Curriculum Vitae 1. Dokter (dr)  1987, Unhas Nama : Muhammad Akbar Pendidikan : 1. Dokter (dr)  1987, Unhas 2. Spesialis Saraf (Sp.S)  1995, Unhas 3. Doktor (Ph.D)  2001, Hiroshima, Jepang. 4. Diploma in Forensic Medicine (DFM)  2003, Groningen, Belanda. 5. Konsultan Cerebro Vascular (Sp.S(K)  2013 Amanah : 1. Kepala Pusat Kajian Media dan Sumber Belajar, Lembaga Kajian dan Pengembangan Pendidikan UNHAS, 2006-2010 2. Ketua IDI Wilayah Sul-Sel 2006-2009 3. Ketua III Perhimpunan Dokter Spesialis Saraf (PERDOSSI) Pusat, 2007-2011 4. Ketua II Perhimpunan Dokter Emergensi Indonesia Pusat 2007-2011 5. Ketua POKDI Nasional Neuro-Epidemiologi 2007-2011 6. Kepala Bagian Ilmu Penyakit Saraf FK UNHAS, periode 2001-2006 dan periode 2011- 2015 serta 2015-2019 7. Ketua Bidang Leadership PB IDI 2012-2015.

Penanganan Dini & Terapi Pemeliharaan Epilepsy Penanganan Dini & Terapi Pemeliharaan Muhammad Akbar Neurology Department Hasanuddin University Neurology Department Hasanuddin University Muhammad Akbar

Historical Figures Neurology Department Hasanuddin University Muhammad Akbar

PENDAHULUAN Epilepsi pada hakekatnya adalah suatu diagnosa klinis : Bila tampil klasik : MUDAH DIDIAGNOSA Sebagian kasus : MISDIAGNOSA Sebagian lainnya : LUPUT Penyebab 2 dan 3 : Riwayat penyakit tak lengkap Terdapat kondisi medik perancu

DEFINISI Epilepsi suatu keadaan yg ditandai oleh bangkitan epilepsi berulang, berselang lebih dari 24 jam yg timbul tanpa provokasi. Bangkitan epilepsi (epileptic seizure) manifestasi klinik yg disebabkan oleh aktivitas listrik otak yg abnormal dan berlebihan dari sekelompok neuron. Manifestasi klinik ini terjadi secara tiba-tiba dan sementara perubahan perilaku yg stereotipik, dpt menimbulkan gangguan kesadaran, motorik, sensorik, otonom, ataupun psikik.

Key point In epilepsy, there is a problem with the electrical messages in the brain.

Seizures disrupt the way the brain works for a short time. Key point People with epilepsy experience sudden bursts of electricity in their brain - called a SEIZURE. Seizures disrupt the way the brain works for a short time. This burst of electrical activity – a seizure - causes the messages in the brain to become muddled and so it stops it from working properly. Changes behaviour or feelings of person.

EPILEPSY- A CRITICAL BALANCE EXCITATION INCREASE INHIBITION DECREASE SEIZURE SEIZURE Na+ channel antagonists Ca2+ channel antagonists Glutamate receptor antagonists GABAA agonists Enhanced GABA levels K+ channels modulators Neurology Department Hasanuddin University Muhammad Akbar Feb 4, 2005 8

A seizure is a symptom of epilepsy What Is the Difference Between Epilepsy & Seizures? A seizure is a brief, temporary disturbance in the electrical activity of the brain Epilepsy is a disorder characterized by recurring seizures (also known as “seizure disorder”) To understand epilepsy, it is important to review the difference between epilepsy and seizures. Epilepsy is a generic term used to define a variety of disorders characterized by recurring seizures. A diagnosis of epilepsy means that a person has an underlying condition, such as a brain injury, that affects the delicate systems which govern how electrical energy behaves in the brain, making it susceptible to recurring seizures. A seizure is a brief, temporary disturbance in the electrical activity of the brain. Seizures are a symptom of epilepsy. However, having a seizure does not necessarily mean that a person has epilepsy. There are other causes of seizures, including high fever, kidney failure, or lack of oxygen. Epilepsy is not contagious. You cannot catch epilepsy from someone else and nobody can catch it from you. Many misconceptions surround epilepsy, and sometimes people inadvertently add to the negative image of the disorder by choice of language. Like all individuals with a disability, persons with epilepsy dislike labels, such as “he’s an epileptic.” Epilepsy is a condition that a person has, not what they are. The preferred terminology is “person with epilepsy.” In addition, epilepsy should be referred to as a “disorder,” since it is not a disease by definition. It is a disorder characterized by a recurring disturbance in the electrical activity of the brain. A seizure is a symptom of epilepsy Neurology Department Hasanuddin University Muhammad Akbar 9

A. Bangkitan Parsial B. Bangkitan parsial berkembang menjadi umum C. Bangkitan Umum D. Lokasi Bangkitan

ILAE CLASSIFICATION OF SEIZURES Partial seizures have onset in part of the brain; synonymous terms that are frequently used include localization-related or focal seizures. Partial seizures are divided into two main types, depending on whether or not consciousness is fully preserved. During simple partial seizures, consciousness is preserved; the person is alert, can respond to questions or commands, and can remember what occurred during the seizure. During complex partial seizures, consciousness is altered or lost; the ability to pay attention or respond to questions or commands is thus impaired or lost. Often, there is no memory of what happened during all or part of the complex partial seizure. The distinction between simple and complex partial seizures is critical, because activities such as driving and operating dangerous machinery must be restricted in patients with uncontrolled complex partial seizures; restrictions for people with only simple partial seizures depend on the specific seizure manifestations (and, for driving, on regulations in a particular state). Partial onset seizures may progress to secondarily generalized seizures. Secondarily generalized seizures ultimately involve motor activity on both sides of the body and can be difficult to distinguish from primary generalized seizures.

ILAE CLASSIFICATION OF SEIZURES Generalized seizures affect both cerebral hemispheres from the beginning of the seizure. They produce loss of consciousness, either briefly or for a longer period of time, and are sub-categorized into several major types: absence, myoclonic, atonic, tonic, and tonic-clonic.

Klasifikasi Epilepsi berdasarkan ILAE 1989

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Neurology Department Hasanuddin University Muhammad Akbar

Etiologi Epilepsi Idiopatik: etiologi tdk diketahui, tdk terdapat lesi struktural di otak, tdk ada defisit neurologik. Diperkirakan: genetik. Simptomatik: bangkitan epilepsi disebabkan oleh lesi struktural otak, mis: cedera kepala, infeksi SSP, tumor otak, dll Kriptogenik: dianggap simptomatik, tetapi belum diketahui penyebabnya, ct: West Syndrome, Lennox-Gestaut Syndrome.

ETIOLOGY OF EPILEPSY BY AGE (ADAPTED FROM NASHEF) Tumors, sporadic infections & metabolic dis. Malignant tumours Congenital & genetic conditions HS, trauma, genetic predisposition alcohol/drug abuse CVD 20 40 60 80 Age (years)

An approach to Seizures

Diagnosis EEG CT-scan MRI Lain-lain Pasien didiagnosis epilepsi jika mengalami serangan kejang secara berulang Untuk menentukan jenis epilepsinya, selain dari gejala, diperlukan berbagai alat diagnostik : EEG CT-scan MRI Lain-lain Neurology Department Hasanuddin University Muhammad Akbar

DIAGNOSIS EPILEPSI PEDOMAN UMUM  3 langkah: Memastikan apakah kejadian yg bersifat parosksismal adalah mrpk bangkitan epilepsi Apabila BENAR terdpt bangkitan epilepsi, tentukan Tipe Bangkitan (klasifikasi ILAE 1981) Tentukan Etiologi dan sindroma epilepsi, atau penyakit epilepsi apa yg diderita pasien (klasifikasi ILAE 1989)

DIAGNOSIS EPILEPSI – Anamnesis (1) Langkah pertama (lihat slide sebelumnya), ditempuh melalui: ANAMNESIS Gejala sebelum, selama, dan pasca bangkitan Ada tidaknya penyakit yg diderita yg mungkin menjadi penyebab Usia awitan, durasi, frekuensi, interval terpanjang antar bangkitan Riwayat epilepsi sebelumnya dan respons terhadap terapi (dosis, kadar OAE, kombinasi terapi) Riwayat epilepsi dlm keluarga

DIAGNOSIS EPILEPSI – Anamnesis (2) Riwayat keluarga dgn penyakit neurologik lain, psikiatrik, atau sistemik Riwayat saat dlm kandungan, kelahiran, dan perkembangan bayi/anak. Riwayat bangkitan neonatal/kejang demam Riwayat trauma kepala, infeksi SSP, dll

DIAGNOSIS EPILEPSI – Pemeriksaan Fisis P. FISIS UMUM Amati tanda2 gangguan yg berhub dgn epilepsi, mis: trauma kepala, infeksi telinga, kongenital, kecanduan alkohol, kelainan kulit (neurofakomatosis), dll P. FISIS NEUROLOGIS Amati adanya gejala neurologik fokal atau difus, Todd’s paralysis, dll

DIAGNOSIS EPILEPSI – Pemeriksaan Penunjang EEG Rekaman EEG paling berguna pada dugaan suatu bangkitan. EEG membantu menunjang diagnosis dan penentuan jenis bangkitan maupun sindroma epilepsi, dan kadang2 dpt membantu menentukan prognosis dan penentuan perlu/tidaknya pengobatan AED. Brain Imaging: CT Scan kepala, MRI, PET, SPECT Laboratorium

Types of s (focal) Primary

Generalized Seizure (Generalized Tonic-clonic Seizure) (Bangkitan Umum Tonik-klonik) (Grand Mal Epilepsy)

Bangkitan umum tonik-klonik Dapat didahului prodromal seperti jeritan, sentakan, mioklonik Pasien kehilangan kesadaran, kaku (fase tonik) selama 10 – 30 detik, diikuti gerakan kejang kelojotan pada kedua lengan dan tungkai (fase klonik) selama 30 – 60 detik, dapat disertai mulut berbusa Setelah bangkitan berakhir, pasien menjadi lemas (fase flaksid) dan tampak bingung Pasien sering tidur setelah bangkitan selesai

Tonic-clonic seizures A. Tonic phase B. Clonic phase C. Post-ictal confusional fatigue Incontinence Cyanosis Epileptic cry Clonic jerks of limbs, body and head Cyanosis Generalised stiffening of body and limbs, back arched Eyes blinking Limbs and body limp Salivary frothing 32 32

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Focal seizures

(Bangkitan Absans) (Bangkitan Lena) (Petit Mal Epilepsy) Abscence Seizure (Bangkitan Absans) (Bangkitan Lena) (Petit Mal Epilepsy)

Bangkitan Absans Gangguan kesadaran mendadak (‘absence’), berlangsung beberapa detik. Selama bangkitan kegiatan motorik terhenti dan pasien diam tanpa reaksi Mata memandang jauh ke depan Mungkin terdapat automatisme Pemulihan kesadaran segera terjadi tanpa perasaan bingung Sesudah itu pasien melanjutkan aktivitas semula

Absence seizures

Epilepsi lainnya

AUTOMATISM

Psychogenic Non Epileptic Seizure (Psychogenic seizure / Pseudo seizure) Mirip epileptic seizure Kadang-kdang bentuk aneh Cetusan emosi Jarang melukai diri Jarang terjadi pd waktu tidur

Penanganan Epilepsi

Epilepsy Management First seizure Initial consultation Month First seizure 0-1 Initial consultation 3 Seizures controlled Seizures not controlled/diagnosis in question 12 Seizures controlled Seizures not controlled/diagnosis in question 36+ Medication withdrawal Emergency Department Primary Care Neurologist Epilepsy Center Iowa Comprehensive Epilepsy Program Modified from: National Association of Epilepsy Centers, 2010

Seizure first aid Do or don’t? Panic

Call an ambulance immediately Seizure first aid Do or don’t? Call an ambulance immediately

Seizure first aid Do or don’t? Send for help

Put something soft under their head Seizure first aid Do or don’t? Put something soft under their head

Time how long the seizure lasts Seizure first aid Do or don’t? Time how long the seizure lasts

Hold them down so they don’t hurt themselves Seizure first aid Do or don’t? Hold them down so they don’t hurt themselves

Move them away from the chair to avoid injury Seizure first aid Do or don’t? Move them away from the chair to avoid injury

Try to bring them around Seizure first aid Do or don’t? Try to bring them around

Put them on their side (in the recovery position) as soon as possible Seizure first aid Do or don’t? Put them on their side (in the recovery position) as soon as possible

Stay with them until they are fully recovered and reassure them Seizure first aid Do or don’t? Stay with them until they are fully recovered and reassure them

4 1 5 3 6 2 Time the seizure Keep the area safe Stay calm and reassure Get help Put something soft under their head 6 Put them into the recovery position AFTER the shaking has stopped 2

First Aid for Seizures Stay calm and track time Protect head, remove glasses, loosen tight neckwear Move anything hard or sharp out of the way Turn person on one side, position mouth to ground Check for epilepsy or seizure disorder ID Understand that verbal instructions may not be obeyed Stay until person is fully aware and help reorient them Call ambulance if seizure lasts more than 5 minutes or if it is unknown whether the person has had prior seizures This graphic shows general measures to assist a person who is having a seizure. First, stay calm and reassure other people. Track how long the seizure lasts. Protect the person by helping them avoid hazards. Place something soft under the head (a coat, T-shirt or similarly appropriate item that’s handy); if the person is wearing glasses, remove them. Loosen any clothing that is tight-fitting around the neck. With a generalized tonic-clonic seizure, turn the person on one side to keep the airway clear. Check for an epilepsy or seizure disorder ID, and wait for the seizure to end. Understand that verbal instructions may not be obeyed. Finally, stay until the person is fully aware and help reorient them to their surroundings. Call an ambulance if the seizure lasts more than 5 minutes, unless you know that the person’s seizures typically last longer than 5 minutes. Remember, unless you are a primary caregiver who has been trained in use of a special medication, or you have been shown how to use a special VNS magnet, there is NOTHING you can do to stop a seizure -- it will run its own course. You CAN protect the person from injury, observe the seizure, call for an ambulance if necessary, and reassure others that this is just a seizure and everything will be just fine in a few moments. NOTE: If asked, the medication is diazepam rectal gel (Diastat) or a liquid form of diazepam for rectal administration. It is for family/caregiver/nurse use only, not a casual first aid. Question: Sometimes things we do with good intentions can actually be dangerous to the person having a seizure. Can you think of things that may be harmful?

Treatment of epilepsy Therapeutic principle of ntiepilepsy drugs (AEDs) Early treatment Treatment as the types of epileptic seizure Treatment with one drug Individual therapy Long course of treatment Slow drug withdrawal Periodic re-examination

Hal-hal yg perlu diperhatikan dalam pengobatan epilepsi : Tujuan pengobatan : membebaskan penderita dari serangan epilepsi dengan dosis yang memadai tanpa menimbulkan gejala toksik pengobatan epilepsi : sifat individual dan berlangsung lama, minimal 2-3 thn bebas serangan Sekitar 75% kasus dapat ditanggulangi baik dengan satu / kombinasi obat Dianjurkan pengobatan dengan satu jenis obat Neurology Department Hasanuddin University Muhammad Akbar

Prinsip umum terapi epilepsi: monoterapi lebih baik  mengurangi potensi adverse effect, meningkatkan kepatuhan pasien, tidak terbukti bahwa politerapi lebih baik dari monoterapi dan biasanya kurang efektif karena interaksi antar obat justru akan mengganggu efektivitasnya dan akumulasi efek samping dg politerapi hindari atau minimalkan penggunaan antiepilepsi sedatif  toleransi, efek pada intelegensia, memori, kemampuan motorik bisa menetap selama pengobatan jika mungkin, mulai terapi dgn satu antiepilepsi non-sedatif, jika gagal baru diberi sedatif atau politerapi berikan terapi sesuai dgn jenis epilepsinya Memperhatikan risk-benefit ratio terapi Penggunaan obat harus sehemat mungkin dan sedapat mungkin dalam jangka waktu pendek Neurology Department Hasanuddin University Muhammad Akbar

mulai dengan dosis terkecil dan dapat ditingkatkan sesuai dg kondisi klinis pasien  penting : kepatuhan pasien ada variasi individual terhadap respon obat antiepilepsi  perlu pemantauan ketat dan penyesuaian dosis jika suatu obat gagal mencapai terapi yang diharapkan  pelan-pelan dihentikan dan diganti dengan obat lain (jgn politerapi) lakukan monitoring kadar obat dalam darah  jika mungkin, lakukan penyesuaian dosis dgn melihat juga kondisi klinis pasien Neurology Department Hasanuddin University Muhammad Akbar

Kegagalan pengobatan tergantung dari beberapa faktor: Faktor penderita : ketidak mampuan dalam : Minum obat Hidup teratur akibat faktor : keluarga lingkungan pendidikan Cegah faktor provokasi Jenis epilepsi Jenis / dosis obat yg tak tepat / optimal

KEGAGALAN PENANGANAN EPILEPSI INTRACTABLE EPILEPSI DIAGNOSE < TEPAT PENANGANAN TIDAK OPTIMAL

Obat-obat anti epilepsi Obat-obat yang meningkatkan inaktivasi kanal Na+: Inaktivasi kanal Na  menurunkan kemampuan syaraf untuk menghantarkan muatan listrik Contoh: fenitoin, karbamazepin, lamotrigin, okskarbazepin, valproat Obat-obat yang meningkatkan transmisi inhibitori GABAergik: agonis reseptor GABA  meningkatkan transmisi inhibitori dg mengaktifkan kerja reseptor GABA  contoh: benzodiazepin, barbiturat menghambat GABA transaminase  konsentrasi GABA meningkat  contoh: Vigabatrin menghambat GABA transporter  memperlama aksi GABA  contoh: Tiagabin meningkatkan konsentrasi GABA pada cairan cerebrospinal pasien  mungkin dg menstimulasi pelepasan GABA dari non-vesikular pool  contoh: Gabapentin Neurology Department Hasanuddin University Muhammad Akbar

Factors That Affect the Choice of Drug Seizure type/ Epilepsy syndrome Side effects & safety Patient age Ease of Use Lifestyle Age, Sex, Childbearing potential Other medications Since drug therapy is usually the first treatment used, let’s start by talking about it. Different types of seizures and epilepsy syndromes have unique features, which may affect the choice of medication, since some drugs are more effective against specific seizures and syndromes. Achieving good control of seizures with drug treatment generally depends on choosing the right drug, minimizing the number of drugs prescribed, and educating the patient and family to encourage daily use as prescribed. Other factors that can affect the choice of drug include potential side effects, the dosing regimen -- whether it is simple or difficult to follow -- the age of the patient, childbearing potential, use of other medications, lifestyle, and, in some cases, cost. Whenever possible, using one drug is preferred. This drug may be prescribed in increasing doses until seizures are controlled or a side effect occurs. If the drug is not effective, or if side effects are hard to live with, this drug will probably be gradually stopped while another one is slowly introduced. Question: How many of you had to try more than one drug before finding one that effectively reduced your seizures? What was the most common reason for changing the medication? Neurology Department Hasanuddin University Muhammad Akbar 67

ANTIEPILEPTIC DRUG DEVELOPMENT Retigabine ? Rufinamide Lacosamide Brivaracetam 20 Pregabalin Zonisamide Levetiracetam Oxcarbazepine Tiagabine 15 Fosphenytoin Topiramate Lamotrigine Gabapentin Number of Licensed Antiepileptic Drugs 10 Felbamate Sodium Valproate Carbamazepine Ethosuximide Benzodiazepines 5 Phenytoin Primidone Phenobarbital Bromide 1840 1860 1880 1900 1920 1940 1960 1980 2000 Calendar Year

SINCE 1998 Pregabalin Zonisamide Levetiracetam Oxcarbazepine Tiagabine 20 Pregabalin 10 Zonisamide Levetiracetam Number of Licensed Antiepileptic Drugs Oxcarbazepine Tiagabine Topiramate Fosphenytoin 5 Lamotrigine Gabapentin Felbamate 1990 2000 Calendar Year

Antiepileptics - indications Often used antiepileptics with broad indication spectrum (with exception of absences): Carbamazepine, valproate, lamotrigine, phenytoin Partial seizures Carbamazepine, phenytoin, valproate, lamotrigine Alternatives: gabapentin, topiramate, tiagabine Tonic-clonic (grand mal) phenytoin, carbamazepine, valproate Alternatives: lamotrigine, topiramate, phenobarbital (primidone) Absence (petit mal) Ethosuximide Valproate – especially in the case that tonic-clonic seizures are also present Alternatives: lamotrigine Myoclonic clonazepam, valproate Neurology Department Hasanuddin University Muhammad Akbar

TYPE OF SEIZURES AND EPILEPTIC SYNDROME FIRST-LINE DRUG SECOND-LINE DRUG Primary generalized Absence seizures * Myoclonic seizures * Tonic-clonic seizures Absence (Childhood) Absence (adolescence) Juvenile myoclonic epilepsy Infantil spasms (West’s syndrome) Lennox-gastaut syndr. Partial Simple partial seizures, Complex partial seizures SGTC, and partial epileptic syndrome Ethosuximide, valproic acid Valproic acid  Valproic acid , carbamazepine, phenytoin Ethozuximide Corticotropin  Valproic acid , lamotrigine Carbamazepine, phenytoin Lamotrigine Acetazolamide, clonazepam, lamotrigine primidone Lamotrigine, phenobarbital,primidone Ethozuximide, clonazepam, Primidone, lamotrigine Clonazepam, Valproic acid  Carbamazepine  Gabapentin, lamotrigine, phenobarbital, primidone, tiagabine, topiramate, Valproic acid  * Carbamazepine and phenytoin contraindicated  Divalproex sodium may be better tolerated than valproic acid  Vigabatrin may be an alternative first-line drug where available  Clonazepam, felbamate, phenobarbital, primidone, or vigabatrin may be used alternatively  Methsuximide may be used alternatively for any of the partial seizures or partial epilepsy syndrome.

Kejang Umum (generalized seizures) Pemilihan obat : Tergantung pada jenis epilepsinya Kejang parsial Kejang Umum (generalized seizures) Tonic-clonic Abscense Myoclonic, atonic Drug of choice Karbamazepin Fenitoin Valproat Etosuksimid Alternatives Lamotrigin Gabapentin Topiramat Tiagabin Primidon Fenobarbital Clonazepam Klonazepam Felbamat Neurology Department Hasanuddin University Muhammad Akbar

Penghentian OAE Penghentian OAE didiskusikan dgn penyandang epilepsi dan keluarganya setelah bebas bangkitan minimal 2 tahun Gambaran EEG normal Harus dilakukan bertahap, umumnya 25% dari dosis semula, setiap bulan dalam jangka waktu 3-6 bulan Bila digunakan lebih dari 1 OAE, maka penghentian dimulai dari 1 OAE yang bukan utama.

Ketogenic Diet Based on finding that starvation -- which burns fat for energy -- has an antiepileptic effect Used primarily to treat severe childhood epilepsy, has been effective in some adults & adolescents High fat, low carbohydrate and protein intake Usually started in hospital Requires strong family commitment The ketogenic diet is not a drug; however, it helps the body to make substances that have an antiepileptic effect. The diet is based on the observation that starvation, which burns fat for energy and produces ketones, has an antiepileptic effect. The goal of the diet is to make the body get its energy from fat and become ketotic. The diet is used primarily to treat severe childhood epilepsy. Persons who follow the diet are instructed to eat foods high in fat and low in carbohydrate and protein. Usually, the diet is started in the hospital so that physicians may monitor the progress. The exact reasons why the diet works remain unclear. Medical studies suggest that about one-third of patients are substantially helped, another third have some reduction in seizure, and one third have no change. Children may be kept on the diet for months or years. There are side effects, but not all children experience them. Like antiepileptic drugs, the ketogenic diet should be tapered rather than stopping abruptly. A great deal of care must be taken when the diet is used in children taking medications, since these may contain sugar to make them more palatable to the child. Parent and family education and a strong family commitment to the diet, plus administration by a doctor and dietician trained in its use, are generally considered vital to success. People with epilepsy should not fast in the hope that it will help their seizure; in fact, fasting may trigger seizures. The keto diet is serious medicine, with its own set of side effects, and should never be tried without medical advice.

Neurology Department Hasanuddin University Muhammad Akbar

Atas segala perhatiannya, Semoga bermanfaat You never know how high you can fly, unless you spread your wings! Terima Kasih Atas segala perhatiannya, Semoga bermanfaat Neurology Department Hasanuddin University Muhammad Akbar