Epilepsi (Yunani) yang berarti :

To sieze upon or taken hold of

Di Indonesia disebut : sakit ayan,
yang di daerah pedejjsaan masih
banyak dianggap berasal dari ilmu
hitam
Prevalensi epilepsi sekitar 1% 1% dari
200 juta 2,2 juta penderita epilepsi di
Indonesia.
Menurut WHO, 2-5% penduduk dunia
pernah mengalami kejang.
Tan CT (Malaysia) di Malaysia 68%
mengalami treatment gap di Indonesia
akan >>
Epilepsy treatment gap maybe defined as
the percentage of person with active
epilepsy who any time are not receiving
treatment
Epilepsi terdpt pd semua bangsa, laki
sedikit lebih banyak dari wanita.
30% mendpt serangan I pd umur 4 th
50% mendpt serangan I pd umur 10 th
75% pd umur 20 th
15% mengalami setelah 25 th
2% mendpt serangan I pd umur 50 th keatas
& jumlah ini menanjak dgn bertambahnya
persentase penduduk lansia
Insiden epilepsi pd anak I > anak
II > anak III.
Anehnya epilepsi lobus temporalis
sering ada riwayat kejang demam
dan ada masalah pada proses
kelahiran
The new era is beginning in the clinical
and basic investigations of the
epilepsies, and it is not seizure based.
These genetic and genomic approach
which should gradually unravel the
understanding about epilepsy.
Genetic and birth factors
1. Genetic influences (Idiopathic, essential,
cryptogenic)
2. Congenital abnormalities ( including
cromosomal abnormalities)
3. Antenatal factors (infections. drugs anoxia,
etc)
4. Perinatal factors: Birth trauma, asphyxia neo-
natorum. perinatal infections
5. Perinatal jaundice: Prematurity
Infectious disorders:
1. Meningitis: Purulent, tuberculous, viral,
parasitic fungal
2. Epidural and subdural abscess
3. Brain abscess and granuloma;
Metastatic. direct spread
4. Encephalitis: Viral
5. Other (including parasites)
6. Fever (febrile convulsions)
Toxic factor
1. Inorganic substances (eg, carbon monoxide)
2. Metallic substances (eg, lead. mercury)
3. Organic substances: Alcohol, other
4. Drugs
5. Allergic disorders; Ingestion of foreign
protein. vaccination or injection of foreign
protein
6. Pregnancy
7. Other; Uremia or other toxic medical
conditions
Circulatory disturbances:
1. Subarachnoid hemorrhage
2. Sinus thrombosis
3. Encephalomalacia due to thrombosis, embolism,
haemorrhage
4. Hypertensive encephalopathy
5. Arteriosclerosis and arterial occlusive disease,
intracranial and extracranial
6. Vasospasm(eg:migraine)
7. Syncope
8. Changes in blood (anemia, hemorrhagic
diathesis)
Trauma or physical agents:
1. Acute craniocerebral injuries
2. Subdural or epidural hematoma and
effusion
3. Posttraumatic meningocerebral
cicatrization
4. Anoxia or hyperoxia (including
drowning)
Metabolic and Nutritional
disturbances
1. Electrolyte and water imbalance: Sodium,
calcium, overhydration or dehydration, other.
2. Carbohydrate metabolism: Hypoglycemia,
diabetes mellitus, glycogen storage disease
3. Protein metabolism: Phenylketonuria,
porphyria, other
4. Fat metabolism: Lipid storage diseases, other
5. Vitamin deficiency: Pyridoxine deficiency,
other
6. Endocrine Disorders: Menstruation. Other
Neoplasms
I. Primary intracranial tumors
2. Metastatic tumors
3. Lymphoma and leukemia
4. Blood vessel tumors and vascular
malformations (eg. arteriovenous
malformation eg. Sturge Weber
syndrome)
Heredofamilial and degenerative
diseases
1. Multiple sclerosis
2. Tuberous sclerosis
3. Cerebellar degeneration with
convulsion
4. Other
Psychogenic causes
Cause unknown
Human Epilepsy Genes
Disorder

Location

Gene

Idiopathic generalized epilepsies
Juvenile myoclonic epilepsy (EJMI)
Benign neonatal epilepsy (EBN1)
Benign neonatal epilepsy (EBN2)


6p?
20q
8q


?
CHRNA4(possible)
?

Idopathic partial epilepsies
Partial epilepsy with auditory symptoms
Nocturnal frontal lobe epilepsy


10q
20q


?
mat be allelic to
EBN1

Single gene disorders with symptomatic epilepsy as a
major feature
Myoclonic epilepsy with ragged red fibres (MERRF)
Unverricht-Lunborg disease (EPM1)
Northern epilepsy syndrome (EPMR)
Ceroid lipofuscinosis, juvenile type (CLN3)


Mitochondrial
21q22.3
8p
16p


tRNA(Lys)
cystatin B
?
?

Sejarah Klasifikasi Epilepsi
Workshop on Basic Mechanism of the
Epilepsies (BME) pertama pada tahun 1969
di Colorado springs.
Sekitar tahun itu International League
Against Epilepsies (ILAE) membuat
klasifikasi.
Sejarah Klasifikasi Epilepsi
BME kedua dibawah Jasper : idiopathik dan
simptomatis dengan co-editor : genetics,
developmental anatomy, pathology,
neurochemistry, neuropharmacology di St.
Inez Mountains CA tahun 1983 mendahului
ILAE , menggunakan syndrome
classification
We present here the international
classification of epileptic syndro-
mes and related seizure disorders
which was adapted at the New Delhi
Congress of the International
League Against Epilepsies in Octo-
ber 1989 and which is published in
Epilepsia.

Sejarah Klasifikasi Epilepsi
The 3
rd
Workshop BME in San Diego
California USA 1996
Classification of epilepsies, epileptic
syndromes and related seizure disorders
1. Localization-related (focal, local, partial) epilepsies and
syndromes
1.1. Idiopathic (with age-related onset):
Benign childhood epilepsy with centro-temporal spikes
Childhood epilepsy with occipital paroxysms
Primary reading epilepsy
1.2. Symptomatic:
Chronic progressive epilepsia partialis continua of childhood
(Kojewnikow syndrome)
Seizures characterized by specific modes of precipitation
Other epilepsies and syndromes based on localization or
aetiology
1.3. Cryptogenic
Classification of epilepsies, epileptic
syndromes and related seizure disorders
2. Generalized epilepsies and syndromes
2.1. Idiopathic (with age-related onset -listed in order of age):
Benign neonatal familial convulsions
Benign neonatal convulsions
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy (pyknolepsy)
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Epilepsy with generalized tonic-clonic seizures on awakening
Other generalized idiopathic epilepsies not defined above
Epilepsies with seizures characterized by specific modes of
precipitation (e.g. photosensitive epilepsy)
Continued
Classification of epilepsies, epileptic
syndromes and related seizure disorders
2. Generalized epilepsies and syndromes
2.2. Cryptogenic and/or symptomatic (in order of age):
West syndrome (infantile spasms)
Lennox-Gastaut syndrome
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absences
2.3.1. Non-specific aetio!ogy:
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy with suppression-b
ursts
Other symptomatic generalized epilepsies not defined above
2.3.2. Specific syndromes
Classification of epilepsies, epileptic
syndromes and related seizure disorders
3. Epilepsies and syndromes undetermined whether focal or
generalized
3.1. With both generalized and focal seizures:
Neonatal seizures
Severe mvoclonic epilepsy in infancy
Epilepsy with continuous spike-waves during slow wave
sleep
Acquired epileptic aphasia (Landau-Kleffner syndrome)
Other undetermined epilepsies not defined above
3.2. Without unequivocal generalized or focal features.
Classification of epilepsies, epileptic
syndromes and related seizure disorders
4. Special syndromes
4. 1. Situation-related seizures:
Febrile convulsions
Seizures occurring only in the context of acute metabolic or
toxic events
4.2. Isolated seizures or isolated status epilepticus
Simptomatologi : Temporal Lobe Epilepsy
Simple atau complex partial dapat dengan
atau tidak secondary generalized
Anamnesis febrille convulsion
Hipermetabolisme uni atau bilateral
EEG spikes temporal lobe mulai anak atau
dewasa
continued
Simptomatologi : Temporal Lobe Epilepsy
Simple partial seizure dgn gx otonom atau
psikis
Sensorik olfatorik, epigastric sensation
Complex partial motorik berhenti disusul
oro-alimentary automatism
Sering post-ictal confusion
Continued
Simptomatologi : Temporal Lobe Epilepsy
EEG Interictal
Tdk ada kelainan
Ada sedikit/asimetri yg jelas & background
activity
Temporal spikes, sharp wave atau slow wave,
uni atau bilateral
Uni/bilateral background activity interruption.
Temporal multilobar low amplitude fast activity,
rhytmic spike atau rhytmic slow waves

Simptomatologi :Amygdalo hypocampal/
meso basal limbic/ rhinencephalitic
Rising epigastric discomfort, nausea, gang
otonom termasuk borborigmi, belching,
pucat, muka merah, pernafasan berhenti,
dilatasi pupil, rasa takut, panik, serta
olfactory / gustatory hallucination
EEG : inter-ictal dpt normal, uni/bilateral
sharp or slow waves, sinkron/asinkron
Simptomatologi : Lateral Temporal
Simple seizure dgn halusinasi & ilusi
pendengaran atau dreamy states, visual
perception, gang. Bahasa pd langguage
dominant hemisphere focus.
Menjadi kompleks bila ada penyebaran ke
mesial atau struktur extra-temporal.
EEG uni/bilateral midtemporal spikes
yg prominen di wilayah lateral
Simptomatologi :Frontal lobe epilepsy
Simple atau complex partial dpt secondary
generalized
Serangan dpt beberapa kali sehari, sering
waktu tidur
Sering menjadi status epilepticus
Simptomatologi :Frontal lobe epilepsy
Sering serangan singkat, complex partial
seizure & menimbulkan post-ictal confu-
sion.
Generalisasi terjadi cepat lebih sering
frontal dibanding temporal
Gx utama : motorik & postural, sering
dimulai dgn gestural automatism
continued
Simptomatologi :Frontal lobe epilepsy
EEG :
Normal
Kadang
2
background asimetry, frontal
spikes atau sharp waves
Sharp atau slow waves uni/bilateral
Kadang
2
kelainan EEG mendahului
serangan
Simptomatologi : Supplementary motor
Postural, focal tonic dgn vocalisation
Berhenti bicara dan fancy postures
Simptomatologi : Cingulate
Simple, lebih sering complex partial dgn
gestural automatism
Gx otonom disertai perubahan mood dan
emosi
Simptomatologi :Anterior fronto polar
Forced thinking, initial loss of contact
Gerakan adversive kepala & mata
Dpt berubah contra-versive dgn axial
clonic jerks serta gx otonom
EEG dpt normal, spikes, dan wave
disekitar frontal
Simptomatologi :Orbito frontal
Complex partial dgn dimulai motoric
gestural automatism
Olfatoric hallucinations & ilusi serta gx
otonom
Simptomatologi :Dorsolateral
Dapat tonik, jarang klonik dgn versive
head and eye movement dan bicara
berhenti (speech arrest)
Simptomatologi :Operculum
Mastication. Salivation, laringeal swal-
lowing, speech arrest, epigastic aura, rasa
takut, gx otonom
Simple partial dlm bentuk clonic facial
seizure unilateral.
Dapat berupa gangguan sensorik rasa tebal
di tangan dan gustatory hallucination
Simptomatologi :Motor cortex
1. Simple partial tergantung lokasi focus :
Prerolandic : speech arrest, vocalisation,
dysphasia, gerakan tonik muka kontralateral.
Dpt terjadi generalisasi.
Rolandic : partial motor mulai ext atas
kontralat (tdk ada penyebaran Rolandic a la
Jackson)

2. Sering timbul Todds paralysis

Simptomatologi :Kojecnikov Syndrome
Dikenal sebagai Rasmussen syndrome pd anak,
berasal dari mitochondrial encephalopathy dgn
lactic acidosis, dan kejadian spt stroke.
Menyerupai Rolandic partial epilepsy pd dewasa
dan anak oleh karena gangguan pd motor
cortex. Partial seizure sering dgn myoclonus.
EEG: normal background, focal paroxismal slow
wave atau spikes. Dpt timbul pd segala umur &
sering ada etiologinya (tumor/vascular)
Simptomatologi :Lobus Parietalis
Biasanya simple partial & secondary
generalized, dpt juga complex partial,
sensoris seperti semutan, rasa listrik dpt
menyebar a la Jackson.
Ada keinginan untuk merubah posisi
tubuh yg terkena. Sering dimulai pd
tangan dan muka ( proyeksi luas)
continued
Simptomatologi :Lobus Parietalis
Kadang ada perasaan sinking, chokes atau
nausea terutama bila focus di daerah
inferior.
Parietal lobe visual phenomene dpt timbul
sbg halusinasi dlm segala bentuk.
Metamorphopsia dgn distorsi, memendek
atau memanjang terutama bila yg terkena
sebelah non-dominant.
continued
Simptomatologi :Lobus Parietalis
Phenomena negatif seperti rasa tebal,
merasa bagian dari tubuh hilang
(asomatognosia) terutama pada non-
dominan.
Vertigo, disorientasi menunjukkan pd
lobus parietal inferior.
Aphasia sensorik pd dominant lobus.
Sensasi pd genital dpt timbul pd daerah
parasentral
Simptomatologi :Lobus Occipital
Dpt simple/complex partial generalized
Visual(tdk selalu)
Elementary dpt bersifat negatif : scotoma,
hemianopsia, amaurosis atau positif :
sparks, flashes, & phospheneen.
Macropsia, micropsia, perubahan jarak,
inklinasi, distorsi, metamorphopsia
continued
Simptomatologi :Lobus Occipital
Visual hallucination (biasanya complex,
pemandangan beraneka), distorsi atau
melihat dirinya sendiri(he-autoscopy).
Bila yg terkena temporo-parieto-occipital
dpt timbul tonik atau klonik kontraversion
dari mata dan kepala (oculoclonic atau
oculogyric deviation), palpebral jerks,
forced closed of the eyelids.

continued
Simptomatologi :Lobus Occipital
Serangan dpt menyebar ke lobus
temporalis.
Bila fokus primer di supra-calcarine area
dpt menyebar ke supra-sylvian convexity
atau bagian mesial, dan merupakan
epilepsi lobus parietal & frontalis.
Penyebaran ke lobus occipital
kontralateral dpt terjadi cepat.
Serangan dapat menjadi generalized
Patofisiologi
Normal neuronal transmission
menunjukkan propagation of action
potential.
Na
+
, K
+
, Ca
++
, Cl
-
channels in cell
membrane
Chemical transmission between neurons:
- Excitation : Glutamate, aspartate
- Inhibition : Glycine, opioids,
monoamines
Mechanism of epileptic seizure
Common properties of
synaptic neuron
Burst firing or Sustained
Repetitive Firing (SRF)
rapid Na
+
flow
Paroxysmal Depolarization
Shift (PDS) slower Ca
++

influx
After Hyperpolarization
(AHP) prolonged K
+
efflux and Cl
-
influx

SRF
RMP
PDS
AHP
+
0
-
Cara kerja obat epilepsi
neuron inhibisi (GABA-ergic
transmission)
GABA action pd GABA
A
receptor
rusaknya GABA di synaps
Memblok GABA re-uptake di presynaptic
terminal
Cara kerja obat epilepsi
neuron eksitasi (Glutaminergic
transmission)
lepasnya glutamate
Memblokir glutamate action/AMPA/kainate
receptor
Memblokir voltage gate Na
+
channel
Anti-epileptic drug mechanism
Different responses of AED
Variable AED efficacy in different seizure type
AED may act at the pre synaptic terminal/synaptic
cleft/post synaptic membrane.
AED may have anti & preconvulsant action
Not all AED actions are clinically significant
Not all AED actions are according to plasma/CSF
concentration
Sejarah AED
Bromide
1912 Phenobarbital
1938 Phenitoin
1954 Primidon
1960 Ethosuximide
1974 Carbamazepin
1975 Clonazepam
1978 Sodium valproate
Sejarah AED
1985 Clobazam
1994 Vigabatrin
1994 Lamotrigine
1994 Gabapentine
1997 Topiramate
1998 Tiagabine (gabatril)
2001 Levetiracetam, Zonisamide
None of the AED is specific and the offer
only symptomatic control or suppression
of seizure
Begin with one drug
Ideally convulsion disappear without side
effect

Alangkah baiknya untuk
menggunakan sedikit jenis obat
dengan pengetahuan dan
pengalaman yang luas daripada
menggunakan atau mencoba-coba
macam-macam obat tanpa banyak
mengenalnya
Kejang tonik klonik generalized
1. Valproate
2. Topiramate
3. Lamotrigine
4. Carbamazepin
5. Phenitoin
6. Phenobarbital
7. Clonazepam
Partial epilepsi tonik-klonik
1. Carbamazepin
2. Valproate
3. Topiramate
4. Lamotrigine
5. Phenitoin
6. Phenobarbital
7. Clonazepam
Absence untuk anak
1. Valproate
2. Ethosuximide
3. Lamotrigine
4. Valproate + Ethosuzimide
5. Topiramate
Absence pada juvenile
1. Valproate
2. Lamotrigine
3. Valproate + Lamotrigine
4. Valproate + Ethosuximide
5. Topiramate
Partial seizure (idiopathic)
1. Valproate
2. Carbamazepin
3. Lamotrigine
4. Topiramate
5. Clonazepam
6. Ethosuximide
Partial seizure
1. Carbamazepin
2. Topiramate
3. Lamotrigine
4. Valproate
5. Gabapentin
6. Clonazepam
7. Phenitoin
8. Phenobarbital
9. Vigabatrin
Myoclonic seizure(idiopathic)
no tonic
1. Valproate
2. Lamotrigine
3. Clonazepam
4. Ethosuximide
5. Topiramate
Myoclonic seizure(symptomatic)
with tonic
1. Valproate
2. Lamotrigine
3. Topiramate
4. Clonazepam
5. Gabapentin
6. Phenitoin
7. Phenobarbital
8. Vigabatrin
Infantile spasm
1. Pyridoxin
2. Vigabatrin
3. Clonazepam
4. Steroid, ACTH
5. Valproate
6. Topiramate
Status Epilepticus
Diagnosis dari jenis kejang & kausa
Penanganan hrs dilakukan secara
menyeluruh oleh ahli Saraf, internis,
cardiolog, dan kalau perlu anestesis.
Diazepam 1 ml=5mg, 1 amp=10mg
Rectal (Stesolid) 5 mg dan 10 mg
Dosis dewasa 10-20 mg, anak 0,25-0,5
mg/Kg, kecepatan tdk lebih dari 2-5 mg/mt
Phenytoin
15-18 mg/Kg iv infusion
Rate of infusion tdk boleh lebih dari 50
mg/mt (20 mg/mt untuk manula)
Pd anak-anak 20 mg/kg iv infusion
The drug should never be given
intramuscularly