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  • 1

    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)

  • 2

    1.2 (aura) (simple partial seizure) cognitive function (complex partial seizures) 2. (seizure symptoms) (associated symp-tom)

    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)

  • 3

    . .

    . aura, ictal period, postictal period Todds paralysis InternationalClassifi cation of Epileptic Seizures International League Against Epilepsy .. 1981 ( 2)

    3. (postictal symptoms) com-plex 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 refl ex) dolls eye sign 2 (quadriplegia) 3. Migraine headache (basilar migraine) basilar migraine

  • 4

    4. Metabolic disturbances hypo-hyperglycemia, hypo-hypernatremia, hypercalcemia, hepatic renal failure metabolic disturbances 5. Sudden increase intracranial pressure (cerebrospinal fl uid: CSF) CSF 6. Sleep disorders cataplexy

    7. Psychogenic disorders non-epileptic seizures

    1.1

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

    : 6 1 2 3 9

  • 5

    hereditary, perinatal injury, central nervous sys-tem infection (CNS infection), head injury, stroke, brain tumor metabolic disturbance cerebral venous sinus thrombosis : cytomegalovirus, toxoplasma : : :

    1.

    2. 3.

    1. 2.

  • 6

    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

  • 7

    1.2

    Caf au lait spot, adenoma sebaceum, as leaf-shagreen patch, Port-wein stainSurgical scar

    Neurocutaneous syndrome

    Post-head injury, surgeryNeurological defi cit Post-stroke, brain tumor, encephalitisSign of chronic liver disease, fl apping tremor Hepatic encephalopathyFlapping tremor Metabolic encephalopathyEcchymosis Intracranial bleedingSubcutaneons nodule Cerebral cysticercosisVasculitis, malar rash Systemic lupus erythematosusPapilledema Brain tumor, increased intracranial

    pressureMental retardation Post-hypoxia Carpopedal spasms Hypocalcemia

    1.3

    (aura)

    generalized tonic - clonic seizure (GTC)

    ,,

    (focal neurological defi cits)

    partial seizure

    cardiac arrhythmia, bradycardia, asystole

    Tachycardia

    (EEG) CK prolactin

    epileptiform activity GTC GTC

  • 8

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

    1.1

    AED : antiepileptic drug

    16 1 2 2-3 1 2-3

    ( 1.1)

  • 9

    1. . .: ... 2547: 189-204. 2. . . : ; 2551. 4-5, 170. 3. Shorvon SD. Defi nition and classifi cation 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 non-convulsion Convulsion generalized tonic -clonic seizures (GTCs)Non- convulsion absence seizuresEpilepsy 2 (unprovoked seizures)Ictal phase 1-2 Post - ictal phase Inter - ictal phase Todds paralysis ( 24 3 )

    International Classifi ca-tion of Epileptic Seizures International League Against Epilepsy (ILAE) .. 1981

    2

  • 12

    Unclassifi ed seizure e.g. infantile spasms

    2.1 International League Against Epilepsy (ILAE) 1981 Partial Seizure Generalized Seizure

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

    - Absence seizure- Generalized tonic-clonic seizure- Generalized clonic seizure- Generalized tonic seizure- Atonic seizure- Myoclonic seizure

    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 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-and-slow-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

    SPS = Simple partial seizuresCPS = Complex partial seizuresGTC = Partial seizure evolving to secondary generalized seizures

    SPS

    SPS CPS

    SPS GTC

    CPS

    CPS GTC

    SPS CPS GTC

  • 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 fl attening low voltage fast activity 3. Unclassifi ed seizure partial generalized seizure in-fantile spasms ILAE absence seizures sodium valproate absence seizures 2.2

    2.2

    - Sodium valproate - Standard AEDs( Phenytoin Carbamazepine, Sodium valproate Phenobarbital)

    Epilepsy

    Absence seizures Other type of seizures

    , ,

  • 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. Defi nition and classifi cation 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) (fi fth-day fi ts) 1-7 90 4-6 fi fth-day fi ts 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

    3

  • 18

    4. Early myoclonic encephalopathy (EME) myoclonus simple partial seizures infantile spasms suppression-burst ACTH, clonazepam, nitrazepam, valproate, phenobarbital 5. Symptomatic neonatal seizures (hypoxic-ischemic 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 fi eld 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 generalizedspike and wave discharge 3 Hz. valproate carbamaze-pine, 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 myo-clonic 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 phenobar-bital 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

    4

  • 24

    2. (epileptiform discharge) 3. 20-50 80

    EEG ( 1)

    1.2. creatine kinase (CK) general-ized 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) hip-pocampal sclerosis cortical dysplasia CT - scan brain late onset epilepsy partial seizures 4.1

    4.1

    # MRI - brain neuro - med # Intractable seizure 2 (3-6 )

    - -

    - . - ( 8 10 )

    - GTCs- Absence- Other type of generalized seizures

    - Complex partial seizure- Secondary to GTCs- Post - ictal paralysis- Neurological defi cit- Intractable seizure

    Follow up

    CT scan brain

    Un - controlled Controlled

  • 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

    5

    electrical discharge cortical neurons 30

    neuroimaging (CT scan) (MRI) CT scan MRI CT scan intracerebral hematoma ( 1) subdural hematoma ( 2) (calcifi cation) cysticerco-sis ( 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

    1 2 3

  • 30

    MRI (anatomic substrate) MRI (structural abnormalities) substrate (eloquent area) residual recurrent lesion MRI gray-white matter inversion re-covery 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 fi ndings hippocampus (hippocampal atrophy) T2W hippocampus mammilary body fornix, temporal horn temporal lobe white matter hippocampus collateral sulcus CT scan MRI temporal lobe epilepsy

    4 5 6

  • 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, neurofi -bromatosis 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 simplifi ed gyral pattern (oligogyria) pachygyria,dysplastic cortex polymicrogyria

  • 32

    8 Hemimegalencephaly MRI T1W right cerebral hemisphere cortex left lateral ventricle1.2 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 gray-white matter () ventricle () 3. Malformations of secondary to abnormal neuronal migration3.1 Classic lissencephaly sulcation sulci smooth brain agyria complete lissen-cephaly gyri pachygyria incomplete lissencephaly ( 11)

  • 33

    10 11 10 complete lissencephaly smooth surface brain cortex ( 11) incompletelissencephaly 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 heteroto-pia, subcortical heterotopia band or laminarheterotropia CT scan

    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

    13 14 15

  • 35

    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

    16 17 18

  • 36

    20 cavernoma temporal lobe MRI gradient echo

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

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

    21 22

  • 37

    7.3 Infections mycobacterium parasite tuberculosis neurocysticercosis

    Neurocysticercosis brain parenchyma, ventricles, subarachnoid spaces infl ammatory response degenerating dying parasite lesion thin-walled nonenhancing cystic lesions MRI scolex lesion T1W ( 23) CT scan calcifi cation

    Tuberculosis (TB) meninges brain parenchyma ( 24) leptomeningeal in-volvement hydrocephalus, neuropathies, arteritis deep gray matter infarction

    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

    23 24

  • 38

    25 frontotemporal lobes 26 25 2 (J Neurol Neurosurg Psychiatry 2007;78:200-201)

    7.4 Sturge-Weber syndrome fi ndings angioma parietal occipital region ( 27) cortical calcifi cations, 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

    25 26

  • 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

    6

  • 42

    2.3 16 60 2.4 partial seizures generalise

    3. simple partial seizures 4. benign Rolandic epilepsy refl ex 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

    47 13 3 36 1 drug interaction

    - Sodium valproate - Standard AEDs; Phenytoin Carbamazepine, Sodium valproate, Phenobarbital

    Epilepsy

    Absence seizures Other type of seizures

  • 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 )

    Simple and complex partial seizures, primary and secondarily generalized tonic-clonic seizures

    Carbamazepine, valproate, phenytoin

    Clonazepam, gabapentin,lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, topiramate

    Absence seizures Valproate Clonazepam, lamotrigine, phenobarbital

    Atypical absence, tonic and clonic seizures

    ValproateCarbamazepine, clonazepam, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, topiramate

    Myoclonic seizures Valproate Clonazepam, lamotrigine, phenobarbital

    (.)

    (./)

    ()

    (./)

    ()

    Carbamazepine 100 100-200 2 400-1600 2-3

    Clonazepam 0.5 0.5 2 0.5-4 1-2

    Gabapentin 300 300-900 1 900-3600 2-3

    Lamotrigine 25 50-100 2 100-400* 2

    Levetiracetam 1000 500 1 1000-3000 2

    Oxcarbazepine 600 300 2 900-2400 2

    Phenobarbital 30 30-60 2 30-180 1-2

    Phenytoin 100-200 50-100 2 100-300 1-2

    Topiramate 25-50 50-100 2 200-600 2

    Valproate 400-500 500 2 500-2500 2-3

    6.2

  • 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 fi rst unprovoked seizure: a quantitative review.Neurology 1991; 41: 965-72. 4. Camfi eld PR, Camfi eld CS, Dooley JM, Tibbles JA, Fung T, Garner B. Epilepsy after a fi rst unprovoked seizure in childhood.Neurology 1985; 35: 1657-60. 5. Musicco M, Beghi E, Solari A, Viani F. Treatment of fi rst 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 fi rst 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

    7

  • 50

    7.1

    Antiepileptic Drug

    Focal-onset Seizures

    Primary Generalized Seizures Lennox-Gastaut

    SyndromeTonicClonic Absence Myoclonic

    Carbamazepine + + 0Phenytoin + + 0Phenobarbital + + + 0 ?Sodium valproate + + + + +Clobazam + + ? + +Clonazepam + + ? + ?+Vigabatrin + ?+ ?Lamotrigine + + + + +Gabapentin + ?+ ?Topiramate + + ? + +Oxcarbazepine + + 0Levetiracetam + + ?+ + ?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) fi rst 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 develop-ment of intractable epilepsy in children: a prospective study.Neurology 2001; 56: 1445-52.

  • 55

    8

    (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) complexfebrile seizures 1. (semiprone lat-eral 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 fe-brile 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

    9

    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 in-duced seizure(NKHS) EPC neurological defi cit 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 SE (0-5)

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

    2. 1 SE (5-30)

    capillary blood glucose CBC, glucose, elec-trolytes, calcium, magnesium 50% glucose (50 ml) 1 ** 25% glucose 2 ./. 18 6 100 . ()

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

    2.2 SE(30-60 )

    (phenytoin/fosphenytoin sodium valproate

    phenobarbital (i.v. load-ing) phenytoin (i.v. load-ing) sodium valproate (i.v.loading) levetiracetam (i.v.ng)

    3. SE

    (> 60 )

    EEG( ) ,

    Propofol (i.v. bolus &inf) phenobarbitalmidazolam (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*

    Maintenance

    Diazepam 0.3 ./. 2 ./

    10 . 10 ./2 ./vial

    10 2

    10 . 2-5 ./

    Phenytoin 20 ./. 1 ././ 25 ./

    1500 . 5-8 ././

    250 ./5 ./ vial 0.9% NaCl 1-2 . infu-sion pump

    arrhythmia

    20 ./. 50 ./ 30 ./.

    300-500./

    Fosphenytoin 20 .PE/. 3 ././

    NA 5-8 .PE/./

    500 . PE/vial

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

    20 .PE./. 100-150 ./

    300-500 ./PE/

    Phenobarbital 20 ./. 3 ././

    1000 . 4-6 ./. /

    200 ./4 . sterile water 10 .

    0.9% NaCl Ringer lactate 5% Dextrose

    Diaz-epam

    20 ./. 100 ./

    1-4 ././

  • 63

    9.2 convulsive status epilepticus* ()

    Mainte-nance

    Sodium Valproate

    20 -40 ./. 1-3 ././

    NA 1-5 ././.

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

    Topiramate hyperammonia encephalopathy

    20-30 ./. 50

    ./

    1-2 ././.

    Levetiracetam 30-40 ./. 15

    4000 . 10-30 ./12 .

    (oro/nasogas-tic)

    500 ./5 ./vial 0.9%NaCl, Ringer lactate 5% Dextrose 100 . 15 24

    2000-4000 . 15

    Midazolam 0.2 ./. 5

    4 ./

    2 ./. 0.02-0.4 ././.

    1 ././vial5 ././vial 0.9% NaCl 5% Dextrose 24 . Ringer lactate 24 .

    0.1-0.3 ./. 5

    4 ./

    0.05-0.4 ././.

  • 64

    9.2 convulsive status epilepticus* ()

    Maintenance

    Pentobarbital 2-10 ./. 25 ./

    NA 0.5-1 ././.

    0.9% NaCl Sterile water 2% 2.5% solution

    20 ./. 25 ./

    0.5-3 ./.

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

    NA 3-5 ././.

    0.9% NaCl 5% Dextrose Sterile water 2.5 % solution

    100-250 . 20 50 . 2-3

    3-5 ././.

    Propofol 1-2 ./. 50 /./

    NA 2-3 ././.

    10 ./. 0.9% NaCl 5% dextrose volumetric infusion pump

    6 .

    2 ./. 5-10 ./

    .

    NA = not available* non convulsive status epilepticus simple partial status epilepticus absence status epilepticus

    topiramate SE 400 .(loading dose) na-sogastric 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 ./. mainte-nance 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 alcoholicwithdrawal delirium tremens intracranial causes chronic subdural hematoma SE lumbar puncture CNS infection CK, BUN, Cr, urine analysis rhabdomyolysis

    9.3 . (52 ) ()

    Cerebral infarction 18(34.6)CNS infection 10(19.2)Systemic infection 0Hypertensive encephalopathy 3(5.8)Uremia 3(5.8 Intracerebral hemorrhage 2(3.9)Subdural hematoma 2(3.9)Organophosphate poisoning 2(3.9)Mushroom poisoning 1(1.9)Hepatic encephalopathy 1(1.9)Post cardiac arrest 1(1.9)Compression skull bone 1(1.9)Obstructive hydrocephalus 1(1.9)CNS vasculitis 1(1.9)Electrolyte imbalance (hyponatremia) 1(1.9)

  • 67

    9.4 SE . ()

    Acute symptomatic 21 (52.5) Encephalitis 6 (15) Cerebral infarction 3 (7.5) Meningitis 3 (7.5) Hypertensive encephalopathy 2 (5) Head injury 1 (2.5) Craniotomy 1 (2.5) Post-cardiac arrest 1 (2.5) Intracerebral hemorrhage 1 (2.5) Cerebral venous sinus thrombosis 1 (2.5) Septic encephalopathy 1 (2.5)Remote symptomatic 3 (7.5) Post-cerebral infarction 1 (2.5) Post-head injury 1 (2.5) Post-intracerebral hemorrhage 1 (2.5)AEDs withdrawal 10 (25)Alcohol related 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 fi brillation generalized tonic clonic seizures(GTCs) GTCs va-lium 10 mg valium 10 valium 10 mg sodium val-proate 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

    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) 20Tonic status epilepticus tonic-clonic clonic status Lennox-Gastaut syndrome (LGS) tonic status

    10

  • 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 com-plex 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 epilep-ticus 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

    5-10

    20

    2

    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 // ()

    Phenytoin 25-30 // 1 //

  • 74

    30

    3

    35

    4

    Valproate 40 // 5 // ( ) Levetiracetam 40 // 5 //

    5 3 refractory status epilepticus Midazolam 0.2 // 2 0.1 //. 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

    Diazepam 0.3 /. < 2 / 10 . 10 2

    Phenytoin 20 /. < 1 //

    25/

    1500 . arrhythmia 0.9%NaCl

    Phenobarbital 20 /. < 2 //

    100 /

    1000 . diazepam

    Valproate 20 /. 3-5

    1 //.

    Pentobarbital 2-10 /.

    0.5-1 //.

    Thiopenthal 5 /.

    5 //.

    Propofol 1-2 /.

    5

    2-3 //.

    < 50 //

    acidosis

    Midazolam 0.2 /.

    0.02-0.4 //.

    10 .

    Levetirace-tam

    40 /. 5 //

    10.1

  • 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 Classifi cation and Terminology of the International League Against Epilepsy: Proposal for revised clinical and electrographic classifi cation 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 proges-terone estrogen progesterone estrogen pro-gesterone

    estrogen estrogen progesterone estrogen estrogen progesterone estrogen 47 29 24

  • 79

    testosterone temporal lobe epilepsy testosterone/LH idio-pathic generalized epilepsy testosterone carbamazepine testosterone binding globulin free testosterone aromatase testoster-one 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 estra-diol drug interaction drug interaction .. 1972 portal circulation fi rst 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-carbam-azepine enzyme inducer enzyme inducing AEDs progerterone combined pill

  • 80

    enzyme inducing AEDs CYP3A4 non-en-zyme inducing AEDs sodium valproate lamotrigine, gabapentin, topiramate, tiagabine levetiracetam, benzodiazepines, zonisamide sodium valproate combined pill drug interaction progesterone-only pill, medroxy progesterone 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 fi rst 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 devicesHormone-releasing intrauterine system (levonorgestrel-releasing intrauterine system Barrier methods enzyme inducing AEDs

    Combined contraceptive pill/patchProgestogen-only oral contraceptiveProgestogen implant

    11.2

    Phenytoin ValproatePhenobarbital (phenobarbitone) GabapentinPrimidone LevetiracetamCarbamazepine VigabatrinOxcarbazepine PregabalinTopiramate (little effect below 200 mg/day) Benzodiazepines*Lamotrigine Zonisamide

    EthosuximideAcetazolamide

    * 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

    forcep (status epilepticus)

    Mirena coil

    nonenzyme-inducing 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

    11.3

  • 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 bifi da lumbosacral carbamazepine hydrocephalus encephalocele 3 leveiracetam 3 2-3 ( 7 ) 15 neural tube sodium valproate, carbam-azepine 1 1-2, 0.5-1 0.3 ( neural tube 0.2-0.5) sodium valproate 1500 spina bifi da 11.4

  • 85

    2-5 10 generalized tonic - clonic seizures 2-3 ultrasound 10, 18 24 sodium valproate carbamazepine amniotic fl uid 12 Omtzigt serum alpha fetoprotein amniotic fl uid alpha fetoprotein neural tube serum (4 6 ) carbamazepine partial, second-ary generalized seizures idiopathic generalized seizures sodium valproate spina bifi da 5 neural tube 20 12 1 phenobarbitone 300

    11.4 Growth Perinatal growth defi ciency Postnatal growth defi ciency MicrocephalyCraniofacial 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 fi ngersCerebral Mild learning disability Development delaySystemic 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 bifi da aperta after fi rst-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 fi sh) - 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

    (stereotyped repetitive movements) : (gesturing) (rubbing) (patting) (undressing) (wiping and wringing of the hands) postictal phase 72 1. 2. 3. 4. ()

    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. trifl uoperazine 5-20 mg/d haloperidal 2-10 mg/d 5. amitriptyline, fl uoxetine 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 (fl uctuating 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, post- traumatic 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) (fi rst line drug) (second line drug) (broad spectrum) valproate, clonazepam, phenobarbital

    (monotherapy)

  • 98

    monotherapy fi rst line drug 1. 2.

    (polytherapy) fi rst line fi rst 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 propyleneglycol 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

    (nonlinearpharmacokinetics) 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) (ge-neric 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) general-ized 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 (enteric-coated 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. Effi cacy 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 Health- System 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 phar-macokinetics) Cytochrome P450 (CYP) CYP2C9 CY-P2C19 ( 14.1) phenytoin (adherence)

    phenytoin (trough concentration)

  • 110

    2 2 (peak concentration) phenytoin

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  • 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

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  • 112

    phenytoin

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

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

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  • 113

    14.2

    Phenytoin Valproic acid ,aspirin Phenytoin

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  • 114

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  • 115

    carbamazepine autoinduction 3-5 3-5 carbamazepine

    carbamazepine

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  • 116

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    (monotherapy)

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  • 117

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    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

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  • 120

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  • 121

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  • 122

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  • 123

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  • 124

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  • 125

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  • 128

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  • 129

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  • 132

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  • 133

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  • 134

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  • 135

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  • 137

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  • 139

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  • 140

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  • 141

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  • 142

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  • 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

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