Clinical Epilepsy

Dr. MOCH. BAHRUDIN, Sp.S

EPILEPSI : - adalah keadaan serangan klinis akibat cetusan potensial abnormal berlebihan dari sekelompok neuron kortek / subkortek ( Seizure ) - cenderung berulang & Stereotipi - diluar serangan normal
SEIZURE : - adalah bentuk serangan cetusan potensial abnormal berlebihan dari sekelompok neuron kortek / subkortek - Bisa sebagai serangan Epilepsi maupun bukan mis : akibat Uremia , Gangg.Elektrolit dll

FOKUS EPILEPTOGENIK : adalah suatu tempat / fokus di kortek / sub kortek dimana sekelompok neuron menjadi mudah terangsang ( hyperexcitable )

Status Epileptikus, epileptik seizure

> 30 menit atau lebih / berulang, kesadaran (-) Provoked seizure (Symptomatic Seizure) Epileptic Seizure dengan kausa (+)

AURA

: - adalah gejala atau tanda2 yang mendahului serangan Seizure Epilepsi , biasanya berupa Halusinasi pendengaran, pembauan, pengecap, visual , biasanya jenis Epilepsi Partial / Fokal - Sering disebut juga UNCINATE FIT

Fase ICTAL : - adalah fase saat serangan Seizure Epilepsi masih berlangsung, biasanya EEG selalu Abnormal

Fase POST ICTAL : - adalah fase sesudah serangan Seizure Epilepsi sudah berhenti, biasanya tertidur terlihat lemah.

Epidemiology of Seizures and Epilepsy

Seizures
Incidence: approximately 80/100,000 per year Lifetime prevalence: 9% (1/3 benign febrile convulsions)

Epilepsy
Incidence: approximately 45/100,000 per year Point prevalence: 0.5-1%

Classification of Seizures
Generalised - loss of consciousness Partial - no loss of consciousness Unclassified

Classification of Seizures
Generalised Absence Tonic Clonic Myoclonic Clonic Tonic Atonic Partial
Simple Partial

Motor Sensory Autonomic With psychic, cognitive or affective symptoms With automatism's

Complex Partial

Partial seizures with secondary generalisation

Patofisiologi EPILEPSI

Eksitasi

Seizure :
- menurunnya inhibisi - meningkatnya eksitasi Inhibisi

MEKANISME INHIBISI
- Defek inhibisi GABA-A - Defek inhibisi GABA-B - Defek aktivasi neuron GABA - Defek buffer Ca2+ intrasel

MEKANISME EKSITASI
- aktifasi reseptor NMDA - sinkronisasi neuron neuron ok

interaksi ephaptic ( non sinaps/

interaksi elektrolit ekstrasel )

NON GENETIK
Malformasi vascular

Patofisiologi EPILEPSI
Trauma mekanik

E
Struktur abnormal

Tumor otak
Parasit kronik Meningitis Ensefalitis Asfiksia lahir CVA Hipoksemiiskemi Infeksi

P I L

E
P S

Patofisiologi EPILEPSI
Generalized epilepsy with febrile seizure plus (SCNIB)
Benign familial neonatal convulsion(KCNQ2,KCNQ3) Autosomal dominant nocturnal frontal lobe epilepsy (CHRNA4)

GENETIK
DISFUNGSI KANAL ION

Mutasi kanal Na+

Mutasi kanal K+

Mutasi AChR

Juvenile myoclonic E (?CHRNA7)

Tuberous sclerosis(TSC1,TSC2) Neurofibromatosis(NF1) Periventricular nodular heterotopia (FLN1) Hamartin of tuberin Neurofibromin Filamin

PERTUMBUHAN ABNORMAL

FOKUS EPILEPTOGENIK EP. GENERAL

Pusat Epileptogenik Center Cephalic

ARAS

Tak Sadar
Ke Seluruhan Kortek

Kejang Umum
Tonik Clonik

FOCUS EPILEPTOGENIK EP. PARSIAL

Pusat Epileptogenik

Kortek Kejang Fokal

Meluas Jackson March

Tetap Sadar

FOCUS EPILEPTOGENIK EP. PARSIAL

Pusat Epileptogenik

Kortek Kejang Fokal

Meluas Jackson March

Centre Cephalic

Tidak sadar

EPILEPSI GENERAL SEKUNDER

Pusat Epileptogenik

Kortek Kejang Fokal

Meluas Jackson March Centre Cephalic

Tidak sadar
Seluruh Kortek

EPILEPSI GENERAL SEKUNDER

Pusat Epileptogenik

Kortek Kejang Fokal

Meluas Jackson March Centre Cephalic

Tidak sadar
Seluruh Kortek

EPILEPSI GENERAL SEKUNDER

Pusat Epileptogenik

Kortek Kejang Fokal

Meluas Jackson March Centre Cephalic

Tidak sadar
Seluruh Kortek

Kejang Umum

A. EPILEPSI PARSIAL
Fokus epileptik di area terbatas Lobus temporal dan frontal >>>, Lobus Oksipitalis dan Lobus Parietalis Penyebab: (-) Cidera Kepala, Infeksi, CVA, Heriditer, Tumor Penyebab jarang Lama: Detik Menit Kesadaran: N /

I. PARSIAL SEDERHANA
1. Manifestasi Motorik - Jerking/klonus, spasme, stifnes salah satu anggota tubuh separo tubuh - Letak: daerah frontal atau sentral

2. Manifestasi Somatosensor atau Spesial Sensor (Halusinasi Sederhana) - Halusinasi sensasi; rasa tidak enak, mati rasa, sengatan listrik,terbakar, nyeri, panas fokus epileptiknya di sentral atau parietal - Fenomena visual fokus di korteks kalkarina - Rasa tidak enak di epigastrik fokus di lobus temporalis bagian mesial - Ilusi (Distorsi dari sensasi yang sebenarnya)

3. Manifestasi Autonom - Perubahan; warna kulit, tekanan darah, detak jantung, berkeringat, frekwensi nafas, pupil - Rasa aneh dan tak enak di perut, dada dan kepala

4. Manifestasi Psikis - Think, Feel dan Experience - Sebagai Aura dari Parsial Kompleks - Fokus: Temporal, Frontal, Pariental

- Bentuk simptom:
Dysphasic symptom korteks speech Dysmnestic symptom (gangguan memori) lob. Temporalis bag. Mesial Cognitif symptom Lob. Temporalis Affective symptom (takut, depresi, marah, pikiran erotik, tertawa-tawa) Lob. Frontalis Illusion (Bentuk, Ukuran, Berat) Lob. Temporal/Parietooksipital) Structured Hallucination (visual, auditorik, eustatorik) Lobus Temporal dan Parietooksipital & Area Asosiasinya.

II. EPILEPSI PARSIAL KOMPLEKS (PSIKOMOTOR/LOB. TEMPORAL)

Terjadi penurunan kesadaran (impaired) Ada 3 komponen Aura: Parsial sederhana, waktu singkat Gangguan kesadaran: setelah atau simultan dengan aura Tampak bengong dan motor Arres, diikuti spasme atau jerking otot Automatisme: gerakan motorik involunter, kesadaran menurun dan total amnesia Gerakan motorik lebih kompleks dan mempunyai tujuan oro-alimentary, mimicry, verbal automatisme, responsive auto, violent behavior

B. BANGKITAN PARSIAL YG BERKEMBANG MENJADI KEJANG UMUM (SECONDARILY GENERALIZED SEIZURE)

Cetusan abnormal di mulai dari area terbatas meluas melibatkan kedua hemisfer otak Di mulai bangkitan parsial (aura) kejang umum Tonik - Klonik, Tonik atau Klonik

C. EPILEPSI UMUM (GENERALIZED SEIZURE)

Kesadaran: selalu hilang saat onset Mengenai kedua hemisfer otak

1. TYPICAL ABSENCE SEIZURE (PETIT MAL SEIZURE)

Hilangnya kesadaran mendadak (Absans), berhentinya aktifitas motorik, tonus normal, pendrita tidak jatuh bengong dan unaware Dimulai dan di akhiri tiba-tiba, seperti tidak terjadi apa-apa, lama 10 detik, berulang kadang diikuti kedipan mata dan gerakan motorik. Usia: 4 - 14 th, 75% penderita anak, fisik dan intelegensianya normal. Gambaran EEG: Spike-Wave Paroxysm dalam frekwensi 3 Hz, simetris dan sinkron Perbedaan dengan bangkitan parsial kompleks (tabel)

2. ATYPICAL ABSENCE SEIZURE

Berbeda dengan tipikal absans: gambaran klinik, EEG, Etiologi dan Konteks klinik. Ditemukan Learning Disability, kelainan neurologi

Membentuk sindrome Lennox - Gastaut

Perbedaan Atypical dan Typical

3. MYOCLONIC SEIZURE
Kontraksi singkat sekelompok/beberapa kelompok otot, kedua sisi tubuh Discharge di kortikal Kontraksi tunggal / berulang, ringan / Berat Recovery cepat dan segera sadar

Diinduksi: gerakan, suara, kejutan, stimulasi fotik, ketukan

Learning Disability: Juvenil Myoclonic epilepsy, Lennox-Gastaut syndrome

4. CLONIC SEIZURE
Jarang, berupa gerakan jerking ritmik, tanpa konfus/kelelahan setelah serangan Neonatus, bayi dan anak selalu simptomatik

5. TONIC SEIZURE
Kontraksi otot tonik (kaku), mendadak, kesadaran turun, lama 20-60 detik, sering saat tidur
Dimulai ekstensi leher, kontraksi otot wajah, dan pernafasan serta otot ekstremitas (abduksi bahu dan elevasi lengan) Jeritan dan Apneu Kerusakan otak difuse dan Learning Disability

6. TONIC-CLONIC SEIZURE (GRANDMAL SEIZURE)

Bangkitan dengan konvulsive Public imagination

Kehilangan kesadarn (jatuh) dengan epileptic cry fleksi tonik ekstremitas (singkat) fase rigiditas & ekstensi aksial, bola mata ke atas, rahang mengatup kuat, badan kaku (adduksi dan ekstensi), tangan mengepal, sianosis (10 - 30 detik) Fase klonik pada keempat ekstremitas, otot rahang & wajah, saliva banyak, mengumpu di sudut mulut dengan darah. Gerakan klonik makin menurun dalam frekwensi
Gejala autonom, muka merah, tensi, nadi, hipersalivasi, ngompol Mengenai semua umur, kelaianan patologis tidak ada

Lama fase klonik 30 - 60 detik

fase akhir (final) lama 2 - 30 menit fleksid otot-otot tubuh kesadaran pulih tapi onfus sakit kepala

penderita tertidur

7. ATONIC SEIZURE
Kehilangan kekuatan/tonus otot, mendadak

Classic drop attack (Astatic Seizure) Penderita Kolaps/jatuh

Kedua kelopak mata turun, kepala terangguk, badan terkulai Drop ke tanah injuri Lama 15 detik, segera recovery Kerusakan otak difus, Learning Disability, Epilepsi Simptomatik berat.

PENATALAKSANAAN
A. MEDIK :
Diagnosa Dini & Tepat Pengobatan tepat & Teratur Kontrol Dr teratur Cegah Komplikasi Masyarakat Yg SALAH Keluarga Px Px Keluarga Masyarakat

B. SOSIAL :
MERUBAH * Sikap * Pengetahuan * Tindakan * Perilaku

C. PENDIDIKAN :
* * * * Pencegahan Pengobatan Perawatan Rehabilitasi

PENATALAKSANAAN
1. Anamnesa Riwayat

2. Pemeriksaan Fisik
3. Pemeriksaan Laborat 4. EEG = Electro encefalografi = Rekaman Otak 5. X Foto Kepala

6. Cairan Otak LP = Lumbal Pungsi

7. CT Scan

Questions Raised by a First Seizure

Seizure or not? Focal onset? Evidence of interictal CNS dysfunction? Metabolic precipitant? Seizure type? Syndrome type?

Studies?
Start AED?

Seizure Precipitants
Metabolic and Electrolyte Imbalance Stimulant/other proconvulsant intoxication Sedative or ethanol withdrawal Sleep deprivation Antiepileptic medication reduction or inadequate AED treatment Hormonal variations Stress Fever or systemic infection Concussion and/or closed head injury

Seizure Precipitants, cont

Metabolic and Electrolyte Imbalance
Low (less often, high) blood
glucose Low sodium Low calcium Low magnesium

Seizure Precipitants, cont

Stimulation/Other Proconvulsant Intoxication
IV drug use

Cocaine
Ephedrine Other herbal remedies

Medication reduction

Evaluation of a First Seizure

History, physical Blood tests: CBC, electrolytes, glucose, Calcium, Magnesium, phosphate, hepatic and renal function Lumbar puncture only if meningitis or encephalitis suspected and potential for brain herniation is ruled out Blood or urine screen for drugs Electroencephalogram CT or MR brain scan

EEG Abnormalities
Background abnormalities: significant asymmetries and/or degree of slowing inappropriate for clinical state or age Interictal abnormalities associated with seizures and epilepsy Spikes Sharp waves Spike-wave complexes May be focal, lateralized, generalized

Medical Treatment of First Seizure

Whether to treat first seizure is controversial
16-62% will recur within 5 years Relapse rate might be reduced by antiepileptic drug treatment Abnormal imaging, abnormal neurological exam, abnormal EEG or family history increase relapse risk Quality of life issues are important
Reference: First Seizure Trial Group. Randomized Clinical Trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology 1993; 43 (3, part1): 478-483. Reference: Camfield P, Camfield C, Dooley J, Smith E, Garner B. A randomized study of carbamazepine versus no medication after a first unprovoked seizure in childhood. Neurology 1989; 39: 851-852.

Choosing Antiepileptic Drugs

Seizure type

Epilepsy syndrome
Pharmacokinetic profile Interactions/other medical conditions

Efficacy
Expected adverse effects Cost

Choosing Antiepileptic Drugs (cont.)

Partial onset seizures
carbamazepine felbamate gabapentin lamotrigine levetiracetam oxcarbazepine phenobarbital phenytoin primidone tiagabine topiramate valproate zonisamide

Choosing Antiepileptic Drugs (cont.)

AEDs that have shown efficacy for Absence seizures:

Ethosuximide Lamotrigine Levetiracetam Topiramate Valproate Zonisamide

Choosing Antiepileptic Drugs (cont.)

AEDs that have shown efficacy for myoclonic seizures:
Clonazapam Lamotrigine Levetiracetam Topiramate Valproate Zonisamide

Choosing Antiepileptic Drugs (cont.)

AEDs that have shown efficacy for Tonic Clonic seizures: Carbamazepine Felbamate Lamotrigine Levetiracetam Oxcarbazepine Phenytoin Topiramate Valproate Zonisamide

Evaluation After Seizure Recurrence

Progressive pathology?
Avoidable precipitant? If on AED
Problem with compliance or pharmacokinetic factor?
Increase dose?

Change medication?

If not on AED
Start therapy?

Discontinuing AEDs
Seizure freedom for 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes Favorable factors
Control achieved easily on one drug at low dose No previous unsuccessful attempts at withdrawal Normal neurologic exam and EEG Primary generalized seizures except JME Benign syndrome

Consider relative risks/benefits (e.g., driving, pregnancy)

TERAPI EPILEPSI
TIPE 1. Epilepsi Parsial 2. Epilepsi General
-

FIRST LINE CBZ PHB DPH PRM

-

SECOND CLZ VPA BZD

A. Tonik-Klonik

DPH PHB VPA CBZ PRM ETX VPA VPA CLZ BZD

CLZ BZD

B. Absence C. Mioclonic D. Lain

- ETX

Semua Kec. ETX

Treatment/Evaluation Sequence for Pharmacoresistent Epilepsy

Sz-free with 1st A ED

1st

Monotherapy AED Trial

Sz-free with 2nd A ED Sz-free with 3rd A ED / P o lytherapy P harmaco resistant

2nd Monotherapy AED Trial

47%

13%

3rd Monotherapy/Polytherapy AED Trial

4%

Strongly consider videoEEG Monitoring

Non-epileptic Epilepsy

36%

Kwan P, Brodie MJ. NEJM;342:314-319.

Psychogenic, migraine, syncope, sleep disorders, movement disorders, etc.

Epilepsy Surgery/VNS Therapy/ Neuropace Evaluation

Polytherapy AED Trials

Resective Surgery

Stimulator Therapy

Epilepsy Surgery- Neuroimaging

Hippocampal atrophy in temporal lobe epilepsy

Ganglioglioma

DNT

Cortical Dysplasia

AVM

Cavernous Angioma

Evaluation for Surgery- Subdural Grid Electrodes

Left Anterior Temporal Loectomy

Epilepsy Syndromes
Localization-related epilepsies
Idiopathic Symptomatic

Cryptogenic

Epilepsy Syndromes (cont.)

Generalized epilepsies
Idiopathic Symptomatic Cryptogenic

Undetermined epilepsies Special syndromes

SINDROMA EPILEPSI (EPILEPSY SYNDROME)

Epilepsi dengan sekelompok sign & simptom (cluster of Feature): Tipe Bangkitan, Usia, EEG dan Prognosis Macam: Febrile seizure Benign Rolandic Epilepsi Juvenil Myoclonic Epilepsi Infantil spasme Lennox-Gastaut Landau-Kliffner Syndrome Rasmussens Syndrome

3 1. Infantile Spasms (West syndrome) 2. Juvenile myoclonic epilepsy 3. Benign rolandic epilepsy

Etiology of Seizures and Epilepsy

Infancy and childhood
Prenatal or birth injury Inborn error of metabolism Congenital malformation

Childhood and adolescence

Idiopathic/genetic syndrome CNS infection Trauma

Etiology of Seizures and Epilepsy (cont.)

Adolescence and young adult
Head trauma Drug intoxication and withdrawal*

Older adult
Stroke Brain tumor Acute metabolic disturbances* Neurodegenerative

*causes of acute symptomatic seizures, not epilepsy

Status Epilepticus
Definition
More than 30 minutes of continuous
seizure activity or Two or more sequential seizures spanning this period without full recovery between

seizures

Status Epilepticus
A medical emergency
Adverse consequences can include hypoxia, hypotension, acidosis and hyperthermia Know the recommended sequential protocol for treatment with benzodiazepines, phenytoin, and barbiturates.
Goal: stop seizures as soon as possible

Status Epilepticus Treatment

Time post onset Treatment Onset 2-3 min. 4-5 min. Ensure adequate ventilation/O2 IV line with NS, rapid assessment, blood draw Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or rectal diazepam

7-8 min.

( 0.75

Thiamine 100 mg, 50% glucose 25 mg IV Phenytoin or fosphenytoin 20 mg/kg IV (phenytoin PE) at 50 mg/per minute phenytoin or 150 mg per minute fosphenytoin

mg/kg/min) Pyridoxine 100-200 mg IV in children under 18 mo.

Status Epilepticus Treatment (cont.)

Time post onset
10 min. ongoing Treatment Can repeat lorazepam or diazepam if seizures and patient minute (0.75

30-60 min. EEG monitoring unless status ended waking up 40 min. Phenobarbital 20 mg/kg at 5 mg per mg/kg per minute)

continued

Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

Status Epilepticus Treatment (cont.)

Time post onset Treatment
70 min. per Pentobarbital 3-5 mg/kg load, 1 mg/kg hour infusion, increase to burstsuppression OR Propofol 3-5 mg/kg load, 5-10 mg/kg/hr initial infusion then 103 mg/kg/hr Midazolam 0.2 mg/kg load, .25-2 mg/kg infusion
Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

OR

EEG Electro Encephalo Grafi

EEG Electro Encephalo Grafi

5
1 2

Montage = Sadapan
Unipolar Montage : Gel. 1 , 2 , 3 , 4 Bipolar Montage : Gel. 5 , 6 , 7 , 8

Gel. Normal : Alpha 8 - 13 Beta di frontal > 13 Gel. AbNormal : Theta 4-7 Delta <4

EEG
SHARP / Tajam SPIKE / Runing

SPIKE & WAVE

POLI SPIKE-WAVE

EPILEPSI GENERAL TONIC CLONIC = GRAND MAL

PETIT MAL / ABSENCE Typical

3 Hz Spike & Wave

EEG: Simple Partial Seizure

Right temporal seizures with maximal phase reversal in the right sphenoidal electrodes Continued on C-Slide9

EEG: Simple Partial Seizure

Continuation of same seizure (C-slide-8)

Right temporal seizures with maximal phase reversal in the rig sphenoidal electrodes

EEG: Absence Seizure