1

Seizure
(recurrent, episodic) (stereotyped)
2
convulsion non - convulsion convulsion
generalized tonic - clonic seizures non- convulsion
absence seizures
Epilepsy 2 (unprovoked seizures)

glutamate, aspartate () gamma-aminobutyric acid (GABA; )

1. 2. 3.
1. (preictal symptoms)
1.1 (prodromes)

1.2 (aura)
(simple partial seizure)


cognitive function



(complex partial seizures)
2. (seizure symptoms)

(associated symptom)

2.1

2.2

2.3 (automatism)

complex partial seizures absence seizures
2.4

2.5
2.6 (autonomic nervous system)


.

. 1-2
5
. (recurrent) (stereotyped)

.

.

. aura, ictal
period, postictal period Todds paralysis International
Classification of Epileptic Seizures International League Against Epilepsy .. 1981
( 2)
3. (postictal symptoms)
complex partial generalized seizures

(Todds paralysis)
24

1. Syncope syncope

2

(postural hypotension)
(micturition syncope) (defecation syncope)
(vasovagal syncope)
2. Transient ischemic attack (TIA)
(brainstem)

(pupillary light reflex) dolls eye
sign 2 (quadriplegia)
3. Migraine headache (basilar migraine)
basilar migraine

4. Metabolic disturbances
hypo-hyperglycemia, hypo-hypernatremia, hypercalcemia, hepatic renal failure
metabolic disturbances

5. Sudden increase intracranial pressure
(cerebrospinal fluid: CSF)
CSF
6. Sleep disorders cataplexy

7. Psychogenic disorders non-epileptic seizures

1.1

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

1.
1.
1.
1.
1.
1.
1.
1.
1.

2.
2.
2.
2.
2.
2.
2.
2.
2.

: 6

1 2 3 9

hereditary, perinatal injury, central nervous system infection (CNS infection), head injury, stroke, brain tumor metabolic disturbance
cerebral venous sinus
thrombosis

: cytomegalovirus, toxoplasma

1.

2.

3.

1.
2.

1.
syncope, TIA, sleep disorder, psychogenic disorder


1.1 heart murmur, xanthelasma
syncope TIA
1.2 Body mass index sleep disorder
1.3
(generalized tonic - clonic seizures)
1.4
psychiatric disorder
1.5 long tract sign, motor weakness

1.6 Cafe-au lait spot, adenoma sebaceum, ash leaf
shagreen patch, Port-wein stain neurocutaneous syndrome

1.7 postural hypotension syncope

xanthelasma TIA


iPhone

2.
congenital acquired diseases
neurocutaneous syndrome Tuberous sclerosis, Sturge Weber syndrome
skin lesion
post-head injury surgery 1.2

1.2

Caf au lait spot, adenoma sebaceum, as leaf- Neurocutaneous syndrome

shagreen patch, Port-wein stain
Surgical scar
Post-head injury, surgery
Neurological deficit
Post-stroke, brain tumor, encephalitis
Sign of chronic liver disease, flapping tremor
Hepatic encephalopathy
Flapping tremor
Metabolic encephalopathy
Ecchymosis
Intracranial bleeding
Subcutaneons nodule
Cerebral cysticercosis
Vasculitis, malar rash
Systemic lupus erythematosus
Papilledema
Brain tumor, increased intracranial
pressure
Mental retardation
Post-hypoxia
Carpopedal spasms
Hypocalcemia

1.3

(focal
neurological deficits)

(EEG)
CK
prolactin

cardiac arrhythmia,
bradycardia, asystole

(aura)
generalized tonic
- clonic seizure (GTC)
,
,

partial
seizure
Tachycardia
epileptiform activity
GTC
GTC

hypopigmented macules (ash leaf)
tuberous sclerosis infantile spasms, portwine stain hemangioma
Sturge Weber discoid lupus erythematosus systemic lupus erythematosus
1.1

( 1.1)

AED : antiepileptic drug

16 1

2 2-3 1




2-3

1. . .: ...
2547: 189-204.
2. . . : ; 2551.
4-5, 170.
3. Shorvon SD. Definition and classification of epilepsy.In: Shorvon SD. Handbook of
epilepsy treatment. London.2000:1-15.
4. Tiamkao S, Sawanyawisuth K, Asawavichienjinda T, et al. Predictive risk factors of
seizure-related injury in persons with epilepsy. J Neurol Sci 2009;285:59-61.
5. Tiamkao S, Sawanyawisuth K, Paowana W, et al. Seizure presenting to the emergency
department, Srinagarind Hospital. J Med Assoc Thai 2006;89:362-7.
6. Placencia M, Sander JW, Shorvon SD, Ellison RH, Cascante SM.Validation of a screen
ing questionnaire for the detection of epileptic seizures in epidemiological studies.
Brain 1992 ;115:783-94.

11

Seizure
(recurrent, episodic) (stereotyped)
2 convulsion nonconvulsion
Convulsion generalized tonic clonic seizures (GTCs)
Non- convulsion absence seizures
Epilepsy 2 (unprovoked seizures)
Ictal phase 1-2
Post - ictal phase

Inter - ictal phase
Todds paralysis
( 24 3 )

International Classification of Epileptic Seizures International League Against Epilepsy (ILAE) .. 1981

12

2.1 International League Against Epilepsy (ILAE) 1981

Partial Seizure
Generalized Seizure
- Simple partial seizure
- Absence seizure
- Complex partial seizure
- Generalized tonic-clonic seizure
- Partial seizure evolving to secondarily
- Generalized clonic seizure
generalized tonic clonic seizure
- Generalized tonic seizure

- Atonic seizure
- Myoclonic seizure
Unclassified seizure e.g. infantile spasms
1. (partial seizure)
cerebral cortex
1.1 Simple partial seizure (SPS)
simple partial seizure 4 (motor),
(sensory) somatosensory special sensory, (autonomic)
(epigastric sensation) (psychic)
(ictal EEG) (interictal EEG)

1.2 Complex partial seizure (CPS)

(awareness) (responsiveness)
CPS SPS
automatism (ictal EEG)
frontotemporal (interictal EEG)
(bilaterally asynchronous) temporal frontal
1.3 Partial seizure evolving to secondarily generalized seizure
(generalized tonic - clonic seizures
GTCs)
Partial seizure evolving to secondarily generalized seizure partial seizure
SPS CPS
secondary GTC SPS secondary GTC SPS
secondary GTC CPS secondary GTC 2.1

13

2.1 partial seizure

SPS
SPS

CPS

SPS

GTC

CPS
CPS

GTC

SPS

CPS

GTC

SPS = Simple partial seizures

CPS = Complex partial seizures
GTC = Partial seizure evolving to secondary generalized seizures

SPS sensory , autonomic psychic CPS GTCs

aura (aura alone) SPS
CPS (secondarily generalized)
2. (generalized seizure)


2.1 Absence seizure 1
(ictal EEG) spike-and-slow-wave
complex 3 Hz
(interictal EEG) normal background spike spike-andslow-wave complex (paroxysmal)
2.2 Myoclonic seizure
polyspike and
wave spike sharp and slow wave
2.3 Clonic seizure
clonic tonic - clonic clonic tonic - clonic fast activity
( 10 Hz) slow waves

14

2.4 Tonic seizure

low voltage fast activity 9-10 Hz (decreasing in frequency
and increasing in amplitude) sharp and slow waves
(rhythmic) abnormal background
2.5 Tonic - clonic seizure
fast activity ( 10 Hz) tonic activity
spike slow wave clonic phase
2.6 Atonic seizure
polyspike and wave flattening low
voltage fast activity
3. Unclassified seizure partial generalized seizure infantile spasms
ILAE


absence seizures
sodium valproate
absence seizures 2.2
2.2

Epilepsy

Absence seizures

Other type of seizures

- Sodium valproate

- Standard AEDs( Phenytoin,

Carbamazepine, Sodium valproate,
Phenobarbital)

15

: sodium valproate
absence seizures sodium valproate
myoclonic, tonic, atonic sodium valproate

16
1

1

complex partial seizure (CPS)

automatism (), loss of awareness (
) (recurrent and stereotype)

1. ..: ...
2544:9-24.
2. .. : ..
.2544:25-42.
3. . . 3. 2554.
14-15.
4. Shorvon SD. Definition and classification of epilepsy.In: Shorvon SD. Handbook of
epilepsy treatment. London.2000:1-15.
5. Shorvon SD. Precipitating, causes and differential diagnosis of epilepsy.In: Shorvon SD.
Handbook of epilepsy treatment. London.2000:16-33.

17

5
1. Benign familial neonatal seizures
1-2
2-3 autosomal dominant
1-6 6
benzodiazepines, phenobarbital, phenytoin
2-6
2. Benign idiopathic neonatal seizures benign neonatal seizures (non-familial)
(fifth-day fits)
1-7 90 4-6 fifth-day fits

1-3

benzodiazepines, phenobarbital phenytoin

3. Early infantile epileptic encephalopathy with suppression-bursts (ohtaharas

syndrome)
10 1-10
10-300 24
West syndrome Lennox-Gastaut syndrome
suppression-burst
ACTH vigabatrin zonisamide

18

4. Early myoclonic encephalopathy (EME)

myoclonus simple partial seizures infantile spasms
suppression-burst

ACTH, clonazepam,
nitrazepam, valproate, phenobarbital
5. Symptomatic neonatal seizures

(hypoxic-isch
emic encephalopathy)
subtle

clonic, myoclonic, tonic
, ultrasound, CT scan MRI brain,
phenytoin loading 15-20 /. maintenance 2-4 //
phenobarbital phenytoin phenobarbital



Benign neonatal sleep myoclonus

non-REM 3
7 2 10-20
2-7

1. Benign myoclonic epilepsy in infancy

6 3 myoclonic 1-2

( 30) 6 5
valproate clonazepam
levetiracetam 6 1
2. Generalized epilepsy with febrile seizures plus (GEFS+)
GEFS+
generalized seizures
absence, myoclonic, atonic, myoclonic-atonic

19

autosomal dominant with incompletepenetrance GEFS+

( 11 ) epileptic encephalopathy
Dravet syndrome
generalized seizures valproate, lamotrigine, levetiracetam topiramate
3. West syndrome
epileptic encephalopathy triad 1. infantile spasms 2.
3. hypsarrhythmia 3-12 5
2 (idiopathic)
(symptomatic) tuberous sclerosis

vigabatrin
vigabatrin visual field defect

4. Lennox-Gastaut syndrome (LGS)

epileptic encephalopathy triad 1.
tonic seizures atonic seizures, atypical absence seizures myoclonic
seizures 2. 3. slow generalized spike-wavedischarge (< 2.5 Hz)
1-7 3-5 West syndrome LGS
2 (idiopathic)
West syndrome (symptomatic) West syndrome
LGS malformations of cortical development focal cortical dysplasia
LGS 80-90

status epilepticus LGS valproate
LGS, clonazepam clobazam
lamotrigine, topiramate, levetiracetam vigabatrin
Febrile seizures
8

20

1. Benign childhood epilepsy with centrotemporal spikes (rolandic seizures)

7-10 8-9
focal motor sensory
secondary GTC
centrotemporal spikes
2-4 16 10
10-20
secondary GTC carbamazepine
2. Childhood absence epilepsy (CAE)
CAE
4-20 automatism
10 4-10
5-6 CAE
hyperventilation test 3 absence seizure
90 high amplitude generalized
spike and wave discharge 3 Hz. valproate carbamazepine, oxcarbazepine, phenytoin, gabapentin, phenobarbital, vigabatrin
status epilepticus CAE 12
90

1. Juvenile myoclonic epilepsy (JME) (janz syndrome)

JME triad 1. absence 2. myoclonic jerks 3. GTC
absence 5-16 myoclonic jerks 1-9
14-15 GTC 2-3 myoclonic jerks myoclonic jerks

generalized burst of multiplespikes 0.5-2 myoclonic jerks valproate 80

2. Juvenile absence epilepsy (JAE)
JAE typical absence seizures GTC
9-13 CAE
CAE 70-80

21

1
13
: 3
phenytoin phenobarbital
: 10 10
3 phenytoin phenobarbital
20-30
: hyperventilation test
1
: high amplitude generalized spike and wave discharge 3 Hz.
: Juvenile absence epilepsy
: Valproate 20 //

: juvenile absence epilepsy generalized
tonic clonic generalized tonic clonic

hyperventilation test

valproate phenytoin phenobarbital absence epilepsy
2
5
: 40-50 1
generalized tonic seizures phenobarbital
5 // 7.5 //
: 2 2
10 4-5

22

: 39 . (), hypopigmented macules, oval shape

5 1-2 .
: hypsarrhythmia
CT brain : Four periventricular tubers on both lateral ventricles
: West syndrome with tuberous sclerosis
: Vigabatrin 50 // 1 1

: West syndrome triad 1. infantile

spasms, 2. , 3. hypsarrhythmia tuberous sclerosis
hypopigmented macules ash leaf
adenoma sebaceum, shagreen patch
West syndrome tuberous sclerosis vigabatrin

generalized tonic seizures

infantile spasms
2 2

1. . . : ; 2551.
143-180.
2. Panayiotopoulos CP. The epilepsies: Seizures, syndromes and Management. Oxford
shire: Bladon Medical Publishing; 2005.

23

2
1.
2.
1.
1.1. (VDO-EEG)

(electrodes)



. 7 4


EEG EEG
EEG
1. (epileptiform discharge)
1-2

24

2.
(epileptiform discharge)
3. 20-50

80

EEG

( 1)

1.2. creatine kinase (CK) generalized tonic - clonic seizures (GTCs) prolactin GTCs
1-2 prolactin
prolactin prolactin

2.
2.1 blood sugar, renal function, liver function, calcium, phosphate
magnesium

98 2

2.2 (CT-scan brain)
(MRI - brain)
1. 25 (late onset epilepsy)
2. partial seizures hyperglycemic non - ketotic
induced seizures
3.
4.
5.
6. Todds paralysis

25

CT - scan brain MRI - brain MRI - brain

temporal lobe, brainstem , cerebellar
hippocampal sclerosis, cortical dysplasia, heterotropia MRI

CT - scan brain poor

compliance (true intractable seizures) hippocampal sclerosis cortical dysplasia CT - scan brain late onset
epilepsy partial seizures
4.1
4.1

- Complex partial seizure

- Secondary to GTCs
- Post - ictal paralysis
- Neurological deficit
- Intractable seizure

- GTCs
- Absence
- Other type of generalized seizures
Follow up

CT scan brain
Un - controlled

Controlled

# MRI - brain neuro - med

# Intractable seizure 2
(3-6 )

-
-

- .
-
( 8 10 )

26

( 1)

5 (sudden onset)
(involuntary) (self limited) (spontaneous occurrence)
(stereotype)

(electroencephalography, EEG)



CBC,
blood sugar, serum electrolytes, BUN, creatinine, calcium magnesium


(MRI)
(CT scan) MRI
temporal lobe
CT scan
MRI
16
1

1

27

complex partial seizure (CPS)

automatism (), loss of awareness (
) (recurrent and stereotype) CPS
EEG sodium valproate CT scan brain
CPS

3-6 CT scan brain

1. . . 3. 2554. 21-2.
2. Phuttharak W, Sawanyawisuth K, Kawiwungsanon A, Tiamkao S. The appropriate neu
roimaging study in persons with epilepsy. Neurol Sci. 2011 Jun 7. [Epub ahead of print]
3. Shorvon SD. Precipitating, causes and differential diagnosis of epilepsy.In: Shorvon SD.
Handbook of epilepsy treatment. London.2000:16-33.
4. Shorvon SD. General principles of treatment in epilepsy.In: Shorvon SD. Handbook of
epilepsy treatment. London.2000: 34-84.
5. Tiamkao S, Sawanyawisuth K, Paowana W, et al. Seizure presenting to the emergency
department, Srinagarind Hospital. J Med Assoc Thai 2006;89:362-7.

29

electrical discharge cortical neurons 30

neuroimaging
(CT scan)
(MRI)
CT scan
MRI CT
scan intracerebral hematoma
( 1) subdural hematoma ( 2) (calcification) cysticercosis ( 3) cerebral infarction ( 4) , brain abscess (
5), brain tumor, post traumatic brain change ( 6), brain atrophy brain anomaly

CT scan temporal lobe

temporal lobe epilepsy mesial temporal sclerosis
temporal lobe brain tumor
CT scan temporal lobe brain anomaly
CT heterotrophic gray matter

30

MRI (anatomic substrate)

MRI (structural abnormali
ties) substrate
(eloquent area)
residual recurrent lesion
MRI
gray-white matter inversion recovery spoil gradient recall echo T1W spin echo T2W
protocol ( epilepsy protocol )
Epileptogenic substrates imaging MRI
1. Hippocampal sclerosis
2. Malformations of cortical development
3. Neoplasms
4. Vascular abnormalities
5. Gliosis and miscellaneous abnormalities
1. Hippocampal sclerosis
mesial temporal sclerosis neuronal loss gliosis
hippocampus limbic system temporal lobe
surgical epilepsy
MRI findings hippocampus (hippocampal atrophy)
T2W hippocampus
mammilary body fornix, temporal horn temporal
lobe white matter hippocampus collateral sulcus
CT scan MRI
temporal lobe epilepsy

31

7 MRI coronal T2W right mesial temporal sclerosis hippocampus

()
symmetry
hippocampus abnormal signal on T2WI
10-20 hippocampal volumetry / T2 relaxometry
MRI
(dual pathologies) 8-22 cortical dysgenesis
2. Malformations of cortical development
Development of cortex 1.cell proliferation 2.cell migration
3.cortical organization cortical dysgenesis
1. Abnormal neuronal , glial proliferation or apoptosis
1.1 Hemimegalencephaly
cerebral hemisphere dysplastic enlarged
cutaneous syndromes epidermal nevus syndrome, neurofibromatosis type l, Klippel-Trenaunay-Weber syndrome, tuberous sclerosis
Findings enlargement cerebral hemisphere volume
white matter enlargement lateral ventricle dysplastic area
abnormal signal intensity white matter simplified gyral pattern
(oligogyria) pachygyria,dysplastic cortex polymicrogyria

32

8 Hemimegalencephaly MRI T1W right cerebral hemisphere

cortex left lateral ventricle
1.2 Focal cortical dysplasia with balloon cells
Taylor type cortical dysplasia area cerebral mantle
ventricular surface pia MRI partial epilepsy
2-3 focal cortical
thickening, gray-white junction area white matter linear, curvilinear
funnel-shaped gray-white junction superolateral margin lateral ventricular surface

9 Taylors FCD with balloon cells right frontal cortex

gray white matter area white matter graywhite matter () ventricle ()
3. Malformations of secondary to abnormal neuronal migration
3.1 Classic lissencephaly
sulcation sulci
smooth brain agyria complete lissencephaly gyri pachygyria incomplete lissencephaly
( 11)

33

10
11
10 complete lissencephaly smooth surface brain cortex ( 11) incomplete
lissencephaly cortical gyri
3.2 Congenital muscular dystrophies
muscular dystrophy structural abnormality

Walker-Warburg syndrome ( 12)

Nearly completely unmyelinated white matter
Hydrocephalus
Thinned cortex, few sulci
Absent or hypogenesis of corpus collosum
Dysmorphic cerebellum and brain stem
Kinking at pontomesencephalic junction causing mesencephalon pulled posteriorly

12 7 Walker-Warburg syndrome
brain cortex cobblestones ventricle

34

3.3 Heterotopia
gray matter 3 subependymal or periventricular heterotopia, subcortical heterotopia band or laminarheterotropia CT scan

13

14

15

13 Heterotopia 14 subependymal type nodules ventricle, :

periventricular type gray-matter ventricle, 15 band,laminar type
gray matter periventricular white matter
4. Malformations secondary to abnormal late migration and organization
polymicrogyria schizencephaly prenatal
infection, ischemia, toxins chromosomal abnormalities
4.1 Polymicrogyria
MRI maturity of brain neonate cortex irregularly
undulating small gyri ( 16) mature brain cortex (5-8 mm thickness)
(less undulating cortex) broad gyri, shallow sulci, irregular corticomedullary junction
posterior sylvian cortex, frontal, parietal, temporal occipital lobe
4.2 Schizencephaly
CSF extend subarachnoid space lateral
ventricle wall dysmorphic gray matter closed lips ()
17 open lips ( 18) unilateral 2/3 bilateral 1/3 posterior
sylvian cortex

16

17

35

18

16 polymicrogyria 17 closed lip schizencephaly 18 open lip schizencephaly

5. Neoplasms

2-4 epileptic substrate epilepsy tumor

90 cortex temporal lobe 68 MRI
CT scan

19 brain tumor hippocampus () CT scan

6. Vascular malformations
5 epileptic substrate epilepsy
ateriovenous malformations (AVM), cavernous malformation or cavernomas
or cavernous hemangiomas lesion MRI
popcorn like with heterogeneous signal lesion hypointense hemosiderin
gradient echo image MRI sensitivity cavernoma

36

20 cavernoma temporal lobe MRI

gradient echo
7. Gliosis, post traumatic brain
7.1 Gliosis focal ( 21 ) diffuse central nervous system
injuries nonspecific area T2W MRI
volume loss
7.2 Post traumatic epilepsy closed head injury
inferior anterior skull base orbital surface frontal lobe, undersurface temporal lobe, frontal pole temporal pole ( 22) CT scan
artifact skull base

21
22
21 gliosis : post ischemic gliosis neonate 22 post traumatic gliosis
adult ()

37

7.3 Infections
mycobacterium parasite tuberculosis neurocysticercosis
Neurocysticercosis
brain parenchyma, ventricles, subarachnoid spaces
inflammatory response degenerating dying parasite
lesion thin-walled nonenhancing cystic lesions MRI
scolex lesion T1W ( 23)
CT scan calcification
Tuberculosis (TB)
meninges brain parenchyma ( 24) leptomeningeal involvement hydrocephalus, neuropathies, arteritis deep gray matter infarction

23

24

23 scolex neurocysticercosis, 24 tuberculoma TB

Rasmussens encephalitis
chronic encephalitis partial seizure progressive neurologic
cognitive deterioration hemisphere
acute phase areas brain cortex and subcortical white matter
frontoinsular region brain stem

38

25

26

25 frontotemporal lobes 26
25 2 (J Neurol Neurosurg Psychiatry 2007;78:200-201)
7.4 Sturge-Weber syndrome
findings angioma parietal occipital region ( 27) cortical
calcifications, enlarged choroid plexus, atrophy ipsilateral cerebral hemisphere, enlarged
elongated eye globe prominent enlarged subependymal medullary veins,
dilated paranasal sinuses mastoid air cells thickened calvarium

27 Sturge-Weber syndrome abnormal leptomeningeal enhancement

parieto-occipital angioma choroid plexus occipital horn lateral ventricle

39

CT scan MRI CT scan

MRI
CT scan
MRI
MRI

1. Bernasconi N, Bernasconi A, Caramanos Z, et al. Mesial temopral damage in

temporal lobe epilepsy: a volumetric MRI studies of hippocampus, amygdala, and
parahippocampal region. Brain 2003;126:462-9.
2. Phuttharak W, Sawanyawisuth K, Kawiwungsanon A, Tiamkao S. The appropriate
neuroimaging study in persons with epilepsy. Neurol Sci. 2011; 32: 969-71.
3. Quesada CM, Urbach H, Elger CE, Bien CG. Rasmussen encephalitis with ipsilat
eral brain stem involvement in an adult patient. J Neurol Neurosurg Psychiatry
2007;78:200-1.
4. Vattipally VR, Bronen RA. MR imaging of epilepsy : strategies for successful
interpretation. Neuroimaging Clinics of North America 2004;14:349-418.

41

2 - 3





-

1.



2.

27-84 60 6
9 8 6
2.1 100

2.2 spike and wave

42

2.3 16 60
2.4 partial seizures generalise
3. simple partial seizures

4. benign Rolandic epilepsy
reflex seizures photosensitivity VDO game seizures

5.

6.



-
-
-
-
-
-
-
-
-
- /
2 status epilepticus

43

1.

2.
3.

4. CPS
5. epileptiform discharge
6.
7.
seizure threshold

1.
empirical treatment
2.
3. -
4.
5. 1
6.1 6.2

1.
2.
3. drug interaction
2
1. (standard antiepileptic drug)
- Carbamazepine
- Phenobarbital
- Clobazam
- Phenytoin
- Clonazepam
- Sodium valproate

44

2. (new antiepileptic drug)

- Felbamate
- Gabapentin
- Lacosamide
- Lamotrigine
- Levetiracetam
- Oxcarbazepine
- Pregabalin
- Tiagabine
- Topiramate
- Vigabatrin
- Zonisamide

6.1
absence seizures
sodium valproate
4 absence seizures
absence seizures sodium valproate
6.1 2.2
2.2

Epilepsy

Absence seizures

Other type of seizures

- Sodium valproate

- Standard AEDs; Phenytoin

Carbamazepine, Sodium valproate, Phenobarbital

47 13 3
36 1



drug interaction

45

40
3 80

80-90
generalized tonic-clonic
20-30 2 75 6
2

60

1.
2. (monotherapy)

drug interaction

3.
5-7
4. ( 6.1)

5. 2-4
6. (compliance) phenobarbital
1-2
7.
8. 25
3-6 barbiturate

46

6.1 ( 7 )

Clonazepam, gabapentin,
Simple and complex partial seizures, Carbamazepine,
lamotrigine, levetiracetam,
primary and secondarily generalized valproate, phenytoin
oxcarbazepine, phenobarbital,
tonic-clonic seizures
topiramate
Absence seizures

Clonazepam, lamotrigine,
phenobarbital

Valproate

Atypical absence, tonic and clonic Valproate

seizures

Carbamazepine, clonazepam,
lamotrigine, oxcarbazepine,
phenobarbital, phenytoin,
topiramate

Myoclonic seizures

Clonazepam, lamotrigine,
phenobarbital

Valproate

6.2

(.) (./)

(./)
()

()

Carbamazepine

100

100-200

400-1600

2-3

Clonazepam

0.5

0.5

0.5-4

1-2

Gabapentin

300

300-900

900-3600

2-3

Lamotrigine

25

50-100

100-400*

Levetiracetam

1000

500

1000-3000

Oxcarbazepine

600

300

900-2400

Phenobarbital

30

30-60

30-180

1-2

Phenytoin

100-200

50-100

100-300

1-2

Topiramate

25-50

50-100

200-600

Valproate

400-500

500

500-2500

2-3

47

35 secondary to generalized
tonic-clonic seizures (GTCs) 1
CT scan brain

phenytoin (100 mg) 3 capsule
1

1. . . : ; 2551.
176.
2. . . 3. 2554. 35.
3. Berg AT, Shinnar S.The risk of seizure recurrence following a first unprovoked seizure:
a quantitative review.Neurology 1991; 41: 965-72.
4. Camfield PR, Camfield CS, Dooley JM, Tibbles JA, Fung T, Garner B. Epilepsy after a first
unprovoked seizure in childhood.Neurology 1985; 35: 1657-60.
5. 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.
6. 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 unpro
voked seizure.Ann Neurol 2000; 48: 140-7.

49

47 13 3
36 1



drug interaction 7.1

1 poor compliance
50
compliance 2 add on therapy

second monotherapy 2
2
add on therapy
2.4

50

7.1

Antiepileptic
Drug
Carbamazepine

Phenytoin
Phenobarbital
Sodium valproate
Clobazam

Focal-onset
Seizures
+
+
+
+
+
+
+
+
+
+
+
+
+

Primary Generalized Seizures

Tonic
Absence Myoclonic
Clonic

+
+
0
+
+
+
+

LennoxGastaut
Syndrome
0
0
?

+
?
+
+
+
?
+
?+
Clonazepam

?+
?
Vigabatrin
+
+
+
+
Lamotrigine

?+
?
Gabapentin
+
?
+
+
Topiramate

+
0
Oxcarbazepine
+
?+
+
?
Levetiracetam
?
?
?
?
Pregabalin
+
?+
?+
Zonisamide
?+
?+
: , + , ?

1.

2.

2.1 1 3

51

2.2

2.3


2.4 2.1-2.3


( upper limit)

2 add on therapy second monotherapy
add
on therapy
second monotherapy
2-4

2.5 (add on therapy)
drug interaction
7.1

2.5.1
2.5.2

2.5.3
2.5.4 drug -interaction

2.5.5
neuropathic pain

52

70-80
10 5 20-30

partial seizures

CT-scan MRI-brain



-
-
-
-
-
-
7.1

-
-
- (vagus nerve
stimulation)
-

53

(intractable epilepsy)
first line 2 1 18
3 2


1.
2.
3.
4. uremia, SLE
5. antipsychotic haloperidol, risperidol
carbamazepine phenytoin
absence
6.
generalized tonic seizure, tics

infantile spasms, Lennox-Gastaut syndrome, partial seizures
ketogenic diet

10


30
absence seizures sodium valproate absence
seizures 6
CT scan brain

2 lamotrigine lamotrigine

1. . . 3. 2554. 44-5.
2. Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B.Early development of intractable epilepsy in children: a prospective study.Neurology 2001; 56: 1445-52.

55

(febrile seizures)

38 ()
6 60

2-5 5

polygenic autosomal dominant penetrance

24
75 39 25 40 25


86

2
1. Simple febrile seizure
15 5 1 24

56

2. Complex febrile seizure 15

1 24
(Todd paralysis) 24
(febrile status epilepticus)
30

3
1.
2.

3.

2-5

1 6

(CBC)

complex
febrile seizures

1. (semiprone lateral position) 5 5-10
diazepam 0.2-0.3 ././ 0.5 ././
(intrarectal)

57

2.
acetaminophen 15 ././ 4-6 ibuprofen
Reye syndrome
3.

30-35 3 50
2-3 9 3 90 2

(Major risk factors)

1. 1
2. 24
3. 38-39oC
(Minor risk factors)
1.
2.
3. Complex febrile seizure
4.
5.
6.
12, 1
25-50, 2 50-59, 3 73-100

The American Academy of Pediatrics simple febrile seizure

5 rectal diazepam 0.5
// 10 .
diazepam 0.33 // 8

5
0.08

58

33, focal complex febrile seizures 29, 18,
1 11, complex febrile seizures 6, 4,
simple febrile seizures 1

2
: 8 5

:
2-3 2-4
:
: epileptic discharge
: Simple febrile seizures
:
5

: simple febrile seizures
generalized tonic clonic seizures simple febrile
seizures IQ development

1. . . : ; 2551.
181-8.
2. . : .
. 2554 58-62.
3. American Academy of Pediatrics. Practice parameter: longterm treatment of the child
with simple febrile seizure. Pediatrics 1999; 103: 1307-9.
4. Mikati MA. Febrile seizures. In: Kliegman RM, Stanton BF, St Geme III JW, Schor NF,
Behrman RE, editors. Nelson textbook of pediatrics. 19th ed. Philadelphia: Saunders;
2011. p. 2017-8.
5. Subcommittee on Febrile Seizures; American Academy of Pediatrics.Neurodiagnostic
evaluation of the child with a simple febrileseizure. Pediatrics 2011; 127 : 389-94.

59

Status epilepticus (SE)

3-5

SE epileptic activity
30 2
pre-hospital study 10 50
SE emergency room (ER) SE
SE 5 2

SE ER

18-40
11,700-26,000 60
SE

SE 2 convulsive SE (CSE) non-convulsive SE (NCSE) CSE

partial CSE epilepsia partialis continua (EPC)
generalized CSE generalized tonic-clonic SE (GTCSE)
EPC EPC non-ketotic hyperglycemic induced seizure(NKHS) EPC neurological deficit
290 mg% metabolic acidosis
intramuscular intravenous
diabetic ketoacidosis hyperosmolar coma
abnormal movement CT-scan brain

60

GTCSE
SE 30
benzodiazepine 5
NCSE NCSE
coma
nystagmus , myoclonic jerk tonic eye deviation NCSE
NCSE
NCSE

SE
GTCSE 5
60 48

SE
(EEG)
GTCSE 4 9.1 9.1
9.2

9.1 GTCSE

30

61

9.1 convulsive status epilepticus

1
2. 1

2.2

SE
(0-5)
SE
(5-30)

SE
(30-60 )

capillary blood
glucose CBC, glucose, electrolytes,

calcium, magnesium

50% glucose (50 ml) 1
** 25% glucose 2 ./.
18 6 100 .
()

Diazepam (i.v. bolus or p.r.)

Diazepam (i.v. bolus)
phenytoin/fosphenytoin
(i.v. loading) sodium
valproate (i.v. loading)

(phenytoin/
fosphenytoin sodium val
proate

phenobarbital (i.v. loading) phenytoin (i.v. loading) sodium valproate
(i.v.loading) levetiracetam
(i.v.ng)
3.
SE
EEG( ), Propofol (i.v. bolus &inf)

phenobarbitalmidazolam

(> 60 )
(i.v. bolus) pentobarbital
(i.v. bolus &inf) thiopental
(i.v.bolus&inf) topiramate
(ng)
i.v. = intravencus, p.r.= per rectum, i.m.= intramuscular, inf = infusion, ng = naso/orogastric
* non convulsive status epilepticus simple partial status epilepticus absence status epilepticus
** (MIMS Thailand 1/2009)

62

9.2 convulsive status epilepticus*

Diazepam

Mainte
nance

0.3 ./.
2 ./

10 .

10 ./2 ./vial

10 . 2-5
./
Phenytoin

20 ./. 1500 .
1 ././
25 ./

20 .PE/.
3 ././

arrhythmia

NA

5-8
.PE/
./
300-500
./PE/

500 . PE/vial

0.9% NaCl
5 %
Dextrose
15-25 . PE/
.

1000 .

4-6 ./
. /
1-4 ./
./

200 ./4 .
sterile water
10 .

0.9% NaCl
Ringer lactate
5%
Dextrose

Diazepam

20 .PE./.
100-150 ./

Phenobarbital

20 ./.
3 ././
20 ./.
100 ./

10
2

5-8 ./ 250 ./5 ./

./ vial 0.9%
NaCl
1-2 .
300- infu500./ sion pump

20 ./.
50 ./
30 ./.
Fosphenytoin

63

9.2 convulsive status epilepticus* ()

Mainte

nance

Sodium
Valproate

20 -40 ./.
1-3
././
20-30 ./.
50
./

NA

1-5 ./
./.
1-2 ./
./.

400 . /4 .
0.9%
NaCl 5%
10% Dextrose
24

Topiramate

hyperammonia
encephalopathy

500 ./5 ./vial

0.9%NaCl, Ringer
lactate 5%
Dextrose 100 . 15

24

Levetiracetam

30-40 ./. 4000 . 10-30 ./

15
12 .

2000-4000 .

15

(oro/
nasogastic)

Midazolam

0.2 ./. 2 ./. 0.02-0.4 1 ././vial5 ././

5
././. vial 0.9% NaCl

5% Dextrose
24 .

Ringer lactate 24 .
4 ./
0.1-0.3 ./.
0.05-0.4
5
././.

4 ./

64

9.2 convulsive status epilepticus* ()

Mainte

nance

Pentobarbital

2-10 ./.
25 ./

NA

0.5-1 ./ 0.9% NaCl

./. Sterile water
0.5-3 ./ 2% 2.5%
. solution

NA

3-5 ./ 0.9% NaCl

./. 5%

Dextrose Sterile
water
3-5 ./ 2.5 % solution
./.

NA

2-3 ./ 10 ./.
./. 0.9% NaCl
5% dextrose
5-10 ./ volumetric
. infusion pump

6 .

20 ./.
25 ./
Thiopentone

Propofol

5 ./.
3-5 ././.

100-250 .
20
50 . 2-3

1-2 ./.
50 /
./
2 ./.

NA = not available
* non convulsive status epilepticus simple partial status epilepticus absence status
epilepticus
topiramate SE 400 .(loading dose) nasogastric tube maintenance 200 .

phenytoin, phenobarbital
sodium valproate
loading maintenance

65

1. phenytoin loading dose 15-20 ./ 0.9 NSS 50 ./

loading 30 ././ loading
maintenance dose loading dose 6-8 maintenance
300 ./ 100 . 8
phenytoin suspension phenytoin suspension
2 phenytoin

fosphenytoin phenytoin
150 ./

2. phenobarbital loading dose 20 ./. 5 D/W 100 ./
(very high dose phenobarbital)
maintenance dose loading dose 12 maintenance
300 ./ 1 5 % dextrose water 100 1-2
180 ./
3. sodium valproate loading dose 20-25 ./. 20-30
2-3 loading 140 ./. maintenance dose 2 24 2 /
maintenance 6-8 loading dose
1,200 .
() 600 800 .
RSE 9.1
24
maintenance

SE CT scan
brain phenytoin
5% dextrose water maintenance
non-convulsive
seizure status epilepticus
nystagmus
SE

SE

66

CT-scan brain

SE 9.3 9.4 20 poor compliance
SE poor compliance

alcoholic dependent alcoholic
withdrawal delirium tremens
intracranial causes chronic subdural hematoma SE
lumbar puncture CNS infection
CK, BUN, Cr, urine
analysis rhabdomyolysis
9.3 . (52 )

Cerebral infarction
CNS infection
Systemic infection
Hypertensive encephalopathy
Uremia
Intracerebral hemorrhage
Subdural hematoma
Organophosphate poisoning
Mushroom poisoning
Hepatic encephalopathy
Post cardiac arrest
Compression skull bone
Obstructive hydrocephalus
CNS vasculitis
Electrolyte imbalance (hyponatremia)

()
18(34.6)
10(19.2)
0
3(5.8)
3(5.8
2(3.9)
2(3.9)
2(3.9)
1(1.9)
1(1.9)
1(1.9)
1(1.9)
1(1.9)
1(1.9)
1(1.9)

67

9.4 SE .

Acute symptomatic
Encephalitis
Cerebral infarction
Meningitis
Hypertensive encephalopathy
Head injury
Craniotomy
Post-cardiac arrest
Intracerebral hemorrhage
Cerebral venous sinus thrombosis
Septic encephalopathy
Remote symptomatic
Post-cerebral infarction
Post-head injury
Post-intracerebral hemorrhage
AEDs withdrawal
Alcohol related

()
21 (52.5)
6 (15)
3 (7.5)
3 (7.5)
2 (5)
1 (2.5)
1 (2.5)
1 (2.5)
1 (2.5)
1 (2.5)
1 (2.5)
3 (7.5)
1 (2.5)
1 (2.5)
1 (2.5)
10 (25)
6 (15)

SE
SE

68

1 35 generalized tonic
clonic seizures(GTCs) GTCs
valium 10 mg valium 10
valium 10 mg
phenytoin 750 mg 15
phenytoin 300 mg 30 phenytoin
6 24 CT scan brain
phenytoin (100 mg) 3
2 60 ischemic heart disease with atrial fibrillation
generalized tonic clonic seizures(GTCs)
GTCs valium 10 mg valium 10
valium 10 mg sodium valproate 1200 mg 30
8 sodium valproate (200 mg) 2 -

1. Tiamkao S, Mayurasakorn N, Suko P, et al. Very high dose phenobarbital for refractory
status epilepticus. J Med Assoc Thai 2007;90:2597-600.
2. Tiamkao S, ChanonJ ,Sawanyawisuth K, Pratiparnawatr T, Jitpimolmard S. Prediction of
seizure control in non-ketotic hyperglycemic induced seizures. BMC Neurology 2009; 9 : 61.
3. Tiamkao S, Sawanyawisuth K. Predictors and prognosis of status epilepticus patients
treated with intravenous sodium valproate. Epileptic Disord 2009; 11(will be published).
4. Tiamkao S, Suko P, Mayurasakorn N,Srinagarind Epilepsy Research Group. Outcome of
status epilepticus in Srinagarind Hospital.J Med Assoc Thai 2010;93:420-3.

69

10

nonconvulsive
status epilepticus abscence status epilepticus complex partial status epilepticus

The International
League Against Epilepsy, 1981 30
30 30
45-60

Convulsive tonic-clonic
generalized tonic-clonic seizures (GTC)
clonic seizures GTC
1-3 GTC clonic phase (interictal phase)

20
Tonic status epilepticus
tonic-clonic clonic status LennoxGastaut syndrome (LGS)
tonic status

70

Myoclonic status epilepticus

myoclonic jerks
acute hypoxic-ischemic encephalopathy,

Partial convulsive status epilepticus

unilateral status herpes
encephalitis benign partial rolandic epilepsy

Nonconvulsive status epilepticus

Generalized nonconvulsive status epilepticus

spike-wave complexes 2 Lennox-Gastaut
syndrome absence status
synchronous, symmetric epileptic activity 2
Partial nonconvulsive status epilepticus
temporal lobe epilepsy complex partial status simple partial status
simple partial status complex partial status

(speech arrest) (stereotypic automatisms)

convulsive status epilepticus

nonconvulsive status epilepticus


(minor status)
Lennox-Gastaut syndrome

CBC, , blood gas,

71

nonconvulsive status epilepticus

30 5
30

blood gas

The Epilepsy Foundation of America (EFA)

-
-
-
-
-
- 5
-

72

10.1
0-5
ABCDEF 10.1

()
25% Dextrose in water 2 /. 10% Dextrose in water 5 /.
normal saline phenytoin

5

5-10
diazepam 0.3 //
2 / diazepam
0.5 // 0.9%NaCl 3 .
5-10 1 5-10
20 2
phenytoin 25-30 //
1 // phenytoin diazepam diazepam
phenytoin
arrhythmia, phenytoin 3-9 //
2 12-24

73

30 3
valproate 40 // 5 //
levetiracetam 40 //
5 //
phenobarbital
35 4
3 refractory status epilepticus

midazolam 0.2 // 2
0.1 //. 5 midazolam 0.2 // 2
1 0.2 //. 2-3 //.
24 . maintenance
midazolam 0.05 //. 3 .
10.1
10.1

0-5

A: Airway
B: Breathing 100
C: Circulation 0.9% normal saline
D: Drugs 25% 2 /.
E: Environment
F: Fever reduction

Diazepam 0.3 // 1 5-10

diazepam 0.5 // midazolam 0.2 //

phenytoin 20 // ()

20

5-10

Phenytoin 25-30 // 1 //

74

30

Valproate 40 // 5 //

Levetiracetam 40 // 5 //

35

( )

5 3 refractory status epilepticus

Midazolam 0.2 // 2 0.1 //.
4
5 Midazolam 0.2 // 2
5 Midazolam 0.2 // 2
0.2 //. ( 2-3 //.)
24 . maintenance
Midazolam 0.05 //. 3 .

1.
2. nonconvulsive status epilepti
cus

3.
4.
5.

6.

75

10.1

Diazepam

0.3 /.

< 2 /

Phenytoin

20 /.

< 1 //
25/

Phenobarbital 20 /.
Valproate

< 2 //

100 /
20 /.
3-5
1 //.

10 .

10 2
1500 . arrhythmia
0.9%NaCl

1000 .
diazepam

Pentobarbital 2-10 /.

Thiopenthal

5 /.

0.5-1 //.

1-2 /.

5 //.

2-3 //.

0.2 /.

< 50 //

Propofol

Midazolam
Levetiracetam

40 /.

0.02-0.4 //.

5 //

acidosis

10 .

76

1. . Management of status epilepticus in children.

2554; 6: 113-31.
2. Abend NS, Gutierrez-Colina AM, Dlugos DJ. Medical treatment of pediatric status
epilepticus. Semin Pediatr Neurol 2010; 17: 169-75.
3. Berg AT, Shinnar S, Testa FM, Levy SR, Frobish D, Smith SN, et al.Status epilepticus
after the initial diagnosis of epilepsy in children. Neurology 2004; 63: 1027-34.
4. Commission on Classification and Terminology of the International League Against
Epilepsy: Proposal for revised clinical and electrographic classification of epileptic
seizures. Epilepsia 1981, 22: 489-501.
5. Leszczyszyn DJ, Pellock JM. Status epilepticus. In: Pellock JM, Dodson WE, Bourgois
BFD, editors. Pediatric epilepsy: diagnosis and therapy. 2nd ed. New York: Demos
Medical Publishing, Inc.; 2001. p. 275-89.

77

11

20-30
temporal lobe epilepsy 35 60

32 26 4 2
prolactin

sodium valproate 45
androgen
sodium valproate
sodium valproate

phenytoin carbamazepine

78

topiramate sodium valproate, gabapentin,

lamotrigine tiagabine

estrogen ethinyl estradiol 50

3
1-2
2
estrogen progesterone
estrogen
estrogen
progesterone progesterone
estrogen
progesterone
estrogen progesterone

estrogen estrogen

progesterone estrogen
estrogen progesterone
estrogen 47
29 24

79

testosterone
temporal lobe epilepsy testosterone/LH idiopathic generalized epilepsy
testosterone carbamazepine testosterone binding globulin
free testosterone aromatase testosterone estradiol sodium valproate total testosterone
testosterone/LH free testosterone
oxcarbazepine carbamazepine
sodium valproate
lamotrigine

phenytoin
estradiol dehydroepiandrosterone sulfate sodium valproate
lamotrigine sexual function

17.7
25 combined pill ethinyl estradiol drug interaction drug interaction
.. 1972
portal circulation
first pass metabolism cytochrome
P450 (CYP450) CYP3A4 ethinyl estradiol (EE)
phenytoin, phenobarbital , ethosuxamide, carbamazepine
CYP 3A4 EE EE
enzyme inducing AEDs sex hormone
binding globulin (SHBG) topiramate 200 mg , felbamate ox-carbamazepine enzyme inducer enzyme inducing AEDs
progerterone combined pill

80

enzyme inducing AEDs

CYP3A4 non-enzyme inducing AEDs sodium valproate lamotrigine, gabapentin, topiramate,
tiagabine levetiracetam, benzodiazepines, zonisamide sodium valproate
combinedpill drug interaction progesterone-onlypill,medroxyprogesterone
injections levonorgestrel implants etonogestrel implant sodium
valproate, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide
drug interaction
enzyme inducing AEDs
combined pill combined pill EE 50 ug
breakthrough bleeding
combined pill EE 75- 100 ug EE

enzyme inducing AEDs combined pill

enzyme inducing AEDs
10
12
local effect first
pass metabolism enzyme inducing AEDs
Medicated IUDs (Active IUDs)
Synthetic progestogens
subdermal levonorgestrel phenytoin
progestogen-only
enzyme inducing AEDs

progesterone ( 11.1)
non-enzyme inducing AEDs ( 11.2) 11.3

81

11.1
enzyme inducing AEDs
Medroxyprogesterone depot injection (Depo-Provera)
Copper intrauterine devices
Hormone-releasing intrauterine system (levonorgestrel-releasing intrauterine system
Barrier methods
enzyme inducing AEDs
Combined contraceptive pill/patch
Progestogen-only oral contraceptive
Progestogen implant

11.2

Phenytoin
Valproate
Phenobarbital (phenobarbitone)
Gabapentin
Primidone
Levetiracetam
Carbamazepine
Vigabatrin
Oxcarbazepine
Pregabalin
Topiramate (little effect below 200 mg/day)
Benzodiazepines
*Lamotrigine
Zonisamide
Ethosuximide
Acetazolamide
* Lamotrigine is not considered a traditional enzyme-inducing AED but it may induce the metabolism of
progesterone and therefore is included in this table.

82

11.3

Mirena coil
nonenzymeinducing AEDs valproate sodium, benzodiazepines, vigabatrin, gabapentin, tiagabine,
levetiracetam, pregabalin
enzyme-inducing AEDs phenytoin, barbiturates,
carbamazepine, oxcarbazepine, topiramate [>200 mg/day], and lamotrigine

enzyme-inducing AEDs
ethinyl estradiol 50 ug
ethinyl estradiol 75 100 ug

enzyme-inducing AEDs

enzyme-inducing AEDs
progesterone medroxyprogesterone

Mirena coil
levonorgestrel
enzyme-inducing AEDs

lamotrigine

forcep
(status epilepticus)

83

1.
2.
3.
3

(status epilepticus)
generalized seizures
lactic acidosis
(feto-maternal exchange) lactic acidosis

generalized seizures ( absence seizures)


2-3
teratogenicity
teratogenicity
(folic
acid)

3

compliance

(volume of distribution)
liver metabolism
serum protein


drug compliance

84

4
1.
2.
3.
4.
8

neural tube 3
1 phenobarbitone, primidone, phenytoin ethosuximide
2 carbamazepine, sodium valproate, benzodiazepine clobazam, clonazepam,
clorazepate lorazepam
3 oxcarbazepine, lamotrigine, felbamate, topiramate, gabapentin, losigamone,
levetiracetam, progabide, remacemide, stiripentol, tiagabine, vigabatrin zonisamide
1 2 sodium valproate
carbamazepine neural tube hypospadias sodium valproate
spina bifida lumbosacral carbamazepine hydrocephalus
encephalocele 3 leveiracetam

3 2-3 ( 7 )
15
neural tube sodium valproate, carbamazepine 1 1-2, 0.5-1 0.3 ( neural tube
0.2-0.5) sodium valproate 1500
spina bifida
11.4

85

2-5 10



generalized tonic - clonic seizures
2-3 ultrasound
10, 18 24 sodium valproate carbamazepine
amniotic fluid 12 Omtzigt
serum alpha fetoprotein amniotic fluid alpha fetoprotein neural
tube serum (4 6 )
carbamazepine partial, secondary generalized seizures idiopathic generalized seizures sodium valproate
spina bifida 5
neural tube
20 12
1
phenobarbitone
300

11.4
Growth
Perinatal growth deficiency
Postnatal growth deficiency
Microcephaly
Craniofacial
Short nose, low cranial bridge
Hypertelorism
Epicanthic folds
Strabismus and other ocular abnormalities
Low set ears and other aural abnormalities
Wide mouth and prominent lips
Wide fontanelles
Cleft lip and cleft palate

86

Limbs
Hypoplasia of nails
Transverse palmar crease
Short fingers
Cerebral
Mild learning disability
Development delay
Systemic
Short neck, low hairline
Rib, sternal or spinal anomalies
Widely spaced hypoplastic nipples
Hernias
Undescended testicles
Neuroblastoma and neural ridge tumors
Cardiac and renal abnormalities
3
1. 2

folic acid
2.

folic acid folic acid

3.
forcep vaccum

87

1. Crawford PM. Interactions between antiepileptic drugs and hormonal contraception.

CNS Drugs 2002 ; 16 : 263 72
2. Crawjord PM. Managing epilepsy in woman of childbearing age. Drug Saf 2009 ; 32:
293-307
3. Omtzigt JG, Los FJ, Hagenaars AM, Stewart PA, Sachs ES, Lindhout D. Prenatal
diagnosis of spina bifida aperta after first-trimester valproate exposer. Prenat Diagn
1992; 12:893-7.
4. Patsalos PN, Froscher W, Pisani F, Van Rijn CM. The importance of drug interactions in
epilepsy therapy. Epilepsia 2002 ; 43 : 365 85
5. Shorvon SD. Treatment of epilepsy in women. In: Shorvon SD, ed. Handbook of epilepsy
treatment. London: Blackwell Science, 2000: 75-83.

89

12

psychogenic nonepileptic seizures (PNES)

Denial
Anxiety

Shame
Depression

Dependent

Regression
Somatization
Social isolation
Sick role

Aggression (impulsivity)
Suicidal attempt

90

(adjustment disorder)
(Psychiatric symptoms in epilepsy, PSE)
30 50
temporal lobe epilepsy partial epilepsy
(psychosis)
Tonic/clonic seizure (Grand Mal)
prodrome (unusual bodily sensation:
numbness) (sensation of faintness)
(turning of the head and eyes)
aura
(postictal phase)

Absence seizure (Petit Mal)

(ictal phase)
(brief interruption of consciousness during activity : fainting or
falling spells) (blink eyelids) (smack the lips)
(convulsive movement of the arms and legs)
2-10
(acute psychotic episode),
(delirium), (prolong confusion or stupor)
Simple partial seizure
(ictal phase)
- Anterior parietal lobe : focal sensory seizure (paresthesia)
(pins-and-needles) (numbness)
- Language area: (speech arrest) (muteness)
(paraphasic or jargon speech)

91

- Visual cortex area: nonformed, elemental visual sensations = lines, dots, lights

- Posterior medial temporal lobe : more formed visual images

- Inferior medial temporal lobe (uncus) : olfactory hallucinations

(unpleasant and vaguely described odors) (burning rubber)
(dead fish)
- Within temporal lobe: (vertiginous sensation) (auditory hallucina
tion)
Complex partial seizure
(ictal phase) 4
1 . (sensory initially) (aura)
(giddiness) (auditory distortion) (visual aberration)
(micropsia) (macropsia) (unusual tastes)
(disagreeable odors)
2. (psychic symptoms)
(feeling of impending disaster) (altered state
of awareness in seemingly alert patients) (dyscognitive state)
(strangeness) (depersonalization)
(abnormal clarity of perception) (dreamy states)
(twilight states) (forced thoughts) ,
(often complex hallucinations) dj vu
Jamais vu (rage)
3. (autonomic) (palpitation) (piloerection)
(nausea) (increased salivation) (dry mouth)
(hunger pangs) (abdominal pain)
4. (somatomotor : automatisms)
(repetitive,
inappropriate, and fragmented movements or acts without conscious volition)
(facial-oral area) (eye blinking) (grimac
ing) (lip smacking) (chewing) (spitting) (swallowing)

92

1.
2.
3.
4.

(stereotyped repetitive movements) :

(gesturing) (rubbing) (patting) (undressing)
(wiping and wringing of the hands)

postictal phase 72

()

complex partial seizure

1. Interictal personality changes
temporal hyperconnection
(angry, irritability) (impulsivity)
right temporal lobe foci

(hypergraphia, keeping elaborate notes and diaries about everyday life , circumstan
tial, philosophical)
(hyposexuality)
(dependent)
(lack stereotype)

2. Schizophrenic-like psychosis deep temporal lobe dysfunction
TLE 15
()

left temporal foci

(paranoid feature) (late onset),

(lack of autism , no withdrawal)

93

(no bizarre thinking) (peculiar sym

bolism)
(more organic-like)

1.
2.

3.

4. trifluoperazine 5-20 mg/d
haloperidal 2-10 mg/d
5. amitriptyline, fluoxetine
6.
7.
8.

9.
10.
(Psychogenic nonepileptic seizures, PNES)
motor, sensory, autonomic,
cognitive, emotional functions
pseudoseizure or hysterical seizure or hysteroepilepsy

9-16
co-occurrence of epilepsy PNES
(reliance upon clinical observation of the event)

frontal lobe seizures short duration, stereotype features, and
occurrence during physiologic sleep
Incidence rate of PNES = 1.4/100000 individuals over age 15 years, prevalence
estimated = 2-33/100000 general population. 5-25
25-40

94

learning disabilities
physical or psychological trauma, stressful situations, dysfunctional family rela
tionships
( 66-99)
30
(fluctuating course) asynchronous movements, pelvic thrusting, side-to-side head or
body movements, ictal eye closing, ictal crying, memory recall, absence postictal
confusion

PNES depression, anxiety, somatoform disorder, posttraumatic stress disorder, dissociative disorder, personality disorders (esp. border
line, narcissistic, histrionic, and antisocial)
Video-EEG monitoring combines extended EEG monitoring with time-locked video
acquisition 73-96 PNES 48
cognitive behavior therapy, psychody
namic interpersonal therapy
25-38 PNES 70-80
19.6
77
IQ

PSE



PNES
(psychic trauma)

asynchronous movements, pelvic thrusting, side-to-side head or body movements,
ictal eye closing, ictal crying, memory recall, absence postictal confusion

95

1. Bannister R. Epilepsy. In : Brains clinical neurology 5th ed. Great Britain: Oxford Univer
sity Press, 1978:164-85.
2. Ettinger AB. Psychogenic nonepileptic seizures. From available website : www.upto
date.com (Cited date 18 Nov 2011)
3. Gilliam F, Hecimovic H, Sheline Y. Psychiatric comorbidity, health, and function in
epilepsy.
4. Epilepsy & Behavior 2003;4: S26S30.
5. Sadock BJ, Sadock VA. Kaplan & Sadocks synopsis of psychiatry : behavioral sciences
clinical psychiatry 10th ed. Philadelphia : Lippincott Williams & Wilkins, 2007
6. Wells CE, Duncan GW. Epilepsy. In : Neurology for Psychiatrist 3rd ed. Philadelphia :
F.A. Davis Company, 1981:115-64.

97

13

(antiepileptic drugs, AEDs) 2

(standard AEDs) carbamazepine, clonazepam, phenytoin, phenobarbital valproic acid

(complex pharmacokinetics)
Cytochrome P450 (drug interaction)
(newer AEDs) gabapentin, lamotrigine, topiramate, levetiracetam, oxcarbazepine,
vigabatrin pregabalin



(dosage regimen)

( 6)
(first line drug) (second line drug)
(broadspectrum)valproate,clonazepam,phenobarbital

(monotherapy)

98

monotherapy first line drug

1.

2.

(polytherapy)
first line first line second line

1.
2.

3.
(Dosage regimen)

1. (pharmacokinetic properties)

(high protein binding)

Cytochrome P450 13.1
Cytochrome
P450 ( 13.1)
phenytoin loading dose 300-400 mg
2 . (half life) valproate carbamazepine
2-3 phenytoin , valproate (sodium
valproate chrono) phenobarbital

99

2.
13.2
(suspension) (chewable tablet)
(immediate release) (extended release controlled release)
(nasogastric tube)
()
2
carbamazepine, valproate

13.1

13.2
phenobarbital phenytoin loading dose
phenytoin phenobarbital propylene
glycol phenobarbital loading dose
50 ./ 1 ././ 30 ./

100

phenytoin 1-3 ./ ./ 50 ./
rosphenytoin 150 ./

3.





lamotrigine topiramate
13.2

(usual maintenance dose)

(dose escalation) 13.3

101

(nonlinear
pharmacokinetics) phenytoin

4. (special populations)
4.1
(volume of distribution)

13.3

4.2
phenytoin, carbamazepine, phenobarbital valproate

lamotrigine, topiramate, leveti-

102

racetam, gabapentin
levetiracetam levetiracetam

4.3

4.4

( 13.1)
(free form)


( 13.1)
( 13.1)

5. (generic substitution)
(generic substitution)
(bioavailability)

(systematic review)

103

subtoxic level (steady state)

5 (half life)
13.1

2
(dose-dependent) (idiosyncratic)


(slow titration)
(sustained
controlled-release)
(life threatening) 13.4
13.5

(aromatic AEDs) carbamazepine, phenytoin, lamotrigine, oxcarbazepine, phenobarbital
(28) anticonvulsant hypersensitivity syndrome (AHS)
2-3
benzodiazepine

(cross reactivity)

28
(drug interaction)
( 13.6)
( 13.7) ( 13.8)

104

Cytochrome P450 enzyme inducer phenobarbital, carbamazepine

phenytoin
( 13.6 13.7) carbamazepine
(autoinducer) 3-5
3-5

Cytochrome P450 enzyme inhibitor valproate
( 13.6
13.7)
13.4

antacids phenytoin salicylates

13.8

105

13.5

13.6

2
1-2
4-8
15-20

106

5
13.7

13.8

1
24 55 10
.. 2549 3 /
phenytoin 300 mg PO hs, sodium valproate CR 500 mg 2x1 PO hs clonazepam 0.5
mg 2x1 PO hs 20 . .. 2552 3
phenytoin 350 mg PO hs sodium valproate CR 500 mg 2x1 PO
hs clonazepam 0.5 mg 2x1 PO hs 30 . .. 2552
(ataxia) (nystagmus)

phenytoin
phenytoin nonlinear pharmacokinetics

107

50 mg


325 mg

2
17 systemic lupus erythrematosus (SLE) generalized tonic clonic seizures 4 phenobarbital 180 mg 2

phenobarbital
anticonvulsant hypersensitivity syndrome 3
(systemic organ involvement)
transaminase (lymphadenopathy) neutropenia
phenobarbital
generalized tonic clonic valproate
()


3
45 absence seizure depakine (valproate) 200
mg 1x3 pc

depakine valproate (entericcoated tablet)

108

()

1. , . ().
. 2554.
2. Chong DJ, Bazil CW. Update on anticonvulsant drugs. Curr Neurol Neurosci Rep 2010;
10: 308-18.
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;62:1261-73.
4. KarenBeth H, Mansuri TF, Wilson NM. Anticonvulsant hypersensitivity syndrome:
implications for pharmaceutical care. Pharmacotherapy 2007;27 : 1425-39.
5. The Treatment of Epilepsy: Principles and Practice2006. (p596-599). 4 th ed. USA:
Lippincott Williams&Wilkins Kesselheim AS, Stedman MR, Bubrick EJ, et al. Seizure
outcomes following use of generic vs. brand-name antiepileptic drugs: a systematic
review and meta-analysis. Drugs 2010;70: 605-21.
6. Kylonen KC, Gupta A. Selected drug interactions between antiepileptic drugs and other
types of medications. In Wyllie E. (editor).
7. Mims (Thailand). [online]. Access from: http://www.mimsonline.com/Thailand/drug/
info (November 28, 2010).
8. Murphy JE. Clinical Pharmacokinetics. 4 th ed. Maryland: American Society of HealthSystem Pharmacists. 2008.
9. Patel KK, Peterson AM. (2001). Pharmacotherapeutics for Advanced Practice. USA:
Lippincott Williams&Wilkins.

109

14

(therapeutic drug monitoring; TDM)

(biological specimen)

(narrow therapeutic window)

Phenytoin
phenytoin (non-linear pharmacokinetics) Cytochrome P450 (CYP) CYP2C9 CYP2C19 ( 14.1)
phenytoin (adherence)

phenytoin
(trough concentration)

110

2
2 (peak concentration)

phenytoin

14.1

Phenytoin

Valproic acid

Carbamazepine

Phenobarbital

1 ( )
90%
( CYP2C9 CYP2C19)
10-20 mg/L (1-2 mg/L)
1 () 0.95 ()
90%
( UGT )
12-17
50-100 mg/L
0.9 ()
75-90%
( CYP3A4 )
25-65 (single dose) 12-17
(chronic dose)
4-12 mg/L
0.9-1 ()
51%
( CYP2C19 )
96
10-40 mg/L

111

phenytoin 3-5
(toxic range) (steady state)

7 phenytoin
3-5 phenytoin
7
phenytoin

phenytoin


phenytoin 14.2
phenytoin total concentration

phenytoin
(bound form) (free fraction)
phenytoin 0.1
(free concentration)
total concentration phenytoin
11.1
14.1

( . )

Cnormal binding = phenytoin

Creported =
Albumin = (mg/dL)
end-stage renal disease (ESRD)
14.2
14.2

( . )( .

112

phenytoin

phenytoin
16 mg/L
3 mg/L end-stage renal disease
14.1
=

( . )

/
( . )

= 22.42 mg/L

14.1
total concentration 16 mg/L
phenytoin 22.42 mg/L

phenytoin

20 mg/L nystagmus 15 mg/L 50 mg/L

phenytoin CYP2C9 CYP2C19

phenytoin ( 14.2) phenytoin

113

14.2

Phenytoin

Valproic acid ,aspirin

Amiodarone, isoniazid, fluconazole

Rifampicin, folic acid, phenobarbital
Valproic acid

Phenytoin

Carbapenems
Carbamazepine Fluconazole, isoniazid, diltiazem, verapamil, valproic acid
Rifampicin, phenytoin, Phenobarbital, cisplatin, doxorubicin
Phenobarbital Valproic acid
Rifampicin, thioridazine

Phenytoin
Valproic acid aspirin

Valproic acid
Phenytoin

Valproic acid
valproic acid uridine glucuronosyltransferase (UGT) ( 14.1) 3-7

75 mg/L
100-125 mg/L
15-22 75 mg/L


valproic acid total concentration

114

valproic acid
(bolus administration)
(suspension)
24
valproic acid
4- 14 24
14
valproic acid

3-5 (steady state)
valproic acid ( 14.1)
2
phenytoin

valproic

100 mg/L 150 mg/L
valproic acid
valproic acid
phenytoin
valproic acid carbapenems
valproic acid carbapenems
valproic acid carbapenems
valproic acid
carbapenems
valproic acid 14.2
Carbamazepine
carbamazepine

(4-12 mg/L)

115

carbamazepine autoinduction
3-5 3-5

carbamazepine

carbamazepine

carbamazepine
tremor 12 mg/L

hyponatremia syndrome of inappropriate antidiuretic hormone secretion (SIADH) osteomalacia
CYP3A4 carbamazepine 10,11-epoxide metabolite
CYP1A2 UGT 10,11-epoxide metabolite
carbamazepine
(parent drug) 10,11-epoxide metabolite
(routine laboratory)
CYP1A2 UGT (
14.2) carbamazepine substrate P-glycoprotein (P-gp)
P-gp
Phenobarbital
phenobarbital

(baseline concentration) ( 14.1)
electroencephalography (EEG)
(steady state)

status epilepticus

116

phenobarbital
(impaired cognition)
coma

phenobarbital CYP3A4

phenobarbital
phenobarbital 14.2

(monotherapy)

lamotrigine oxcarbazepine

topiramate 30
gabapentin, levetiracetam, pregabalin, vigabatrin


14.3

117

14.3

()
(mg/L)
Gabapentin
0.35-0.6
< 10%

5-7
2-20
Lamotrigine
1
55%

22
3-14
Levetiracetam
1
< 10%

6-8
12.46
Oxcarbazepine 0.9
60% (Oxcarbazepine)

2 (Oxcarbazepine)
3-35
40% (Active metabolite)
9 (Active metabolite)
Pregabalin
0.9
None

5-6.5
2.8-8.3
Topiramate
0.8
13-41%

18-23
5-20
Vigabatrin
0.6
None

5-8
0.8-36

F = (Bioavailability)

1. . . 2554
2. Krasowski MD. Therapeutic drug monitoring of the newer anti-epilepsy medications.
Pharmaceuticals 2010;3 : 1909-35.
3. Mori H, Takahashi K T M. Interaction between valproic acid and carbapenem antibiotics.
Drug Metabolism Reviews 2007;39:647-57.
4. Murphy JE, editor. Clinical pharmacokinetics. 4th ed. Bethesda: American Society of
Health-System Pharmacists; 2008.
5. Shargel L, Wu-Pong S, Yu ABC, editors. Applied biopharmaceutics and pharmacokinetics.
5th ed. New York: Appleton & Lange Reviews/McGraw-Hill, Medical Pub. Division;
2005.

119

15

( antiepileptic drugs; AEDs)

(drug
related problems; DRPs)

.. 2548
255 63.53
366 58.47
32.79
39

1.
2.
(support group)

120

3.

4.

5.

1.
1
2.
2.1

2.2
3.
2

50
1 20 2

1.

2. (support group)

121

2.1 (initial stage)

2.2 (acceptance stage)

2.3 (working stage)

2.4 (closing stage)

3.

(rational use of drug)
(actual drug therapy problems)
(potential drug therapy problem)


1.
1.1
1.2

1.3

122

1.4
1.5
2.
IESAC ( ) (indication) (efficacy) (safety)
(adherence) (cost)
3.

3.1 (adverse drug reactions; ADRs)

- (side effect) (toxicity)
- (idiosyncrasy)
- (teratogenicity)

3.2 (non adherence)

- :

- :

- :
- :


-

123

-


-

-

3.3 (drug interaction)

3.4 (failure to receive medication)

-

-

124

4.



5.
- (drug identification)

- (drug availability)
- (pharmacokinetics)
- (drug interaction)
- (adverse drug reaction/side effects)
- (indication, dose and dosage regimen)
- (cost)
-

-
-
-
-
-

125

1. , , .
. 2553; 5 : 7-18.
2. , , .
. 2553; 5 : 19-26.
3. , , .
.
2552; 4 : 39-50.
4. . . : , ().
, : .2539: 1-21.
5. .. . . 2549.

127

16

2 3

69



1.
2.
3.
1.


CT scan , MRI brain
(electroencephalography; EEG)
7 (. 7) 65.5

CT scan, MRI brain EEG
1.1 CT scan
1.1.1 indication CT scan refer
CT scan


1.1.2 refer

128

1.1.3 ()
1.1.4 9
8 (9.00-12.00 .)(13.00.16.30 .)
(9.00-12.00 .) (13.00-17.00 .)
CT scan
1.1.5 CT scan

indication CT scan
Consult ,
CT scan -

.
.
.,
.

16.1 CT scan brain

CT scan

( refer)

()

()

,
CT scan

16.2 CT scan brain

129

1.2 MRI
1.2.1 indication MRI brain refer
MRI brain

1.2.2
refer
1.2.3 ()
1.2.4 MRI brain
1.2.5. MRI brain

indication MRI brain

Neuro-med*
. . 089-2026702 (.)
. . 085-0108664 (.)
. .081-7089026 (.)
.. .081-0504626 (.)
MRI .
16.3 MRI brain

* MRI-brain Neuro-Med

130

MRI-brain

( refer)

- ()
- ()
MRI brain

16.4 MRI brain

1.3 EEG
2
1.3.1 EEG mobile EEG
EEG 8-10
1.3.2 EEG
. 082-7419606 , 086-6432902 043-366399
.

1.

131

2.
3.

4. 4




5.


1.
2. EEG
3. refer EEG
4. refer
5. ()
6. EEG
7. EEG refer

8. .1 12
EEG

EEG mobile
EEG

8-10 /

EEG
082-7419606 , 086-6432902
043-366399
.

16.5 EEG
: EEG

132

EEG
EEG
. 082-7419606 , 086-6432902
043-366399

refer

refer

()

()

EEG

.1 12

16.6 EEG

133

1.4 (therapeutic drug monitoring; TDM)

8.30-16.30 .
- -

1. total phenytoin , valproic acid, phenobarbital, carbamaze

pine 300
2. unbound (free) phenytoin unbound (free) valproic acid
850

1. 1
2. clot blood 2-8 ()
1
hemolysis
3.
.

4.
(central laboratory)
5.

6.

(081-717-6295)
7.
7.1 ( 11.30 .) 14.30 .

7.2 ( 15.30 .)
16.30 .
8.
. .

. . 40002
086-7753873 e-mail:denpat@kku.ac.th

134

tube clot blood 5-10 cc

specimen
2-8
1

specimen .

.
specimen

specimen

specimen

16.7 (drug level)

135

. .
tube clot blood
5-10 cc

(081-717-6295)

specimen

16.8 (drug level)

1.5
. 7

49.1

136

+
Screening

-
-

-
-

-
-
-
-
Neuro-med*
- . . 089-2026702 (.)
- . . 085-0108664 (.)
- . .081-7089026 (.)
- .. .081-0504626 (.)

16.9
* : Neuro-med

137

1.6
. 7




1.
2.

- ,

-
-
16.10

1. . : .
2549; 24: 445-52.
2. , , ,
. .
2554; 6: 19-27.
3. , .
. 2554.
4. Ferri C, Chisholm D, Van Ommeren M, Prince M. Resource utilization for neuropsy
chiatric disorders in developing countries: a multinational Delphi consensus study.
Soc Psychiatry Epidemiol 2004; 39:218-27.

139

50 85
1 6

2 3
80-90

69


7 (. 7)
. 7 . 2553
. 7 64 55
82.08

. 7
1.

22
22 1 1
.7

140

5.0 38.8 31.3

68.3 85.1 49.1

(status epilepticus)

2.




CT Scan brain MRI brain
EEG

International League Against Epilepsy (ILAE), International Bureau for Epilepsy (IBE) World Health Organization (WHO)
56
.7 65.5
EEG, CT Scan MRI EEG
1.8 EEG CT Scan 10.9
MRI
Clinical Practice Guideline

3.
. 7
4 phenobarbital,
phenytoin , carbamazepine sodium valproate 100
60.8, 94.1, 90.2 80.4 topiramate, gabapentin,
lamotrigine pregabalin 100 levetiracetam 50 gabapentin
100 topiramate pregabalin 50 gabapentin
19.6

141

sodium valproate, gardinal sodium phenytoin 2.0, 7.8 13.7

.
7 76.4 21.8
1.8
4.






. 7


87.3, 67.3, 65.5, 54.5 40.0

60.0, 45.5 38.2

87.3, 45.5 16.4

142

- 76.4
- 49.1
- 29.1
- 21.8

-
34.5
-
45.5
-
40.0
-
9.1

-EEG 1.8
- CT 10.9
- MRI

(Drug level)
-
1.8
- 21.8
- 76.4

-
87.3
-

16.4
-
16.4
-
12.7
-
12.7

17.1

143

. 7


7

1. , , ,
. .
2554; 6: 19-27.
2. . . 2553; 5:
54-6.
3. Dua T, De Boer HM, Prilipko LL, Saxena S. Epilepsy care in the world: results of an
ILAE/IBE/WHO Global Campaign Against Epilepsy Survey. Epilepsia 2006; 47:1225-31.
4. Ferri C, Chisholm D, Van Ommeren M, Prince M. Resource utilization for neuropsy
chiatric disorders in developing countries: a multinational Delphi consensus study.
Soc Psychiatry Epidemiol 2004; 39:218-27.
5. Meinardi H, Scott RA, Reis R, et al. The treatment gap in epilepsy: the current
situation and the way forward. Epilepsia 2001; 42:136-49.

144

1.
2.

3.

4.
5.
6.
7.

8.
9.
10.
11.

12.