EPILEPSI

J.Eko Wahono dr,SpS,MKes

Seksi Epilepsi
Lab/SMF IP Saraf
FK Unair/RSUD Dr Soetomo
Surabaya

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 PENDAHULUAN
 TIU :
 Mhs sm VII FK , akan dapat merencanakan
perawatan pt epilepsi dgn benar ~ PDT
 TIK :
 menyelaskan definisi
 menyelaskan epidemiologi
 menerangkan 3 mekanisme dasar epilepsi
 menguraikan klasifikasi
 menerangkan Gx klinis epilepsi
 menjelaskan rencana diagnosa & DD
 menguraikan aspek sosial epilepsi
 menjelaskan rencana terapi
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 Batasan
Epilepsi (WHO) :

kelainan otak kronik dgn berbagai causa

serangan epilepsi (seizure) berulang
ok bangkitan neuron berlebihan
 Gb klinis
 kejang
 perubahan tingkah laku
 perubahan kesadaran

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 Batasan
 Seizure :
 Manifestasi klinik dari bangkitan
hipersinkron, berlebihan dan abnormal
yang bersifat mendadak (paroxysmal)
dari populasi neuron kortek
 Epilepsi :
 Suatu kelainan neurologik yg bersifat
kronik dan ditandai seizure berulang
(recurrent seizure)

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 Batasan
status epilepsi

 Keadaan dimana serangan epilepsi

berlangsung lama ( > 5 menit )

 serangan epilepsi (seizure)

 berkali kali
 kesadaran diantaranya tak pulih

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 Recurrent

Acute seizure Serial seizure

Without full recovery

Prolonged
between seizure

Status epilepticus

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 Etiologi Epilepsi
Primary - Idiopathic

Symptomatic or Cerebrovascular

Cryptogenic (23%) CNS Neoplasma

5% 4% 4%
4%
3%
2% Congenital CNS
1%
Malformation
Trauma

CNS Infection

77% Other known

Primary – Birth asphyxia

Idiopathic (77%)

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Frekuensi relatif
Etiologi Epilepsi

Idiopathic

Vascular

Tumor

Herediter Trauma lahir Trauma

10 20 30 40 50 60 USIA

Perkiraan frekuensi macam-macam etiologi epilepsi berdasarkan usia

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 Epidemiologi 1

Insidens (pertahun) :Kasus baru yg timbul dlm masy

pertahun
• Epilepsi
(tak termasuk kejang tunggal & kejang demam) : 50 / 100.000
• Serangan tungal 20 / 100.000
• Kejang demam 50 / 100.000

Prevalens: semua kasus dlm masy pd saat tertentu

• Epilepsi aktif
(tak termasuk epilepsi inaktif & kejang demam) : 500 / 100.000
• Kasus yg pernah alami kejang 2000 / 100.000

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Origin and Spread of Seizure

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Origin & spread of seizure

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 3 mekanisme dasar
epilepsi
1. Altered neurotransmitter balance
 Increased glutamate ( excitatory )
 Decreased GABA ( inhibitory )
 Altered neuromodulator activity
2. Altered ionic homeostasis – K, Ca, Chloride
3. Rearrenged neuronal circuits
 loss of inhibitory synapses
 Overgrowrth of excitatory synapses
 Simplified circuits that improved neuronal
synchronization

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 Keseimbangan Neurotransmiter
eksitasi & inhibisi
Paradigm of rational AED
discovery

Excitation increase
Inhibition decrease
Seizure
Seizure
 Na+ channel antagonists
 Ca2+ channel antagonists  GABAA agonists
 Glutamate receptor antagonists  Enhanced GABA levels
Klitgaard. 3rd Global Epilepsy Summit, Cape Town152005
 Klasifikasi Epilepsi ILAE 1981
utk klinisi lebih praktis

I.Serangan Parsial
A. Serangan parsial sederhana
1. Dgn manifestasi motorik
2. Dgn manifestasi sensorik
3. Dgn manifestasi autonomik
4. Dgn manifestasi psikis
B. Serangan parsial kompleks
1. Seperti A1-4 pd awalnya disusul
serangan lena
2. Serangan lena pd awalnya (B1-2
diikuti otomatisme
C. Serangan umum sekunder

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II. Serangan umum
A. Serangan Lena
B. Serangan mioklonik
C. Serangan klonik
D. Serangan tonik
E. Serangan tonik klonik (Grand mal)
F. Serangan atonik ( astatik )

III. UNCLASIFIED
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 Klasifikasi epilepsi
ILAE 1989
 Partial epilepsy
 Idiopathic • simple partial
• complex partial
 Symptomatic
• secondary generalized
 Uncertain etiology
 Generalized epilepsy
 Idiopathic
 Symptomatic - West sy, Lennox gastaut

 Epilepsies undertemined focal or generalized

 Special syndromes
 Febrile convulsion
 Acute metabolic dearengement
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Gejala klinis epilepsi

Tergantung daerah otak mana yang terkena

serangan :

• Kejang
• Gg kesadaran sesaat
• Gg perilaku
• Gg penglihatan - penciuman

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Generalized Tonic- Clonic seizures

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Generalized Tonic-Clonic Seizures

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Absence Seizures

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Absence Seizures

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Simple Partial Seizures

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Complex partial Seizure

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Partial motor & Somatosensory Seizure

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Partial Sensory & Autonomic Seizures

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Automatism

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Epilepsy Syndrome

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 PRINSIP PRINSIP
DIAGNOSA EPILEPSI

Terutama -->
HT Ax klinis +
Dx epilepsi saksi

dampak sosial & ekonomi

Jangan buat Dx Ep pd orang bukan EP

Tunda Dx Ep  kerugian minimal
False positip  kerugian max

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 Diferential diagnosa
epilepsi

• Syncope
• Reflex syncope
• Cardiac syncope
• Perfusion failure
• Psychogenic attacks
• TIA
• Migrain
• Narcolepsy
• Hypoglycemia

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 DD Syncope vs Seizure
Syncope Seizure
Posture Upright Any
Pucat-Keringat Invariable Tak ada
Onset Gradual M’dadak - aura
Luka Jarang Sering
Convulsive jerk Jarang Sering
Incontinence Jarang Sering
Tak sadar Detik Menit
Recovery Segera Pelan pelan
Post ictal Jarang Sering
confustion
Precipating Tempat ramai Jarang
factor

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 DD Epileptic vs Pseudo Seizure
Epileptic.seiz Pseudo seizure
Onset M’dadak gradual

Pelvic trusting jarang Sering

Cyanosis sering jarang

Tongue bite sering Jarang

Stereo type attacks biasa Jarang

Resistance to passive eye Tak biasa Sering

opening

Prevention of hand falling jarang sering

into face
falling sering jarang

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Penyebab sistemik dari seizure

Fever Electrolyte imbalance

Hypoxia Drug witdrawal
Hypoglycemia Respiratory failure
Hepatic failure Pyridoxin deficiency
Drug Porphyria
Renal failure Inborn error metab
toxinism

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Causes of Seizure
Partial seizures

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 Kontibusi EEG
dalam DX Epilepsi ?

Kenyataan

•Abn EEG tidak selalu menunjukkan Epilepsi

•10 - 15 % populasi umum -- EEG nya ABN

•EEG yg normal, tidak kesampingkan Dx Epilepsi

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EEG

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Mechanisms of EEG

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 Peran EEG
dalam Dx Epilepsi

• Menambah bobot pada Dx klins

• Membantu nenentukan klasifikasi
epilepsi
• Memperlihatkan kemungkinan adanya
lesi strutural diotak

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 Peran CT scan kepala
dlm epilepsi

• 60 - 80 % pt epilepsi terdpt kel di CT scan

(atrophic) --- 10 % nya tumor otak
• CT scan pd semua pt Epilepsi BOROS
 CT pd serangan I --> false positip
 50 % pt epilepsi nofebrile = general EP
 Angka kejadian TO jarang diluar 20-65 th
 Pd usia 20-65 th pun, hanya 10 %= TO extrinsik
 90 % penyebab epilepsi = intrinsik

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PURPOSE OF EPILEPSY THERAPY

Stop the Epilepsy seizure as soon as

possible- but no harm pt

Allows pt develop themselves max,

normally within society should be

ekowr 2011 53
PURPOSE OF EPILEPSY THERAPY

Stop the Epilepsy seizure as soon as

possible- but no harm pt

Allows pt develop themselves max,

normally within society should be

ekowr 2011 54
 Epilepsy treatment

 Medical Care
Not only
 Surgical Care

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 EPILEPSY TREATMENT
CONDITIONS

Proper diagnosis must be met

AED only given if > 1 time seizure
Positive attitude to accuse AED , pt
should know :
importance of regular Tx
 target
 purpose Tx

ekowr 2011 56
 PRINCIPLES OF USING AED
The terms of use AED filled
Active Etiologic factors that must be
removed
Selection AED based on Dx & side effects
Initial Tx & small dose monotherapy
Gradual increase in AED
Monitor the side effects, idiosyncratic,
interaction
AED reduced gradually
Failed – surgery

ekowr 2011 57
The balance of neurotransmitters?
Excitation and inhibition
Paradigm of rational AED
discovery

Excitation increase
Inhibition decrease
Seizure
Seizure
 Na+ channel antagonists
 Ca2+ channel antagonists  GABAA agonists
 Glutamate receptor antagonists  Enhanced GABA levels
582005
Klitgaard. 3rd Global Epilepsy Summit, Cape Town
 Action of AED

1. Phenytoin
2. Cbz & oxcarbazepine
3. Lamotrigine
4. Felbamate
5. Topiramate
6. Ethosuximide (T) & oxcarbazepine (N.P/Q)
7. Ketamin
8. Mg2+
Action of AED
1. Phenobarbital –
open Cl channel
2. Benzodiazepine
3. Vigabatrine
4. Tiagabine
5. Gabapentine

Valproate : inhibit
reuptake GABA
& preventing
degradation
GABA & activasi
GAD
 Mode of Action of AED

AED Na Ca K Neuro Neuro

channel channel channel Trans Trans
Inhibisi exitasi
DPH +++ +
CBZ +++
VPA + + ++ +
ETZ +++
LUM +++
BZP +++ +

ekowr 2011 61
 MoA of New AED
AED Na Ca K Neuro Neuro
channel channel channe Trans Trans
l Inhibisi exitasi
GBP + + ++
LAM +++ +
OXC +++ + +
TPM ++ ++ ++ ++
TGB +++
ZON ++ ++ +++ +
LEV + + + +
FLB ++ + ++ ++
VGB ++
ekowr 2011 62
 Main mode of action AED
AED Main mode of action
CBZ Blocks voltage-dependent Na+ channels (Na), Block Ca
Clobazam Increase inhibition by GABAa (GABAa)
Clonazepam Increase inhibition by GABAa (GABAa)
Gabapentine Multiple (modifies Ca2+ channels & neurotransmitter
release)
Oxcarbazepine Blocks voltage-dependent Na+ channels (Na)
Phenobarbital Multiple (Na, Ca; GABAa, Glutamat)
Phenytoin Blocks voltage-dependent Na+ channels (Na)
Topiramate Multiple (Na, Ca; GABAa, Glutamat)
Valproate Multiple (Na, Ca; GABAa, Glutamat)
 Table
Focal
Secondarily Primarily Myoclonic
AED simple or Absance
GTCS GTCS jerk
complex

CBZ Effective Effective Effective Exaggerates Exaggerates

Effective
Clobazam Effective Effective Effective? Effective?
?
Exaggerates
Clonazepam Effective ? Effective ? ?
Effective Effective

Oxcarbama
Effective Effective Effective Exaggerates Exaggerates
zepine

Phenytoin Effective Effective Effective Ineffective Exaggerates

Valproate Effective Effective Effective Effective Effective

 Table
Focal
Secondarily Primarily Myoclonic
AED simple or Absance
GTCS GTCS jerk
complex

Gabapentine Effective Effective ineffective Exaggerates Exaggerates

Lamotrigine Effective Effective Effective Exaggerates Effective

Effective
Topiramate Effective Effective Effective Effective
?

vigabatrine Effective Effective Ineffective Exaggerates Exaggerates

Levetiracetam Effective Effective Effective Effective effective

Treatment/Evaluation Sequence for
Pharmacoresistent Epilepsy
1st Monotherapy AED Trial S z - f re e wit h 1s t A E D

S z - f re e wit h 2 nd A E D

S z - f re e wit h 3 rd
A E D / P o lyt he ra p y
2 Monotherapy AED Trial
nd
P h a rm a c o re s is t a n t

13%
47%

3rd Monotherapy/Polytherapy AED Trial

4%

Strongly consider videoEEG Monitoring 36%

Kwan P, Brodie MJ.

Non-epileptic Epilepsy NEJM;342:314-319.

Psychogenic, migraine, syncope, Epilepsy Surgery/VNS Therapy/

sleep disorders, movement disorder’s, etc.
Neuropace Evaluation

Polytherapy AED Trials Resective Surgery Stimulator Therapy

 SELECTION of AED ~ SEIZURE TYPE

JENIS OAE LINI OAE LINI OAE LAIN OAE HRS

BANGKITAN DIHINDARI
1 2
UMUM VPA, CBZ CLB,LEV, CZP,
LAM,TPM OXC PB,PHT

LENA VPA, CLB -- CBZ,GBPO

LAM TPM XC

MYOLONIC VPA,TPM CLB,LEV, -- CBZ,GBPO

TPM XC

ekowr 2011 67
 SELECTION of AED ~ SEIZURE TYPE
JENIS OAE LINI OAE LINI OAE LAIN OAE HRS
BANGKITAN DIHINDARI
1 2
TONIK VPA, LAM CLB,LEV, PB,PHT CBZ.OXC
OXC

ATONIK VPA, LAM CLB,LEV, PB CBZ,OXC,

OXC ACETAZOL PHT
AMIDE

FOKAL CBZ, OXC CLB,LEV CZP

VPA, LAM TPM,GBP PB --
TPM PHT,TGB ACETAZOL
AMIDE

ekowr 2011 68
 DRUGS THAT CAUSE EXACERBASI
epileptic seizure
 Aminophylline  Cocaine
 Amphetamine  INH
 Tramadol  Ketamine
 Cephalosporine, quinolone  Lidocaine
 Antidepresant  Lithium
 Procchlorperazine  Opiate
 CPZ  Oral Kontrasepsi
 Baclofen  Vincristine
 Donepezil

ekowr 2011 69
 Therapy for
new epileptic patient
• Diagnosis for Epilpesi without a doubt
• AED given when a seizure attack> 1 times
• AED selection based on the type Epilepsy
• MONO THERAPY
• Doses as low as possible
• Compliance
• if Failed Therapy •Compliance
•Diagnosis
•Precipitating F
•First line failed --> second line
•Progresif

ekowr 2011 70
 What to do?
WHEN first Line AED FAILED

2 OPTIONS :

Trying a new first-line OAE

 Adding a second line AED

ekowr 2011 71
 What to do? WHEN first Line AED
FAILED
Trying a new first-line AED

 Give another first line AED

 If success, draw the old first-line AED
gradually
 +  never subtherapeutic
 - ends with politherapy

ekowr 2011 72
 WHAT TO DO ?
WHEN first Line AED FAILED

Trying a new first-line OAE

 Give another first line AED

 Draw old first-line AED simultaneously

 +  side effects from combination therapy is rarely

 -  often subtherapeutic

ekowr 2011 73
 WHAT TO DO ?
WHEN first Line AED FAILED
Adding second line AED

 First line AED failed  second line

 not all second-line AED can be used For
monotherapy

 > 2 AED rarely improve efficacy Tx

 Severe epilepsy poorly controlled with 1 OAE is

better
 than less controlled 4 AED plus bonus side effect of more

ekowr 2011 74
 How to combine AED
 Combination therapy do when
 therapy using 2 different first-line AED failed
 First line AED seizures diminished, but not gone

 Choose AED that is not the same / similar mechanism

of action

 Assess whether the AED to be combined classified as

 Enzyme inhibiting drug
 Enzyme inducing drug
 Consider the possibility of additional side effects

ekowr 2011 75
 Treatment for
chronic epilepsy

• Epilepsy Diagnosis is needs to be check

• Search AED that has been used :
•Useful or not
•AED that has not been used

• Treat with 1 or maximum 2 AED

ekowr 2011 76
 Treatment for
chronic epilepsy
Choose AED useful, without toxic

Avoid sedatives

AED changes slowly,

give information to the patient about the

possibility of seizure recurrence

ekowr 2011 77
 Guidelines to withdraw AED
Free of seizure for at least 3 th
EEG normal, if ABN -- offer
No structural lesion
Each time only 1 AED which lwithdraw
Educate patient -- recurrence -- 25-35%
Max speed reduction is 25% of the last dose
If Relapse again , the dose is given as a dose before
withdrawal

ekowr 2011 78
 Epilepsy Patient with pregnancy

•: Prospective couples often ask

• How big is my child has a chance epilepsy?
• Is AED taken by the mother can cause disability in children?

• Birth defects ( Norwegian study )

• general population : 3.5 %
• mother with epilepsy : 4.4 %

ekowr 2011 79
Treatment of Epilepsy patients who are
pregnant
Guidelines :
• AED that has been able to control the seizures do
not need to be replaced
• Monotherapi
• Check the levels of AED serum 2 times before /
after
• Give Vitamin K 20 mg / day orally within the last
months of pregnancy
• Give Vitamin K 10 mg / day IM before labor
• Give As folate 1 mg / day prior to conception
• Give Education

ekowr 2011 80
 AED INTERACTION WITH ORAL
CONTRACEPTION
 lowering efficacy NOT

 CBZ VGB
 OXC GBP
 PHB TGB
 PHT VPA
 TPA CLB
 LAM CNZ
LEV

ekowr 2011 81
EEG Status Epilepsy

ekowr 2011 82
 Status epilepticus
should be immediately stopped because

The longer a seizure lasts

more difficult to to control and cause brain
damage

status epilepticus should be stopped

within 30 minutes

ekowr 2011 83
ACUTE MANAGEMENT OF TONIC
CLONIC SEIZURE

ekowr 2011 84
ACUTE MANAGEMENT OF TONIC CLONIC
SEIZURE

ekowr 2011 85
 SOCIAL ASPECTS OF EPILEPSY
at school

 The vast majority - an ordinary school

 The ability of children epilepsy depends
on :
Epilepsy, AED, environment
 In the event of a seizure in the
classroom it is necessary give a first aid
and explanations to his friends
 Children epilepsy ~ ~ ~ normal children

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 Epilepsy and jobs

Epileptic seizure is a brief event

beyond seizure attack is more
important
People with epilepsy who have
controlled their seizures = non-
epileptic

Not yet fully controlled epilepsy

requested to avoid jobs that endanger
themselves and others

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 Epilepsy and driving

May drive if :

Seizure free within at

least 2 years
seizures occur at night?
Normal EEG ?

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 Refractory Epilepsy
 DEFINITION
 Recurrent seizures despite
 AED levels are achieved within 1 year after
onset ultimate
 Seizure is true due to AED failed to control
the epileptic focus
 not because of :
 Incorrect dose
 Not obey taking AED

ekowr 2011 89
PREOPERATIVE EVALUATION

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RESECTIVE SURGERY

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DISCONECTIVE SURGERY

ekowr 2011 92
 Take home massage
“All substances are
poisons; there is
none which is not a
poison. The right
indication and dose
differentiates a
poison from a
remedy.”
Paracelsus (1493-1541)
 KESIMPULAN

Telah dibahas :
Definisi epilepsi
Epidemiologi
Patofisiologi epilepsi
Gx klinik epileps
Diagnosa & diagnosa banding
Aspek sosial epilepsi
Jenis Obat Anti Epilepsi
Rencana terapi epilepsi

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 Buku acuan
Neurology and Neurosurgery Illustrated 1997
Lindsay, KW, Bone, I Callander, R
A practical Approach to Epilepsy, ed Prof M.Dam
1991
Epilepsy Current Concepts 1996 ).Charles
Cockerell and Simon d Shorvon
Epilepsy, Fast Fact 2001Martin J Brodie
Practical Guide to Epilepsy. Manford,M 2003
Pedoman Tatalaksana Epilepsi. Edisi II.
Kelompok studi Epilepsi.Perdossi 2006
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