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Epilepsy 2

Dr. ZURAINI, Sp.S

Antiepileptic agents

Who should be treated after


two or more seizures?
Recurrence

after two seizures

80-90%
Two unprovoked seizures
Conventional recommendation for
most patients is to initiate therapy af
ter a minimum of two clearly describ
ed seizures
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Treat or not to Treat


The

risk of recurrence of seizures


is about 30-35% after the first
unprovoked seizure
The risk of recurrence is about
60% after second seizure

Drug Therapy
basic principles

Use a single drug whenever possible.


However, remember that roughly 60% of patients
are controlled on monotherapy.
Start low and go slow
Increase the dose of that drug to either seizure
control or toxicity (decreasing the dose if toxicity
occurs).
If a drug does not control seizures without
toxicity, switch to another appropriate drug used
alone, and again increase the dose until seizure c
ontrol occurs or toxicity intervenes.
5

Drug therapy
Partial and Secondarily
Generalized Seizures

Carbamazepine, phenytoin, and valproic acid are


the first-line agents among most specialists for pa
rtial and secondarily generalized seizures
Gabapentin, lamotrigine, oxcarbazepine,
tiagabine, topiramate, and levetiracetam are new
anticonvulsants that are recommended for treatm
ent of partial seizures.

Generalized seizures
Primary Generalized Seizures

Ethosuximide and valproic acid are effective for


treating absence seizures, but ethosuximide is no
t effective for treatment of primary generalized to
nic-clonic seizures.
lamotrigine
felbamate
zonisamide
topiramate
levetiracetam

J Neurol (2005) 252 : 125-130

What to start?
Treatment indicated
NO
Yes
Absence

Partial +/- Gen

Ethosuximide
Valproic acid

PHT
Phenobarb
CBZ

other

Phenobarb
PHT
Valproic acid
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How to start?

Use a first line drug for the seizure type


Start at a low dose
Gradually increase until seizure stop or
adverse effects develop start slow, go slo
w
If seizures remain uncontrolled, review the
diagnosis and underlying etiology
Substitute gradually another first-line drug
for the seizure type and increase dosage
until seizures stop or adverse effects devel
op
If necessary, try drug combination.
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Effectiveness of first antiepileptic drug


Newly diagnosed epilepsy
47%
Seizure free
First drug
Second drug
40%
Refractory
Rational duotherapy

13%

Seizure free

Surgical assessment
Epilepsia
11 2001;42:1255-60

Factors That Influence


Response to Medication

Consistent use
Inadequate dosage or
ineffective
medication
Drug factors
Disease
Seizures
eliminated
(50% of people)

Seizures do
not
respond
(20%)

Seizures markedly
reduced (30%)
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AED

Anti-epileptic agents
Mechanism

Side effect

Enzyme
involved

PHB

Prolong opening of
GABAergic Cl
channel, increase
GABA inhibition

Sedation
Cognitive slowing
Lupus-like

CYP2C, CYP3A
Microsomal EH,
UGT

PHT

Block voltage
dependent Na and
Ca channel, reduces
high freq. firing

Cerebellar
atrophy, ataxia,
megaloblastic
anemia, gingival
hyperplasia,
osteomalacia

CYP2C, CYP3A
Microsomal EH,
UGT

Carbamazepin
e

Blocks voltage
dependent Na and
Ca channels, reduces
high freq. firing

Sedation, ataxia,
CYP2C, CYP3A
hyponatremia,
Microsomal EH,
elevated LFT,
UGT
osteomalacia,
photosensitiviey13

AED

Anti-epileptic agents
Mechanism

Side effect

Enzyme
involved

Valproic acid

Blocks voltage
Tremor, weight
CYP2C, CYP3A
dependent Na and
gain, elevated
Microsomal EH,
Ca channel, reduces
LFTs, increase
UGT
high frequency firing,
bleeding,
? Potentiate GABA
thrombocytopenia
, PCOD,
pancreatitis,

Gabapentin

Increases brain GABA


levels, may work at
Ca channel

Somnolence,
fatique, ataxia,
weight gain,
edema

No effect on
hepatic
clearance,
renal
metabolism
>95%

LTG

Voltage dependent
Na channel blocker,
decreases release of

Rash, SJS,
nausea, dizziness

UGT

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AED

Anti-epileptic agents

TPM

Oxcarbamazepine

Levetiracetam

Mechanism

Side effect

Enzyme
involved

Blocks repetitive
neuron firing, block
kainate and AMPA
receptors, improve
GABA inhibition

Nephrolithiasis,
acute angle
closure glaucoma,
metabolic
acidosis,
anorexia, weight
loss

CYP2C19.
CYP3A4
Predominantly
renal excretion

As CBZ

Hyponatremia,
fatique ataxia

Metabolite by
cytosolic liver
enzymes and
renal excretion

Decrease high
voltage N-type Ca
channel

Personally
changes,
irritability

Renal
excretion
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Risk factors for recurrence

Etiologic factor and neurologic status


Age
EEG findings
Duration and number of seizures
Seizure type
Type of medication and serum drug
level
Duration of therapy
Method of withdrawal
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Etiologic factors and


Neurologic status

Complete seizure control


- remote symptomatic epilepsy < cryptogenic
epilepsy (RR 1.55)
26%

42%
P<0.005

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Age

Adolescent and adult-onset : poorer


prognosis
Good in <12 y/o (73%)
Remote symptomatic : poor prognosis
<2 y/o
No convincing data indicate that
withdrawing AEDs during puberty raises
the risk of recurrence

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EEG findings

In children : any electroencephalographic


abnormality increase risk
Change in EEG pattern between onset
and medication withdrawal
Only in cryptogenic epilepsy
Adult : inconclusive

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Duration and number of


seizures
seizure type

Duration and number


- Neither the duration nor number of
seizures
was associated with an increased of
recurrence
Seizure type
- no definite evidence
- prognosis : etiologic factors and specific
epileptic syndrome
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Type of medication and serum drug


level
- no correlation
Duration of therapy
- 2, 4 years
- higher in 1 year after onset
Methods of medication withdrawal
- abrupt discontinuation : seizure , SE
(normal level)
- as long as medication is not abruptly
withdraw, duration of taper does not aff
ect recurrence risk
- duration ?? : 1-3 months, 6-12 months
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Risk of discontinuing AEDs


Status

epilepticus : very low


Serious injury : low
Driving privileges
- recommend 6- 12 months
Job-related injuries
- risk : small
- considered carefully in each
individual
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Epilepsy Surgical
Treatment

A proportion of the pts with intractable


epilepsy will benefit from surgery.
Epilepsy surgery procedures: Curative
(removal of epileptic focus) and palliative (sei
zure-related risk decrease and improvement
of the QOL)
Curative (resective) procedures: Anteromesial
temporal resection, selective
amygdalohippocampectomy, extensive lesion
ectomy, cortical resection, hemispherectomy.
Palliative procedures: Corpus callosotomy and
Vagal nerve stimulation (VNS).

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Epilepsy Surgery
Factors influencing decision
Likelihood seizures are due to epilepsy
Likelihood surgery will help
Ability to identify focus of seizures
Other treatments attempted, and
seizures couldnt be treated with 2-3
medications
Benefits vs risks
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Vagus Nerve
Stimulation

Device is implanted to
control seizures by
delivering electrical
stimulation to the vagus
nerve in the neck, which
relays impulses to
widespread areas of the
brain
Used to treat partial
seizures when medication
Courtesy of Cyberonics Inc.
does not work

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Status Epilepticus

A condition when consciousness does not


return between seizures for more than 30 min
. This state may be life-threatening with the d
evelopment of pyrexia, deepening coma and
circullatory collapse. Death occurs in 5-10%.
Status epilepticus may occur with frontal lobe
lesions (incl. strokes), following head injury,
on reducing drug therapy, with alcohol withdr
awal, drug intoxication, metabolic disturbance
s or pregnancy.
Treatment: AEDs intravenously , event.
general anesthesia with propofol or thipenton
e should be commenced immediately.

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Approach to the treatment of status epilepticus in adults

Epilepsy in Women

Hormonal effects

Sexuality & contraception

Hormonal changes during puberty,


menopause, and the monthly cycle may affect
seizure frequency
Polycystic ovary syndrome
Sexual dysfunction
Birth control pills may be less effective

Pregnancy & motherhood

Need to continue medication


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Slight increased risk for birth defects

Epilepsy in Older Adults

Epilepsy is common in the elderly,


and is often unrecognized or
misdiagnosed
Older people face increased
treatment risks
Maintaining independence is a
challenge after the diagnosis of
epilepsy
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Groups at Increased Risk


for Epilepsy

About 1% of the general population


develops epilepsy
The risk is higher in people with
certain medical conditions:

Mental retardation
Cerebral palsy
Alzheimers disease
Stroke
Autism
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Utility of EEG

EEG should be obtained in all definite or


suspected seizure patients.
Epileptiform discharges on EEG support
diagnosis of epilepsy in appropriate clinical
setting
Epileptiform diacharges are not
pathognomonic for epilepsy: 0.5-2% of pat
ients without epilepsy can have these disc
harges
A normal EEG does not exclude diagnosis
of epilepsy
When epilepsy is suspected, sleepdeprived EEG is useful if routine 32EEG is nor

MR Imaging of Epilepsy
All

cases of partial epilepsy


Neonatal onset seizures
Seizure onset after age 20
Generalized Seizure not responsive
to medication
Presence of focal neurological signs

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Hippocampal

sclerosis
Malformations of cortical
development
Neoplasm
Vascular abnormalities
Gliosis and miscellaneous
abnormalities
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Cysticercosis

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lanjutan
Tidak
sembuh

Lanjutkan
terapi
Tidak kambuh
Selama > 2
th ?
ya
tidak
Hentikan
Kembali ke
pengobatan Assesment
awal

Efek samping dapat


ditoleransi ?
Tidak

Ya

Hentikan AED yang tdk Tingkatkan dosis


efektif,
AED2, cek interaks
Tambahkan AED2 yang
Cek kepatuhan
lain
Sembuh ?
Y
a
Lanjutkan
terapi

Tidak
Rekonfirmasi diagnosis,
Pertimbangkan
pembedahan

H
T

K
N
A

U
O
Y

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