Epi Lepsi

Epilepsi (Yunani) yang berarti : “To sieze upon or taken hold of”

Di Indonesia disebut : sakit ayan, yang di daerah pedejjsaan masih banyak dianggap berasal dari ilmu hitam

Prevalensi epilepsi sekitar 1% 1% dari 200 juta 2,2 juta penderita epilepsi di Indonesia.Menurut WHO, 2-5% penduduk dunia pernah mengalami kejang.Tan CT (Malaysia) di Malaysia 68% mengalami “treatment gap” di Indonesia akan >>Epilepsy treatment gap maybe defined as the percentage of person with active epilepsy who any time are not receiving treatment

Epilepsi terdpt pd semua bangsa, laki sedikit lebih banyak dari wanita.30% mendpt serangan I pd umur 4 th50% mendpt serangan I pd umur 10 th75% pd umur 20 th15% mengalami setelah 25 th2% mendpt serangan I pd umur 50 th keatas & jumlah ini menanjak dgn bertambahnya persentase penduduk lansia

Insiden epilepsi pd anak I > anak II > anak III.Anehnya epilepsi lobus temporalis sering ada riwayat kejang demam dan ada masalah pada proses kelahiran

The new era is beginning in the clinical The new era is beginning in the clinical and basic investigations of the and basic investigations of the epilepsies, and it is not seizure based.epilepsies, and it is not seizure based.

These genetic and genomic approach These genetic and genomic approach which should gradually unravel the which should gradually unravel the understanding about epilepsy.understanding about epilepsy.

Genetic and birth factors

1. Genetic influences (Idiopathic, essential, cryptogenic)

2. Congenital abnormalities ( including cromosomal abnormalities)

3. Antenatal factors (infections. drugs anoxia, etc)

4. Perinatal factors: Birth trauma, asphyxia neo natorum. perinatal infections

5. Perinatal jaundice: Prematurity

Infectious disorders:

1. Meningitis: Purulent, tuberculous, viral, parasitic fungal

2. Epidural and subdural abscess3. Brain abscess and granuloma;

Metastatic. direct spread4. Encephalitis: Viral5. Other (including parasites)6. Fever (febrile convulsions)

Toxic factor

1. Inorganic substances (eg, carbon monoxide)2. Metallic substances (eg, lead. mercury)3. Organic substances: Alcohol, other 4. Drugs5. Allergic disorders; Ingestion of foreign protein.

vaccination or injection of foreign protein6. Pregnancy7. Other; Uremia or other toxic medical conditions

Circulatory disturbances: 1. Subarachnoid hemorrhage2. Sinus thrombosis3. Encephalomalacia due to thrombosis, embolism,

haemorrhage4. Hypertensive encephalopathy5. Arteriosclerosis and arterial occlusive disease,

intracranial and extracranial6. Vasospasm(eg:migraine)7. Syncope8. Changes in blood (anemia, hemorrhagic diathesis)

Trauma or physical agents:

1. Acute craniocerebral injuries2. Subdural or epidural hematoma and

effusion3. Posttraumatic meningocerebral

cicatrization4. Anoxia or hyperoxia (including

drowning)

Metabolic and Nutritional disturbances 1. Electrolyte and water imbalance: Sodium,

calcium, overhydration or dehydration, other.2. Carbohydrate metabolism: Hypoglycemia,

diabetes mellitus, glycogen storage disease3. Protein metabolism: Phenylketonuria,

porphyria, other4. Fat metabolism: Lipid storage diseases, other5. Vitamin deficiency: Pyridoxine deficiency, other6. Endocrine Disorders: Menstruation. Other

Neoplasms

I. Primary intracranial tumors2. Metastatic tumors3. Lymphoma and leukemia4. Blood vessel tumors and vascular

malformations (eg. arteriovenous malformation eg. Sturge Weber syndrome)

Heredofamilial and degenerative diseases1. Multiple sclerosis2. Tuberous sclerosis3. Cerebellar degeneration with

convulsion4. Other

Psychogenic causes

Cause unknown

Human Epilepsy GenesDisorder Location Gene

Idiopathic generalized epilepsies Juvenile myoclonic epilepsy (EJMI) Benign neonatal epilepsy (EBN1) Benign neonatal epilepsy (EBN2)

6p?20q8q

?

CHRNA4(possible)?

Idopathic partial epilepsies Partial epilepsy with auditory symptoms Nocturnal frontal lobe epilepsy

10q20q

?

mat be allelic to EBN1

Single gene disorders with symptomatic epilepsy as a major feature Myoclonic epilepsy with ragged red fibres (MERRF) Unverricht-Lunborg disease (EPM1) Northern epilepsy syndrome (EPMR) Ceroid lipofuscinosis, juvenile type (CLN3)

Mitochondrial

21q22.38p

16p

tRNA(Lys)cystatin B

??

Sejarah Klasifikasi Epilepsi

Workshop on Basic Mechanism of the Epilepsies (BME) pertama pada tahun 1969 di Colorado springs.Sekitar tahun itu International League Against Epilepsies (ILAE) membuat klasifikasi.


BME kedua dibawah Jasper : idiopathik dan simptomatis dengan co-editor : genetics, developmental anatomy, pathology, neurochemistry, neuropharmacology di St. Inez Mountains CA tahun 1983 mendahului ILAE , menggunakan syndrome classification

We present here the international classification of epileptic syndro-mes and related seizure disorders which was adapted at the New Delhi Congress of the International League Against Epilepsies in Octo-ber 1989 and which is published in Epilepsia.


The 3rd Workshop BME in San Diego California USA 1996

Classification of epilepsies, epileptic syndromes and related seizure disorders

1. Localization-related (focal, local, partial) epilepsies and syndromes

1.1. Idiopathic (with age-related onset): Benign childhood epilepsy with centro-temporal spikes Childhood epilepsy with occipital paroxysms Primary reading epilepsy1.2. Symptomatic: Chronic progressive epilepsia partialis continua of childhood

(Kojewnikow syndrome) Seizures characterized by specific modes of precipitation Other epilepsies and syndromes based on localization or

aetiology1.3. Cryptogenic


2. Generalized epilepsies and syndromes2.1. Idiopathic (with age-related onset -listed in order of age): Benign neonatal familial convulsions Benign neonatal convulsions Benign myoclonic epilepsy in infancy Childhood absence epilepsy (pyknolepsy) Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalized tonic-clonic seizures on awakening Other generalized idiopathic epilepsies not defined above Epilepsies with seizures characterized by specific modes of

precipitation (e.g. photosensitive epilepsy)Continued


2. Generalized epilepsies and syndromes2.2. Cryptogenic and/or symptomatic (in order of age): West syndrome (infantile spasms) Lennox-Gastaut syndrome Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences2.3.1. Non-specific aetio!ogy: Early myoclonic encephalopathy Early infantile epileptic encephalopathy with suppression-b

ursts Other symptomatic generalized epilepsies not defined above 2.3.2. Specific syndromes


3. Epilepsies and syndromes undetermined whether focal or generalized

3.1. With both generalized and focal seizures: Neonatal seizures Severe mvoclonic epilepsy in infancy Epilepsy with continuous spike-waves during slow wave

sleep Acquired epileptic aphasia (Landau-Kleffner syndrome) Other undetermined epilepsies not defined above3.2. Without unequivocal generalized or focal features.


4. Special syndromes4. 1. Situation-related seizures: Febrile convulsions Seizures occurring only in the context of acute metabolic or

toxic events 4.2. Isolated seizures or isolated status epilepticus

Simptomatologi : Temporal Lobe Epilepsy

Simple atau complex partial dapat dengan atau tidak secondary generalizedAnamnesis febrille convulsionHipermetabolisme uni atau bilateralEEG spikes temporal lobe mulai anak atau dewasa

continued


Simple partial seizure dgn gx otonom atau psikisSensorik olfatorik, epigastric sensationComplex partial motorik berhenti disusul oro-alimentary automatismSering post-ictal confusion

Continued


EEG InterictalTdk ada kelainanAda sedikit/asimetri yg jelas & background activityTemporal spikes, sharp wave atau slow wave, uni atau bilateralUni/bilateral background activity interruption. Temporal multilobar low amplitude fast activity, rhytmic spike atau rhytmic slow waves

Simptomatologi :Amygdalo hypocampal/ meso basal limbic/ rhinencephalitic

Rising epigastric discomfort, nausea, gang otonom termasuk borborigmi, belching, pucat, muka merah, pernafasan berhenti, dilatasi pupil, rasa takut, panik, serta olfactory / gustatory hallucinationEEG : inter-ictal dpt normal, uni/bilateral sharp or slow waves, sinkron/asinkron

Simptomatologi : Lateral Temporal

Simple seizure dgn halusinasi & ilusi pendengaran atau dreamy states, visual perception, gang. Bahasa pd langguage dominant hemisphere focus.Menjadi kompleks bila ada penyebaran ke mesial atau struktur extra-temporal.EEG uni/bilateral midtemporal spikes yg prominen di wilayah lateral

Simptomatologi :Frontal lobe epilepsy

Simple atau complex partial dpt secondary generalizedSerangan dpt beberapa kali sehari, sering waktu tidurSering menjadi status epilepticus


Sering serangan singkat, complex partial seizure & menimbulkan post-ictal confu-sion.Generalisasi terjadi cepat lebih sering frontal dibanding temporalGx utama : motorik & postural, sering dimulai dgn gestural automatism

continued


EEG :NormalKadang2 background asimetry, frontal spikes atau sharp wavesSharp atau slow waves uni/bilateralKadang2 kelainan EEG mendahului serangan

Simptomatologi : Supplementary motor

Postural, focal tonic dgn vocalisationBerhenti bicara dan fancy postures

Simptomatologi : Cingulate

Simple, lebih sering complex partial dgn gestural automatismGx otonom disertai perubahan mood dan emosi

Simptomatologi :Anterior fronto polar

Forced thinking, initial loss of contactGerakan adversive kepala & mataDpt berubah contra-versive dgn axial clonic jerks serta gx otonomEEG dpt normal, spikes, dan wave disekitar frontal

Simptomatologi :Orbito frontal

Complex partial dgn dimulai motoric gestural automatismOlfatoric hallucinations & ilusi serta gx otonom

Simptomatologi :Dorsolateral

Dapat tonik, jarang klonik dgn versive head and eye movement dan bicara berhenti (speech arrest)

Simptomatologi :Operculum

Mastication. Salivation, laringeal swal-lowing, speech arrest, epigastic aura, rasa takut, gx otonomSimple partial dlm bentuk clonic facial seizure unilateral.Dapat berupa gangguan sensorik rasa tebal di tangan dan gustatory hallucination

Simptomatologi :Motor cortex

1. Simple partial tergantung lokasi focus : Prerolandic : speech arrest, vocalisation,

dysphasia, gerakan tonik muka kontralateral. Dpt terjadi generalisasi.

Rolandic : partial motor mulai ext atas kontralat (tdk ada penyebaran Rolandic

a la Jackson)

2. Sering timbul Todd’s paralysis

Simptomatologi :Kojecnikov Syndrome

Dikenal sebagai Rasmussen syndrome pd anak, berasal dari mitochondrial encephalopathy dgn lactic acidosis, dan kejadian spt stroke.Menyerupai Rolandic partial epilepsy pd dewasa dan anak oleh karena gangguan pd motor cortex. Partial seizure sering dgn myoclonus.EEG: normal background, focal paroxismal slow wave atau spikes. Dpt timbul pd segala umur & sering ada etiologinya (tumor/vascular)

Simptomatologi :Lobus Parietalis

Biasanya simple partial & secondary generalized, dpt juga complex partial, sensoris seperti semutan, rasa listrik dpt menyebar a la Jackson.Ada keinginan untuk merubah posisi tubuh yg terkena. Sering dimulai pd tangan dan muka ( proyeksi luas)

continued


Kadang ada perasaan sinking, chokes atau nausea terutama bila focus di daerah inferior.Parietal lobe visual phenomene dpt timbul sbg halusinasi dlm segala bentuk.Metamorphopsia dgn distorsi, memendek atau memanjang terutama bila yg terkena sebelah non-dominant.

continued


Phenomena negatif seperti rasa tebal, merasa bagian dari tubuh hilang (asomatognosia) terutama pada non-dominan.Vertigo, disorientasi menunjukkan pd lobus parietal inferior.Aphasia sensorik pd dominant lobus.Sensasi pd genital dpt timbul pd daerah parasentral

Simptomatologi :Lobus Occipital

Dpt simple/complex partial generalizedVisual(tdk selalu)Elementary dpt bersifat negatif : scotoma, hemianopsia, amaurosis atau positif : sparks, flashes, & phospheneen.Macropsia, micropsia, perubahan jarak, inklinasi, distorsi, metamorphopsia

continued


Visual hallucination (biasanya complex, pemandangan beraneka), distorsi atau melihat dirinya sendiri(he-autoscopy).Bila yg terkena temporo-parieto-occipital dpt timbul tonik atau klonik kontraversion dari mata dan kepala (oculoclonic atau oculogyric deviation), palpebral jerks, forced closed of the eyelids.

continued


Serangan dpt menyebar ke lobus temporalis.Bila fokus primer di supra-calcarine area dpt menyebar ke supra-sylvian convexity atau bagian mesial, dan merupakan epilepsi lobus parietal & frontalis.Penyebaran ke lobus occipital kontralateral dpt terjadi cepat.Serangan dapat menjadi generalized

PatofisiologiNormal neuronal transmission menunjukkan propagation of action potential.Na+, K+, Ca++, Cl- channels in cell membraneChemical transmission between neurons:

- Excitation : Glutamate, aspartate- Inhibition : Glycine, opioids, monoamines

Mechanism of epileptic seizure

Common properties of synaptic neuronBurst firing or Sustained Repetitive Firing (SRF) rapid Na+ flowParoxysmal Depolarization Shift (PDS) slower Ca++ influxAfter Hyperpolarization (AHP) prolonged K+

efflux and Cl- influx

SRF

RMP

PDS

AHP

+

0

-

Cara kerja obat epilepsi

neuron inhibisi (GABA-ergic transmission) GABA action pd GABAA receptor

rusaknya GABA di synapsMemblok GABA re-uptake di presynaptic terminal

Cara kerja obat epilepsi

neuron eksitasi (Glutaminergic transmission) lepasnya glutamateMemblokir glutamate action/AMPA/kainate receptorMemblokir voltage gate Na+ channel

Anti-epileptic drug mechanism

Different responses of AEDVariable AED efficacy in different seizure typeAED may act at the pre synaptic terminal/synaptic cleft/post synaptic membrane.AED may have anti & preconvulsant actionNot all AED actions are clinically significantNot all AED actions are according to plasma/CSF concentration

Sejarah AED

Bromide1912 Phenobarbital1938 Phenitoin1954 Primidon1960 Ethosuximide1974 Carbamazepin1975 Clonazepam1978 Sodium valproate

Sejarah AED

1985 Clobazam1994 Vigabatrin1994 Lamotrigine1994 Gabapentine1997 Topiramate1998 Tiagabine (gabatril)2001 Levetiracetam, Zonisamide

None of the AED is specific and the offer only symptomatic control or suppression of seizureBegin with one drugIdeally convulsion disappear without side effect

Alangkah baiknya untuk menggunakan sedikit jenis obat

dengan pengetahuan dan pengalaman yang luas daripada

menggunakan atau mencoba-coba macam-macam obat tanpa banyak

mengenalnya

Kejang tonik klonik generalized

1. Valproate2. Topiramate3. Lamotrigine4. Carbamazepin5. Phenitoin6. Phenobarbital7. Clonazepam

Partial epilepsi tonik-klonik

1. Carbamazepin2. Valproate3. Topiramate4. Lamotrigine5. Phenitoin6. Phenobarbital7. Clonazepam

Absence untuk anak

1. Valproate2. Ethosuximide3. Lamotrigine4. Valproate + Ethosuzimide5. Topiramate

Absence pada juvenile

1. Valproate2. Lamotrigine3. Valproate + Lamotrigine4. Valproate + Ethosuximide5. Topiramate

Partial seizure (idiopathic)

1. Valproate2. Carbamazepin3. Lamotrigine4. Topiramate5. Clonazepam6. Ethosuximide

Partial seizure

1. Carbamazepin2. Topiramate3. Lamotrigine4. Valproate5. Gabapentin

6. Clonazepam7. Phenitoin8. Phenobarbital9. Vigabatrin

Myoclonic seizure(idiopathic)no tonic

1. Valproate2. Lamotrigine3. Clonazepam4. Ethosuximide5. Topiramate

Myoclonic seizure(symptomatic)with tonic

1. Valproate2. Lamotrigine3. Topiramate4. Clonazepam

5. Gabapentin6. Phenitoin7. Phenobarbital8. Vigabatrin

Infantile spasm

1. Pyridoxin2. Vigabatrin3. Clonazepam4. Steroid, ACTH5. Valproate6. Topiramate

Status Epilepticus

Diagnosis dari jenis kejang & kausaPenanganan hrs dilakukan secara menyeluruh oleh ahli Saraf, internis, cardiolog, dan kalau perlu anestesis.Diazepam 1 ml=5mg, 1 amp=10mgRectal (Stesolid) 5 mg dan 10 mgDosis dewasa 10-20 mg, anak 0,25-0,5 mg/Kg, kecepatan tdk lebih dari 2-5 mg/mt

Phenytoin

15-18 mg/Kg iv infusionRate of infusion tdk boleh lebih dari 50 mg/mt (20 mg/mt untuk manula)Pd anak-anak 20 mg/kg iv infusionThe drug should never be given intramuscularly

Epi Lepsi

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