Clinical Practice Guidelines for epilepsy

Clinical Practice Guidelines for epilepsy

Clinical Practice Guidelines for epilepsy

 2

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Clinical Practice Guidelines for epilepsy

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..2534 ..2535 ..2541
..2543 5.9 7.2
1,000 65 3.8 4.7

1. 8 2552 21 2553
2. ()

28 2553
3. / () 10-11 2553

( )

11-0259pA-H.indd 3 8/29/11 5:10:08 PM



..
2545
2 .. 2546 .. 2548
.. 2549




.. 2549

3 ..2554

.. 2551
MRI CT EEG
4 Phenobarbital phenytoin Carbamazepine sodium valproate

Sodium valproate .. 2543

8.2 .. 2551 45.1

10

11-0259pA-H.indd 4 8/29/11 5:10:08 PM



1. .
2. ..
3. .
4. ...
5. .
6. ..
7. ...
8. ...
9. ...
10. ...
11. ...
12. ...
13. ...
14. .
15. ..
16. ..
17. .
18. .
19. .
20. ..
21. ..
22. ..
23. .
24. .
25. .
26. .
27. .
28. .
29. .
30. .
31. .
32. .

11-0259pA-H.indd 5 8/29/11 5:10:08 PM







3
1
2 12
3


1.

2. 1
3. 1

2 5
4.
5.

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1
1 : 10
2 14
3 21
4 24
5 31
6 34
7 44
8 (Status epilepticus) 48
9 (Febrile seizure) 58
10 Infantile spasms & West syndrome 63
11 (Epileptic surgery) 66
12 69

1 78
2 79
3 81
4 82
5 84
6 85
7 87
8 88
9 Ketogenic diet 90
10 92

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1 International classification of epilepsies and epileptic syndromes 17
(commission on classification and terminology of the ILAE, 1989)
2 24
3 35
4 36
5 (adverse reaction) 37
6 38
7 39
8 41
9 (AED interaction) 42
10 convulsive status epilepticus 52

11 53
12 71
13 72

1 3
2 4
3 5
4 6
5 7
6 8
7 9

11-0259pA-H.indd 8 8/29/11 5:10:10 PM





..
2545
2 .. 2546 .. 2548
.. 2549
.. 2547



.. 2549

.. 2551 MRI CT EEG
4 Phenobarbital phenytoin Carbamazepine sodium valproate

Sodium valproate .. 2543

8.2 .. 2551 45.1

10

11-0259p1-10.indd 1 8/29/11 5:10:40 PM

 2

11-0259p1-10.indd 2 8/29/11 5:10:41 PM

 1

( 1,2,3,4)

3 10,11
2
( 5) ( 8) ( 4) ( 3)
( 5)

3,4
( 6)

2-5
5
( 7) ( 6 35.)

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 2

- 1
Neurological deficit
Remote symptomatic
Partial Seizure
Abnormal EEG*
FHx of epilepsy**

- ***

- Reassure - Inform risk of seizure recurrence
- Advice seizure precaution, - May consider AEDs ( 5,6)
seizure first aid, avoidance of - Advice seizure precaution, seizure
provoking factors of seizure first aid, avoidance of provoking
- Advice risk of seizure recurrence factors of seizure
- Follow up - Inform potential side effect of medicine
- May consider neuro imaging ( 3)

* BECT
** idiopathic epilepsy
***


( 1)

11-0259p1-10.indd 4 8/29/11 5:10:43 PM

 3

*
( 1,2 1,2)

( 5)

( 4, 8, )

( 2) -

( 6, 2)
-
( 4, 6) ( 7, 2)

* Infantile spasm

11-0259p1-10.indd 5 8/29/11 5:10:44 PM

 4

( 2)

Absence seizure Generalized clonic seizure

Myoclonic seizure Generalized tonic-clonic seizure
Atonic seizure Simple / complex partial seizure
Tonic seizure
Unclassified seizure type

VPA 6, 3 PB, PHT, CBZ VPA 6, 3

( 8) ( 8)

( 5 7) ( 5 7)

11-0259p1-10.indd 6 8/29/11 5:10:45 PM

 5

( 6)
(Difficult to treat)

(Intractable Epilepsy)

/*
6,8 5

(Medical refractory)
()
( 7)

* MRI epilepsy protocol

* psycho-social
*
* focal MRI Mesial temporal sclerosis

11-0259p1-10.indd 7 8/29/11 5:10:47 PM

 6

* ( 9 1 84)

( 9)

**

Febrile seizure
-
-
-
( 2)
-
-
-
-
-

*
** 1.
1) 12 12-18

2)
-
- 5
- anterior fontanel
2.

11-0259p1-10.indd 8 8/29/11 5:10:48 PM

 7

( 11)

( 11) ( 6)

( 12)

:
1) 2 ,
MRI hippocampal sclerosis, malformation of cortical development

2) MRI Brain with contrast brain tumor, vascular
malformation

11-0259p1-10.indd 9 8/29/11 5:10:49 PM

 1
:

1. (preictal symptoms)
(prodromes)

(aura) (simple
partial seizure)


cognitive function



(complex partial seizure)

2. (seizure symptoms)


(associated symptom)

10

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(automatism)

complex partial

seizure absence seizure

(autonomic nervous system)

1) (sudden onset, paroxysm)
2) 5
status epilepticus
3) (precipitating factor)
4) (stereotype)

3. (postictal symptoms)
complex
partial generalized seizure

(Todds paralysis)
24

4. (precipitating or trigger factors)



5.



6.

11

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 7.


8. (psychosocial history)



9.
tuberous sclerosis, neurofibromatosis


1.
: , atrial fibrillation , hypertension
:
cranial bruit

- Axillary freckling, cafe-au-lait spots neurofibromatosis
- Port wine stain Sturge-Weber syndrome
- Facial sebaceous adenoma, ash leaf spots, shagreen patch tuberous sclerosis
- Spider nevi, palmar erythema chronic liver disease
- Pallor, ecchymoses and hematomas, pruritus, excoriations, poor skin turgor, dry

mucous membranes chronic renal failure

- Signs of needle marks intravenous drug abuse


2.

12

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1. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in

children: report of the quality standards subcommittee of the American Academy of

Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology

2000;55:616-23.
2. Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent

unprovoked first seizure in adults (an evidence-based review): report of the Quality

Standards Subcommittee of the American Academy of Neurology and the American

Epilepsy Society. Neurology 2007;69:1996-2007.

3. Aicardi J. Epilepsy and other seizure disorders. In: Diseases of the nervous system in

chidlhood. Oxford : Blackwell Scientific Publications, 1992:991-1000.

4. Annegers JF, Hauser WA, Beghi E, Nicolosi A, Kurland LT. The risk of unprovoked seizures

after encephalitis and meningitis. Neurology. 1988; 38:1407-10.

5. Prego-Lopez M, Devinsky O. Evaluation of a first seizure. Is it epilepsy? Postgrad Med 2002;

111:34-6, 43-8.
6. Prego-Lopez M, Devinsky O. Evaluation of a first seizure. Is it epilepsy? Postgrad Med 2002;

111:34-6, 43-8.

13

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 2

(seizure)
(epileptiform activity)



(provoked seizure) ( 5)


International League Against Epilepsy (ILAE) classification 1981 3

1. Partial seizure cortical area

simple partial seizure (
) complex partial
seizure ()
1.1 Simple partial seizure ()
occipital
motor cortex /
sensory cortex
1.2 Complex partial seizure ()

automatism
2-3
postictal phase

1.3 Partial seizure evolving to secondarily generalized tonic clonic seizure

2. Generalized seizure 2

14

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2.1 Absence seizure ()
2.1.1 Typical absence 4-20
10 automatism postictal
phase 100

2.1.2 Atypical absence typical
absence
2.2 Generalized tonic-clonic seizure ()

5 postictal phase

2.3 Generalized clonic seizure ()

2.4 Generalized tonic seizure ()

2.5 Atonic seizure ()

2.6 Myoclonic seizure ()



3. Unclassified seizure

(epilepsy) (provoking factor)

epileptiform discharge


(provoked seizure)

International League Against Epilepsy classification of
epilepsies and epileptic syndromes 1989

15

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 4
( 1)
1. Localization related (focal) epilepsy partial
seizure
2. Generalized epilepsy generalized seizure
cortical area 2
3. Undetermined epilepsy
localization related epilepsy generalized epilepsy
4. Special syndrome


3
1. Idiopathic

2. Symptomatic

3. Cryptogenic


ILAE .. 1981 ILAE
classification of epilepsies and epileptic syndromes .. 1989

16

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 1 International Classification of Epilepsies and Epileptic Syndromes (Commission on
Classification and Terminology of the ILAE, 1989)

1. Localization-related (focal, local, partial) epilepsies and syndromes
1.1 Idiopathic (with age-related onset)
Benign childhood epilepsy with centrotemporal spikes Childhood epilepsy with occipital

paroxysms Primary reading epilepsy

1.2 Symptomatic
Chronic progressive epilepsia partialis continua of childhood (Kojewnikows syndrome)

Syndromes characterized by seizure with specific modes of precipitation (i.e. reflex

epilepsy) Temporal lobe epilepsy (amygdalohippocampal, lateral) Frontal lobe epilepsies

(supplementary motor, cingulate, anterior frontopolar, orbitofrontal, dorsolateral,

opercular, motor cortex) Parietal lobe epilepsies Occipital lobe epilepsies

1.3 Cryptogenic
2. Generalized epilepsies and syndromes
2.1 Idiopathic (with age-related onset)
Benign neonatal familial convulsions Benign neonatal convulsions Benign myoclonic

epilepsy in infancy Childhood absence epilepsy Juvenile absence epilepsy (pyknolepsy)

Juvenile myoclonic epilepsy (impulsive petit mal) Epilepsy with grand mal seizures

(generalized tonic-clonic seizures) on awakening Other generalized idiopathic epilepsies

not defined above Epilepsies with seizures precipitated by specific modes of activation
2.2 Cryptogenic or symptomatic
West syndrome (infantile spasms, Blitz-Nick-Salaam Krampfe) Lennox-Gastaut syndrome

Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences

2.3 Symptomatic
2.3.1 Nonspecific cause
Early myoclonic encephalopathy Early infantile epileptic encephalopathy with

suppression-burst Other symptomatic generalized epilepsies not defined above

2.3.2 Specific syndromes
Epileptic seizures complicating disease states
3. Epilepsies and syndromes undetermined whether focal or generalized
3.1 With both generalized and focal seizures
Neonatal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous

spike-wave activity during slow-wave sleep Acquired epileptic aphasia (Landau-Kleffner

syndrome) Other undetermined epilepsies not defined above

3.2 Without unequivocal generalized or focal features
4. Special syndromes
4.1 Situation-related seizures
Febrile convulsions Isolated seizures or isolated status epilepticus Seizures occurring only

with acute metabolic or toxic event

17

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Benign childhood epilepsy with centrotemporal spikes (Benign rolandic epilepsy)
3-15





Frontal lobe epilepsy
frontal lobe
simple, complex partial seizure (secondarily generalized seizure)
complex partial seizure frontal lobe epilepsy
(hyperkinetic movement) (vocalization)
(versive seizure) (automatism)
(bipedal) (pelvic thrust) (sexual
automatism)
postictal aphasia Todds paralysis
artifact
MRI
temporal lobe epilepsy

Temporal lobe epilepsy
temporal lobe
30 febrile seizure complex febrile seizure
simple, complex partial seizure secondarily generalized seizure
(epigastric sensation) (autonomic
features) (psychic symptoms)
(dj vu) (jamai vu)
(olfactory/gustatory symptoms) (visual
phenomenon) temporal lobe epilepsy
automatism (oroalimentary)
(bimanual) (gestural) MRI

18

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 Parietal lobe epilepsy
parietal lobe
complex partial
seizure secondarily generalized seizure

Occipital lobe epilepsy
occipital lobe
visual hallucination positive phenomenon ( )
negative phenomenon ( ) visual illusion (
) complex partial seizure secondarily generalized seizure

Childhood absence epilepsy
4-10 5-7

4-20
automatism ( 10 /)
hyperventilation 3 Hz generalized spike and wave
complexes

Juvenile absence epilepsy
7-16 10-12
childhood absence epilepsy
3.5-4.0 Hz generalized spike and wave complexes

Juvenile myoclonic epilepsy (JME)
12-30
myoclonic seizure, absence generalized tonic-clonic seizure
generalized polyspike and wave-complexes 3.5-4.5 Hz
frontal



West syndrome (infantile spasms, Blitz-Nick-Salaam Krampfe) 9

Lennox-Gastaut syndrome
1-10
atypical absence, generalized tonic clonic seizure, atonic seizure (drop attack),

19

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 focal motor seizure 1-2.5 Hz slow spike and
wave complexes run of rapid spikes


Acquired epileptic aphasia (Landau-Kleffner syndrome)
4-8

spikes centrotemporal area




1. Bendadis SR. Epileptic seizures and syndrome. Neurol Clinic 2001; 19: 251-70.
2. Commission on Classification and Terminology of the International League Against Epilepsy.

Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 1985; 26:268-78.
3. Commission on Classification and Terminology of the International League Against Epilepsy.

Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;

30:389-99.
4. Commission on Classification and Termionology of the International League Against

Epilepsy. Proposal for revised clinical and eletro-encephalographic classification of epileptic

seizures. Epilepsia 1981; 22:489-501.

5. Commission on Pediatric Epilepsy of the International League Against Epilepsy. Workshop

on infantile spasms. Epilepsia 1992; 33:195.

20

11-0259-p11-52.indd 20 8/29/11 5:11:21 PM

 3

(acute symptomatic
seizure)

1.
2. (seizure type and epileptic syndrome)
(seizure focus)
3.
4.

3
1.
2. electroencephalography (EEG), single photon emission
computerized tomography (SPECT), positron emission tomography (PET)
3. computed tomography (CT), magnetic resonance imaging (MRI)




CBC, blood sugar, serum electrolytes, BUN, creatinine, LFT
calcium serum magnesium, toxicology screening, metabolic screening

21

11-0259-p11-52.indd 21 8/29/11 5:11:22 PM



1.
2.
3.
18



(Electroencephalography, EEG)

1. epileptiform discharges
2.
3.
epileptiform discharges 50
3-4
24




(neuroimaging)
MRI
CT scan mesial temporal sclerosis,
cortical dysplasia temporal lobe

(neuroimaging)
1. localization related
2.
3.
4. (intractable epilepsy)
5.
CT scan MRI
1.
2.
3.

22

11-0259-p11-52.indd 22 8/29/11 5:11:22 PM

 4.
MRI CT scan
1.
2. temporal lobe
3. cortical dysplasia
4.

neuroimaging

1. generalized tonic clonic
2. partial

(non-progressive brain lesion)
3. partial



1. Cascino GD. Use of routine and video electroencephalography. Neurol Clinic 2001; 19: 271-87.
2. Chiran C.ILAE Imaging Commission. Recommendations for neuroimaging of patients with

epilepsy. In: The use of neuroimaging techiques in the diagnosis and treatment of epilepsy.

Second Europian Epileptology Congress Education Course. The Hage, Netherlands :

September 1,1996:1-7.
3. Fabinyi G. Operative Diagnostic Methods in the Treatment of Epilepsy. In: Kaye AH, Black

PMcL, eds. Operative Neurosurgery. London: Churchill Livington 2000, p1251-58.

4. King MA, Newton MR, Jackson GD, Fitt GJ, Mitchell LA, Silvapulle MJ, Berkovic SF.

Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and

magnetic resonance imaging study of 300 consecutive patients. Lancet 1998; 352 :1007-11.
5. Kuzniecky RI. Neuroimaging in pediatric epilepsy. Epilepsia 1996; 37 (Suppl 1):S10-S21.
6. Neufeld MY, Chistik V, Vishne TH, Korczyn AD. The diagnostic aid of routine EEG findings in

patients presenting with a presumed first-ever unprovoked seizure. Epilepsy Res 2000;

42:197-202.
7. Ramirez-Lassepas M, Cipolle RJ, Morillo LR, Gumnit RJ. Value of computed tomographic

scan in the evaluation of adult patients after their first seizure. Ann Neurol 1984; 15:536-43.
8. Schreiner A, Pohlmann-Eden B. Value of the early electroencephalogram after a first

unprovoked seizure. Clin Electroencephalogr 2003; 34:140-4.

23

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 4

( 2)
2
Late childhood
Newborn Infancy-early childhood adolescent-adult Adult

Generalized Breath holding Syncope

tonic-clonic Benign paroxysmal torticollis Psychogenic
Sandifer syndrome non-epileptic attack
- panic attack
- hyperventilation
syndrome
Complex Night terrors Migraine Transient global
partial Sleep walking Sleep disorders amnesia
seizure (somnambulism)
REM sleep behavior disorder
Myoclonic Benign Benign paroxysmal Tics / tourette
neonatal sleep myoclonus of early infancy Physiologic or
myoclonus Opsoclonus/myoclonus nocturnal
Hypnagogic myoclonic jerk myoclonus
(sleep startles)
Atonic Syncope Brainstem CVA
Cataplexy
Narcolepsy
Absence Daydreaming
Jitteriness Stereotyped movement Movement disorders Periodic limb
Non - Shuddering Metabolic disorders movement in
convulsive - Spasmus nutans Psychogenic sleep
apnea Self-stimulation (gratification) disorders Recurrent TIA
Self-stimulation activities (transient
Benign paroxysmal vertigo of ischemic attack)
childhood
Cyclic vomiting syndrome

24

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 (Newborn)
(Jitteriness)

hypoxic-ischemic
encephalopathy

Non convulsive apnea
(irregular respiratory pattern)
3-6 1-10


Benign neonatal sleep myoclonus
1-2
1-2 1-2
rapid eye movements (REM)
3-4

(Infancy-early childhood)

(Breath holding spell)
6 5 2
1. Cyanotic breath holding spell


2. Pallid breath holding spell

( 8 )


Benign paroxysmal torticollis
2 3

25

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 Sandifer syndrome





Self-gratification disorders
3 5
(dystonia) (moaning, grunting)



Self-stimulation activities Stereotyped movement

Shuddering
8-10 /

210

Cyclic vomiting syndrome
39
EEG slow wave
spikes

benign
paroxysmal vertigo of childhood cyclic vomiting syndrome precursor migraine

Benign non-epileptic myoclonus of early infancy
612

12

26

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Opsoclonus-myoclonus

(dancing eyes, dancing feet)
neuroblastoma ganglioneuroblastoma
CMV, EBV
autoimmune

Sleep disorders
1. Non-REM parasomnias (Night terrors and sleep walking)

slow wave sleep
partial seizure
nocturnal frontal lobe epilepsy

Hypnagogic myoclonic jerks (sleep startles)

Benign paroxysmal vertigo of childhood
1 5

(nystagmus) 1


( Late childhood adolescent-adult )
Psychogenic non-epileptic seizure
conversion
disorder malingering
pseudoseizure epileptic seizure
pseudoseizure

27

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 (non-stereotyped)


complex partial seizure
(postictal phase)

(Migraine)
classical migraine

(scintillation) (fortification spectra) (scotoma)
partial seizure migraine


Sleep disorders
1. Obstructive sleep apnea

nocturnal epilepsy
2. Periodic limb movement in sleep
restless
leg syndrome (peripheral neuropathy)


3. Narcolepsy

(sleep attack)
(cataplexy)
atonic seizure

(Syncope)



(autonomic symptoms)
(convulsive syncope) tonic
clonic seizure

28

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 Hyperventilation syndrome



Movement disorders
hemi-facial spasm, tics,
Tourettes syndrome, chorea, dystonia, tonic spasms of multiple sclerosis, subcortical myoclonus

(Transient ischemic attack, TIA)
24

Transient global amnesia
(recent memory)

non-convulsive epileptiform
discharge

Metabolic disorders
hypoglycemia,
hyperglycemia, hyponatremia / hypernatremia, hypocalcemia, hypomagnesemia

Psychogenic disorders
1. Panic attacks
hyperventilation

simple partial sensory seizure
2. Psychosis
hallucination delusion complex partial seizure

29

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 Benign paroxysmal positional vertigo
(vertigo)

repositioning exercise

Physiologic or nocturnal myoclonus





1. Paroxsymal / Non-epileptic events. : Epilepsy digest :

2002 ;1 : 4-9.
2. Bruni J.Episodic impairment of consciousness. In: Bradley WG, Daroff RB, Fenichel GM,

Marsden CD, eds. Neurology in clinical practice, principles of diagnosis and management.

3rd ed. Boston:Butterworth-Heinemann, 2000.

3. Chadwick D, Smith D. The misdiagnosis of epilepsy. BMJ 2002; 324:495-6.

30

11-0259-p11-52.indd 30 8/29/11 5:11:24 PM

 5

2 ( 2)
1. Provoked seizure seizure threshold

- alcohol drug withdrawal benzodiazepine
- hypoglycemia, hyperglycemia, hyponatremia, hypocalcemia
- CNS stimulant amphetamine
- Eclampsia
-
-
-
Provoked seizure seizure threshold

2. Unprovoked seizure

25-50
( 1, 3)

(first unprovoked seizure)


( 4)

25-50 80
2 2
idiopathic partial epilepsy 2

31

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-

-
-

- partial idiopathic partial epilepsy ( 2)
- epileptiform discharge
( 1 84)
( 8) seizure threshold

( 2 85)

( 3)
1

(unprovoked seizure) (epilepsy)

( 4)
benign rolandic
epilepsy (benign childhood epilepsy with centro-temporal spike, BECT)


( 6)




1. Berg AT, Levy SR, Testa FM, Shinnar S. Treatment of newly diagnosed pediatric epilepsy: a

community-based study. Arch Pediatr Adolesc Med 1999 ;153:1267-71.

2. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed

neurocysticercosis.Neurology 2002 ; 59:1730-4.

3. Cutting S, Lauchheimer A, Barr W, Devinsky O. Adult-onset idiopathic generalized epilepsy:

clinical and behavioral features. Epilepsia 2001; 42:1395-8.

4. Glauser T, Ben-Meachem E, ILAE treatment guidelines: evidence-based analysis of

antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures

and syndromes. Epilepsia 2006; 47:1094-120.

5. Guerrini R, Arzimanoglou A, Brouwer O. Rationale for treating epilepsy in children.

32

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 Epileptic disord 2002;4 (suppl 2) : S9-S21.
6. Hauser WA, Anderson VE, Loewenson RB, McRoberts SM. Seizure recurrence after a first

unprovoked seizure. N Engl J Med 1982; 307:522-8.

7. Hauser WA, Annegers. JF, Kurdland LT. The incidence of epilepsy and unprovoked seizure

in Rochester, Minnesota. Epilepsia 1993; 34:453-68.

8. Herman ST. Single Unprovoked Seizures. Curr Treat Options Neurol. 2004; 6:243-255.
9. Hirtz D, Berg A, Bettis D, Camfield C, Camfield P, Crumrine P, Gaillard WD, Schneider S,

Shinnar S; Quality Subcommittee of the American Academy of Neurology: Practice

Committee of the Child Neurology Society. Practice parameter: treatment of the child

with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the

American Academy of Neurology and the Practice Committee of the Child Neurology.

Neurology 2003; 60:166-75.

10. Iudice A, Murri L. Pharmacological prophylaxis of post-traumatic epilepsy. Drugs 2000;

59:1091-9.
11. Lindsten H, Stenlund H, Forsgren L. Seizure recurrence in adults after a newly diagnosed

unprovoked epileptic seizure. Acta Neurol Scand. 2001; 104:202-7.

12. Musicco M, Beghi E, Solari A, Viani F. Treatment of first tonic-clonic seizure does not

improve the prognosis of epilepsy. First Seizure Trial Group (FIRST Group). Neurology 1997;

49:991-8.
13. Rennie JM, Boylan GB. Neonatal seizures and their treatment. Curr Opin Neurol 2003;

16:177-81.
14. Sankar R. Initial treatment of epilepsy with antiepileptic drugs: pediatric issues 2004; 63

(10 suppl 4): S 30-9.

15. Schierhout G, Roberts I.Anti-epileptic drugs for preventing seizures following acute t

raumatic brain injury. Cochrane Database Syst Rev 2001; (4):CD000173 .

16. Shinnar S, Berg AT, ODell C, Newstein D, Moshe SL, Hauser WA. Predictors of multiple

seizures in a cohort of children prospectively followed from the time of their first

unprovoked seizure. Ann Neurol 2000; 48:140-7.

17. Shorvon SD. Medical assessment and treatment of epilepsy. Br Med J 1991; 302;363-6.

33

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 6

1.

( 5
2, 3)
2. ( 3)
(broad spectrum
AEDs)
3.
3.1 (monotherapy) 6070

(drug interaction)

3.2 (low maintenance
dose) carbamazepine, topiramate, lamotrigine

low maintenance dose
6
3.3 (status epilepticus)
( 7)
(oral loading dose)
4.

(maximal tolerated
dose) (maximal maintenance dose)

2

( 44)
5. ( 5)

34

11-0259-p11-52.indd 34 8/29/11 5:11:25 PM

 ( 2
( 85)

3



()

Absence Sodium valproate Lamotrigine Clonazepam
Myoclonic, atonic, tonic Sodium valproate Topiramate*
Lamotrigine*
Clonazepam
Nitrazepam
Levetiracetam
Generalized tonic clonic Phenobarbital Lamotrigine Oxcarbazepine Levetiracetam
Sodium valproate Topiramate Clonazepam
Phenytoin Clobazam
Carbamazepine
Partial Carbamazepine Lamotrigine Oxcarbazepine Gabapentin
Phenytoin Topiramate Clonazepam
Sodium valproate Levetiracetam Clobazam
Phenobarbital Pregabalin
Infantile spasms Vigabatrin Sodium valproate
Nitrazepam
Clonazepam
Clobazam
Topiramate

* Lennox-Gastaut Syndrome
( 10 98)

35

11-0259-p11-52.indd 35 8/29/11 5:11:25 PM

11-0259-p11-52.indd 36
4

Drug Dosing regimen Ped initial dose Ped escalation Ped usual dose Adult initial dose Adult escalation Adult usual dose Time to steady
(mg/kg/day) (mg/kg/day) (mg/day) (mg/day) state (day)

36
Carbamazepine bid-tid 10-15 5 mg/kg/wk 10-30 200 200 mg/wk 600-1200 3-4
Gabapentin tid-qid 10 300 mg/d 30-100 300 300 mg/day 900-3600 1-2
Lamotrigine bid ** **** && * *** & 3-10
Levetiracetam bid 10 10 mg/kg/wk 20-80 500 500 mg/wk 1000-3000 2
Oxcarbazepine bid 10 10 mg/kg/wk 20-50 150-300 300 mg/wk 600-2400 2
Phenobarbital od-bid 4-6 1-2 mg/kg/2wk 3-5 60-90 30 mg/4wk 90-120 15-20
Phenytoin od-bid 5 1-2 mg/kg/2 wk 5-8 200-300 50-100 mg/wk 300-500 15-20
Pregabalin bid NA NA NA 75-150 75 mg/wk 150-600 < 2
Sodium valproate bid-tid 10-15 5-10 mg/kg/wk 20-60 500-1000 200-250 mg/wk 1000-3000 2
Topiramate bid 1 1 mg/kg/wk 5-9 25-50 25 mg/wk 200-400 3-5
Vigabatrin bid 40-50 10-20 mg/kg/wk 100-150 500-1000 500 mg/wk 2000-4000 2

* 25 mg/day monotherapy, 25 mg/alternate day with VPA, 50 mg/day with inducer
** 0.5 mg/kg/day monotherapy, 0.1-0.3 mg/kg/day with VPA, 1 mg/kg/day with inducer
*** 25 mg/wk monotherapy, slowly titration with VPA, 50 mg/wk with inducer
**** 0.5 mg/kg/2 wk monotherpy, 0.1-0.3 mg/kg/2 wk with VPA, 1 mg/kg/d with inducer
& 150-400 mg/day monotherapy, 100-300 mg/kg/day with VPA, 200-800 mg/kg/day with inducer
&& 10 mg/kg/day monotherapy, 5 mg/kg/day with VPA, 15 mg/kg/day with inducer

8/29/11 5:11:26 PM
 5 (adverse reaction)

Carbamazepine Stevens Johnson syndrome*,
SIADH, aplastic anemia

Clonazepam hypotonia ()

Gabapentin
Lamotrigine Stevens-Johnson syndrome
Levetiracetam
Nitrazepam Hypotonia
Oxcarbazepine Hyponatremia
Phenobarbital : Stevens-Johnson syndrome, serum
sickness
:

Phenytoin (nystagmus) Stevens-Johnson syndrome
choreo-athetosis
hirsutism

megaloblastic anemia (folate deficiency)
Pregabalin
Sodium valproate hyperammonemia
hyperammonemia
Topiramate

Vigabatrin

* HLA B-1502*

37

11-0259-p11-52.indd 37 8/29/11 5:11:26 PM

 6
Route of Half life (hr) Half life (hr) Therapeutic Protein
Drug Elimination (adult) (hr) (ped) (hr) range (g/ml) binding (%)
Carbamazepine Hepatic 14-27 14-27 (children) 4-12 75
8-28 (neonates)
Gabapentin Renal 5-7 ** 0
Lamotrigine Hepatic 15-30 ** 55
Levetiracetam Renal 7-8 ** <10
Oxcarbazepine Hepatic 8-10 ** 40
(MHD*)
Phenobarbital Hepatic 40-136 37-73 10-40 40-60
Phenytoin Hepatic 12-36 5-14 (children) 10-20 69-96
10-60 (neonates)
Pregabalin Renal 5-7 NA ** 0
Sodium valproate Hepatic 6-15 8-15 50-150 80-95
Topiramate Renal (70%) 20-30 ** 15
Vigabatrin Renal 5-7 ** 0

* MHD : monohydroxy derivative
**

6. ( 6)
6.1 (half life, T ) T carbamazepine, Sodium valproate
2-3 T 24 phenytoin, phenobarbital
1
6.2 Steady state
steady state 5 T
steady state


7. (preparation)
bioavailability


phenytoin (nasogastric tube)

38

11-0259-p11-52.indd 38 8/29/11 5:11:27 PM

 (infatab)
3 2
controlled or sustained release
release
8. ( 7)
7

1.
2.

3.
4.

5.

dose-response relationship

upper level sub-toxic level therapeutic range
Therapeutic range ( 6)

upper
limit therapeutic range
lower limit therapeutic range


total level
(trough level)
steady state
(drug interaction) free drug
level
(compliance)
9. (efficacy)

(seizure free)

39

11-0259-p11-52.indd 39 8/29/11 5:11:27 PM



aura motor
aura
(global assessment)
(effectiveness)
(psychosocial)

10. (adverse reaction) ( 5)

3
. (toxicity)

. (idiosyncrasy)
Stevens-Johnson syndrome 1-3 2

Stevens-Johnson syndrome phenobarbital, phenytoin,
carbamazepine, oxcarbazepine, lamotrigine
benzodiazepine
. (teratogenicity)
( 5 90)
11.

(paroxysmal disorders) syncope,
tics, abnormal movements, breath holding spell, hyperventilation syndrome ( 4)
-

- absence
seizure carbamazepine phenytoin
-
-


-

-

40

11-0259-p11-52.indd 40 8/29/11 5:11:27 PM

 12. (drug interaction) 1
( 8, 9)

Carbamazepine
Phenobarbital
Phenytoin

Sodium valproate

Alcohol
Nicotine
Oral contraceptives
Steroid
Phenothiazine
Rifampicin

Allopurinol
Chloramphenical
Cimetidine
Coumadins
Diltiazem Ca-channel blocker
Disulfiram
Erythromycin
Isoniazid
Para-aminosalicylic acid
Propranolol
Propoxyphene
Sulfa drugs

41

11-0259-p11-52.indd 41 8/29/11 5:11:28 PM

 9 (AED interaction)

Drug Effect on other drugs

Carbamazepine phenobarbital
Sodium valproate, topiramate
phenytoin
Gabapentin None
Lamotrigine None
Sodium phenytoin(free), phenobarbital, 10,11-epoxide of carbamazepine
valproate phenytoin(total), carbamazepine
Phenobarbital carbamazepine, Sodium valproate
phenytoin
Phenytoin carbamazepine, Sodium valproate
phenobarbital
Topiramate phenytoin
Sodium valproate

13.
2






- 4-8
-
1.
2.
3.
-



1.

42

11-0259-p11-52.indd 42 8/29/11 5:11:28 PM

 1.1 Juvenile myoclonic epilepsy, Lennox-Gastaut
syndrome
1.2 Benign Rolandic epilepsy (Benign childhood
epilepsy with centro-temporal spike)
2. (remote symptomatic epilepsy)
(cryptogenic epilepsy)
3.

4.



status epilepticus



5




1. Davies J, Richens A. Neuropharmacology. In: Laidlaw J, Richns A, Chadwick D, eds. A

textbook of epilepsy. London: Churchill Livingstone, 1993:475-87.

2. Engel J Jr. Pharmacological treatment of epilepsy. In: Engel J Jr,ed. Seizures and epilepsy.

Philadelphai: FA Davis 1989:381-98.

3. Holland KD. Efficacy, pharmacology, and adverse effects of antiepileptic drugs. Neurol

Clinic 2001; 19: 313-345.

4. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Prognostic index for

recurrence of seizures after remission of epilepsy. Br Med J 1993: 306:1374-8.

5. ODell C, Shinnar S. Initiation and discontinuation of antiepileptic drugs. Neurol Clin. 2001;

19:289-311.
6. Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients?

CNS Drugs 2004; 18:201-12.

7. Tomson T. Drug selection for the newly diagnosed patient: when is a new generation

antiepileptic drug indicated? J Neurol 2004; 251:1043-9.

43

11-0259-p11-52.indd 43 8/29/11 5:11:28 PM

 7

(Difficult-to-treat epilepsy)



1.
sleep disorders, TIA, migraine, psychogenic problem,
hyperventilation syndrome
2. arterio-venous malformation
3.

4.
5. /
(Medical refractory epilepsy) ( 5)

CBZ, PHT, VPA, PB (monotherapy) 2
(polytherapy)
(Novel antiepileptic drugs)

linear pharmacokinetic correlation liver enzyme

partial secondarily generalized seizure
idiopathic generalized seizure

44

11-0259-p11-52.indd 44 8/29/11 5:11:29 PM

 add on therapy


-
-
-



1. partial generalized tonic-clonic seizure Gabapentin (GBP),
Lamotrigine (LTG), Levetiracetam (LEV), Oxcarbazepine (OXC), Topiramate (TPM), Vigabatrin (VGB),
Zonisamide (ZNS) Pregabalin (PGB)
2. infantile spasms VGB, TPM
3. Lennox-Gastaut Syndrome LTG, TPM, ZNS
4. monotherapy LTG, GBP, OXC TPM
5. (broad spectrum) LTG, TPM, ZNS LEV

6

Ketogenic diet ( 9 96) ( 11)



1. Bergin AN, Connolly M. New epileptic drug therapies. Neurol Clin 2002;20:1163-82
2. Dihter MA, Brodie M, New anti-epleptic drugs. N Engl J Med 1996; 334:1583-90.
3. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic

drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology

Assessment Subcommittee and Quality Standards Subcommittee of the American

Academy of Neurology and the American Epilepsy Society. Neurology 2004; 52:1261-73.
4. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic

drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology

Assessment Subcommittee and Quality Standards Subcommittee of the American

Academy of Neurology and the American Epilepsy Society. Neurology 2004; 52:1252-60.
5. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342:314-9.

45

11-0259-p11-52.indd 45 8/29/11 5:11:29 PM

 8
(Status epilepticus)

(Status epilepticus)
1. 30
2. 30


5 2

( 10)

1.
2.

3.

4. seizure threshold
theophylline, imipenem, quinolone, metronidazole, tricyclic antidepressant, cyclosporine,
phenothiazine, amphetamine, antihistamine
5.
6. benzodiazepine, barbiturates
7.
8.



1. (Convulsive status epilepticus)
2. (Non-convulsive status epilepticus)
1.
1.1 (generalized convulsive status epilepticus)

46

11-0259-p11-52.indd 46 8/29/11 5:11:29 PM

 (generalized tonic-clonic) (tonic) (clonic)

(subtle seizures)

1.2 (simple partial status epilepticus)
(partial motor)
epilepsia partialis continua
5
2.
electrographic seizure
2.1 (complex partial status epilepticus)


2.2 (absence status epilepticus)




1.
2.
3.
4. arrhythmia, hyperthermia/ hypothermia, hyperkalemia, DIC,
rhabdomyolysis, myoglobinuria,



1.
2.

3.
4. 60
5.



1.

47

11-0259-p11-52.indd 47 8/29/11 5:11:29 PM

 2.
3.
4.


1.

2.
3.

4. ( 38 )
5. 1669

(definitive care) 10 ()
1.
2.
3. CBC, glucose, electrolytes,
calcium, magnesium

4. 60 ./.

4.1 : 25% glucose 2 ./. 5-10%
4.2 : 50% glucose 50 . thiamine (vitamin B1) 100 .
10%
5. 18 4 pyridoxine
(vitamin B6) 100 .
6.
7. Diazepam 5
- : 0.3 ./. 0.5 ./. ( 10 . )
- : 10 .
diazepam 15
( 8)
diazepam 10
diazepam 1
8.
30 ( 8.1 8.2

48

11-0259-p11-52.indd 48 8/29/11 5:11:30 PM

 )
8.1 Phenytoin fosphenytoin
Phenytoin
: (loading) 20 ./. 1 ./
./ 30 10 ./. ( 30
./.) 8 5-8 ././ 8
1 ././
: 20 ./. 50 ./
30 10 ./. ( 30 ./.)
8 300-500 ./ 8 50 ./
Fosphenytoin
isotonic
: 20 .PE (phenytoin equivalence)/ .
3 .PE/./ 30 10 . PE /.
( 30 . PE /.) 8 5-8 . PE /./
8 3 . PE /./ 5
phenytoin
: 20 .PE/. 150 .PE/
100 .PE/ 30
10 .PE/. ( 30 .PE/.) 8
300-500 .PE/ 8 150 .PE/
5 phenytoin

8.2 Phenobarbital
: 20 ./. 2
././ 30 10 ./. 8
4-6 ././ 12
: 20 ./.
100 ./ 30 10 ./. 8
180-240 ./ 12
8.1 8.2
(8.1, 8.2)
8.3 Valproic acid
: 20 ./. 1-
3 ././ 1-5 ./. 2

49

11-0259-p11-52.indd 49 8/29/11 5:11:30 PM

 : 20 ./.
50 ./ 1-2 ./.
8.4 Levetiracetam
: 4 30-40 ./.
15 10-30 ././12 .
: 2000-4000 . 15
10-30 ././12 .

9. 60
diazepam 2 8
(refractory status epilepticus) ICU
oxygen saturation

9.1 Midazolam
: 0.2 ./. 0.020.4
././. burst suppression 24

: 0.1-0.3 ./. 4 ./
0.05 0.4 ././. burst
suppression 24
9.2 Pentobarbital
: 2-10 ./. 25 ./
0.5-1 ././. burst suppression 24

: 20 ./. 25 ./
0.5-1 ././. 3 ././.
burst suppression 24
9.3 Thiopental
: 5 ./. 5 ././.
3-5 ././. burst suppression 24

: 100250 . 50 . 2-3
3-5 ././. burst suppression
24
9.4 Propofol
: 1-2 ./. 2-3 .//

50

11-0259-p11-52.indd 50 8/29/11 5:11:30 PM

 . 50 /./ burst suppression 24

: 2 ./. 5-10 ././
. burst suppression 24
1-3 ././.
9.5 Topiramate
: 10 ./ . 12 . 2
25 ./. 5 ././ 12 .
: 500 . 12 . (naso/orogastric)
2 150-750 . 12
300 1,600 ./
9 ( 9.5) 1 8
24 monitor
burst suppression 24
9 12-24
10.

1. diazepam diazepam insulin syringe
plastic 2 2

2. absence status epilepticus sodium valproate levetiracetam

3. post anoxic myoclonic status epilepticus barbiturate, propofal
periodic lateralized epileptiform discharge

51

11-0259-p11-52.indd 51 8/29/11 5:11:30 PM

 10 convulsive status epilepticus*

11-0259-p11-52.indd 52
Stage of status General measures AED treatment
1 Premonitory Diazepam (i.v.bolus or p.r.)
(0-5
minutes)

52
2.1 Early capillary blood glucose Diazepam (i.v.bolus) phenytoin
(5-30 CBC, glucose, electrolytes, (i.v. loading) phenobarbital (i.v.loading)
minutes) sodium valproate (i.v.loading) levetiracetam
calcium, magnesium (i.v.,ng.)
50% glucose (50 ml) 1 **
25 %glucose 2 ./. 18 6
100 . ()
2.2 Established (phenytoin phenobarbital)
(30-60
minutes) phenobarbital (i.v. loading )
phenytoin (i.v. loading) sodium valproate
(i.v. loading) levetiracetam (i.v.,ng.)
3 Refractory EEG, Propofol (i.v. bolus & inf) midazolam
(> (i.v.bolus)
60minutes) pentobarbital (i.v.bolus & inf) thiopental
(i.v. bolus & inf) topiramate (ng)
i.v.=intravenous, p.r.=per rectum, i.m.=intramuscular, inf=infusion, ng.=naso/orogastric
* non convulsive status epilepticus simple partial status epileticus absence status epilepticus
** (MIMS Thailand 1/2009)

8/29/11 5:11:31 PM
11-0259p53-78.indd 53
11 convulsive status epilepticus*

maintenance

Diazepam 0.3 ./. 2 ./ 10 . 10./2 ./vial
10 2
10 . 2-5 ./
Phenytoin 20 ./. 1 ././ 1500 . 5-8 ././ 250 ./ 5 ./ vial arrhythmia
25 ./ 0.9% NaCl
20 ./. 50 ./ 300-500 .// 1-2 .
infusion pump

Fosphenytoin 20 .PE /. 3 ././ NA 5-8 .PE/./ 500 . PE / vial
0.9% NaCl
20 .PE/. 100-150 300-500 .PE / 5% Dextrose
./ 1.5-25 .PE/.

Phenobarbital 20 ./. 3 ./ ./ 1000 . 4-6 ././ 200 ./ 4 . sterile
water 10 . diazepam
20 ./. 100 ./ 1-4 .//./ 0.9% NaCl
Ringer lactate 5%
Dextrose

53

8/29/11 5:12:02 PM
 11 () convulsive status epilepticus*

11-0259p53-78.indd 54

maintenance

Sodium 20-40 ./. 1-3 ./ NA 1-5 ././. 400 ./4 .

54
valproate ./ 0.9% NaCl 5%
20-30 ./. 50 ./ 1-2 ././. 10% Dextrose
24 topiramate
hyperammonia
encephalopathy
Levetiracetam 30-40 ./. 15 4,000 . 10-30 ./12 . 500 ./ 5 ./vial
0.9% NaCl, Ringer
lactate
5% Dextrose 100 . 15

(oro/nasogastric) 24
2,000-4,000 . 15
Midazolam 0.2 ./.. 5 2 /. 0.0.2-0.4 ./ 1././vial, 5 ././vial
./. 0.9% NaCl
4 ./ 5% D/W 24
0.1-0.3 ./. 5 0.05 0.4 ./ . Ringer lactate
./. 4 .
4 ./
NA= not available

8/29/11 5:12:02 PM
11-0259p53-78.indd 55
11 () convulsive status epilepticus*

maintenance

Pentobarbital 2-10 ./. 25 ./ NA 0.5-1 ././. 0.9% NaCl sterile water
2%
20 ./. 25 ./ 0.5-3 ././.
2.5% solution
Thiopentone 5 ./. 3-5 ././. NA 3-5 ././. 0.9% NaCl
5% Dextrose sterile
water 2.5% solution
100-250 .. 20 3-5 ././.
50 . 2-3
Propofol 1-2 ./. 50 / NA 2-3 .//. 10 ./. 0.9%
./ NaCl 5% Dextrose
2 ./. 5-10 .//. volumetric infusion pump

6 .
Phenobarbital 20 ./. 3 ./ ./ 1000 . 4-6 ././ 200 ./ 4 . sterile water 10
.
20 ./. 100 ./ 1-4 .//./ 0.9% NaCl Ringer lactate diazepam
5% Dextrose

NA= not available

* non convulsive status epilepticus simple partial status epileticus absence status epilepticus

55

8/29/11 5:12:02 PM


1. Lowenstein DH, Bleck T, Macdonald RL. Its time to revise the definition of status

epilepticus. Epilepsia 1999 ;40:120-2.

2. Lowenstein DH. The Management of Refractory Status Epilepticus: An Update. Epilepsia

2006, 47(Suppl. 1):3540.

3. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status

epilepticus. Epilepsia. 1994;35:27-34.

4. Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid IV administration of

valproic acid for status epilepticus. Neurology 2005;64:353-5.

5. Trinka E. The use of valproate and new antiepileptic drugs in status epilepticus. Epilepsia

2007; 48(Suppl.8) : 49-51.

6. Niebauer M, Gruenthal M. Topiramate reduces neuronal injury after experimental status

epilepticus. Brain Res 1999;837:263-9.

7. Perry MS, Holt RJ, Sladky JT. Topiramate loading for refractory status epilepticus. Epilepsia
2006;47:1070-1.
8. Towne AR, Garnett LK, Waterhouse EJ, Morton LD, DeLorenzo RJ. The use of topiramate in

refractory status epilepticus. Neurology 2003;60:332-4.

9. Gonzalo GL; Luis AJ; Emilio F, Julio P. Experience with Intravenous levetiracetam in

status epilepticus: A retrospective case series. CNS Drugs 2009; 23:983-7.

10. Rossetti AO, Bromfield EB. Determinants of success in the use of oral levetiracetam in

status epilepticus. Epilepsy Behav2006;8:651-4.

11. Rupprecht S, Franke K, Fitzek S,Witte OW, Hagemann G. Levetiracetam as a treatment

option in non-convulsive status epilepticus. Epilepsy Res 2007;73:238-44.

12. Knake S, Gruener J, Hattemer K, Klein KM, Bauer S, Oertel WH, Hamer HM, Rosenow F.
13. Intravenous levetiracetam in the treatment of benzodiazepine refractory status

epilepticus. J Neurol Neurosurg Psychiatry 2008;79:588-9.

14. Trinka E, What is the relative value of the standard anticonvulsants: Phenytoin and

fosphenytoin, phenobarb, valproate, and levetiracetam?. Epilepsia 2009;50(suppl12):40-43.

15. International League against epilepsy.Gray matters. Epilepsia 2008;49:1277-84.
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15:10-4.
17. Abend NS, Marsh E. Convulsive and nonconvulsive status epilepticus in children. Current

Treatment Options in Neurology 2009;11:262-72.

18. Lowenstein DH. The management of refractory status epilepticus: An update. Epilepsia

2006; 47 (Suppl. 1):3540.

56

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 19. Bensalem MK, Fakhoury TA. Topiramate and status epilepticus: report of three cases.

Epilepsy Behav 2003;4:75760.

20. Perry MS, Holt PJ, Sladky JT. Topiramate loading for refractory status epilepticus in

children. Epilepsia. 2006;47:1070-1.

21. Towne AR, Garnett LK, Waterhouse EJ, Morton LD, DeLorenzo RJ. The use of topiramate in

refractory status epilepticus. Neurology. 2003;60:332-4.

22. Appleton RE, Sweeney A, Choonara I, Robson J, Molyneux E. Lorazepam versus diazepam

in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol

1995; 37:682-688.
23. Riviello JJ, Holmes. The treatment of status epilepticus: Seminars Pediatric Neurology

2004; 11 : 129-38.
24. Smith BJ. Treatment of status epilepticus. Neurol Clin 2001; 19:347-69.
25. Treiman DM. Treatment of status epilepticus. In Engel J,Jr, Pedley TA (eds). Epilepsy: a

comprehensive textbook. Philadelphia: Lippicott-Raven Publishers 1997:1317-1323.

57

11-0259p53-78.indd 57 8/29/11 5:12:03 PM

 9

(Febrile seizure)

1.
2.
3.
toxic encephalopathy

4.


6 5 1-3

24
1. Simple febrile seizure generalized seizure (generalize tonicclonic
generalized tonic) 15 ( 5 )
24
2. Complex febrile seizure
15
24


2-5





multifactorial autosomal dominant

58

11-0259p53-78.indd 58 8/29/11 5:12:03 PM


cognitive function
febrile status epilepticus
(IQ)

30-40 10
3

1.
2. 18 50
3.

4.



Complex febrile seizure febrile status epilepticus
simple febrile seizure


1-3
1.
2. complex febrile seizure


1.


( ) ( 5 ) diazepam
(0.2 - 0.3 /. ) (0.5 ./. )
10 .
status epilepticus ( 8)
2.

3. 12 ( 6)

59

11-0259p53-78.indd 59 8/29/11 5:12:03 PM

 12



Brudzinskis Kernigs sign
4. (blood sugar, electrolytes, calcium
magnesium)
blood sugar
5.
complex febrile seizure

6. CT scan
7.
8.

1.
(
)

2. (
) 5

1
Recurrent simple febrile seizure

Recurrent complex febrile seizure focal neurological deficit


diazepam
0.75-1 ././ 6-8 24 48


phenobarbital sodium valproate


60

11-0259p53-78.indd 60 8/29/11 5:12:04 PM



1. Committee on Quality Improvement, subcommittee on Febrile Seizures, American

Academy of Pediatrics. Practice parameter: Long-term treatment of the child with simple

febrile seizures. Pediatrics 1999;103:1307-9.

2. Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management

of febrile seizures: Ad Hoc Task Force of LICE Guidelines Commission. Epilepsia.

2009 ;50 Suppl 1:2-6.

3. Ellenberg JH, Nelson KB. Febrile seizures and later intellectual performance. Arch Neurol

1978;35:17-21.
4. Hirabayashi Y, Okumura A, Kondo T, Magota M, Kawabe S, Kando N, Yamaguchi H, Natsume

J, Negoro T, Watanabe K. Efficacy of a diazepam suppository at preventing febrile seizure

recurrence during a single febrile illness. Brain Dev. 2009 ;31:414-8.

5. Lemmens EM, Aendekerk B, Schijns OE, Blokland A, Beuls EA, Hoogland G. Long-term

behavioral outcome after early-life hyperthermia-induced seizures. Epilepsy Behav. 2009 ;

14:309-15.
6. Lux AL. Antipyretic drugs do not reduce recurrences of febrile seizures in children with

previous febrile seizure. Evid Based Med 2010;15:15-6.

7. Mohebbi MR, Holden KR, Butler IJ. FIRST: a practical approach to the causes and

management of febrile seizures. J Child Neurol. 2008 ;23:1484-8.

8. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile

seizures. N Eng J Med 1976; 295:1029-33.

9. Ostergaard JR. Febrile seizures. Acta Paediatr 2009 ;98:771-3.
10. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile

Seizures American Academy of Pediatrics. Febrile seizures: clinical practice guideline

for the long-term management of the child with simple febrile seizures. Pediatrics.

2008 ;121:1281-6.
11. Pavlidou E, Tzitiridou M, Panteliadis C. Effectiveness of intermittent diazepam prophylaxis

in febrile seizures: long-term prospective controlled study. J Child Neurol. 2006 ;21:1036-40.
12. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from

birth. I. Prevalence and recurrence in the first five years of life. Br Med J 1985a; 290:1307-10.
13. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from

birth. II. Medical history and intellectual ability at 5 years of age. Br Med J 1985b;

290:1311-15.

61

11-0259p53-78.indd 61 8/29/11 5:12:04 PM

 14. Visudtibhan A, Chiemchanya S, Visudhiphan P, Kanjanarungsichai A, Kaojarern S, Pichaipat

V. Serum diazepam levels after oral administration in children. J Med Assoc Thai. 2002

Nov;85 Suppl 4:S1065-70.

15. Yucel O, Aka S, Yazicioglu L, Ceran O. Role of early EEG and neuroimaging in determination of

prognosis in children with complex febrile seizure. Pediatr Int. 2004; 46:463-7.
16. Camfield P, Camfield C, Hirtz D. Treatment of febrile seizures. In: Engle J Jr, Pedley TA, eds.

Epilepsy a comprehensive textbook. Philadelphia : Lippincott-Raven Publishers, 1998:1305-9.

17. Committee on Quality Improvement, subcommittee on Febrile Seizures, American

Academy of Pediatrics. Practice parameter: Long-term treatment of the child with simple

febrile seizures. Pediatrics 1999;103:1307-9.

18. Lahat E, Goldman M, Barr J, Bistritzer T, Berkovich M. Comparison of intranasal midazolam

with intravenous diazepam for treating febrile seizures in children: prospective randomised

study. Br Med J 2000; 321:83-6.

19. Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978; 61: 720-7.
20. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from

birth. I. Prevalence and recurrence in the first five years of life. Br Med J 1985; 290:1307-10.
21. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from

birth. II. Medical history and intellectual ability at 5 years of age. Br Med J 1985; 290:1311-5.
22. Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of

children with febrile convulsions. N Engl J Med 1998; 338:1723-8.

23. Yucel O, Aka S, Yazicioglu L, Ceran O. Role of early EEG and neuroimaging in determination of

prognosis in children with complex febrile seizure. Pediatr Int 2004; 46:463-7.

62

11-0259p53-78.indd 62 8/29/11 5:12:04 PM

 10
Infantile spasms & West syndrome

Infantile spasms


West syndrome 3
1. infantile spasms
2.
3. hypsarrhythmia
infantile spasms
myoclonic

ILAE 1989


infantile spasms 2.9 4.5 /100,000
referral center infantile spasms 4.9
3 7


infantile spasms 3 (flexion) (extension)
(mixed flexion and extension)


(asymmetry)


(symptomatic) (idiopathic /
cryptogenic)
60 90

63

11-0259p53-78.indd 63 8/29/11 5:12:04 PM

 - Developmental anomaly / congenital malformation lissencephaly, cortical dysplasia,
polymicrogyria, schizencephaly, agenesis corpus callosum 30
-


- tuberous sclerosis (neurocutaneous
syndrome) infantile spasms 50
- maple syrup urine disease, phenylketonuria



(atypical presentation)



hypopigmented macule tuberous sclerosis



CT scan
anomaly, infarction, vascular disease CT scan
MRI




infantile spasms
(startle) colic gastro-esophageal reflux
myoclonic


infantile spasms
ACTH vigabatrin 60
ACTH
vigabatrin myelin myelinolysis
(permanent visual field defect) ACTH

64

11-0259p53-78.indd 64 8/29/11 5:12:05 PM

 vigabatrin
30 50 ././ 2
30- 50 ././ 2 3 200 ././
prednisolone ACTH adrenal
insufficiency
sodium valproate, benzodiazepines
3040 topiramate, zonisamide
lamotrigine vigabatrin ACTH

pyridoxine (150 - 300 ././) hypotonia, neuropathy
ketogenic diet
ketosis
vigabatrin vigabatrin
sodium valproate benzodiazepines nitrazepam
clonazepam vigabatrin


10
(remission)
20 2 75
(mental retardation) 50 60 2
Lennox-Gastaut

65

11-0259p53-78.indd 65 8/29/11 5:12:05 PM

 11
(Epilepsy surgery)

60-70

2 3

5
25-70

(candidates for surgical treatment)
(pre-surgical evaluation)
(multi-disciplinary)


(epileptogenic
foci)


1. (medically refractory epilepsy)
2. (surgical remediable epilepsy) mesial

temporal sclerosis
3.

(arterio-venous malformation)


1. Benign epileptic syndrome benign childhood epilepsy with centrotemporal spikes
2. Metabolic syndrome, neurodegenerative disease


( 7)

66

11-0259p53-78.indd 66 8/29/11 5:12:05 PM

 Video electroencephalogram monitoring (VEEG)
MRI Epilepsy protocol
SPECT, PET Scan, WADA test, fMRI, (subdural electrodes
for brain mapping)


1. (resection of epileptogenic zone for curative surgery)

1.1 Hippocampal sclerosis and/or mesial temporal sclerosis

temporal lobe epilepsy

a. Benign brain tumor dysembryoplastic neuroepilthelial tumor

(DNET), ganglioglioma, low grade astrocytoma, oligodendroglioma

(complete

lesionectomy)
b. Malformation of cortical development (MCDs)

epileptogenic zone

c. Vascular malformation cavernous hemangioma

hemosiderin (complete

lesionectomy)
2. (palliative surgery)

corpus callosum (corpus callosotomy)
(multiple subpial transections) (vagal
nerve stimulation)


(seizure free)
(cost effectiveness of surgery) ,

resective surgery 6090 mesial
temporal sclerosis non-resective surgery
50

67

11-0259p53-78.indd 67 8/29/11 5:12:06 PM



35
0.5




1. Kwan P, Sperling MR. Refractory seizures: try additional antiepileptic drugs (after two have

failed) or go directly to early surgery evaluation? Epilepsia 2009;50 Suppl 8:57-62.

2. Chan CH, Bittar RG, Davis GA, Kalnins RM, Fabinyi GC. Long-term seizure outcome following

surgery for dysembryoplastic neuroepithelial tumor. Journal of neurosurgery 2006;104(1):62-9.

3. Ferroli P, Casazza M, Marras C, Mendola C, Franzini A, Broggi G. Cerebral cavernomas and

seizures: a retrospective study on 163 patients who underwent pure lesionectomy. Neurol

Sci 2006;26(6):390-4.
4. Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol.

2002; 1:477-82.
5. Kim R, Spencer D. Surgery for Mesial Temporal Sclerosis.In: Schmidek A, Sweet WH ed

Operative Neurosurgical Techniques: Indications, Methods and Results. Philadelphia: W.B.

Saunders, 2000; p 1436-44.

6. Murphy JV, Torkelson R, Dowler I, Simon S, Hudson S. Vagal nerve stimulation in refractory

epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy

center. Arch Pediatr Adolesc Med 2003; 157:560-4.

7. NIH Consens Statement Online Surgery for Epilepsy. NIH Consens Statement Online 1990;

8:1-20.
8. Shield WD, Peacock WJ, Roper SN. Surgery for epilepsy: special pediatric consideration.

Neurosurgical Clin North Am 1993; 4:301-10.

9. Wieser H-G, Engel J JR, Williamson PD, Babb TL, Gloor P. Surgically remediable temporal

lobe syndromes. In: Engel J Jr. ed. Surgical treatment of the epilepsies. 2nd ed New York:

Raven Press 1993: 49-63.

10. Wyler AR, Vossler DG. Surgical Strategies for Epilepsy. In: Grossman RG, Loftus CM. ed

Principles of Neurosurgery, 2nd ed. Philadelphia: Lippincott-Raven 1999 : p 737-55.

68

11-0259p53-78.indd 68 8/29/11 5:12:06 PM

 12

1. blood-brain barrier permeability

2. neuronal excitability excitatory inhibitory

neurotransmitters
3.
4.
5.


(Renal failure)
uremic encephalopathy 7-10


multifocal myoclonus

10 chronic renal insufficiency

69

11-0259p53-78.indd 69 8/29/11 5:12:06 PM

 uremic encephalopathy hypertensive
encephalopathy, ,
erythropoietin, cyclosporin
disequilibrium syndrome cerebral water intoxication
24-48 dialysis dementia
distinctive speech abnormality, psychiatric disturbance, cognitive changes, asterixis,
myoclonus, gait ataxia aluminium dialysate
aluminium
dialysate

1. gabapentin, pregabalin,

levetiracetam, topiramate
2. hemodialysis

phenobarbital carbamazepine

gabapentin, levetiracetam, topiramate

70

11-0259p53-78.indd 70 8/29/11 5:12:06 PM


12
Molecular Total daily dose (GFR, in ml/min)
Drug
weight* 60-89 30-59 15-29 <15 Hemodailysis
Gabapentin 171 400-600 mg 200-300 mg 200-300 mg/ 100-150 mg/ 200-300 mg after
TID BID day day or 300 mg hemodialysis
every other only or 100-150
day mg/day with
supplement of
125-250 mg
Levetiracetam 170 500-1000 mg 250-750 mg 250-500 mg 250-500 mg 250-500 mg BID;
BID BID BID BID 250-500 mg after
hemodialysis
Topiramate 339 100-200 mg 50-100 mg 50-100 mg 50-100 mg BID 50-100 mg BID;
BID; 50-100 BID BID 50-100 mg after
mg BID for hemodialysis
GFR<70 ml/
min
Zonisamide 212 100-400 mg 100-400 mg Insufficient Insufficient Supplement 50%
data, use data, use with dose if sezure
with caution caution after
hemodialysis
Oxcarbazepine 252 300-600 mg 300-600 mg 50% starting Insufficient Insufficient data,
BID BID dose data, use with avoid
caution
Felbamate 238 1200-3600 Reduce by Insufficient Insufficient Insufficient data,
mg 50% data, reduce data, reduce avoid
dose by 50% dose by 50%
use with use with
caution caution
Lamotrigine 256 100-500 mg Insufficient Insufficient Insufficient Insufficient data,
data, may data, may data, may may benefit from
benefit from benefit from benefit from decrease dose
decrease decrease decrease dose
dose dose
Tiagabine 412 32-56 mg No dose No dose No dose No dose
adjustment adjustment adjustment adjustment
necessary necessary necessary necessary

* For low molecular weight substances such as urea and the AEDs listed here, clearance is increased with
the use of high-efficiency dialyzers that have a large surface area.
BID, twice a day; TID, three times a day.

71

11-0259p53-78.indd 71 8/29/11 5:12:07 PM

 13

Carbamazepine 1,2 50-75 5

1,2 1-2
5
3
Phenobarbital CrCl < 10 mL/min
50-75 5
12-16 3,4
1-2
5
Phenytorin 6 50-75 5
hyperphosphatemia
fosphenytion3 1-2
5
Valproate sodium 2,4 25-50 5

2,4 1-2
5

1. Garnett WR. Antiepileptics. In: Schumacher GE, ed. Therapeutic drug monitoring. London;

Appleton & Lange; 1995:345-95.

2. Baghdady NT, Banik S, Swartz SA, Mclntyre RS. Psychotropic drugs and renal failure:

translating the evidence for clinical practice. Adv Ther 2009;26:404-24.

3. Israni RK, Kasbekar N, Haynes K, Nerns JS. Use of antiepileptic drugs in patients with kidney

disease. Semin Dial 2006;19:408-16.

4. Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug information handbook. 18th ed,

Lexi-Comp;2009.
5. Boggs JG. Seizure management in the setting of hepatic disease. Curr Treat Options Neurol

2011 May 3. [Epub ahead of print].

6. Lacerda G, Krummel T, Sabourdy C, Ryvlin P, Hirsch E. Optimizing therapy of seizures in

patients with renal of hepatic dysfunction. Neurology 2006;67(Suppl 12):S28-33.

72

11-0259p53-78.indd 72 8/29/11 5:12:07 PM

 (Hepatic disease)




1. phenytoin, valproate, carbamazepine, phenobarbital,
primidone tiagabine lamotrigine
2. oxcarbazepine, felbamate, topiramate, zonisamide,
levetiracetam


1. gabapentin, pregabalin, vigabatrin
2. levetiracetam topiramate

3. carbamazepine, phenytoin lamotigine

4. sodium valproate
5. benzodiazepine midazodam

6. phenytoin phenobarbital

(Alcohol withdrawal syndrome)

48


1. benzodiazepines diazepam 10 .
2. B1 100 . glucose




(cardiogenic embolism) (cardiac arrest) subacute
bacterial endocarditis septic emboli intracranial mycotic aneurysms
acute focal ischemia ruptured aneurysm subarachnoid hemorrhage

73

11-0259p53-78.indd 73 8/29/11 5:12:08 PM

 transient hypoxia (syncopal myoclonus
convulsive syncope)
cardiac arrest cerebral hypoxia hypercapnia,
systemic acidosis hypoperfusion anoxia 5
(postanoxic myoclonus)
myoclonic status epilepticus

hypoxic injury barbiturate
continuous hypothermia phenobarbital
phenytoin
cardiac arrhythmia 25
./ fosphenytoin, levetiracetam,valproic acid
drug interaction phenytoin
quinidine (ectopy) ventricular arrhythmias
hepatic microsomal enzymes phenytoin phenobarbital
quinidine, digoxin lidocaine, amiodarone phenytoin,
calcium-channel blocking ( verapamil) carbamazepine



(Respiratory disease)
(respiratory arrest) (acute
hypoxia) local acid-base shifts acute
hypercapnia seizure threshold chronic stable hypoxia chronic
hypercapnia COPD (multifocal
myoclonus)

(Electrolyte disturbance)

74

11-0259p53-78.indd 74 8/29/11 5:12:08 PM


0.8 mEq/L



(Endocrinopathies)

(hypothyroid)
10
Hashimoto (autoimmune disorders)

Hashimotos encephalopathy
myxedema coma 20 -25
obstructive sleep apnea

( ketone)


phenytoin insulin

(hypoparathyroidism)
30-70
tetany




30 brain abscess 50 subdural
empyema acute viral encephalitis
neurocysticercosis opportunistic infection
focal

( 10)


(direct invasion) (metastasis)
cerebral cortex leptomeninges

75

11-0259p53-78.indd 75 8/29/11 5:12:08 PM

 paraneoplastic syndrome





1. Boggs JG. Seizures in medically complex patients. Epilepsia. 1997:38(suppl 4); S55-9.
2. Delanty N, Vaughan CJ, French JA. Medical causes of seizures. The Lancet. 1998: 352;383-90.
3. Israni RK, Kasbekar N, Haynes K, Berns JS. Use of antiepileptic drugs in patients with kidney

disease. Seminar in Dialysis. 2006:19(5);408-16.

4. Parent JM, Aminoff MJ. Seizures and general medical disorders. In: Aminoff MJ, ed.

Neurology and general medicine. 4th ed. Churchill Livingstone, Elsevier, 2008;1077-94.
5. McKeon A, Frye MA, Delanty. The alcohol withdrawal syndrome. J Neurol Neurosurg

Psychiatry. 2008:79;854-62.
6. Cohen BH. Metabolic and degenerative diseases associated with epilepsy. Epilepsia 1993;

34(Suppl 3): S62-S70.

76

11-0259p53-78.indd 76 8/29/11 5:12:08 PM



77

11-0259p53-78.indd 77 8/29/11 5:12:09 PM


1

1.

2.
3.

4. ( 38 )
5. 1669

78

11-0259p53-78.indd 78 8/29/11 5:12:09 PM


2

1.

2.
3.

4.

(side effect)

Steven Johnson

Syndromes 3

5.

6.

7.
8. whole cell
9.

79

11-0259p79-102.indd 79 8/29/11 5:12:37 PM



1. S.Thomas,C Vijaykumar,R Naik,et.al.:Comparative effectiveness of tepid sponging and

antipyretic drug versus only antipyretic drug in the management of fever amonge children:

A randomized controlled trial. Indian Pediatrics 2009; 46:133-136.

2. Gaily E, Gamstrom ML, Hiilesmaa V, Bandy A. Minor anomalies in offspring of epileptic

mother. J Pediatr 1988; 112 :520-29.

80

11-0259p79-102.indd 80 8/29/11 5:12:37 PM


3

1. 10-15 /./ 4-6
Reyes syndrome,
ibuprofen

ibuprofen
2.

3.






15-20

15-30

81

11-0259p79-102.indd 81 8/29/11 5:12:37 PM


4

1.
2.
3.

2.4-4.6 ( 1 )

20

1. generalized epilepsy
- idiopathic with generalized onset childhood absence,

juvenile absence, juvenile myoclonic epilepsy

4-9
- generalized

spike and wave discharges generalized spike and wave discharges

photoparoxysmal response

6-8
- cryptogenic symptomatic epilepsy West syndrome, Lennox-

Gastaut syndrome

2. Focal localization related epilepsy
- idiopathic with age-related onset benign childhood epilepsy with centro-

temporal spikes 12-15

- symptomatic localization related epilepsy

82

11-0259p79-102.indd 82 8/29/11 5:12:38 PM

 3. febrile seizure
3.1 10-20
3.2 febrile seizure identical twins

febrile seizure 9-30 non- identical twins

5-12
4. Mendelian

inheritance tuberous sclerosis

Mendelian

tuberous sclerosis

1. Elmslie F. Genetic counseling. In: Engel J Jr., Pedley TA, eds. Epilepsy: A comprehensive

textbook. Philadelphia, PA: Lippincott-Raven Publishers; 2008.

2. Ottman R, Annegers JF, HauserWA, et al. Higher risk of seizures in offspring of mothers

than of fathers with epilepsy. Am J Hum Genet 1988;43:25764.

3. Annegers J, Hauser WA, Anderson BE. Risk of seizures among relatives of patients with

epilepsy: families in a defined population. In: Anderson VE HW, Penry JK, eds. Genetic

basis of the epilepsies. New York: Raven Press; 1982. 1519.

4. Ottman R, Annegers JF, Hauser WA, et al. Seizure risk in offspring of parents with generalized

versus partial epilepsy. Epilepsia 1989;30:15761.

5. Vadlamudi L, Andermann E, Lombroso CT, et al. Epilepsy in twins: insights from unique

historical data of William Lennox. Neurology 2004;62:112733.

6. Berkovic SF,Howell RA, HayDA, et al. Epilepsies in twins: genetics of the major epilepsy

syndromes. Ann Neurol 1998;43:43545.

7. Kjeldsen MJ, Corey LA, Christensen K, et al. Epileptic seizures and syndromes in twins: the

importance of genetic factors. Epilepsy Res 2003;55:13746.

8. Winawer MR, Rabinowitz D, Barker-Cummings C, et al. Evidence for distinct genetic

influences on generalized and localization related epilepsy. Epilepsia 2003;44:117682.

9. Berg AT, Shinnar S, Shapiro ED, et al. Risk factors for a first febrile seizure: a matched

case-control study. Epilepsia 1995;36:33441.

10. Hauser WA, Annegers JF, Anderson VE, et al. The risk of seizure disorders among relatives

of children with febrile convulsions. Neurology 1985;35:126873.

11. Winawer MR, Shinnar S. Genetic epidemiology of epilepsy or what do we tell families?

Epilepsia 2005:46;s24-30.

83

11-0259p79-102.indd 83 8/29/11 5:12:38 PM


5

1.
2.

3.

( 7)
4. infantile spasms ( 10)




1. Dansky LV, Andermann E, Rosenblatt D, Sherwin AL, Andermann F. Anticonvulsants, folate

levels, and pregnancy outcomes: a prospective study. Ann Neurol 1987; 21:176-182.
2. Hauser WA, Hesdorffer DC, Pregnancy and teratogenesis. In : Hauser WA, Hesdorffer DC,eds.

Epilepsy: frequency, causes, and consequences. New York: Demos Publications, 1990:147-96.
3. Hopkins A, Shorvon S. Cascino G. Epilepsy, menstuation, oral contraception and pregnancy.

Epilepsy. 2nd ed. Chapman & Hall Medical, 1995; 521-30.

84

11-0259p79-102.indd 84 8/29/11 5:12:38 PM


6

1.
- phenytoin
- Sodium valproate
- topiramate

2. Sodium
valproate
3. (catamenial seizure)

clobazam

4.
5. (cytochrome
P-450 enzyme system) phenobarbital, phenytoin carbamazepine
50

6. Sodium valproate
polycystic ovarian syndrome
7.

85

11-0259p79-102.indd 85 8/29/11 5:12:38 PM

 8.

neural tube defect
0.5-3 Sodium valproate
- 2
-

- 5 . neural
tube defect


12-16
(dysmorphic)
9. phenobarbital
benzodiazepine

86

11-0259p79-102.indd 86 8/29/11 5:12:39 PM


7

1. transient ischemic
attack, syncope, metabolic derangement

2.


phenytoin, phenobarbital carbamazepine

3.

87

11-0259p79-102.indd 87 8/29/11 5:12:39 PM


8

1. pharmacokinetic maturation

() (1-12 ) ( 2 )

2. therapeutic effect maximal plasma concentration

(Tmax) gastric emptying time

3. volume of distribution

water-soluble drugs receptor sites

4. mg/kg/day

- cytochrome P450 drug metabolism CYP 2C9, CYP 2C19

enzyme

- (T 1/2) carbamazepine phenytoin

- CYP 3A4 activity carbamazepine

carbamazepine 3
5. plasma protein

protein binding phenytoin Sodium valproate

unbound fraction relative clearance

3-4 relative clearance

6. adverse drug reaction idiosyncratic reaction

88

11-0259p79-102.indd 88 8/29/11 5:12:39 PM

 7. 2 fatal hepatotoxicity Sodium valproate

1/500
8. drug elimination

9. phenytoin, carbamazepine, lamotrigine, vigabatrin Sodium

valproate

barbiturate



1. Perrucca E. Pharmacological problems in the management of epilepsy in children. Seizure

1995;4:139-143.
2. Tetelbaum M, Finkelstein Y, Nava-Ocampo AA, Koren G. Understanding drugs in children:

Pharmacokinetic maturation. Peds in Review 2005;26:321-328.

3. Anderson GD. Pharmacokinetic, pharmacodynamic and pharmacogenetic targeted therapy

of antiepileptic drugs. The Drug Monit 2008;30:173-180.

89

11-0259p79-102.indd 89 8/29/11 5:12:39 PM


9
Ketogenic diet (KD)

Ketogenic diet (KD)

(ketosis)

(ketone bodies)

KD classic KD, medium-chain-triglyceride diet,

modified medium-chain-triglyceride diet, modified Atkins diet, low-glycemic-index diet


KD
KD
KD
antioxidant KD
-aminobutyric acid (GABA) neurotransmitter
GABA GABA receptor

KD
KD absence seizure, myoclonic seizure,
infantile spasms, atonic seizure, generalized seizure partial seizure

pyruvate carboxylase deficiency porphyria

mitochondrial cytopathies
KD KD




2-3

4-6 20-40

90

11-0259p79-102.indd 90 8/29/11 5:12:39 PM

 ./.

160 / ketostix 4+ 48
KD KD KD
KD

KD 2-3
urine ketostix 4+
KD

classic KD
KD 60-80 / / KD KD 4 1
4 1 1 //

60-65 //




KD 90 20-30
50 60-80 20-40

KD
dyslipidemia

prolonged QT interval,
cardiomyopathy, optic neuropathy,

91

11-0259p79-102.indd 91 8/29/11 5:12:40 PM


10

..

..


/

() / ..
..
() /
.. ( ) ..
() /
.. ( ) ..
() ( ) .. ..
( ) ..
() ..
( ) ..
..
()
()
()
..

92

11-0259p79-102.indd 92 8/29/11 5:12:40 PM




















(Drug Utilization Evaluation, DUE)


()

()
(
)

()



(authorized system)

93

11-0259p79-102.indd 93 8/29/11 5:12:40 PM



..

( )

Drugs used in the control of epilepsy

1. Carbamazepine tab, syr, susp
2. Magnesium sulfate sterile sol
3. Phenobarbital tab (as base or sodium)
4. Phenytoin (as base) chewable tab
5. Phenytoin sodium cap, SR, cap
6. Sodium valproate EC tab, oral sol
Post-traumatic seizure
7. Carbamazepine SR tab
8. Clonazepam tab
4
9. Sodium valproate SR tab
10. Lamotrigine tab ( 25, 50, 100 mg)

11. Levetiracetam tab ( 250, 500 mg)

1.
2.
12. Nitrazepam tab
infantile spasms
13. Topiramte cap, tab

94

11-0259p79-102.indd 94 8/29/11 5:12:41 PM

 14. Vigabatrin tab

1.
2. infantile spasms
Drugs used in status epilepticus
1. Diazepam sterile sol
2. Phenobarbital sodium sterile pwdr
(phenobarbitone sodium)
3. Phenytoin sodium sterile sol
4. Sodium valproate sterile pwdr
5. Midazolam hydrochloride sterile sol
refractory status epilepticus

95

11-0259p79-102.indd 95 8/29/11 5:12:41 PM



1. , :

2549 66
2. , . :

.. 2534 - 2535. : 2539.

3. . The epilepsy quality of life survey in Thailand. 10

63-70.
4. . Medical Facilities

10 56-62.
5. Asawavichienjinda T, Sitthiamorn C, Tanyanont W. Prevalence of epilepsy in rural

Thailand : A population based study. J Med ASSOC Thai 2002; 85 : 1066-73.

6. Wibulpolprasent S. Mental health indicators. In : Thailand Health Profile. Bureau of

Policy and Strategy, Ministry of Public Health; 1999-2000 : 187.

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(Guideline of Epilepsy)

Simple partial seizure
Partial complex seizure
Partial secondarily generalized tonic-clonic seizure
Generalized seizure
Absence
Tonic
Clonic
Tonic-clonic seizure
Atonic
Myoclonic
Infantile spasm

Guideline of Epilepsy

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PB Phenobarbital
PHT Phenytoin
CBZ Carbamazepine
VPA Valproic acid
GBP Gabapentin
LTG Lamotrigine
LEV Levetiracetam
OXC Oxcarbazepine
TGB Tiagabine
TPM Topiramate
VGB Vigabatrin
ZNS Zonisamide
PGB Pregabalin
FBM Felbamate

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 (Glossary)

Idiopathic epilepsy

Cryptogenic epilepsy

Symptomatic epilepsy

Recent symptomatic seizure

Remote symptomatic seizure

Precipitating factor/trigger

Provoked seizure/symptomatic seizure

Unprovoked seizure
Convulsive status epilepticus
Non convulsive status epilepticus
absence status epilepticus
Monotherapy
Polvthnerapy / polyphamacy
Controlled / sustain release drug
Trough level (fasting, lowest level)

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Clinical Practice Guidelines for epilepsy

Clinical Practice Guidelines for epilepsy

Clinical Practice Guidelines for epilepsy