Saraf 070830 Dr Epilepsi

1

EPILEPSI

Blok Sistem Saraf

2

• 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

3

• 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 tonik–klonik saja dengan umur onser 3-20 thn

• Atypical IGE: meliputi pasien dengan atypical absence dan epilepsi mioklonik dan bangkitan tonik-klonik saja, diluar umur onset yang sesuai

Sumber: ILAE Report on Classification and Terminology, 2003

4

Epilepsi

• Bangkitan paroksismal berulang akibat abnormalitas aktivitas listrik di otak

(WHO,2001)

5

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 EpilepsiPokdi Epilepsi Perdossi

2003

6

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

Epilepsi

7

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

8

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

9

Ambang serangan

Sebagian besar ambang serangan diwariskan secara genetik

Umur muda (< 5 tahun) mempunyai ambang serangan yang lebih rendah

Demam menurunkan ambang serangan

10

Pencetus serangan epilepsi

o Kurang tiduro Stres emosionalo Kelelahan fisiko Infeksio Demamo Alkoholo Rangsangan cahayao Obat tertentuo Perubahan hormonalo Rangsangan suara

11

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

II. 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

III. Unclassified epileptic seizures (caused by incomplete data)

12

International Classification of Epilepsies and Epileptic syndromes

(1989)1. Localization-related (focal, local, partial):

Idiopathic (primary):-Benign childhood epilepsy with centro-temporal 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 specific

modes of precipitation

13

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

14

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, eclampsia, nonketotic hyperglycemia

15

P r o d r o m a

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.

16

A u r a

• 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.

17

Spread ofdepolarizationthrough spinal

cord

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

Cortical excitation

Increased cerebralblood flow & oxygen/glucose consumption

Neurons reset toNormal resting state

Cerebral blood flow& metabolism returns

to pre-seizure level

Intermittent clonic burstsbecome less frequent until

cessation

Consciousness returns

18

Cerebral lesions, biochemical disorders,

cerebral trauma, &various seizure disorders

Affected neurons more permeableand reactive to hyperthermia,

hypoxia, hypoglycemia, hyponatremia, or repeated sensory

stimulus & repeatedly depolarize withincreasing amplitude & frequency

Depolarization spreads through adjacent normal

neurons via corticocortical synapses

Clinical manifestations of seizure

Prodroma – a manifestationthat may occur hours to days

prior to the actual seizure

Aura – a partial seizure orsensory warning that preceeds

generalized seizure activity

1

2

3

19

Depolarization spreads through intrahemispheric

tracts to contralateral cortex,basal ganglia, thalamus,

& brainstem

3

Impaired or loss ofconsciousness

Spread of depolarizationthrough spinal cord

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

Increased cerebral bloodflow & oxygen/glucose

consumption

4a

4b

4c

Tonic phase of muscle contraction as impulse

reaches motor units

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

actions

5a

5b

20

Increased cerebral blood flow and oxygen/glucose

consumption

Cerebral hypoglycemia

Cerebral hypoxia

Metabolic acidosis

Cerebral blood flow &metabolism returns to

pre-seizure level

Neuron resets to normal resting state

5a 5b

Intermittent clonic burstsbecome less frquent

until cessation

Consciousness returns

Status epilepticus

D e a t h6

7

8

9

28

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 berkedip-kedip secara cepat, mulut komat-kamit

29

Serangan umum tonik-klonik

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

Kadang-kadang ngompol

Serangan berlangsung beberapa menit

Ketika serangan reda: napas menjadi teratur kembali, kesadaran pulih secara bertahap, penderita tampak bingung

30

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

31

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

tersembunyi (sulit diidentifikasi)

32

ETIOLOGI EPILEPSI

1. Epilepsi Idiopatik

2. Epilepsi Simptomatik:

a. Usia 0 – 6 bl:- intra uterin

-selama persalinan

-kongenital

-metabolik

-defisiensi piridoksin

33

ETIOLOGI EPILEPSI

2 Epilepsi Simptomatik: b.usia 6 bl-3 th:-kejang demam

-trauma kepalac.anak-remaja: - infeksid.usia muda: -trauma kepala

-tumor - infeksi

e. usia lanjut: -GPDO -tumor -trauma kepala - degenerasi

34

Causes of Epilepsy

Symptomatic E Cryptogenic E Idiopathic E

(Etiologic unkn) = Residual Process 30% of Epilepsy Genetic E

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

35

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%

36

Causes of Seizure

Kim BG, 2000, Interdisciplinary Neuroscience, Epilepsy

37

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,obat3. Trauma kepala : PTS, terjadi 2 tahun pasca trauma4. Tumor otak5. Kardiovasculer : stroke6. Infeksi : Ensefalitis, meningitis, abces otak7. Penyakit degenerativ :Demensia Alzheimer

38

Sumber: Molecular genetics of human epilepsies, 1999

EPILEPSY

41

1. Partial Simplex2. Partial Complex

Modified: Crank, 2003

Patofisiologi

42

Clinical Simposia, no I 1994

43

Basic Mechanism of Epilepsy

44

Basic Mechanisms Underlying Seizures and Epilepsy

Ionic channel Na+, Ca++, K+, Cl-

Lignad-gated Channel excitatory - Glutamate inhibitory - GABA

Excitatory postsynaptic potentialInhibitory postsynaptic potentialAction potentialExcessive discharge

45

Neuronal Excitation

• Action Potential

46

Mechanism: Increase Inhibition

47

MEKANISME SELULER TIMBULNYA EPILEPTOGENESIS

DARAH hemolisis Fe++ atau Fe+++

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

Radikal Bebas

Peroksidasi Lipid

Aktivasi asam arakhidonat

Asam arakhidonik fosfitate (IP3)

Osilasi kalsiumPada sel glia

Ca++ intrasel

Kerusakan eksitotoksik

Kematian neuron/jar. Parut sel glia

AKTIVITAS EPILEPTIFORM

48

Basic Mechanism of Epilepsy

49

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

50

Gelombang EEG normal :

• Alpha : 8 – 13 cps

• Beta : > 13 cps

• Theta : 4 – 7 cps

• Delta : < 4 cps

51

EEG Abnormal :

• Gel. Lambat (slow wave)

• Gel. Paroksismal : spike/ sharp wave

• Amplitudo abnormal.

52

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

531 second

Beta activity: > 13 Hz

Alpha activity: 8-13 Hz

Theta activity: 4-7.5 Hz

Delta activity: < 4 Hz

55

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)

56

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

57

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 terapi

58

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

59

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

60

Dx Epilepsi

• Px Penunjang– EEG– Neuroimejing– Lab

Pedoman Tatlaksana Epilepsi

Pokdi Epilepsi Perdossi

2003

61

Dx Pasti Epilepsi

• Gejala dan tanda klinis bangkitan

• Gambaran epileptiform pada eeg

62

Algoritma diagnosis epilepsi

63

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


2003

64

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


2003

65

Tx Epilepsi

66

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

67

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

68

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

69

Classification of AnticonvulsantsAction on Ion

ChannelsEnhance GABA

Transmission

Inhibit EAA

TransmissionNa+:

Phenytoin, Carbamazepine, Lamotrigine

Topiramate

Valproic acid

Ca++:

Ethosuximide

Valproic acid

Benzodiazepines

(diazepam, clonazepam) Barbiturates (Fenobarbital)

Valproic acid

Gabapentin

Vigabatrin

Topiramate

Felbamate

Felbamate

Topiramate

Na+:

For general tonic-clonic and partial seizures

Ca++:

For Absence seizures

Most effective in myoclonic but also in tonic-clonic and partial

Clonazepam: for Absence

70

Classification of AnticonvulsantsClassical

• Phenytoin• Phenobarbital• Primidone• Carbamazepine• Ethosuximide• Valproic Acid• Trimethadione

Newer• Lamotrigine• Felbamate• Topiramate• Gabapentin• Tiagabine• Vigabatrin• Oxycarbazepine• Levetiracetam• Fosphenytoin• Others

71

• 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/kgMaintenance 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

discontinued after 7 to 10 days

PHENYTOIN

73

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

74

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 cause drowsiness

75

• 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 doses10-15 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 serum iron level prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision;

Carbamazepine

76

TERAPI ANTIOKSIDAN

DARAH hemolisis Fe++ atau Fe+++Hidrogen Peroksida (H2O2)Radikal Hidroksil (OH-)Radikal Superoksid (O2-)

Radikal Bebas

Peroksidasi Lipid

Aktivasi asam arakhidonat

Asam arakhidonik fosfitate (IP3)

Ca++ intrasel

Kerusakan eksitotoksik

Kematian neuraon/jar. Parut sel glia

AKTIFITAS EPILEPTIFORM

Tokoferol 2 mg/kg bb

Selenium

Peroksidase/ katalase

77

Dosis obat antiepilepsi

Phenytoin 100-200mg/h 5 mg/kgBB

Fenobarbital 30 mg/hari 3-4 mg/hari

Carbamazepin 100 mg 10-40 mg/kg/hr

Clonazepam 0,25 mg/hari

Sod.Valproat 400-500mg/h 20 mg/kgBB/hr

Gabapentin 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

78

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

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

4-12

10-20

50-150

10-40

5-12

40-120

none

79

GUIDELINES FOR DOSES OF 2nd LINE AEDS IN Adults (Brodie 1996, Browne 2001)

Drug Indication Starting

Dose

Maintenance dose

Plasma Half Life(hrs)

Plasma Binding

(%)

Gabapetin

Lamotrigine

Felbamat

Clobazam

Oxcarbazpn

Tiagabin

Topiramat

Vigabatrin

Zonisamide

Partial & SGTCS

(Adults)

Partial & SGTCS

(Adults)

Partial & SGTCS

(Adults)

L-G Syndrome

Partial & GTCS

Partial & GTCS

Partial & SGTCS

Partial & SGTCS

Partial & SGTCS

Possibly inf Spasm

Partial & SGTCS

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/q1-2wk

10mg qb or

2 x 10mg/d

2x300mg/d

Not available

100 mg/d

100mg/d/q1wk

2x500 mg/d

100-200 mg/d

1200-2400mg/d

Up to 700mg/d

(100-150mg/d with VP)

1800-4800mg/d

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

6

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

20-23

30-46

8-24

6-8

20-24

4-8(effect last 3 d)

30-68(27-38 with enzyme inducing drug)

0

54

22-25

85

40

96

10-20

Minimal

38-40

80

AEDS CHOICE BASED ON SEIZURE TYPE (Jarrar 2003)

Seizure type & subtype

First choice drug

Other options

Generalized

• infantile spasm

• absence

•Atonic

•Tonic

•Myoclonic

•Tonic-clonic

Partial

• with and without secondary generalization

corticotropin

Ethosuximide

Valproic acid

Valproic acid

Valproic acid

Valproic acid

Carbamazepin

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, tiagabine, gabapentin, VPA, phenobarbital, felbamat

81

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

82

Mechanisms of ActionAntiepileptic Drugs

• Sodium channel effects

• Potassium channels and GABA release

• GABAergic effects– Precursors, mimicry, and transporters

• Glutamate regulation-neuroprotection

• Calcium channels and transmitter release

83

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.

84

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.

85

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

86

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

87

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

88

Kesempatan untuk sekolah

o Tidak larangan untuk sekolaho 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

89

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

No syndromeSyndromeGeneralized, Partial, Partial secundary generalization, unclassified

Localization related Not localization related

90

Epilepsi Pasien Kejang

Psikogenik 1. Pencetus Biasanya tidak ada Tidak ada Faktor emosi

2. Suasana Biasa waktu tidur dan sendirian

Santai, sedikit orang Jarang waktu tidur, lingkungan banyak orang

3. Prodroma Jarang Biasa

4. Awal Biasa mendadak, mungkin ada aura

Mendadak, ada aura Berangsur dg meningkatnya emosi

5. Jeritan pada awal Biasa terjadi Tidak ada Tidak biasa

6. Fenomena motorik Stereotipe Stereotipe Bervariasi

7. Lidah tergigit Biasa terjadi Jarang terjadi

8. Kesadaran Dapat terjadi penurunan kesadaran

Tidak sadar Tidak terjadi

9. Pengekangan Tidak berpengaruh Tidak berpengaruh Dapat melawan, kdg menghentikan

10. Lama/durasi Biasanya pendek 3 – 5 menit Dapat memanjang

11. Henti serangan Biasanya pendek, kdg memanjang bila dg autisme. Biasanya bingung, menmgantuk atau tidur

Badan lemah dan agak bingung

Dapat berangsur, serig dg penampakan emosi: bingung, mengantu atau tidur tidak biasa terjadi

91

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

92

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

94

Promoting Control factors

• Adequate amount of AED in blood

• Adequate sleep and rest

• Correct AED

• Good Nutrition

• Alcohol Abstinence

• Fluid& electrolyte balance

• Low anxiety levelHandbook of epilepsy, Browne&Holmes

95

Glu

Glu

Glu

Ca2+

Ca2+

NM

DA

VS

CC

Na+

Ca2+

Na+

AMPANa+C

Na+

G l u

Inflammatorymediators

Depolari- zation

Celldistension

Membranedegradation

Free radicals

Enzymeinduction

Mitochondrialinjury

DNA injury

Apoptosis

Neuronal injury cascadeNeuronal injury cascadeDirnagl et al. Trends Neurosci 22:391-397

96

Glu

Glu

Glu

Ca2+

Ca2+

NM

DA

VS

CC

Na+

Ca2+

Na+

AMPA

Na+

G l u

Depolari-zation

Celldistension

Membranedegradation

Free radicals

Enzymeinduction

Na+C

Neuronal injury cascade / Action of AEDsNeuronal injury cascade / Action of AEDs

TopiramatePhenytoin

CarbamazepineValproic acidLamotrigine

Na+ channel blockers:

97

Glu

Glu

Glu

Ca2+

Ca2+

NM

DA

Na+

Ca2+

Na+

AMPA

Na+

G l u

Depolari- zation

Celldistension

Membranedegradation

Free radicals

Enzymeinduction

Na+C

VS

CC


FelbamateMK801

Ketamine

NMDA antagonists

98

Glu

Glu

Glu

Ca2+

Ca2+

NM

DA

Na+

Ca2+

Na+

AMPA

Na+

G l u

Depolari-zation

Celldistension

Membranedegradation

Free radicals

Enzymeinduction

Na+C

VS

CC


TopiramatePhenobarbital

AMPA antagonists

99

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)

100

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

101

• 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

Saraf 070830 Dr Epilepsi

Documents

Transcript of Saraf 070830 Dr Epilepsi