EPILEPSI Berasal dari kata Epilambanein = serangan 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 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 ) Etiolog i Penyebab spesifik epilepsi
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EPILEPSIBerasal dari kata Epilambanein = serangan
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
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 )8. Diturunkan dari orang tua
Keadaan Polarisasi ( normal ) diatur olehSodium pump
Ion ( Na,K,Cl,Ca ) bekerja di membran.
Ion Ektra sel Intra sel
K rendah tinggi
Na,Ca,Cl Tinggi Rendah
Depolarisasi
KNaCaCl
PolarisasiNa
Ca
K tinggi Na rendahCa rendahCl rendah
Na
Ca
Cl
Klasifikasi serangan epilepsiI. Serangan parsial ( fokal,lokal ) kesadaran tdk berubahA. Serangan parsial sederhana ( kesadaran tetap baik1. dgn gej motorik2. dgn gej somatosensorik atau sensorik khusus3. dgn gej. Autonom4. dgn gej psikis.B. Serangan parsial kompleks( kesadaran menurun )1. Awalnya parsial sederhana berkemb jadi penrn kesadaran
a. tanpa gambaran lainnyab. dgn gambaran seperti A 1-4c. dgn automatismus
2. dengan penurunan kesadaran sejak awitana. tanpa gambaran lainnyab. dgn gambaran seperti A 1-4c. dgn automatismus
II. Serangan umum ( konvulsi atau non konvulsi )A. Absence C Absence tak khasB. Mioklonik D. Klonik E. Tonik F. Tonik-klonik G. Atonik
III. Serangan epilepsi tak terklasifikasikan ( rith mata,mengunyah, gerk berenang
Epilepsy—Epilepsy—GlutamateGlutamate 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
Epilepsy—GlutamateEpilepsy—Glutamate
Modulation of glutamate receptors– Glycine, polyamine sites, Zinc, redox site
B-Slide B-Slide 1616
Epilepsy—GlutamateEpilepsy—Glutamate
Diagram of the various glutamate receptor subtypes and locationsFrom Takumi et al, 1998
B-Slide B-Slide 1717
Epilepsy—GABAEpilepsy—GABA Major inhibitory neurotransmitter in the
CNS Two types of receptors
– GABAA—post-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
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
Classification of AEDsClassification of AEDs MECHANISMS OF ACTIONMECHANISMS OF ACTION
Pharmacology & Therapeutics 113 (2007) 165–183
1. Na+ channel blockers
2. GABAergics
3. Ca++ channel blockers
4. EAA inhibition
B-Slide B-Slide 2626
Hippocampal AnatomyHippocampal Anatomy
From Chang and Lowenstein, 2003From Chang and Lowenstein, 2003
B-Slide B-Slide 2727
Basic Mechanisms Underlying Basic Mechanisms Underlying Seizures and EpilepsySeizures and Epilepsy
Feedback and feed-forward inhibition, illustrated via cartoon and schematic of simplified hippocampal circuit
Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed. 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.Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.
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