EPILEPSI

KONDISI NEUROLOGIS KRONIS BANGKITAN REKUREN abnormal, excessive or synchronous neuronal activity in the brain

I. DEFINISI
Epilepsi adalah manifestasi klinis yang serupa dan berulang, yang timbulnya paroksismal, akibat hiperaktifitas listrik sekelompok sel saraf di otak yang spontan, bukan disebabkan oleh suatu penyakit otak akut.

DEFINISI
Epilepsy is a disorder characterized by the occurrence of at least 2 unprovoked seizures 24 hours apart. Some clinicians are also diagnosing epilepsy when 1 unprovoked seizure occurs in the setting of an interictal discharge. Seizures are the manifestation of abnormal hypersynchronous discharges of cortical neurons. The clinical signs or symptoms of seizures depend on the location of the epileptic discharges in the cortex and the extent and pattern of the propagation of the epileptic discharge in the brain.

INSIDENS & PREVALENSI

> 2 JUTA ORANG DI AS > 300 RIBU UMUR < 14 TAHUN > 500 RIBU UMUR > 65 TAHUN > 50 JUTA DI SELURUH DUNIA

outline
Classifications Pathophysiology clinical manifestations treatment of epileptic seizures and some common epileptic syndromes

KLASIFIKASI EPILEPSI
IDIOPATK TIDAK ADA TANDA-TANDA PENYAKIT NEUROLOGIS LAIN SIMTOMATIK AKIBAT KONDISI NERUOLOGIS YANG DIKETAHUI : STROK, TRAUMA KEPALA, CEREBRAL PALSY DST

II. KLASIFIKASI BANGKITAN

2.1. Klasifikasi menurut the Internatioanl League Against (ILAE) 1981 untuk tipe bangkitan: 1. Bangkitan parsial 1.1. Bangkitan parsial sederhana (sadar) 1.1.1. Dengan gejala motorik 1.1.2. Dengan gejala sensorik 1.1.3. Dengan gejala otonom 1.1.4. Dengan gejala psikis

II. KLASIFIKASI BANGKITAN

1.2. Bangkitan parsial kompleks (kesadaran terganggu) 1.2.1.Bangkitan parsial sederhana diikuti gangguan kesadaran 1.2.2.Bangkitan parsial sederhana dengan gangguan kesadaran sejak awal

II. KLASIFIKASI BANGKITAN

1.3. Bangkitan umum sekunder 1.3.1. Parsial sederhana menjadi tonik klonik 1.3.2. Parsial kompleks menjadi tonik klonik 1.3.3. Parsial sederhana menjadi parsial kompleks menjadi tonik klonik

II. KLASIFIKASI BANGKITAN

2. Bangkitan umum 2.1. Absans (lena) 2.2. Mioklonik 2.3. Klonik 2.4. Tonik 2.5. Tonik klonik 2.6. Atonik

II. KLASIFIKASI BANGKITAN

3. Tak tergolongkan (sehubungan dengan data kurang lengkap)

BANGKITAN
PENGIRIMAN SIGNAL : - MERUBAH KADAR ION DALAM SEL (Na+, K+, Ca++, Cl-) - PELEPASAN NEUROTRANSMITTER - PERUBAHAN KADAR ION MENIMBULKAN PENJALARAN IMPULS DARI BADAN SEL NEURON KE UJUNG DISTAL AKSON.

PELEPASAN NEUROTRANSMITTER - INHIBITORI - EKSITATORI GABA-A receptors are coupled to chloride channels GABA-B receptor is coupled to potassium channels

decreased inhibition defective gamma-aminobutyric acid (GABA)-A inhibition defective GABA-B inhibition defective activation of GABA neurons defective intracellular buffering of calcium.

increased excitation increased activation of NMDA receptors increased synchrony between neurons due to ephaptic interactions increased synchrony and/or activation due to recurrent excitatory collaterals.

NORMALNYA TRANSMISI IMPULS DI OTAK TERATUR ALIRAN LISTRIK BERJALAN MULUS KADAR ION YANG TIDAK SESUAI & PERUBAHAN AKTIFITAS NEUROTRANSMITTER AKAN MERUBAH AKTIFITAS LISTRIK YANG TERATUR & DAPAT TIMBUL BANGKITAN.

Panel A shows the normal thalamocortical circuit. Thalamic relay neurons can activate the cortical pyramidal neurons in either a tonic mode or a burst mode, the latter made possible by T-type calcium channels. The mode of thalamocortical activation is controlled largely by input from the thalamic reticular neurons, which hyperpolarize the relay neurons through -aminobutyric acid type B (GABAB) receptors and are themselves inhibited by neighboring reticular neurons through activation of GABA type A (GABAA) receptors. Cortical pyramidal neurons activate the thalamic reticular neurons in a feed-forward loop. Ascending noradrenergic, serotonergic, and dopaminergic inputs from brain-stem structures appear to modulate this circuit. Panel B shows EEG patterns of wakefulness, non-REM sleep, and absence seizures. During wakefulness, the cortex is activated by the thalamus in a tonic mode, allowing for processing of external sensory inputs. This results in a desynchronized appearance of the EEG. During non-REM sleep, the cortex is activated in a burst mode, resulting in the EEG appearance of rhythmic sleep spindles. During an absence seizure, the normal thalamocortical circuit becomes dysfunctional, allowing burst activation of the cortex to occur during wakefulness, which results in the EEG appearance of rhythmic spike-wave discharges and interrupts responsiveness to external stimuli.

Panel A shows normal neuronal-ion-channel function and the action potential. Sodium and potassium channels are responsible for the primary components of the action potential, which involve a depolarizing phase mediated by sodium-channel opening and a repolarizing phase due to potassium-channel opening and sodium-channel inactivation. Other potassium channels contribute to a longer-term repolarization that helps prevent repetitive firing of the neuron. Mutations in SCN1B, which encodes a voltage-gated sodium-channel subunit, are associated with generalized epilepsy with febrile seizures plus (Panel B). The apparent effect of these mutations is to allow passage of an increased sodium current, which would lead to a greater depolarization during the action potential and an increased tendency to fire repetitive bursts. Mutations in KCNQ2 and KCNQ3, which both encode potassium channels, are associated with benign familial neonatal convulsions (Panel C). These mutations, which appear to decrease the potassium outflow underlying the longer-lasting "M current," are likely to cause a loss of spike-firing adaptation and therefore an increase in neuronal firing frequency.

Hippocampal sclerosis is the most common identified pathological feature in cases of mesial temporal-lobe epilepsy Normally, input to the hippocampus comes from the entorhinal cortex to the dentate granule cells through the perforant path Dentate granule cells project to the CA3 sector as the first step in the hippocampal output pathway. A close-up of the dentate granule-cell layer reveals several morphologic changes characteristic of hippocampal sclerosis that may play a part in epileptogenesis. Newly sprouted mossy fibers from dentate granule cells can synapse on dendrites of neighboring dentate granule cells, resulting in a recurrent excitatory circuit. They can also sprout onto inhibitory interneurons. Excitation interneurons, which normally activate inhibitory interneurons, may be selectively vulnerable to brain insults. Finally, neurogenesis of new dentate granule cells continues into adult life, and these neurons may integrate themselves into abnormal circuits.

BEBERAPA DAERAH DI OTAK YANG CENDERUNG TIMBUL BANGKITAN : - KORTEKS MOTORIK - LOBUS TEMPORALIS SANGAT SENSITIF TERHADAP PERUBAHAN BIOKIMIA : - HIPOKSIA - GANGGUAN METABOLIK - GANGGUAN ELEKTROLIT

III. ETIOLOGI
1.Idiopatik 2.Simtomatik Trauma Infeksi Kongenital Lesi desak ruang Gangguan peredaran darah Toksik dan metabolik

IV. KLINIS
Sesuai dengan tipe serangan epilepsi. (lihat

klasifikasi)

Absence Epilepsy
Generalized epilepsy syndrome begins between the ages of four and eight years absence seizures and, more rarely, generalized tonic clonic seizures.9 Patients stare and cease normal activity for a few seconds, then return immediately to normal and have no memory of the event Occur tens or hundreds of times a day Can be misdiagnosis of attention-deficit disorder or daydreaming is frequently made Classic EEG pattern : three-per-second, generalized spike-wave discharges
Panayiotopoulos CP. Absence epilepsies. In: Engel J Jr, Pedley TA, eds. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven, 1997:2327-46. http://www.medical-journals.com/r03102b.htm

V. DIAGNOSIS
Atas dasar : 1. Anamnesis Auto dan alo anamnesis Pola serangan yang terjadi Usia saat terjadinya serangan pertama Riwayat penyakit terdahulu Riwayat penyakit epilepsi dalam keluarga

V. DIAGNOSIS
2. Pemeriksaan fisik dan neurologis Ada tidaknya defisit neurologis dan atau neuropsikologis 3. Pemeriksaan EEG untuk konfirmasi ada tidaknya aktifitas epileptiform 4. Pemeriksaan neuroimajing struktur dan fungsional 5. Pemeriksaan kromosom dan mitochondria bila dicurigai adanya kelainan genetik 6. Laboratorium darah dan likuor serebrospinalis

V. DIAGNOSIS
Diagnosis pasti atas dasar ditemukannya gambaran epileptiform pada EEG saat serangan klinis.

Diagnosis banding
a. Pada semua usia: Migren Sinkop Meniere Episodik diskontrol Serangan psikogenik Serangan absans serangan parsial kompleks

dengan

Diagnosis banding
b. Pada anak Gangguan ekstrapiramidal Breath holding spell Pallid infantile syncope Prolong QT syndrome Gangguan tidur : parasommnia, narkolepsi Migren abdominal/ penyakit intra abdominal

Diagnosis banding
c. Pada dewasa TIA Transient global amnesia Narkolepsi

Diagnosis banding
d. Pada neonatus dan bayi . Jitteriness . Apneu . Serangan angkat bahu . Refluks gastroesofagus

VI. PEMERIKSAAN PENUNJANG

6.1. Indikasi EEG pada epilepsi: Membantu menegakkan diagnosis Menentukan jenis serangan dan lokasi fokus Menentukan prognosis pada kasuskasus tertentu Melacak fokus pada kasus-kasus yang klinis dicurigai epilepsi

VI. PEMERIKSAAN PENUNJANG

6.2. Indikasi pemeriksaan neuroimaging pada epilepsi Semua kasus serangan pertama yang diduga ada kelainan struktur Ada defisit neurologik fokal Serangan pertama di atas 40 tahun Intractable epilepsy untuk persiapan operasi

Treatment
Medications Vagus nerve stimulation therapy Ketogenic diet Surgery Complementary treatment

The goal of treatment is to achieve a seizure-free status without adverse effects This goal is accomplished in more than 60% of patients who require treatment with anticonvulsants However, many people have adverse effects, and some have seizures that are refractory to medical therapy Monotherapy is important because it decreases the likelihood of adverse effects and avoids drug interactions In addition, monotherapy may be cheaper than polytherapy, as many of the anticonvulsants have hepatic enzymeinducing properties that decrease the serum level of the concomitant drug, increasing the required dose of the concomitant drug.

VII. TATALAKSANA
7.1. Prinsip pengobatan . Mengurangi sampai menghilangkan serangan untuk perbaikan kualitas hidup . Terapi diberikan seawal mungkin . Pilihan obat sesuai dengan jenis epilepsi . Obat diupayakan tunggal . Dosis minimal yang efektif . Efek samping yang minimal . Biaya yang terjangkau .Terapi harus berdasarkan evidence based clinical practice

VII. TATALAKSANA
7.2. Jenis Obat Anti Epilepsi A. OAE pilihan pertama . Difenilhidantoin . Fenobarbital . Karbamazepin . Klonazepam . Valproat

VII. TATALAKSANA
B. OAE pilihan kedua Gabapentin Klobazam Lamotrigin Okscarbazepin Topiramat Vigabatrin

8 large groups Anticonvulsants based on their mechanisms

Blockers of repetitive activation of sodium channel Phenytoin, carbamazepine, oxcarbazepine GABA enhancers - Phenobarbital, benzodiazepines Glutamate modulators - Topiramate, lamotrigine, felbamate T-calcium channel blockers - Ethosuximide, valproate N- and L-calcium channel blockers - Lamotrigine, topiramate, zonisamide, valproate H-current modulators - Gabapentin, lamotrigine Blockers of unique binding sites - Gabapentin, levetiracetam Carbonic anhydrase inhibitors - Topiramate, zonisamide

VII. TATALAKSANA
7.3. Tatacara penghentian obat 1. Penurunan bertahap (25 % dari dosis sebelumnya setiap bulan) 2. penghentian obat atas persetujuan pasien atau keluarga 3. Bebas serangan sama sekali 2-5 tahun dengan rekaman EEG tanpa epileptiform.

Ketogenic diet
Diet: The ketogenic diet has a role in children with severe epilepsy One major problem is that, despite television programs and a movie supporting its use, <10% of patients continue the diet after a year Furthermore, any small carbohydrate intake (eg, lollypop, piece of candy) resets ketone metabolism for 2 weeks, eliminating antiseizure efficacy The diet, which relies heavily on Crisco (shortening product), is difficult to maintain The diet is unquestionably effective in some refractory cases, but the present authors do not consider this treatment in teenagers or adults unless all of their intake is being delivered by means of a gastric tube.

Vagus nerve stimulation therapy

VNS: The VNS is a palliative device approved to treat medically refractory partial-onset epilepsy in adults Some studies demonstrate its efficacy in partial-onset seizures and in a small number of patients with primary generalized epilepsy Randomized studies showed modest efficacy at 3 months, but postmarketing experience shows delayed improvement in another group of patients According to the manufacturer's registry, efficacy of the device at 18 months is 40-50%, where efficacy is defined as a reduction in seizures of 50% or more Many patients report improvement in seizure intensity and general mood. However, seizure-free rates for pharmacologically intractable partial-onset epilepsy are <10%.

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