Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Definition

Epilepsy:
A condition characterized by recurrent
discharge of brain caused by intermittent
electrical charges off abnormal and excessive
on neurons in paroxismal based on the
various etiologies

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Definition

Epileptic seizure:
Clinical manifestations of seizures which
excessive and abnormal, sudden, temporary,
with or without change in consciousness,
because the electricity group hiperactivity of
the nerve cells in the brain is not due to acute
brain disease (unprovoked)

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Definition
Seizure:
Clinical manifestation of abnormal excitation
and the excess of cortical neurons
Epileptogenesis:
Series of events that alter the normal
neuronal network into hiperexcitable network
Epileptic Sindrome :
Groups of symptoms and signs that describe
specific epileptic condition
ILAE Report on Classification and Terminology, 2003
Etiologies

Idiopathic:
cause ?, fx genetic >>

Criptogenic:
considered simptomatic, cause?
( Sindr west, Lennox Gestaut )

Symptomatic:
CNS lesion (+)
ex: trauma, inf, congenital, toxic, metab, SOP,CV

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Etiologies epileptic seizures
(simptomatik)
1. Metabolic: Congenital
Acquired : hypoglicemia
hyperglicemia
hypoxia
hypocalcemia
hcpercalcemia
uremia
intoxication
2. Struktural : gliotic scar
congenital malformation
tumor vascular malformation
3. Infeksi : meningitis, encephalitis,
meningoencephalitis,
abses cerebri, lues,SLE
Pathofhysiologic defect

Stafstrom C, 1998
Penyebab sesuai umur

Kim BG, 2000, Interdisciplinary Neuroscience, Epilep

Faktor Pencetus Bangkitan

o Sleep deprivation
o Emotional stress
o Physical fatigue
o Infection
o Fever
o Alcohol
o Light stimulation
o Certain medications
o Hormonal Changes
o Sound stimulus
Patofisiologi

Epileptic seizures
Paroxysmal hypersynchronous transient
electrical discharges in the brain that
result from too much excitation or too little
inhibition in the area in which the
abnormal discharge starts
Patofisiologi
Exitation > Inhibition

Seizure attack = abnormal neuron

prolonged depolarization with regard to action
potential spark quickly and repeatedly

Electric spark abnormal => surrounding

neurons => electrical storm activity in the
brain
Patofisiologi

Stafstrom C, 1998
Patofisiologi

Stafstrom C, 1998
Patofisiologi

Stafstrom C, 1998
Basic Mechanisms Underlying seizures
and Epilepsy

Excitation (too much)

Ionic - inward Na, Ca currents.
Neurotransmitter - glutamate, aspartate

Inhibition (too little)

Ionic - inward Cl-, outward K+ currents.
Neurotransmitter - GABA
Neuronal Excitation
Action Potential
 Mekanisme bangkitan

Aktivasi sistem inhibisi Normal

Blokade Ca+
Peningkatan adenosin Epileptogenesis
Pemulihan
EPSP
IPSP
Potensiasi EPSP Ca
Hambatan IPSP
Ca dan inhibisi K+
PDS : spike/ sharp waves

Ictal Browne dan Holmes, 2000 Inter ictal

Glutamate

The brains major excitatory neurotransmitter

Two groups of glutamate receptors:
-Ionotropic fast synaptic transmission
-NMDA, AMPA, Kainate
-Gated Ca++ channels
-Metabotropic slow synaptic transmission
-Quisqualate
-Regulation of second messengers (cAMP & inositol)
-Modulation of synaptic activity
Modulation of glutamate
-Glycine, polyamine sites, zinc, redox site
GABA

Major inhibitory neurotransmitter in the CNS

GABA / benzodiazepine complex

- Linked to Cl- channel

Two types of receptors

-GABAA postsynaptic, specific recognition
sites
-GABAB presynaptic autoreceptors
Basic Mechanisms Seizures and Epilepsy

Ionic channel
Na+, Ca++, K+, Cl-

Lignad-gated Channel
excitatory - Glutamate
inhibitory - GABA

Excitatory postsynaptic potential

Inhibitory postsynaptic potential
Action potential
Excessive discharge
Klasifikasi Bangkitan Epilepsi
motorik
Sederhana Sederhana
diikuti disertai sensorik
penkes penkes
otonom

psikis
Sederhana
Kompleks

Sederhana tonik klonik

Menjadi kompleks tonik klonik
Parsial umum
sekunder Sederhana kompleks
tonik klonik
Klasifikasi Bangkitan Epilepsi

Lena/absence

Mioklonik

Tonik
Umum
Klonik

Tonik klonik

Atonik
 Klasifikasi Bangkitan Epilepsi
I. Partial (focal, local) seizures
A. Simple partial seizures (consciousness not impaired)
1. With motor sign
2. With sensory symptoms
3. With autonomic symptoms or signs
4. With psychic symptoms
B. Complex partial seizures (temporal lobe or psychomotor seizures; consciousness impaired)
1. Simple partial onset, followed by impairment
a. With simple partial features (A.1-A.4), followed by impaired consciousness
b. With automatisms
2. With impairment of consciousness at onset
a. With impairment of consciousness only
b. With automatisms
C. Partial seizures evolving to secondarily generalized seizures (tonic-clonic, tonic or clonic)
1. Simple partial seizures (A) evolving to generalized seizures
2. Complex partial seizures (B) evolving to generalized seizured
3. Simple partial seizures evolving to complex partial seizures, evolving to generalized seizures
II. Generalized seizures (convulsive or nonconvulsive)
A. Absence (petit mal) seizures
B. Myoclonic seizures
C. Tonic seizures
D. Atonic seizures
E. Clonic seizures
F. Tonic-clonic (grand mal) seizures
III. Unclassified epileptic seizures (caused by incomplete data)

International Classification of Epileptic Seizures

Klasifikasi Sindrom Epilepsi
1. Localization-related
Idiopathic (primary):

-Benign childhood epilepsy with centro-temporal spike

-Childhood epilepsy with occipital paroxysms
-Primary reading epilepsy
Symptomatic (secondary)
-Temporal lobe epilepsy
-Frontal lobe epilepsy
-Parietal lobe epilepsy
-Occipital lobe epilepsy
-Chronic progressive epilepsi partial continue of childhood
-Syndr characterized by seizures with specific
modes of precipitation

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Klasifikasi Sindrom Epilepsi2
2. Generalized, aged related
Idiopathic:
- Benign neonatal familial convulsions
- Benign neonatal convulsions
- Benign myoclonic epilepsy in infancy
- Childhood absence epilepsy (pyknolepsy)
- Juvenile absence epilepsy
- Juvenile myoclonic epilepsy
- Epilepsies with grand mal seizures on
awakening
- Other idiopathic generalized epilepsies
- Epilepsies with seizures precipitated by
specific modes of activation

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

 Generalized, aged related.cont
Cryptogenic or symptomatic:
-West syndrome
-Lennox-Gastaut syndrome
-Epilepsy with myoclonic-astatic seizures
-Epilepsy with myoclonic seizures

Nonspecific etiology:
-Early myoclonic encephalopathy
-Early infantile epileptic encephalopathy with
suppression bursts
-Other symptomatic generalized epilepsies

Specific syndromes:
-Epileptic seizures may complicate many disease
states

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Klasifikasi Sindrom Epilepsi3

3. Undetermined epilepsy
- With both generalized and focal seizures
- Neonatal seizures
- Severe myoclonic epilepsy in infancy
- Epilepsy with continuous spike-waves during
slow wave
sleep
- Acquired epileptic aphasia (Landau-Keffner
syndrome)
- Other undetermined epilepsies
- Without unequivocal generalized or focal
features

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Klasifikasi Sindrom Epilepsi4

4. Situation-related seizures
- Febrile convulsions
- Isolated seizure or isolated status epilepticus
- Seizures occuring only when there is an acute
or toxic
event due to factors such as alcohol, drugs,
eclampsia,
nonketotic hyperglycemia

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Parsial n general

The pathways
for seizure propagation
in partial seizures
and primary generalized
seizures (Lothman 1993)
Parsial n general

Stafstrom C, 1998
 Absence/Lena

sudden conciusness dysfunction

Silence without reaction
Maybe there automatisme
The eye can see far ahead
EEG spike wave 3 cycles per second

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Tonik Klonik

Preceded scream, jolt, mioklonik

Loss of consciousness
Stiff (Tonic) 30dtk 10 (clonic) 30-60s
Limp after the seizures and looked confused
Sleep after awakening

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Simple Partial

Alteration of consciousness (-)

seizures began-hand, feet and face
(unilateral / focal) spread on the same side
Head may turn toward the body that
experienced seizures

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Complex Partial

seizures focal + GGN awareness

Automatism which followed stereotipik
(chewing, swallowing, laughing)
Head may turn toward the body that
experienced seizures

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

seizure threshold

def boundary stimuli level (stimulus) that

allows the brain seizures or not
inherited
Young age (<5 years) generally have a
threshold lower attack
Fever seizures threshold
Karakteristik Bangkitan
Epilepsi
DRUGS THAT MAY INDUCES SEIZURES

1. ANTIBIOTIC: peniciline, Izoniazid, Cycloserine

2. HYPOGLYCAEMIA drugs: Insulin, Phenformin
3. HORMONAL/ METABOLIC drugs:
Prednisone, Oral contraceptives, Oxytoxin
4. CARDIAC DYSRHYTHMIC agents: Lidocain,
Procainamide, Dysopyramide

5. ANTIDEPRESANT/ ANTIPSYCHOTIC:
Phenothiazines, Tricyclik antidepresant, Anticholinergic drugs,
Lithium, Clozapine
6. STIMULANTS: Aminophylline, Doxapram, Theophyline,
Amphetamine
7. ANESTHETICS: Methohexital, Ketamine, Halothane,
Propofol, Althesin
8. WITHDRAWL SEIZURES: Alcohol, Benzodiazepin,
Barbiturat
9. OTHER ANTIEPILEPTIC drugs: Amphetamin, Opiates
10. RADIOGRAPHIC CONTRAST: Meglumin derivats, Metrizamide
11. ANTIMALARIA drugs: Mefloquine, Chloroquine, Praguanil
12. ANTISPASTIC drug: Baclofen
Epilepsy and Non Epilepsy Event

Feature Non-epileptic seizure Epileptic seizure

Bizarre motor behavior common rare

Duration > 2 minutes common rare
Frequency > 1/day common rare
Crying during event common rare
Psychiatric disease common rare
When others present common rare
Onset only while awake common rare
Seizure induction common rare
Responds during episode common rare
Syncope vs Seizure

Clinical Finding Seizure Syncope

Injury Common Rare

Urinary Incontinence Common Rare
Confusion Common Rare
Headache Common Rare
Focal Neuro deficit Occasionally Rare
Posture Any Stand
Skin color Pale Pale
Premonition Aura Occ
Prolactin Increased Never
EEG Common Rare
EKG Rare Common
Syncope

Suddenly lost consciousness due to lack of

blood flow to the brain
Ec. Hypotension, asistole, refx sympathetic
failure, arrhythmias
Diagnosis
Bangkitan

Bangkitan epilepsi ?

Jenis bangkitan

Sindrom epilepsi Gejala dan tanda klinik

dalam bentuk bangkitan berulang
( minimum 2 kali )

Cari etiologi Gambaran epileptikform EEG

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Anamnesis

Seizures Pattern / shape

Long seizures
Prev symptoms, during, post-seizures
Frequency
Trigger
Accompanying disease
Age at first seizures
Antenatal, perinatal, growth history
Previous history of epilepsy
Family history

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

EEG

Done after waking

Stimulation, hyperventilation triggers
Interiktal EEG epileptiform abnormalities in
adults 29-38%
When the EEG (N) suspect epy (+) re-
EEG after 24 - 48 hours after seizures

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Indikasi EEG

determinig dx
Determining prognosis
Consideration of termination AED
Determine the position of focus
If there are changes in the form of seizures
EEG wave
Beta:
- Many see the use of barbiturates pd
- Dominant in the frontal region
Delta:
- Normal all ages sleep skate
- Abnormal young adults wake skate
Theta:
- Physiology found pd neonates
- Often pd young adults and age> 50
 Beta activity: > 13 Hz

Alpha activity: 8-13 Hz

Theta activity: 4-7.5 Hz

Delta activity: < 4 Hz

1 second
Imaging indikasi

All the first seizures of the alleged existence

of structural abnormalities
Change of seizures
Focal neurological deficit
Epilepsy with seizures partial
Age> 25 years
Surgery preparation

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

MRI vs CT Scan

MRI sensitive and specific

MRI sclerosis hypocampus, disgenesis
cortical, tumor and cavernous
hemangioma

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Video EEG

Allows for correlation of EEG change with

behavior
Confirm diagnosis of epilepsy
Confirm seizure type
Choose correct medication
Make safe and rapid medication
adjustments
Assess for seizures in sleep
MRI
Magnetic Resonance Imaging
MEG
Magnetoencephalogram
PET
Positron Emission Tomography

Arrows point to abnormalities

 SPECT
Single Photon Emission Computed Tomography

Newton MR, et al. J Neurol Neurosurg Psychiatry. 1992;55:891-894.

Status Epileptikus

seizures
> 30 minutes
2 seizures or more where there is no
recovery of such awareness

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Manajemen Status Epileptikus

Stadium 2 Stadium 3

Stadium 1 Px Neurologis Etiologi

EKG Kejang(+)
Airway Px darah phenitoin
Breathing Dzpm 10 20 mg iv 15-18mg/kg iv
Circulation ( < 2-5 mg/mnt ) (kecp 50mg/mnt)
Koreksi Asidosis Vasopresor kp
( 0 10 menit ) 50cc Glukosa 50% Koreksi komplikasi

(1 -60 menit ) (0 90 menit )

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Manajemen Status Epileptikus
Stadium 4

Bila Kejang (+) selama 30 60mnt

ICU propofol 2mg/kg bolus iv

Atau
Thiopentone 100-250mg bolus iv dlm 20mnt
Bolus 50mg tiap 2 3 mnt
Tappering stlh bangkitan (-)

Pemberian rumatan

(30 90 menit )

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Febrile seizures
Seizures rise because of increases in body
temperature (rectal> 38C) because the
process extrakranium
6 months - 5 years
Seizures without fever and febrile seizures
again not included in febrile seizures
Seizure + fever in infants <1 month is not a
febrile seizures

Konsensus Penangan febrile seizures, IDAI, 2005

Febrile seizures classification

Simple seizures
Fever
Short, <15 min, a general tonic or with clonic,
with no movement or repeated focal in 24
hours

Konsensus Penangan febrile seizures, IDAI, 2005

Febrile seizures classification

Fever seizures Complex

With the characteristics of febrile seizures
(one below):
1. > 15 minutes
2. Focal or partial seizures 1 side, or seizures

generally preceded by partial seizures.

3. Recurring or more than 1 times in 24 hours

Konsensus Penangan febrile seizures, IDAI, 2005

Reccurent febrile seizures

Risk factors Recurrence febrile seizures:

1. family history
2. Age <15 months
3. Low temperatures during seizures
4. Rapid seizures after fever

(+4) 80%
(-) 10-15%
Most likely repeat the first year
Konsensus Penangan febrile seizures, IDAI, 2005
Tx febrile seizures

Antipiretik
- Acetaminofen 10 - 15mg/kg/x ( 4x/hr)
- Ibuprofen 5 - 10 mg/kg/x (3-4 x/hr)

Antikonvulsan
- Dzp oral 0,3mg/kg/8j (demam)
- Dzp rektal 0,5 - 0,75mg/kg (kejang)
AED Therapy

AED start provided:

- Dx epilepsy (+)
- Patients & families know 7an tx
- ESO
Monotx appropriate type and epilepsy
syndrome
Start low go slow
Drug of Choice
Drug of Choice
Action of AED

Stafstrom C, 1998
Action of AED

Stafstrom C, 1998
AED Mechanism
 AED dose < 6 th
Obat Dosis Awal Jumlah Kadar tx Jenis bangkitan
Mg/kg/hr dosis/hr tercapai
Fenobarbital 45 2 2 3 mgg Grand mal, SE

Karbamazepi 10 30 2-4 3 - 4 hari Parsial, tonik klonik

n
Etoksuksimid 15 20 3-4 7 10 hari absant

As Valproat 15 20 2-4 1 4 hari Mioklonik, absans,

tonik klonik
Fenitoin 57 4 7 10 hari Tonik klonik, parsial

Klonazepam 0,05 34

Clobazam 0,1 0,8 General, paarsial,

Lennox Gestaut
Adult AED dose
Obat Dosis awal Mg/hrRumatan Steady state
Mg/hr Hari

Carbamazepin 400 600 400 -1600 27

Phenytoin 200 300 200 -400 3 15

As valproat 500 1000 500 2500 24

Phenobarbital 50 100 50 -200

Clonazepam 1 4 2 10

Clobazam 10 10 -30 26

Oxcarbazepin 600 900 600 3000

Topiramate 100 100 400 25

Gabapentin 900 1800 900 3600 2

Lamotrigine 50 -100 20 - 200 2-6

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

 GUIDELINES FOR DOSES OF 1ST LINE AEDS IN
Adults (Brodie 1996, Browne 2001)

Drug Indication Starting Most Standard No of Target

Common maintenance plasma
dose Doses drug
Daily dose(range) / day concentr.
Dose mg/kg/day (range)
g/ml

CBZ Partial & GTCS 400 600 600-1200 2-3 4-12

PHT Partial & GTCS /SE 300 300 300-500 1 10-20
VPA Partial & GTCS 500-1000 1000 1000-3000 2 50-150
BAR Partial & GTCS 60-90 120 90-120 1 10-40
Neonatal seizure/SE
PMD Partial & GTCS 100-125 500 250-1500 3 5-12
ETX Generalized absense 500 1000 1000-2000 2 40-120
seizure
CNP Myoclonic epilepsi, L 1 4 2-8 1 or 2 none
Gestaut Syndrome
infantile spasm / SE
ESO OAE

No Obat Efek samping

1 Carbamazepin Diplopia, dizziness, mual, nyeri kepala,

mengantuk, ruam, anemia aplastik, Steven
johnson, teratogenik, hiponatremi
2 Phenitoin Nistagmus, ataxia, hipertrofi gusi, hirsutism,
ruam, teratogenik, Steven johnson

3 As Valproat Tremor, gemuk, alopesia, pankreatitis,

hepatotoksik

4 Phenobarbital Kelelahan, depresi, insomnia, hiperkinesia,

iritable, ruam

5 Clonazepam Kelelahan, sedasi, hiperkinesia, ruam

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

ESO OAE ..2

No Obat Efek samping

6 Gabapentin Somnolen, astenia, ataksia, dizziness, ggn

TGI

7 Lamotrigine Ruam, dizziness, tremor, ataksia, diplopia,

nyeri kepala

8 Clobazam Sedasi, dizziness, irritable, depresi

9 Oxcarbazepin Dizziness, ataksia, diplopia, nyeri kepala,

ruam, hiponatremi

10 Topiramate Ggn kognitif, dizziness, tremor, ataksia,

kelelahan, batu ginjal, ggn TGI

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

AED Discontinuation

Free seizures at least 2 years

Normal EEG
Gradually reduced doses, 25% of the original
dose, each month for 3 - 6 months
Starting from 2nd AED

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Relapse after AED discontinuation

The older age

Symptomatic epilepsy
EEG abnormal
Hard controlled seizures
AED> 1
Resurrection (+) after starting tx
Tx> 10yr

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Prenatal Development

1 to 1 Weeks: Implantation and Human

Chorionic Gonadotropin
(hCG)
2 to 4 Weeks : Germ Layers & Organ
Formation
3 to 4 Weeks : The Folding of the Embryo
5 Weeks : Cerebral Hemispheres
6 Weeks : Motion and Sensation
7 Weeks : Hiccups and Startle Response
8 Weeks : Brain Development
Prenatal Development
9 Weeks : Swallows, Sighs, and Stretches
10 Weeks : Rolls Eyes and Yawns,
Fingernails & Fingerprints
11 Weeks : Absorbs Glucose and Water
3 to 4 Months (12 to 16 Weeks)
: Taste Buds, Jaw Motion, Rooting
Reflex, Quickening
4 to 5 Months (16 to 20 Weeks)
: Stress Response, Vernix Caseosa,
Circadian Rhythms
Prenatal Development
5 to 6 Months (20 to 24 Weeks)
: Responds to Sound; Hair and Skin; Age of
Viability
6 to 7 Months (24 to 28 Weeks)
: Blink-Startle; Pupils Respond to Light; Smell
and Taste
7 to 8 Months (28 to 32 Weeks)
: Sound Discrimination, Behavioral States
8 to 9 Months (32 to 36 Weeks)
: Alveoli Formation, Firm Grasp, Taste
Preferences
9 Months to Birth (36 Weeks through Birth)
Perkembangan Janin 1-4 Bulan
Perkembangan Janin 5-9 Bulan
APGAR Score
APGAR scoring

7-10 Normal

4-6 mild asphyxia

3 moderate to severe
Tahap perkembangan (dalam bulan)

Telentang dari tengkurap 3 - 4

Tengkurap dari telentang 4 - 5,5
Duduk bertopang 5 -6
Duduk 6 - 6,5
Meragap 6 - 7,5
Berbaringlangsung duduk sendiri 7 -8
Merangkak 7 - 8,5
Berdiri (ditarik) 8 - 9
Rambatan 8,5 - 10
Jalan (maju) 9 - 13
Jalan (mundur) 14 - 15
Lari15 - 16
Sindroma Lennox Gestaut

Onset < 8 th, peak 3-5th

Laki male>>
Tonic seizures >>, bi / unilateral
Diffuse slow spike waves during wake, fast
rhythms during sleep 10/dtk
mental development and behavior
dysfunction

Buku Ajar Neurologi Anak, IDAI, 1999

Sindroma West
Spasm
Mental retardation or deterioration
Hipsaritmia
Onset < 1 yr, peak 3 -7 mth

Buku Ajar Neurologi Anak, IDAI, 1999

Hipsaritmia

Irregular mixture of slow wave high voltage

with a frequency 200uv exceed 1-7 per
second mixed with spike wave with a sharp
and amplitude, morphology, location and
speed varied
Epilepsi Refrakter

Reccurent seizures, although it has reached

levels AED therapy in the last 1 years after
onset.
AED control due to failure of the focus, not
because of improper dosage, medication
non-compliance, mistake or change delivery
formulations

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Epilepsi Refrakter evaluasi

Diagnosis is correct?
Obedient patient medications?
AED been appropriate?
disturbance of absorption in the
gastrointestinal tract?
interactions with other drugs?
structural abnormalities in the brain?
precipitation factor?
Epilepsi Refrakter ( manajemen )

Surgical Therapy
Vagus nerve stimulation
Behavior modification
Relaxation
Reduce AED dose

Pedoman Tatalaksana Epilepsi Pokdi Epilepsi Perdossi 2006

Metabolic encephalopathy

Mitochondria abnnormality
Paroksismal dis
Def selenium
Def glutation sintesis
Def glukose transpor
Def sulfat oksidase

Not routine available

Epidemiology

Incidensy 20 70 per 100.000 per year

Prevalensy 4 10 per 1000 populasi
male > female

Passat J, 1999
Genetik fact

Prevalence at monozygotic twins 70,2%

Prevalence at byzygotic twins 5,6%

Lumbantobing, 1999
Diff diagnose
Neonatus
- Jittering
- Apneic spell
children
- Sincope
- Migrain
- convertion
- Night terror
- Tics
- Hipercyanotic attack ( ToF )
Diff diagnosis

Adult
- Sincope
- Vertigo
- Transient global amnesia
- Panik psikogenik
- Sindr menier
- Tics
Mimicking seizures
Benign paroxysmal vertigo
Night terrors
Breath-holding spells
Syncope
Paroxysmal kinesigenic Choreoathetosis
Shuddering attacks
Benign paroxysmal torticollis of infancy
Hereditary chin trembling
Narcolepsy
Rage attacks
Pseudo seizures
Masturbation
 Jitteriness Versus Seizure
CLINICAL FEATURE JITTERINESS SEIZURE

Abnormality of gaze or eye O +

movement
Movements exquisitely stimulus + O
sensitive
Predominant movement Tremor Clonic jerking

Movements cease with passive + O

flexion
Autonomic changes O +
------------------------------------------------------------------------------------------------------------------
Inborn Errors of Metabolism Associated With
Neonatal Seizures

Conditions That Have a Specific Treatment

Pyridoxine (B6) dependency
Folinic acid-responsive seizures
Glucose transporter defect
Creatine deficiency
Other Conditions
Nonketotic hyperglycinemia
Sulfite oxidase deficiency
Molybdenum cofactor deficiency (combined deficiency)
Carbohydrate-deficient glycoprotein disorder
Lactic acid disorders
Mitochondrial disorders
Maple syrup urine disease
Isovaleric acidemia (sweaty feet, cheesy odor)

NeoReviews vol.5 no.6 June 2004

Inborn Errors of Metabolism Associated
With Neonatal Seizures
Other conditions

Isovaleric acidemia (sweaty feet, cheesy odor)

3-methylcrotonyl-CoA carbosylase deficiency
Propionic acidemia
Mevalonic aciduria
Urea cycle defects
Hyperornithemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome
Neonatal glutaric aciduria type ll
Biotin deficiencies, holocarboxylase synthetase deficiency
Fructose 1,6-diphosphatase deficiency
Hereditary Fructose intolerance
Menkes disease (trichopoliodystrophy
Peroxisomal disorders

NeoReviews vol.5 no.6 June 2004

Laboratory Studies to Evaluate
Neonatal Seizures
Indicated

Complete blood count, differential, platelet count; urinalysis

Blood glucose (Dextrostix), BUN, Ca, P, Mg, electrolytes
Blood oxygen and acid-base analysis
Blood, CSF and other bacterial cultures
CSF analysis
EEG

NeoReviews vol.5 no.6 June 2004

Laboratory Studies to Evaluate
Neonatal Seizures
Clinical Suspicion of Specific Disease

Serum immunoglobulins, TORCH antibody titers, and viral

cultures
Blood and urine metabolic studies (bilirubin,ammonia, lactate,
FECl, reducing substance.)
Blood and urine toxic screen
Blood and urine amino and organic acid screen
CT or ultrasound scan

NeoReviews vol.5 no.6 June 2004

 Metabolic Evaluation for Refractory
Neonatal Seizures
Consider individually by case specifics
Serum
Glucose
Electrolytes (sodium, potassium, chloride, carbon dioxide), blood urea
nitrogen, chromium, calcium, phosphorus, magnesium
Uric acid
Creative kinase
Serum ammonia
Lactic and pyruvic acids
Biotinidase
Amino acids
Serum carnitine, acylcarnitines
Serum transferrin
Copper and ceruloplasmin
Cholesterol
Fatty acids (short-chain, medium-chain, long-chain)
Pipecolic acid

NeoReviews vol.5 no.6 June 2004

 Metabolic Evaluation for Refractory
Neonatal Seizures
Urine
Organic acids
Acylglycines
Uric acid
Sulfites
Xanthine, hypoxanthine
Guanidinoacetate
Pipecolic acid
Cerebrospinal Fluid
Cell count, glucose,protein
Lactic and pyruvic acids
Amino acids
Organic acids
Neurotransmitters
Other Studies
Skin biopsy
Muscle biopsy
Magnetic resonance imaging with magnetic resonance spectroscopy
(especially for creatine)

NeoReviews vol.5 no.6 June 2004

Leukodystrophy

Inborn error metabolism

Causing disruption of myelin development
Infants and children>>, but has adults
manisfestation
Sex linked
Adrenal insuf, myelin deffect
Type:
- Metachromatic
- Globoid cell
- Adenomyeloneuropathy / adenoleukodystrophy
> swap
Craniosynostosis

Closing early 1/more sutura

Interfere with bone growth and brain
Type
- Sagittal synostosis - coronal synostosis
Neurocutaneus Syndr

= Phakomatoses / Phakos Greek birthmark

Hereditary
Multiorgan malformation and tumours
Tipe
- Neurofibromatosis overgrowth endo &
mesodermal

- Tuberous Sclerosis Sebasea adenoma

- Sturge Weber Syndr Facial angioma
- Hippel Lindau disease cerebelum
hemangiblastoma
Tuberous Sclerosis
Neurofibromatosis

Sturge Weber Syndr

Hypoxic encephalopathy

Etiologi
arterial oxygen pressure lung dis

transport O2 anemia / blood loss

blood flow fs heart

Biomechanic Block in brain toxin

 Depolarization spreads through intrahemispheric tracts to
contralateral corex, basal ganglia, thalamus, brain stem

Spread Inhibitory neuron in Increased CBF,

depolarization coretex, ant. Thalamus, O2, glucosa
through spinal ganglia basalis begin to
cord inhibit cortical excitation

TONIC CLONIC STATUS

EPILEPTICUS
Neuron resets to normal resting state
DEATH
 Pendahuluan Absence/Lena
Tonik Klonik
Critical Appraisal Parsial sederhana
Parsial kompleks
Definisi
Ambang
Etiologi Epilepsi drug induced
Epilepsy and Non Epilepsy
Pathofhysiologic defe Syncope vs Seizure
ct Diagnosis
Penyebab sesuai umu EEG
Imaging
r Status Epileptikus
Fx Pencetus febrile seizures
Tx febrile seizures
Patofisiologi Terapi OAE
Glutamate Drug of Choice
Action of AED
GABA Dosis OAE
ESO OAE
Klasifikasi Bangkitan
Penghentian OAE
Epilepsi
Parsial n general
 Kekambuhan
Surgical
VNS
Prenatal Development
APGAR
Tahap perkembangan
Lennox Gestaut
Sindroma West
Epilepsi Refrakter
Epidemiologi
Genetik fact
Dx Banding
Jitter vs Seizure
Error metab