EPILEPSI

Berasal dari kata Epilambanein = serangan

Etiologi
1. Primer ( idiopatic ) = # penyebabnya
- Ggn imbangan cairan / zat kimia dlm sel saraf
2. Sekunder ( ada kel struktur jar otak )
- dpt sejak lahir, kerusakan saat/setelah lahir
Penyebab

epilepsi

spesifik

1. saat dlm kandung (obatan,infeksi, alkohol,radiasi)

2. Saat kelahiran ( hipoksia,Forcep,facum )
3. Cedera kepala 4. Tumor ( tidak umum )
5. Penyumbatan pembuluh darah otak )
6. Radang / infeksi ( mengitis,encfalitis )
7. Peny.turunan
( FKU,Tuberosklerosis,neurofibromatois )

Faktor
pencetus
Kurang tidur ( Mgg sel otak )
Sres emosional
Infeksi ( demam )
Obat-obatan (TAD,Setadin,fenotiasin )
Alkohol ( menghilangkan GABA )
Perubahan hormonal (Estrogen )
Terlalu lelah ( Co2 )
Foto sensitif ( flas ligh,TV, Bising )

Mekanisme dasar
serangan epilepsi
Lepas muatan listrik neuron otak yg berlebihan
1. Ggn fs neuron dan transmisi sinaps
2. Potensial membran sel
Ion
Ektra sel Intra sel
K
rendah
tinggi
Na,Ca,Cl Tinggi Rendah

Keadaan Polarisasi ( normal )

diatur oleh
Sodium pump

Depolarisasi
K
Na
Ca
Cl

K
tinggi
Na
rendah
Ca
rendah
Cl
rendah

Polarisasi
Na

Na

Ca

Ca
Cl

Klasifikasi serangan epilepsi

I. Serangan parsial ( fokal,lokal ) kesadaran tdk berubah
A. Serangan parsial sederhana ( kesadaran tetap baik
1. dgn gej motorik
2. dgn gej somatosensorik atau sensorik khusus
3. dgn gej. Autonom
4. dgn gej psikis.
B. Serangan parsial kompleks( kesadaran menurun )
1. Awalnya parsial sederhana berkemb jadi penrn kesadaran
a. tanpa gambaran lainnya
b. dgn gambaran seperti A 1-4
c. dgn automatismus
2. dengan penurunan kesadaran sejak awitan
a. tanpa gambaran lainnya
b. dgn gambaran seperti A 1-4
c. dgn automatismus
II. Serangan umum ( konvulsi atau non konvulsi )
A. Absence C Absence tak khas
B. Mioklonik D. Klonik
E. Tonik F. Tonik-klonik G. Atonik
III. Serangan epilepsi tak terklasifikasikan ( rith mata,mengunyah, gerk berenang

Pathophysiology of Seizure
Cellular level
Sodium channels
Calcium channels
Potassium channels

Synaptic level
Glutamate
(excitatory)
GABA
(inhibitory)

Pathophysiology of Seizure

EpilepsyBasic
Neurophysiology
Causes of Hyperexcitability:
excitatory post synaptic
potentials (EPSPs)
inhibitory post synaptic
potentials (IPSPs)
changes in voltage gated ion
channels
alteration of local ion
concentrations

B-Slide 8

EpilepsyBasic
Neurophysiology

Major Neurotransmitters in the brain:

Glutamate
GABA
Acetylcholine
Dopamine
Serotonin
Histamine
Other modulators: neuropeptides,
hormones
B-Slide 9

Cellular Mechanisms of
Seizure Generation
Excitation (too much)
Ionicinward Na+, Ca++ currents
Neurotransmitterglutamate,
aspartate
Inhibition (too little)
Ionicinward CI-, outward K+
currents
NeurotransmitterGABA
B-Slide 10

Vezzani A,2005
annamaritagelgelsinardjaepilepsipalembang08

11

Abbas K,2007
annamaritagelgelsinardjaepilepsipalembang08

12

EpilepsyGlutamate
The brains major excitatory
neurotransmitter

Two groups of glutamate receptors

Ionotropicfast synaptic transmission
Three subtypes AMPA, kainate, NMDA
Glutamate-gated cation channels

Metabotropicslow synaptic
transmission
G-protein coupled, regulation of second
messengers (cAMP and phospholipase C)
Modulation of synaptic activity

B-Slide 14

EpilepsyGlutamate
Modulation of glutamate
receptors

Glycine, polyamine sites, Zinc,

redox site

EpilepsyGlutamate

Diagram of the
various glutamate
receptor
subtypes and
locations
From Takumi et al, 1998

B-Slide 16

EpilepsyGABA

Major inhibitory neurotransmitter

in the CNS
Two types of receptors
GABAApost-synaptic, specific
recognition sites, linked to CI- channel
GABAB presynaptic autoreceptors
that reduce transmitter release by
decreasing calcium influx,
postsynaptic coupled to G-proteins to
increase K+ current

B-Slide 17

CORTICAL STRUCTURE OF PARTICULAR

IMPORTANCE IN GENERATION OF
EPILEPTIC SYNDROMES
HUMAN CEREBRAL CORTEX HAS 3-6 CELL
LAYERS
HIPPOCAMPUS PART OF ARCHIPALLIUM 3
CELL LAYERS: DENTATE GYRUS,
SUBICULUM ,AMMON HORN
PRINCIPAL NEURONEXCITATORY ON POST
SYNAPTIC, PROJECTION TO DISTANT AREAS
INTERNEURON :INHIBITORY, LOCAL
CIRCUITRY TO PRINCIPAL OR OTHER
INTERNEURON

EpilepsyGABA
GABA site
Barbiturate site

Benzodiazepine
site
Steroid site
Picrotoxin site

Diagram of the GABAA receptor

From Olsen and Sapp, 1995

B-Slide 19

Pathophysiology of Seizure
Cellular level
Sodium channels
Calcium channels
Potassium channels

Synaptic level
Glutamate
(excitatory)
GABA
(inhibitory)

Pathophysiology of Seizure

Normal CNS Function

Excitation

Inhibition

glutamate,
aspartate

GABA
Modified from White, 2001
B-Slide 22

Classification of AEDs
1.
2.
3.
4.

Na+ channel blockers

GABAergics
Ca++ channel blockers
EAA inhibition

MECHANISMS OF ACTION

Pharmacology & Therapeutics 113 (2007) 165183

Hippocampal Anatomy

B-Slide 25

From Chang and Lowenstein, 2003

Underlying
Seizures and Epilepsy
Feedback and
feed-forward
inhibition,
illustrated via
cartoon and
schematic of
simplified
hippocampal
circuit
B-Slide 26
Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed.
Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.

Neuronal (Intrinsic) Factors

Modifying Neuronal
Excitability
Ion channel type, number, and distribution
Post-translational modification of channels
(phosphorylation, etc).
Activation of second-messenger systems
that affect channel function (e.g. G proteins)
Modulation of gene expression of ion
channels
B-Slide 27

Epilepsy and
Channelopathies
Inherited
Voltage-gated ion channel mutations
Ligand-gated ion channel
(neurotransmitter receptor) mutations
Different mutations in the same gene can
result in radically different types of
seizures and epilepsy

Acquired
Auto-immune (anti-potassium channel
antibodies)
Changes in channel expression after B-Slide 28
seizures

Ion Channel &

Neurotransmitter Receptors
Mutated in Epilepsy Voltage-gated Potassium Channel
Mutations
KCNQ2, KCNQ3

Benign Familial Neonatal Convulsions

(BFNC)
KCND2

Temporal Lobe Epilepsy (TLE)

KCNMA1

Generalized Epilepsy with Paroxysmal

Dyskinesia (GEPD)
B-Slide 29

Modifying Neuronal
Excitability
Alterations in expression of
transmitter gated ionotropic channels
Post-translational changes in
neurotransmitter channels
Remodeling of synapse location or
configuration (deafferentation,
sprouting)
Changes in gap-junction synaptic
function
B-Slide 30

Non-synaptic (Extrinsic)
Factors Modifying Neuronal
Excitability
Changes in extracellular ion
concentration
Changes in extracellular space
Modulation of transmitter
metabolism or uptake by glial
cells

B-Slide 31

Timm Stain Showing

Mossy Fiber Sprouting
Timm stain
(black) for
mossy fiber
terminals
containing zinc

Normal Rat Dentate Gyrus

Epileptic Rat Dentate Gyrus

Epileptic Human
Dentate Gyrus

Cavazos and Cross, 2006

B-Slide 32

SIMPULAN

PENGGUNAAN OBAT ANTI EPILEPSI

Epileptic seizures

Partial
clonic

Absences

General
Myoclonic

Infn spasm

Lennox
gastaut

Bilateral tonic-

juv. myoclonic

Sod valproat ACTH

Sod valproat Sod valproat
Carbamazepin
Clonazepam Vigabatrin lamotrigin
luminal
dilantin
Ethosuksimid
clonazepam Sod Valproat
luminal
Vigabatrin
Lamotrigin
Gabapentin

Epilepsi jenis umum

1.

Infantile spasme
- 6 -12 bulan
- obat yang sangat efektif ACTH 20 50 IU Im sekali
sehari
- hasil terlihat sesudah 2-3 minggu kemudian
- Jika ACTH gagal Coba Prednisolon 1 - 2 mg / kg /
hari oral
( 4 minggu)
- Jika masih gagal ( clonazepam,Nitrazepam,Sod
Valproat,
vigabatrine)

2.

Lennox Gastaut ( Myoclonic epilepsi )

- 1,5 3 tahun
- Asam Valproat, Clonazepam,Lamotrigin
- Biasanya umur 5 15 tahun
- Ethosuximide, clonazepam, sodium valproate

3. Absensi epilepsi anak dan bayi

- Biasanya umur 5 15 tahun
- Ethosuximide, clonazepam, sodium
valproate
4. Epilepsi myoclonic juvenilis.
- Remaja dan dewasa muda
- kejang otot pagi hari hari, serangan 2
jam setelahjalan
- sangat responsif dengan carbamsepin
- Vodium valproat, Clonazepam,
Luminal, Primidon

5.

Tonic clonic ( epilepsi umum )

- Ditemukan pada semua umur umumya18
tahun
- obat efektif :Carbamasepin, phenitoin, Asam
valproat