
• Also useful to treat primary generalized tonic clonic .
• Dosage:
• 20-60 mg/kg/day. Tt may be started with 10-20mg/kg/day and adjusted according to response , by
increments of 10-20 mg/kg/day every 2 weeks
• Serum Oxcarbazepine levels are reduced by enzyme inducing AEDs by promoting its clearance.
• Oxcarbazepine may increase the levels of phenytoin and Phenobarbital.
• Main advantage is that it is better tolerated and has fewer interactions
than carbamazepine. Risk of hepatotoxicity is estimated to be lower
than carbamazepine.
• Main disadvantage is efficacy spectrum restricted to partial epilepsies.
Higher incidence of hyponatremia compared with carbamazepine.
• Not indicated for absence, myoclonic and other types of generalized
seizures other than tonic-clonic seizures and indeed may exacerbate
them.

ZONISAMIDE
• Multiple including blockade of voltage
• gated Na channels, blockade of T-type calcium channels, potentiation of GABAergic transmission
and
• inhibition of Carbonic anhydrase.
• Indications –
• Adjunctive therapy for partial and secondary generalized seizures.
• May also be used as adjunctive therapy in primary eneralized seizures. Myoclonic Epilepsies
• Dosage:
• Serum Zonisamide levels are reduced by enzyme inducing AEDs.
• Administration with food does not reduce the extent but decreases the rate of absorption.
• increase in the incidence of renal stones if given with topiramate (CA Inhibitors)
• adverse effects –
• Agitation, irritability, confusion, depression, anorexia, Weight loss, Nephrolithiasis, skin rashes
(including Stevens Jonhnson Syndrome), blood dyscrasias and hypersensitivity reaction.
• broad spectrum of Efficacy Main advantage Main
disadvantage is CNS adverse effects.
• No proven safety in Pregnancy,

ESLICARBAZEPINE ACETATE
• Blockade of voltage gated sodium channels resulting in stabilization of hyper-
excitable neuronal membranes.
• Indications –
• Adjunctive therapy for partial seizures.
• Dosage:
• Enzyme inducing AEDs reduce serum Eslicarbazepine levels. Eslicarbazepine
acetate decreases the levels of OCPs.
• Dizziness , blurred vision, headache, nausea, diplopia, nausea, vomiting, visual
disturbances
• Main advantage is usually well tolerated, once daily
dosing
• Main disadvantage is limited clinical experience,
efficacy spectrum probably restricted to partial
epilepsies.

RETIGABINE
• Activation of voltage gated neuronal Potassium channels [KCNQ (kv7)], resulting
in enhanced M-current, and thereby stabilization of resting membrane
potential.
• Indications –
• Adjunctive therapy for refractory partial-onset seizure.
• Dosage:
• Retigabine increases Lamotrigine levels by about 20%.
• Enzyme inducing AEDs reduce serum Lacosamide levels by approx 30 %.
• Dizziness , somnolence, fatigue, confusion, dysarthria, confusion, tremor,
urinary hesitancy/retention.
• Main advantage is clearly defined dose related efficacy, low
interaction potential.
• Main disadvantage is need for gradual titration and for frequent
dosing, CNS adverse effects

Perampanel
• A highly selective, non competitive AMPA (a-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid) receptor antagonist.
• The mechanism of action
• Reduces neuronal hyperexcitability by targeting glutamate activity at postsynaptic AMPA
receptors.
• Approved as an adjunct therapy for focal-onset seizures and primary generalized
tonic-clonic seizures (GTCS) in patients aged 12 years and older
• Once-daily dosing and has a half-life of 106 hours.
• Common adverse events are dizziness, fatigue, headache and somnolence.
Specific adverse effects to monitor are neuropsychiatric events, including
aggression, anger, homicidal ideation, hostility, and irritability

Cannabidiol (CBD)
• Reduces neuronal hyperexcitability through a unique multimodal mechanism of action.
• It antagonizes G protein-coupled receptor 55 (GPR55) at excitatory synapses.
• The inhibition of intracellular calcium release decreases excitatory currents and
seizure activity.
• CBD desensitizes transient receptor potential vanilloid type 1 (TRPV1) channels The
resultant decrease in extracellular calcium influx decreases neurotransmission.
• CBD inhibits equilibrative nucleoside transporters (ENT1), reducing adenosine
reuptake. The increase in extracellular adenosine reduces hyper excitability and
neurotransmission.
• NICE guidelines published in December 2019 states that cannabidiol with clobazam is
recommended as an option for treating seizures associated with Dravet syndrome and
LGS in patients aged 2 years and older,

Ketogenic Diet and Atkin’s diet
• The ketogenic diet (KD) is a stringently controlled high fat and low
protein/carbohydrate diet given with/without a restricted fluid
intake to maintain ketosis on a long term basis.
• It has been shown that it is more efficacious than newer AEDs in
controlling refractory seizures
• A ‘ketogenic’ ratio of at least 3:1 is usually needed for maintenance
of a good state of ketosis and optimal seizure control

Surgical Remedies
Hemispheric epilepsies
Developmental tumors, cortical dysplasias, AVMs
Mesial temporal lobe epilepsy caused often by hippocampal sclerosis
Drop attacks with injuries respond well to corpus callosotomy

Epilepsy in Children.pptx

Epilepsy in Children.pptx

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