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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 spesifik
1. epilepsi

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

Mekanisme dasar serangan epilepsi “ Lepas muatan listrik neuron otak yg berlebihan” 1. Ggn fs neuron

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

  • I N

K Cl C

b

k

di

Depolarisasi

Depolarisasi K Na Ca Cl K tinggi Na rendah Ca rendah Cl rendah Polarisasi Na Na

K

Na

Ca

Cl

K

tinggi

  • Na

  • rendah

  • Ca

  • rendah
    Cl rendah

Polarisasi

Na

  • Na

Ca

  • Ca
    Cl

  • 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 Cellular level – Sodium channels – Calcium channels – Potassium Synaptic level 

Pathophysiology of Seizure

Epilepsy—Basic

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 B-Slide 88

Epilepsy—Basic

Neurophysiology

Major Neurotransmitters in the brain:

Glutamate

GABA Acetylcholine Dopamine Serotonin Histamine

Other modulators: neuropeptides, hormones

B-Slide B-Slide 99

Cellular Mechanisms

Cellular

Mechanisms of

of

Cellular Mechanisms Cellular Mechanisms of of Seizure Generation Seizure Generation  Excitation (too much) – Ionic—inward

Seizure Generation

Seizure

Generation

Cellular Mechanisms Cellular Mechanisms of of Seizure Generation Seizure Generation  Excitation (too much) – Ionic—inward

Excitation (too much) Ionic—inward Na + , Ca ++ currents Neurotransmitter—glutamate, aspartate

Inhibition (too little)

Ionic—inward CI - , outward K + currents

Neurotransmitter—GABA

B-Slide B-Slide 1010

Vezzani A,2005

annamaritagelgelsinardja-

epilepsipalembang08

11

Abbas K,2007

annamaritagelgelsinardja-

epilepsipalembang08

12

Epilepsy—Glutamate

Epilepsy—

Glutamate

The brain’s major excitatory neurotransmitter Two groups of glutamate receptors

Ionotropic—fast synaptic transmission

Three subtypes – AMPA, kainate, NMDA Glutamate-gated cation channels

Metabotropic—slow synaptic transmission

G-protein coupled, regulation of second messengers (cAMP and phospholipase C)

Modulation of synaptic activity

B-Slide B-Slide 1414

Epilepsy—Glutamate

Epilepsy—Glutamate

Modulation of glutamate receptors

Glycine, polyamine sites, Zinc, redox site

Epilepsy—Glutamate

Epilepsy—Glutamate

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

Diagram of the various glutamate receptor subtypes and locations

From Takumi et al, 1998

B-Slide B-Slide 1616

Epilepsy—GABA

Epilepsy—GABA

Major inhibitory neurotransmitter in the CNS

Two types of receptors

GABA A post-synaptic, specific recognition sites, linked to CI - channel

GABA B presynaptic autoreceptors that reduce transmitter release by decreasing calcium influx, postsynaptic coupled to G-proteins to increase K + current

B-Slide B-Slide 1717

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 NEURON—EXCITATORY ON POST SYNAPTIC, PROJECTION TO DISTANT AREAS

INTERNEURON :INHIBITORY, LOCAL CIRCUITRY TO PRINCIPAL OR OTHER INTERNEURON

Epilepsy—GABA

Epilepsy—GABA

Epilepsy—GABA Epilepsy—GABA GABA GABA site site Barbiturate Barbiturate site site Benzodiazepine Benzodiazepine site site Steroid Steroid

GABA

GABA site

site

Barbiturate

Barbiturate site

site

Benzodiazepine

Benzodiazepine

site

site

Steroid

Steroid site

site

Picrotoxin

Picrotoxin site

site

Diagram of the GABA A receptor

From Olsen and Sapp, 1995

B-Slide B-Slide 1919

Pathophysiology of Seizure

Cellular level

Sodium channels Calcium channels Potassium channels

Synaptic level Glutamate (excitatory) GABA (inhibitory)

Pathophysiology of Seizure Cellular level – Sodium channels – Calcium channels – Potassium Synaptic level 

Pathophysiology of Seizure

Normal

Normal CNS

CNS Function

Function

Excitation

Inhibition

glutamate, GABA aspartate
glutamate,
GABA
aspartate

Modified from White, 2001

B-Slide B-Slide 2222

Classification of

Classification

of AEDs

AEDs

1. Na+ channel blockers 2. GABAergics 3. Ca++ channel blockers 4. EAA inhibition
1.
Na+ channel blockers
2.
GABAergics
3.
Ca++ channel blockers
4.
EAA inhibition

MECHANISMS OF

MECHANISMS

OF ACTION

ACTION

Classification of Classification of AEDs AEDs 1. Na+ channel blockers 2. GABAergics 3. Ca++ channel blockers
Classification of Classification of AEDs AEDs 1. Na+ channel blockers 2. GABAergics 3. Ca++ channel blockers
Classification of Classification of AEDs AEDs 1. Na+ channel blockers 2. GABAergics 3. Ca++ channel blockers
Classification of Classification of AEDs AEDs 1. Na+ channel blockers 2. GABAergics 3. Ca++ channel blockers

Pharmacology & Therapeutics 113 (2007) 165–183

Hippocampal

Hippocampal Anatomy

Anatomy

B-Slide B-Slide 2525

From Chang

From

Chang and

and Lowenstein,

Lowenstein, 2003

2003

Underlying

Underlying

Seizures and

Seizures

and Epilepsy

Epilepsy

Underlying Underlying Seizures and Seizures and Epilepsy Epilepsy  Feedback and feed-forward inhibition, illustrated via cartoon

Feedback and feed-forward inhibition, illustrated via cartoon and schematic of simplified hippocampal circuit

Babb TL,

Babb

TL, Brown

Brown WJ.

WJ. Pathological

Pathological Findings

Findings inin Epilepsy.

Epilepsy. In:

In: Engel

Engel J.

J. Jr.

Jr. Ed.

Ed.

Surgical

Surgical Treatment

Treatment of

of the

the Epilepsies.

Epilepsies. New

New York:

York: Raven

Raven Press

Press 1987:

1987: 511-540.

511-540.

B-Slide B-Slide 2626

Modifying Neuronal

Modifying

Neuronal

Excitability

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 B-Slide 2727

Epilepsy and

Epilepsy

and

Channelopathies

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 seizures

B-Slide B-Slide 2828

Ion Channel

Ion

Channel &&

Neurotransmitter

Neurotransmitter Receptors

Receptors

Mutated inin Epilepsy

Mutated

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 B-Slide 2929

Modifying Neuronal

Modifying

Neuronal

Excitability

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 B-Slide 3030

Non-synaptic (Extrinsic)

Non-synaptic

(Extrinsic)

Factors Modifying

Factors

Modifying Neuronal

Neuronal

Excitability

Excitability

Changes in extracellular ion concentration

Changes in extracellular space

Modulation of transmitter metabolism or uptake by glial cells

B-Slide B-Slide 3131

Timm Stain

Timm

Stain Showing

Showing

Mossy Fiber

Mossy

Fiber Sprouting

Sprouting

Timm Timm stain stain (black) (black) for for mossy mossy fiber fiber terminals terminals containing containing
Timm
Timm stain
stain
(black)
(black) for
for
mossy
mossy fiber
fiber
terminals terminals
containing
containing zinc
zinc

Normal Rat Dentate Gyrus

Epileptic Rat Dentate Gyrus

Timm Stain Timm Stain Showing Showing Mossy Fiber Mossy Fiber Sprouting Sprouting Timm Timm stain stain

Epileptic Human

Dentate Gyrus

Cavazos and Cross, 2006

B-Slide B-Slide 3232

SIMPULAN

PENGGUNAAN OBAT ANTI EPILEPSI

Epileptic seizures

SIMPULAN PENGGUNAAN OBAT ANTI EPILEPSI Epileptic seizures General Partial Absences Myoclonic Bilateral tonic- clonic Infn spasm
General Partial Absences Myoclonic Bilateral tonic- clonic Infn spasm Lennox juv. myoclonic gastaut
General
Partial
Absences
Myoclonic
Bilateral tonic-
clonic
Infn spasm
Lennox
juv. myoclonic
gastaut

Sod valproat

Carbamazepin

dilantin

Clonazepam

Ethosuksimid

ACTH

Sod valproat Sod valproat

Vigabatrin

lamotrigin

luminal

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 hari oral

gagal Coba Prednisolon 1 - 2 mg / kg / ( 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