EPILEPSI

Blok Sistem Saraf

Epilepsi: gangguan kronik ditandai bangkitan epileptik berulang akibat gangguan fungsi otak secara intermiten yang terjadi oleh lepas muatan listrik abnormal neuron neuron secara paroksismal akibat berbagai etiologi (Perdossi, 2003) Seizure: manifestasi klinis dari eksitasi yang abnormal dan berlebihan dari neuron kortikal Epileptogenesis: rangkaian kejadian yang mengubah jaringan neuronal normal menjadi jaringan hipereksitabel. Sindrome Epilepsi: kelompok gejala dan tanda yang menggambarkan kondisi epilepsi khusus
Sumber: ILAE Report on Classification and Terminology, 2003
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Idiopathic epilepsy Syndrome: suatu sindrome epilepsi tanpa lesi struktural yang mendasarinya dan tanpa tanda dan gejala neurologis lain. Generalized Seizures: melibatkan 2 hemisfer otak, dengan masifestasi bilateral Partial Seizures: melibatkan 1 hemisfer otak, dengan manifestasi asimetrik/ bangkitan menjadi general. Typical IGE: CAE, JAE, JME, atau sindrom bangkitan tonikklonik saja dengan umur onser 3-20 thn Atypical IGE: meliputi pasien dengan atypical absence dan epilepsi mioklonik dan bangkitan tonikklonik saja, diluar umur onset yang sesuai
Sumber: ILAE Report on Classification and Terminology, 2003
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Epilepsi

Bangkitan paroksismal berulang akibat abnormalitas aktivitas listrik di otak

(WHO,2001)

Bangkitan epilepsi
Manifestasi klinis dari bangkitan serupa (stereotipik) yang berlebihan dan abnormal, berlangsung secara mendadak dan sementara dengan atau tanpa perubahan kesadaran, disebabkan oleh hiperaktifitas listrik sekelompok sel saraf di otak yang bukan disebabkan oleh suatu penyakit otak akut (unprovoked)
Pedoman Tatlaksana Epilepsi Pokdi Epilepsi Perdossi 2003
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Epilepsi
Seizure: manifestasi klinis dari eksitasi yang abnormal dan berlebihan dari neuron kortikal Epileptogenesis: rangkaian kejadian yang mengubah jaringan neuronal normal menjadi jaringan hipereksitabel. Sindrome Epilepsi: kelompok gejala dan tanda yang menggambarkan kondisi epilepsi khusus

ILAE Report on Classification and Terminology, 2003 6

Serangan (seizure)
Serangan berupa efek fisik dari energi listrik abnormal di otak Signal yang terganggu diteruskan ke seluruh tubuh melalui jalur saraf Jenis serangan bergantung pada jumlah neuron yang terlibat dan area otak yang terkena: gangguan kesadaran, perilaku, motorik, sensorik, otonom, involuntar
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Ambang serangan (seizure threshold)

Ambang serangan adalah batas tingkat rangsang (stimulus) yang memungkinkan otak mengalami serangan atau tidak Penderita epilepsi memiliki ambang serangan yang lebih rendah daripada orang normal : hanya denga sedikit rangsangan (dibandingkan dengan orang normal) maka serangan dapat terjadi

Ambang serangan
Sebagian besar ambang serangan diwariskan secara genetik Umur muda (< 5 tahun) mempunyai ambang serangan yang lebih rendah Demam serangan menurunkan ambang
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Pencetus serangan epilepsi

o o o o o o o o o o Kurang tidur Stres emosional Kelelahan fisik Infeksi Demam Alkohol Rangsangan cahaya Obat tertentu Perubahan hormonal Rangsangan suara
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Table 2-1 International Classification of Epileptic Seizures

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 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 Unclassified epileptic seizures (caused by incomplete data)

II.

III.

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International Classification of Epilepsies and Epileptic syndromes (1989) 1. Localization-related (focal, local, partial):
Idiopathic (primary): -Benign childhood epilepsy with centrotemporal spike -Childhood epilepsy with occipital paroxysms -Primary reading epilepsy

Cryptogenic (secondary) -Temporal lobe epilepsy -Frontal lobe epilepsy -Parietal lobe epilepsy -Occipital lobe epilepsy -Chronic progressive epilepsia partialis continua of childhood -Syndrome characterized by seizures with

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International(2)
2. Generalized 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 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 13

International (3)
3. Undetermined epilepsies -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 4. Situation-related seizures (Gelegenheitsanfalle): -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, 14 eclampsia, nonketotic hyperglycemia

Prodroma
During the prodromal phase slight alterations in neurological function may or may not be detected. Often the patient might report a mood change or you might observe a behavior change.

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Aura
Many times the patient will report the aura as a peculiar smell, taste, feeling, or sound. Sometimes patients will experience sudden onset of dizziness, headache, spots before their eyes, or even cry out. Once the patient experiences this aura, more pronounced seizure activity is soon to follow.

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Spread of depolarization through spinal cord

Inhibitory neurons in cortex, anterior thalamus & basal ganglia begin to inhibit Cortical excitation

Increased cerebral blood flow & oxygen/ glucose consumption

Intermittent clonic bursts become less frequent until cessation

Neurons reset to Normal resting state

Cerebral blood flow & metabolism returns to pre-seizure level

Consciousness returns
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Clinical manifestations of seizure

Cerebral lesions, biochemical disorders, cerebral trauma, & various seizure disorders 1
Affected neurons more permeable and reactive to hyperthermia, hypoxia, hypoglycemia, hyponatremia, or repeated sensory stimulus & repeatedly depolarize with increasing amplitude & frequency

Prodroma a manifestation that may occur hours to days prior to the actual seizure

2 Aura a partial seizure or sensory warning that preceeds generalized seizure activity Depolarization spreads through adjacent normal neurons via corticocortical synapses
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3 Depolarization spreads through intrahemispheric tracts to contralateral cortex, basal ganglia, thalamus, & brainstem

Impaired or loss of consciousness 4a Tonic phase of muscle contraction as impulse reaches motor units

Spread of depolarization through spinal cord

4b

Clonic phase of muscle contraction/relaxing as sporadic impulses are lessened by inhibitory actions

Inhibitory neurons in cortex, anterior thalamus, & basal ganglia begin to inhibit cortical excitation

4c

5a

Increased cerebral blood flow & oxygen/glucose consumption

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5b

Cerebral hypoglycemia
Increased cerebral blood flow and oxygen/glucose consumption

Cerebral hypoxia

Metabolic acidosis 5a 5b Cerebral blood flow & metabolism returns to pre-seizure level 8 Intermittent clonic bursts become less frquent until cessation Neuron resets to normal resting state Status epilepticus 9 6 Consciousness returns Death
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Serangan umum absence

Penderita menghentikan aktivitasnya secara mendadak
Mata terbuka, seolah-olah melihat jauh atau melamun Berlangsung selama beberapa detik Penderita kemudian melanjutkan aktivitasnya kembali, seolah-olah tak terjadi apa-apa Penderita tidak sampai terjatuh Kadang-kadang disertai mata berkedipkedip secara cepat, mulut komat-kamit
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 Mendadak berteriak, kemudian jatuh, tak sadar Seluruh tubuh kaku (tonik), kemudian menyentak-nyentak (klonik) Bola mata terputar ke atas, mulut berbuih Kulit kebiruan, napas dangkal atau terhenti Lidah dapat tergigit

Serangan umum tonikklonik

Kadang-kadang ngompol
Serangan berlangsung beberapa menit Ketika serangan reda: napas menjadi teratur kembali, kesadaran pulih secara bertahap, 29 penderita tampak bingung

Precipitating Factors
Trauma/ illness/ fever Hiperventilation Lack of sleep Photosensitivity Increase emotional stress Hormonal changes Fluid& electrolyte imbalance Alcohol/ drugs
Handbook of epilepsy, Browne&Holmes 30

Etiologi epilepsi
Merupakan kombinasi antara ambang serangan (genetik), abnormalitas jaringan otak (predisposisi), dan faktor lingkungan (presipitasi) Penyebab yang spesifik: belum diketahui (60%) Idiopatik: tak diketahui penyebabnya Simtomatik: diketahui penyebabnya Kriptogenik: penyebabnya 31 tersembunyi (sulit diidentifikasi)

ETIOLOGI EPILEPSI
1. Epilepsi Idiopatik 2. Epilepsi Simptomatik: a. Usia 0 6 bl:- intra uterin -selama persalinan -kongenital -metabolik -defisiensi piridoksin
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ETIOLOGI EPILEPSI
2 Epilepsi Simptomatik: b.usia 6 bl-3 th:-kejang demam -trauma kepala c.anak-remaja: - infeksi d.usia muda: -trauma kepala -tumor - infeksi e. usia lanjut: -GPDO -tumor -trauma kepala - degenerasi
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Causes of Epilepsy
Symptomatic E Cryptogenic E Idiopathic E = Genetic E

(Etiologic unkn) Residual Process 30% of Epilepsy

- Idiopathic" epilepsy = unknown cause - "Cryptogenic" epilepsy = presumed to be due to an unidentified structural abnormality - "Symptomatic" epilepsy = due to know

structural abnormality
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Etiological Newly Dx Epilepsy

( National General Practice Study of Epilepsy )
Cryptogenic/ Idiopathic: 61% ( 83%: 0-9 yr ; 38%: > 60 yr ) Symptomatic ~ Vascular disease : 15% ~ Alcohol : 6% ~ Cerebral Trauma : 6% ~ Trauma : 3% ~ Infection : 2% ~ Other : 7%
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Causes of Seizure

Kim BG, 2000, Interdisciplinary Neuroscience, Epilepsy

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Penyebab atau faktor resiko epilepsi

1. Idiopatic - terutama kelompok umur 5 20 tahun - tidak didapatkan kelainan neurologis - sering ada riwayat epilepsi pada keluarga 2. Metabolik : DM, ggn. Elektrolit, uremia, alkohol,obat 3. Trauma kepala : PTS, terjadi 2 tahun pasca trauma 4. Tumor otak 5. Kardiovasculer : stroke 6. Infeksi : Ensefalitis, meningitis, abces otak 7. Penyakit degenerativ :Demensia Alzheimer
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EPILEPSY

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Sumber: Molecular genetics of human epilepsies, 1999

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Patofisiologi

1. Partial Simplex 2. Partial Complex

Modified: Crank, 2003

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Clinical Simposia, no I 1994

Basic Mechanism of Epilepsy

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Basic Mechanisms Underlying Seizures and Epilepsy

Ionic channel Na+, Ca++, K+, ClLignad-gated Channel excitatory - Glutamate inhibitory - GABA

Excitatory postsynaptic potential Inhibitory postsynaptic potential Action potential Excessive discharge

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Neuronal Excitation
Action Potential

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Mechanism: Increase Inhibition

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MEKANISME SELULER TIMBULNYA EPILEPTOGENESIS

DARAH
hemolisis Fe++ atau Fe+++

Hidrogen Peroksida (H2O2) Radikal Hidroksil (OH-) Radikal Superoksid (O2-) Radikal Bebas

Osilasi kalsium Pada sel glia

Ca++ intrasel Peroksidasi Lipid Kerusakan eksitotoksik Aktivasi asam arakhidonat Kematian neuron/jar. Parut sel glia Asam arakhidonik fosfitate (IP3)
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AKTIVITAS EPILEPTIFORM

Basic Mechanism of Epilepsy

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Fungsi EEG
Mendukung diagnosa klinik epilepsi Membedakan tipe general dari partial Identifikasi sydroma epilepsi Menentukan prognosis pada kasus tertentu Pertimbangan dalam penghentian OAE Membantu dalam menentukan letak fokus
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Gelombang EEG normal :

Alpha : 8 13 cps Beta : > 13 cps Theta : 4 7 cps Delta : < 4 cps

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EEG Abnormal :
Gel. Lambat (slow wave) Gel. Paroksismal : spike/ sharp wave Amplitudo abnormal.

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Gelombang EEG
Beta :
- Banyak terlihat pd pemakaian barbiturat - Dominan di daerah frontal

Delta : - Normal semua umur dlm keadaan tidur

- Abnormal dewasa muda dlm keadaan bangun

Theta : - Fisiologi dijumpai pd neonatus

- Sering pd dewasa muda dan usia > 50 th
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Beta activity: > 13 Hz

Alpha activity: 8-13 Hz

Theta activity: 4-7.5 Hz

Delta activity: < 4 Hz

1 second
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COMMON DIAGNOSTIC INDICATIONS FOR EEG

Clinical seizures Definite epilepsy Headache Syncope Learning disabilities Movement disorders Patients with altered mental status and coma Attention-deficit hyperactivity disorder (ADHD)
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Indikasi Neuroimejing
Kasus bangkitan pertama yg diduga ada kelainan struktural Perubahan bentuk bangkitan Terdapat defisit neurologik fokal Epilepsi bangkitan parsial Bangkitan pertama diatas usia 25 tahun Untuk persiapan operasi epilepsi
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Diagnosis
Diagnosis epilepsi didasarkan atas bukti klinis; EEG membantu penentuan jenis epilepsi Jenis serangan perlu dideskripsikan: untuk keperluan terapi Diupayakan agar mencapai diagnosis etiologik Penyampaian diagnosis kepada penderita memerlukan penjelasan yang cukup sekaligus disertai rencana 57 terapi

Dx Epilepsi
Ax
Pola/ bentuk serangan Lama serangan Gejala sebelum, selama, dan paska serangan Frekuensi serangan Faktor pencetus Ada/ tdk penyakit lain yg diderita sekarang Usia saat terjadi serangan pertama Riw kwhamilan, persalinan, dan perkembangan Riw peny, penyebab, atau tx sebelumnya
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Dx Epilepsi
Px fisik
Melihat tanda dari gangguan yg berhub dg epilepsi spt trauma kepala, infeksi sinus, gangg kongenital, defisit neurologi fokal atau difus, alkohol, obat terlarang, kanker

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Dx Epilepsi
Px Penunjang
EEG Neuroimejing Lab

Pedoman Tatlaksana Epilepsi Pokdi Epilepsi Perdossi 2003

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Dx Pasti Epilepsi
Gejala dan tanda klinis bangkitan Gambaran epileptiform pada eeg

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Algoritma diagnosis epilepsi

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Prinsip terapi
Min 2x bangkitan dlm setahun Dx tegak, informasi u/ pasien dan keluarga Tepat obat Sebaiknya monoterapi Dimulai dari dosis rendah dianikkan sampai efektif Dimulai dg obat lini pertama, bila perlu penggantian obat pertama diturunkan bertahap, obat kedua dinaikkan bertahap Bila gagal monoterapi, kombinasi Bila mungkin pantau kadar obat
Pedoman Tatlaksana Epilepsi Pokdi Epilepsi Perdossi 2003

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Serangan pertama diterapi

Dijumpai fokus epilepsi yang jelas pada EEG Pada CT/ MRI otak dijumpai lesi yg berkorelasi dg bangkitan Ada kelainan neurologis mengarah pada kerusakan otak Ada riw epilepsi pada orang tua dan saudara kandung kec kejang demam sederhana Ada riw infeksi otak atau trauma kapitis disertai penurunan kesadaran Serangan pertama berupa status epileptikus
Pedoman Tatlaksana Epilepsi Pokdi Epilepsi Perdossi 2003

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Tx Epilepsi

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Terapi (2):
Mekanisme aksi OAE: Meningkatkan inhibisi neuronal (GABAergic transmission): -meningkatkan aksi GABA pada reseptor GABAA -menghambat pemecahan GABA di sinapsis -blokade ambilan GABA di terminal presinaptik Menurunkan eksitasi neuronal (glutaminergic transmission): -menurunkan pelepasan glutamat -blokade aksi glutamat di NMDA/AMPA/reseptor kainat

Blokade terhadap voltage-gated Na channels

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Terapi (3)
Obati/atasi serangan epileptik, bukan EEG! Mulailah dengan dosis rendah dan bila perlu dosis dinaikkan secara bertahap Naikkan dosis OAE sampai mencapai efek klinis, atau toksik Monitor kadar OAE dalam serum Hentikan OAE secara bertahap
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T e r a p i (4)
Monitor/evaluasi: - apakah OAE efektif atau tidak efektif - apakah ada efek samping - apakah ada rasa bosan minum obat - perubahan berat badan - perubahan jenis serangan
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Classification of Anticonvulsants
Action on Ion Channels
Na+: Phenytoin, Carbamazepine, Lamotrigine Topiramate Valproic acid Ca++: Ethosuximide Valproic acid Na+: For general tonic-clonic and partial seizures Ca++: For Absence seizures

Enhance GABA Transmission

Benzodiazepines (diazepam, clonazepam) Barbiturates (Fenobarbital) Valproic acid Gabapentin Vigabatrin Topiramate Felbamate Most effective in myoclonic but also in tonic-clonic and partial Clonazepam: for Absence

Inhibit EAA Transmission

Felbamate Topiramate

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Classification of Anticonvulsants
Classical
Phenytoin Phenobarbital Primidone Carbamazepine Ethosuximide Valproic Acid Trimethadione

Newer
Lamotrigine Felbamate Topiramate Gabapentin Tiagabine Vigabatrin Oxycarbazepine Levetiracetam Fosphenytoin Others
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PHENYTOIN
May act in motor cortex, inhibit spread of seizure activity. Activity of brainstem centers inhibittonic phase of grand mal seizures Irritation administer with or immediately after meals. Rapid injection or direct IV injection severe hypotension or CNS depression IV rate not to exceed 50 mg/min; in elderlyIV rate not to exceed 25 mg/min; in childrenIV at rate not to exceed 0.5-1 mg/kg/min and do not exceed 50 mg/min; in infants, do not give via scalp veins. Adult Dose IV loading dose for patients who have not received phenytoin in preceding 7 days: 10-15 mg/kg Maintenance dose: 4-7 mg/kg/d PO/IV Pediatric Dose IV loading dose: 15-18 mg/kg Maintenance dose: 5 mg/kg/d PO/IV divided bid If the patient has not experienced a seizure, phenitoin should be 71 discontinued after 7 to 10 days

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PHENYTOIN (Cont)
Contraindications Reduce dose in hepatic impairment; sino-atrial block; Adams-Stokes syndrome; second- or third-degree AV block Pregnancy C - Safety has not been established. Precautions Rapid IV infusion may result in death from cardiac arrest, marked by QRS widening Has narrow therapeutic index monitoring of plasma levels Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash : exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate bloodglucose); discontinue use if hepatic dysfunction occurs
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MEDIKAMENTOSA: Sodium valproate

As adjunctive therapy: 10-15 mg/kg/d. May increase by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses <60 mg/kg/d. Adult Dose 600 mg/d PO divided bid, preferably after food; increase by 200 mg/d at 3-d intervals; not to exceed 2.5 g/d (20-30 mg/kg/d) Pediatric Dose <2 years: Not recommended because of risk of fatal hepatotoxicity >2 years: 20 mg/kg/d initially in divided doses; can be increased, not to exceed 35 mg/kg/d Contraindications hypersensitivity; active liver disease; porphyria; family history of hepatic dysfunction Pregnancy D - Unsafe in pregnancy Precautions Thrombocytopenia and abnormal coagulation parameters have occurred; Monitor for hepatotoxicity (perform LFTs periodically)Hyperammonemia malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may 74 cause drowsiness

Carbamazepine
Indicated for complex partial seizures. Adult Dose 100-200 mg PO qd/bid; slowly increase to usual dose of 0.8-1.2 g/d in divided doses; not to exceed 1.6-2 g/d Pediatric Dose <1 year: 100-200 mg/d PO in divided doses 1-5 years: 200-400 mg/d PO in divided doses 10-15 years: 0.6-1g/d PO in divided doses Contraindications Documented hypersensitivity; AV conduction abnormalities (unless paced); porphyria; history of bone marrow depression; concurrent MAOIs Pregnancy C - Safety has not been established. Precautions In first trimester, risk of teratogenesis, Risk of neonatal bleeding; Counseling, and folate supplements advised Increased intraocular pressure; obtain complete blood cell counts and 75 serum iron level prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and

TERAPI ANTIOKSIDAN
Peroksidase/ katalase DARAH
hemolisis Fe++ atau Fe+++ Hidrogen Peroksida (H2O2) Radikal Hidroksil (OH-) Radikal Superoksid (O2-)

Tokoferol 2 mg/kg bb
Radikal Bebas

AKTIFITAS EPILEPTIFORM

Selenium

Peroksidasi Lipid

Aktivasi asam arakhidonat Ca++ intrasel Kerusakan eksitotoksik Kematian neuraon/jar. Parut sel glia Asam arakhidonik fosfitate (IP3)
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Dosis obat antiepilepsi

Phenytoin Fenobarbital 100-200mg/h 5 mg/kgBB 30 mg/hari 3-4 mg/hari 10-40 mg/kg/hr

Carbamazepin 100 mg

Clonazepam
Sod.Valproat Gabapentin

0,25 mg/hari
400-500mg/h 20 mg/kgBB/hr 300 mg/hari 15-30 mg/kg/hr

Okskarbazepin 600mg/hari Lamotrigin 12,5-25mg/hr 0,5 mg/kg/hr Topiramat 25-50mg/hr 0,5-1 mg/kg/hr

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GUIDELINES FOR DOSES OF 1ST LINE AEDS IN Adults (Brodie 1996, Browne 2001)
Drug
Indication Starting dose Most Common Daily Dose Standard maintenance dose(range) mg/kg/day No of Doses / day Target plasma drug concentr. (range) g/ml 4-12 10-20 50-150 10-40 5-12 40-120 none

CBZ PHT VPA BAR PMD ETX CNP

Partial & GTCS Partial & GTCS /SE Partial & GTCS Partial & GTCS Neonatal seizure/SE Partial & GTCS Generalized absense seizure Myoclonic epilepsi, L Gestaut Syndrome infantile spasm / SE

400 300 500-1000 60-90 100-125 500 1

600 300 1000 120 500 1000 4

600-1200 300-500 1000-3000 90-120 250-1500 1000-2000 2-8

2-3 1 2 1 3 2 1 or 2

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GUIDELINES FOR DOSES OF 2nd LINE AEDS IN Adults (Brodie 1996, Browne 2001)
Drug Indication Starting Dose
300mg/d; 300 mg/d q1-3d 25-50mg/d; 50mg q1-2wk or25mgq2d with VP 2-3x 400mg/d; with dose by 400-600mg/d q2wk 3-4x 15mg/kg/d 15mg/kg/d/q12wk 10mg qb or 2 x 10mg/d 2x300mg/d Not available 100 mg/d 100mg/d/q1wk 2x500 mg/d

Maintenance dose
1200-2400mg/d Up to 700mg/d (100-150mg/d with VP) 1800-4800mg/d 6

Plasma Half Life(hrs)

Plasma Binding (%)

0 54

Gabapetin Lamotrigine

Partial & SGTCS (Adults) Partial & SGTCS (Adults) Partial & SGTCS (Adults) L-G Syndrome

Felbamat

25(12-24 with enzyme inducing drug; 60 with VP 20-23

22-25

Clobazam Oxcarbazpn Tiagabin Topiramat Vigabatrin Zonisamide

Partial & GTCS Partial & GTCS Partial & SGTCS Partial & SGTCS Partial & SGTCS Possibly inf Spasm Partial & SGTCS

Up to 45mg/kg/d 20-30mg/d Up to 60 mg/d 1200-2400mg/d 32-56mg/d 400-100mg/d Up to 3g/d 400-600mg/d

30-46 8-24 6-8 20-24 4-8(effect last 3 d) 30-68(27-38 with enzyme inducing drug)

85 40 96 10-20 Minimal 38-40 79

AEDS CHOICE BASED ON SEIZURE TYPE (Jarrar 2003)

Seizure type & subtype
Generalized infantile spasm absence Atonic

First choice drug

corticotropin Ethosuximide Valproic acid

Other options

Tonic
Myoclonic Tonic-clonic Partial with and without secondary generalization

Valproic acid
Valproic acid Valproic acid

Topiramate, lamotrigine, zonisamide, Valproic acid, felbamat Lamotrige, zonisamide, VPA Topiramate, lamotrigine, phenytoin, Phenobarbital, zonisamide, felbamat Topiramate, lamotrigine, phenytoin, Phenobarbital, zonisamide, felbamat Topiramate, lamotrigine, phenytoin, Phenobarbital, zonisamide, felbamat Topiramate, lamotrigine, phenytoin, Phenobarbital, zonisamide, felbamat Oxcarbazepin lamotrigine, topiramate, phenytoin, levetiracetam, zonisamide, 80 tiagabine, gabapentin, VPA, phenobarbital, felbamat

Carbamazepin

Determining a Loading Dose of an AED

Dose (mg) = Weight (kg) x VD (L/kg) x Change in concentration
VD= Volume of distribution

Change in concentration = Desired AED level Current AED level

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Mechanisms of Action Antiepileptic Drugs

Sodium channel effects Potassium channels and GABA release GABAergic effects
Precursors, mimicry, and transporters

Glutamate regulation-neuroprotection Calcium channels and transmitter release

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FIG. 4. Schematic diagram of an inhibitory synapse in the central bervous system, and the putative major sites of actions of various antiepileptic drugs (AEDs). GABA, -aminobutryc acid; GABA-T, GABA transaminase; GAD, glutamic acid decarboxylase.
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FIG. 5. Schematic diagram of an excitatory synapse in the central nervous system, and the putative major sites of actions of various antiepileptic drugs (AEDs). NMDA, N-methyl-D-asparate; AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. 84

Pertolongan waktu serangan

Jangan panik Biarkan serangan berlalu karena serangan akan berhenti dengan sendirinya Amankan penderita dari lingkungan yang membahayakan penderita Longgarkan pakaian yang ketat Posisi kepala dimiringkan (bila kejang sudah berhenti) Bila serangan berkepanjangan: kirim ke RS
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Faktor psikososial
Cenderung dikucilkan dari lingkungan Cenderung ditolak untuk sekolah Sulit mencari pekerjaan Merupakan aib bagi keluarga Menurunkan rasa percaya diri Lebih mudah mengalami cedera
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Kesempatan bekerja
Pada dasarnya tidak ada larangan untuk bekerja bagi penderita epilepsi Pekerjaan disesuaikan dengan jenis serangan Penderita harus paham tentang penyakit yang dideritanya Dukungan positip dari keluarga dan lingkungan kerja
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Kesempatan untuk sekolah

o Tidak larangan untuk sekolah o Bila perlu guru dan orang tua penderita berkonsultasi dengan dokter yang merawatnya o Antara orang tua dan guru diperlukan sifat terbuka dan saling mengerti o Masalah yang ada pada penderita bukan sekedar cerdas atau bodoh
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Spells

Seizure

Other

Non-Epileptic

Epileptic

Syncope, Panic attack, migraine, TIA, Movement disorder, sleep disorder

Psychogenic Pseudosizure

Syncope with anoxic seizure

Recurent seizures

Febrile seizure

Single Seizure (unprovoked)

Acute seizure(s)

Epilepsy

Recurent Febrile seizures Metabolic, head trauma, stroke, drugs, alcohol withdrawl, etc

Seizure type (s)

Etiology

Generalized, Partial, Partial secundary generalization, unclassified

Syndrome

No syndrome

Localization related

Not localization related

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Epilepsi
1. Pencetus 2. Suasana Biasanya tidak ada Biasa waktu tidur dan sendirian Jarang Biasa mendadak, mungkin ada aura Biasa terjadi Stereotipe Biasa terjadi Dapat terjadi penurunan kesadaran Tidak berpengaruh Biasanya pendek Biasanya pendek, kdg memanjang bila dg autisme. Biasanya bingung, menmgantuk atau

Pasien
Tidak ada Santai, sedikit orang

Kejang Psikogenik
Faktor emosi Jarang waktu tidur, lingkungan banyak orang Biasa

3. Prodroma 4. Awal 5. Jeritan pada awal 6. Fenomena motorik 7. Lidah tergigit 8. Kesadaran

Mendadak, ada aura Tidak ada Stereotipe

Berangsur dg meningkatnya emosi Tidak biasa Bervariasi Jarang terjadi

Tidak sadar

Tidak terjadi

9. Pengekangan 10. Lama/durasi 11. Henti serangan

Tidak berpengaruh 3 5 menit Badan lemah dan agak bingung

Dapat melawan, kdg menghentikan Dapat memanjang Dapat berangsur, serig dg penampakan emosi: bingung, mengantu90 atau tidur tidak biasa

PNEs (Psychogenic Nonepileptic seizures)

Sinonim : Pseudoseizure, pseudoepileptic seizure, hysteroepilepsi, Psychogenic seizure, psychogenic nonepileptic seizures, nonelectrical seizure, non epileptic pseudoseizure Insidensi ; 5 20 % populasi umum Definisi adalah kejadian paroksimal dimana terjadi perubahan fungsi neurologis yang menghasilkan tanda motorik, sensorik, autonom atau gejala psikis yang mirip dengan kejadian selama serangan epilepsi Merupakan maifestasi penyebab fisiologik dan psikologik

91

Psichogenic nonepileptic seizure

Definisi ; Serangan yang berupa gangguan tingkah laku mirip serangan eoilepsi tetapi tidak berhubungan dengan kelainan elektrofisiologi otak seperti pada epilepsi Gejala : perubahan tingkah laku, kesadaran dan atau kejang Serangan timbul bila ada beberapa orang disekitarnya, kejang berhenti tanpa disertai bingung Manifestasi ; kejang extremitas yang tidak sinkron, gemetar, gerakan pinggul, kepala, epistotonus, bicara keras

92

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Promoting Control factors

Adequate amount of AED in blood Adequate sleep and rest Correct AED Good Nutrition Alcohol Abstinence Fluid& electrolyte balance Low anxiety level
Handbook of epilepsy, Browne&Holmes
94

Neuronal injury cascade

Dirnagl et al. Trends Neurosci 22:391-397

Na+
Na+

u Gl

Glu

Ca2+
Gl u

Gl u

lu

Ca2+

Na+ Ca2+ Enzyme induction

Depolarization Cell distension Mitochondrial injury DNA injury

Free radicals Apoptosis Membrane degradation Inflammatory mediators

95

Neuronal injury cascade / Action of AEDs

Na+
Na+

u Gl

Glu

Ca2+
Gl u

Gl u

lu

Ca2+

Na+ Ca2+ Enzyme induction Free radicals Membrane degradation

Depolarization Cell distension

Na+ channel blockers: Topiramate Phenytoin Carbamazepine Valproic acid Lamotrigine

96

Neuronal injury cascade / Action of AEDs

Na+
Na+
Glu

Ca2+
Gl u

Ca2+

Na+ Ca2+ Enzyme induction Free radicals Membrane degradation

Depolarization Cell distension

NMDA antagonists Felbamate MK801 Ketamine

97

Neuronal injury cascade / Action of AEDs

Na+
Na+
Glu

Ca2+
Gl u

Ca2+

Na+ Ca2+ Enzyme induction Free radicals Membrane degradation

Depolarization Cell distension

AMPA antagonists Topiramate Phenobarbital

98

Mechanism of antiepileptic Drug associated Bone Disease

Hepatic induction of the citochrome P450 enzyme system leading to increased catabolism of vitD is the principal mechanism. (Allison M.Pack, 2003)

99

Mechanism of antiepileptic Drug associated Bone Disease

AED that induced cytochrome P450 enzymes may cause increased conversion of vitD to polar inactive metabolism in the liver microsomes, reducing bioavailable vitD. Decreased biologically active vitD leads to decreased absorption of calcium in the gut, resulting in hypocalcemia and an increase in circulating PTH. PTH then increases the mobilization of bone calcium stores and subsequent boMne turnover
100

 AED may interfere with intestinal absorption of calcium. Impaired absorption would lead to hypocalcemia and feedback hypersecretion of PTH increase mobilization bone calcium store and bone turnover

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