REFERAT MIGREN

PEMBIMBING : dr.H. Awaludin Noor Sp.S

Oleh: Aga Haris S.Ked

LATAR BELAKANG :

NYERI KEPALA

90% penddk nyeri kepala/ th9 dari 10 org/th 1 kali

• mengganggu aktivitas, produktiv.• menghentikan keg.sehari-hari• dampak sosial-ekonomi

MIGRENPrevalensi tidak banyak, namun merugikan (AS, 13jt dolar)

Tidak terdiagnosis, terapi kurang baik

Pemahaman patof, teori blm jelasVaskuler

Neurovaskuler

Sistem trigeminovaskuler CGRP

Peny.neurologi yg kompleks

MASALAH

MIGREN : - Morbiditas sedikit dampak merugikan:

- aktivitas terganggu - pe produktivitas pekerjaan/ sekolah (dampak sos-ek)- tdk terdx/ tx :

- kurang dlm pemahaman patofisiologi- penyebab blm pasti- jrg yg periksa ke dokter

- teori neurovaskuler:- sistem trigeminovaskuler pelepasan- neuropeptida (CGRP)nyeri kepala migren?

PEMBAHASAN :1.SEJARAH PERKEMBANGAN TEORI MIGREN:

Eber Papyrus (1200 SM) supranatural

•Hipocrates (400 SM) sesuatu dari perutmenjalar ke kepala aura•Gallen : hemikrania

Thomas Willis (1664) : migren ok dilatasi pemb.darah

(I kali teori vasc.diajukan) tdp beberapa kelemahan

Edward Liveing (1873) : migren ok gangg.saraf di talamus (neurogenik)

Moebius (1898): disfungsi otak & PD.

DEFINISI :

MIGREN : • Konsep klasik : gg. Fungs. otak dg manifest.nyeri kepala unilateral, b’denyut, mendadak disertai mual atau muntah (Marquardt et al.,2000).

• Lance (1998) : NK episodik, disertai mual, fotofobia, mgkn didahului aura cit Harsono,1999

• Djoenaedi W (‘93): NK b’ulang, b’denyut, unilat, 2-72 jam, bebas nyeri ant. serangan dg gg.keprib,GIT, aura (Basjiruddin, 2004).

• Rapoport et al.,(2004) dokter umum : “Migren: NK, intensitas sedang-berat, pola stabil, hilang timbul, kemampuan, normal 48 jam, perburukan (-), Sampai ada bukti bahwa itu bukan migren”

• The Research group on Migraine and Headache of the World Federation of Neurology: “familial, serangan berulang, intensitas, frek,lama bervariasi. NK unilateral, disertai anoreksia, mual, muntah, bbrp diawali gejala neurologik, gangguan mood” (Evan & Mathew, 1999)

KRITERIA DIAGNOSTIK:

Gambaranklinik

•Fase prodromal/ premonitori•F. serangan utama: aura & nyeri kepala•F. postdromal

Klasifikasi formal

ICHD th 2004:1. MWO paling sering dijumpai2. MWA3. Childhood periodic syndromes that are commonly precursors of migraine

4. Retinal migraine 5. Complications of migraine 6. Probable migraine

Gambaran klinik:

Fase karakteristik Gejala/ bukti penelitianProdromal •Trigger

•60% pend.migren•Bbrp jam-hari

25%:•Sensitif (mdh marah)•Euforia, ngantuk, depresi,lapar, haus

Aura •30% pend.migren•5-20mnt (b’akhir 60’)•Visual (V), sensorik (S), mtrk (M), g.btg otak, gg.bicara/afasia (A)

Thomsen (Denmark):

1881 sampel,72% ♀; 28%♂ :•VSMA : 70% pasien•VS : 17% ; SMA : 7%•SM : 4%; AM : 1%; VMA : 1%

Nilai median memberatnya g/ aura:•V 10’(1-180’); S 15’(1-720’); M 15’(1-720’); Nilai median lamanya aura:•V 45’ (1-1440’) ; S 90’ (10-2880’)•M 120’ (10-4320’); A 60’ (5-1440’)

Nyeri kepala •Onset unilat, b’denyut, Sedang – Berat, aktiv. m’brt •4-72 j,Frek : 1-3 x/bln

postdromal •Lelah, iritabel, gg.mood, gg.konsentr, NT klt kpl.

Migren dengan aura Migren tanpa aura

A. Min.2 serangan yang sesuai kriteria B

B. Min.3 dari 4 kriteris dibawah ini:

1. Satu/ lebih gjl aura yg reversibel, mengarah ada kel.dikorteks serebri dan/ disf.otak

2. Plg t’ tdp 1 gjl aura yg makin m’brt dlm 4 mnt, atau 2/ lbh gjl yg tjd b’samaan

3. Aura < 60 menit

4. NK tjd dlm wkt 60 mnt sth aura berakhir

C. min.1 dari kriteria berikut:

1. Ggn.NK sekunder (-), pd: p.neuro,fsk, r.peny.

2. Pem.neuro, fsk, r.peny.mengarah NK sekunder, tp disimgkirkan oleh pem.yg teliti

3. NK sekunder (+), tapi serangan migren yg pertama kali tdk bersamaan dengan timbulnya gangg.tersebut.

A. Min. 5 serangan yg memenuhi kriteria B-D

B. NK 4-72 jam (tidak membaik dengan tx)

C. Karakter.NK plg tdk memenuhi 2 dibwh:

1. Lokasi unilateral

2. Nyeri berdenyut

3. Intensitas sedang-brt (sedang: mengganggu aktiv.sehari-hari; berat: tdk dpt melaks.keg)

4. Memberat bl jalan naik tangga/ aktiv.fisik

D. Selama NK min.disertai:

1. Mual dan atau muntah

2. Fotofobi dan fonofobi

E. Min.1 dari kriteria berikut:

1. Ggn.NK sekunder (-),pd: p.neuro,fsk,r.peny.

2. Pem.neuro, fsk, r.peny.mengarah NK sekunder, tp disimgkirkan oleh pem.yg teliti

3. NK sekunder (+), tapi serangan migren yg pertama kali tdk bersamaan dengan timbulnya gangg.tersebut.

Klasifikasi Formal (ICHD 2004): Olesen et al., 2003)

PREVALENSI KARAKTERISTIK NYERI KEPALA MIGREN MENURUT IHS

Migren tanpa aura Migren dengan aura

Laki-laki (%) Wanita (%) Laki-laki (%) Wanita (%) N=197 N=145 N=92 N=64

Lokasi unilateral

Memberat pada- aktivitas fisik

Nausea

Vomiting

Fotofobia

Fonofobia

48,2 64,3 55,4 64,1

98,0 95,8 87,0 80,0

85,8 88,9 70,7 81,5

41,6 49,3 37,0 44,6

92,4 92,4 82,6 90,8

78,7 85,4 64,1 78,5

Sumber : Lipton et al., (2000)

TRIGGERS / PENCETUS MIGREN :

Bukti kuat pencetus migren

Diduga pencetus migren

• Stres• menstruasi• caffeine withdrawal• rangsang visual• perubahan cuaca

• nitrat• perut kosong• gangguan tidur• alkohol• monosodium glutamat

Sinclair, 1999; Lipton, 2000

PATOFISIOLOGI MIGREN :

A. FASE TRIGGER

Landy, 2003

B. FASE AURA:

CSD rCBF oligemia iskemik disfungsi neuronal aura

Olesen, 1991

DeVries et al., 1999

C. FASE NYERI KEPALA :

Lanjutan…

MercMedicus Modules, 2001

CALCITONIN GENE-RELATED PEPTIDE (CGRP) :

• Kelomp.kalsit (5): kalsitonin, amilin,CGRP( dan ), adrenomedulin• neuropeptida 37-asam amino hsl pengolahan/ penyambungan alternatif mRNA• di kromosom 11• tdp 2 btk CGRP :

: di sistem saraf sensorik : di sistem saraf enterik

• pertama kali ditemukan th 1983 (pd tikus)• merupakan vasodilator poten.

1.Definisi dan karakteristik :

2. Molekuler genetik :CGRP…

Ma, 2004

CGRP… 3. Struktur CGRP dan hub. aktivitas

• N-terminal loop (disulphide) memicu transduksi sinyal dan aktivitas reseptor• Struktur -helix interaksi molekul dg reseptor.• Residu 19-27 daerah pengatur perlekatan dg reseptornya• C-terminal memastikan interaksi yg sesuai dg reseptornya.

(Conner et al.,2002; Ma, 2004)

(Dikutip dari: Nimmagadda & Ghatta, 2004).

CGRP…

4. DISTRIBUSI :

• SUSUNAN SARAF PERIFER:- Sel kornu post.ganglia sensorik- srg berhub.dg P.D. otot polos ( GIT, gld.parotis, sel endokrin duod, ileum, gangl.mienterik, paru, gld.tiroid, sinusoid dan vena lienalis, kulit manusia, kelj.pituitari.

• KARDIOVASKULER:- Arteri > vena- Arteri: disambungan ant.T.adventisia dan T.media- atrium > ventrikel- otot jantung

RESEPTOR CGRP….

1. Klasifikasi :• CGRP1 dan CGRP2

2. struktur reseptor• CRLR• RAMP(1,2,3)RCP: as.amino 148 +Prot.G

Transduksi sinyal

Department of Neurobiology & AnatomyIan Dickerson's Lab

RESEPTOR CGRP…..

3. DISTRIBUSI DAN IKATAN ;

• Afinitas tertinggi : serebelum dan medula spinalis• diserebelum :

- lap. Molekuler : CGRP densitas tinggi- lap. Purkinje : sedang- lap. Granuler : CGRP (-).

•Afinitas sedang- tinggi : korteks piriformis insula•Af rendah-sedang : area preoptik medial.•Di gangl.radiks dorsalis dan neuron lain CGRP bergab. dg reseptor lain sbg: Neurotransmiter dan neuromodulator

RESEPTOR CGRP….

4. MEKANISME TRANSDUKSI SINYAL :

Wimalawansa, 1996

Fungsi Fisiologis CGRP :

SISTEM SARAF SISTEM PULMO

• tersebar merata di jar. otak:

sistem motorik & sensorik

• informasi auditorius

•Sist.trigeminovaskuler: letak resept=letak respt 5-HT

•Degranulasi sel mast

•Vasodilatasi A-V pulmo,ok resept.tdp di endotel P.D pulmo-CGRP relaks. A.pulmo dilat.a.pulmo

Sistem kardiovaskuler Fungsi lain

•Kontrol tonus P.D perifer

•Vasorelaksasi kuat

•me kontraksi denyut jtg

•>> di jar perivask: dilat.mesenterium, ginjal, ot.skelet jlr endotel dependen/ indep

•Efek inotropik/ kronotopik positif

•Sekresi hormon pertumb.

•Hipertermia

•Aktivitas motorik

•Respon nosiseptik

•Memodulasi Ach

•Tulang: hipokals, prolif.osteoklas,

hbt resorpsi tlg intak

•mepermeab.mikrovask: hiperemia inflam, akumul. netrof, edema lokal

•Inflam neurogenik: kebocoran vaskuler

PERAN cgrp PADA NYERI KEPALA MIGREN:

CGRP :• di prod.di ganglion saraf trigeminal•dilepas, sth terjadi aktivasi saraf•vasodilator poten P.D.serebral dan dural punya peran ptg dlm pengaturan aliran drh ke otak dan meningen.•P.D meningen vasodilat; sel mast :degranulasi inflam. steril •nilai Normal : 2-35 pmol/L

A. CGRP dan MIGREN :

Wimalawansa, 1996; Durham, 2004

TRIGGER / Pencetus

rCBF <23ml ml

CSD

vol.darah tiap denyut jtg

Oligemia

Impuls nosiseptik

Aktivasi btg otak/ migren generator

Nukl. saraf trigeminalyg lebih tinggi

iskemik

korteks

pulsasi P.D

talamus

rCBF

Aura (-)

Disfungsi neuronal (+)

Aktivasi saraf trigeminal

NK migren

Refleks vasodilatasi P.D.& anast.A-V

rCBF >23ml ml

Disfungsi neuronal (-)

Aura (+)

Degranulasi

Sel mast

Pemb. Darah intraserebral

p.darah

meningen

Pelepasan neuropeptida(CGRP)

Vasodilat.

Vasodilatasi Vol.darah ,Pengaliran

cepat

Inflamasisteril

Hipo-talamus

Nausea,vomiting

CTZ

Foto/fonofobia

Dikutip dari:• Olesen, 1991• Goadsby et al., 2002• Villalon et al., 2002• Durham, 2004

B. Penatalaksanaan farmakologis berdasarkan peran CGRP pada migren:

Inhibisi pelepasan CGRP Antagonis reseptor CGRP

Gol. Triptan:(1) vasokonstriksi P.D arteri kranial

dan anastomosis arteri-vena yang mengalami dilatasi melalui stimulasi reseptor 5-HT 1B (Villalon et

al., 2002)

(2) inhibisi pelepasan CGRP dan transmisi nosiseptif pada saraf sensorik trigeminal sentral dan perifer melalui reseptor 5-HT 1B/1D

(Bigal et al., 2002; Goadsby et al., 2002; Swidan, 2002; Tepper et al., 2002).

BIBN4096BS:

1. Menghbt inflamasi neurogenik

2. Menurunkan blood flow di P.D serebral

3. Menghambat transmisi nyeri

(Durham, 2004).

TARGET

OBAT

RINGKASAN

MIGREN

•Morbiditas rendah•Dampak nyeri: - kualitas hdp - produktivitas kerja/ sklh

Teori terbaru neurovaskuler sistem trigeminovaskuler pelepasan CGRP ke reseptor vasodilatasi, inflamasi neurogenik nyeri kepala migren

•Klinis; sulit dx•Pemahaman patof << penanganan krg

BIBN4096BS iv sbg antagonis reseptor CGRP efektif mengurangi NK migren, sbg obat alternatif gol.triptan

PREVALENSI MIGREN:

AstraZeneca Medicines (2005)

what do you do when you are in pain? You stop using that limb, which leads to decreased mobility and reduces your functional status. As you start to not do the things you used to do, there can be a loss of self-esteem and self-efficacy. You start to limit yourself, and this vicious cycle goes on and on. Another way that I like to try and describe it to clinicians is this: as an infant, you are born as this groping little thing trying to find your feet, putting everything into yourmouth, getting sensory awareness. You then grow up as a member of a family; you get integrated into that family; you learn that you are not the only entity that exists. You develop into a mature adult and hopefully you become a viable, contributing member of your community and society. (Brennan, 2002)

Four Headache Questions that can help Diagnose Migraine1. Do you have headaches that interfere with work, social, or family functions?

chronic, periodic, disabling headaches should be considered as migraine.2. Has your headache pattern been stable over the past six months?

any headache pattern that changes over a six-month interval should be investigated as a possible secondary headache disorder.

3. How frequently do you experience headaches?an increase in the frequency, intensity, and duration of headaches may indicate transformed migraine. Patients who at one time experienced an intermittent disabling headache and now suffer from near-daily headaches may be overusing symptomatic medications. The primary medical focus for these individuals should be headache prevention and avoidance of medication overuse.

4. How effective is your current headache treatment?patients who successfully treat their headaches are rarely seen by physicians.Those who treat their headaches with symptomatic medication more than twiceweekly may note that over time their analgesics become less effective. Headacheeducation, lifestyle changes, and preventive medications are necessary to alleviatethese headaches and restore normal daily function.

Unger et al, Emerg Med, 2003

Unger et al., 2003

Unger et al., 2003

The Calssification of Headache :

Characteristics of three common types of headaches

Wagner, 2005

Secondary Headache Disorders :

PATOGENESIS TENSION TYPE HEADACHE:

Schachter, 2004

From Headache, The Newsletter of ACHE. Spring 2002,

Studies of Migraine Trigger Factors

Menstrual migraine:• terjadi 3 hr I fase mens estrogen + progesteronHow so many different migraine triggers can produce such similar disabling headaches? • A migraine trigger is any factor that can lead to the development of a migraine headache. How a specific trigger brings on a head- ache is becoming more clear, thanks to recent scientific studies on the subject. One leading theory suggests that migraine occurs because of an inherited hyperactivity of the nervous system. Individuals with migraine are genetically programmed to be more vulnerable to irritating stimuli such as flickering lights or sudden changes in weather. When one, two, or several of these irritating stimuli occur, their hyperactive nervous systems respond with a full-blown migraine attack.

Philip Bain, Wilkinson Medical Clinic

Diamond, www.Medscape.com

Diamond, www.Medscape.com

“Falling Estrogen Theory”“Serotonin Theory”

SerotoninEstrogen

Trigeminal

Neuron CGRP

-

+

HO

CH3OH

“Falling Estrogen Theory”“Serotonin Theory”

Serotonin Menstruation

Estrogen Serotonin

Trigeminal

Neuron CGRP, SP Vasodilation

Pain & Inflammation

HO

CH3OH

One explanation for the onset of migraine when estrogen levels drop is that estrogen influences the serotonin receptors, which is believed to be an important part in headache pain. Other factors that may play a role in the development of menstrual migraine include:

1.the relative proportions of estrogen and progesterone; 2.dysfunction of platelets, a compenent of the blood which contains serotonin; 3.decreased levels of brain magnesium (which increases brain excitability); 4.decreased natural brain endorphines; and 5.increased secretion of prostaglandins (substances that sensitize pain receptors and cause inflammation around the cerebral blood vessels).

SENSORY

PATHWAYS

the trigeminal nucleus caudalis are the key relay neurons for nociceptive input in head and neck.

There is correlation between input from the trigeminal system and the cervical routes. So there are neurons in this complex that receive convergent input from the trigeminal cutaneous fibers, from the supratentorial dura,

from the posterior routes in the deep musculature, or from the cutaneous dermatome served by the greater occipital nerve. It's sensitization of these neurons that have received convergent input

that may result in the clinical syndromes of spread

Referred pain and perhaps hypersensitivity, central sensitization, and allodynia.

Goadsby et al., 2002

www.medscape.com

Trigeminal nerve activity during migraine and with the addition of a serotonin agonist. During a migraine, the trigeminal nerve releases CGRP, substance P, and neurokinin A, which are vasodilators. The addition of a serotonin agonist inhibits the release of these neuropeptides,

inhibiting vasodilation and migraine pain.

Trigeminal innervation of cranial structures. The ophthalmic division of the trigeminal nerve innervates meningeal, cerebral, and cranial vessels. It is the ophthalmic nerve that is thought to be responsible for the pain associated with migraines. The superior sagittal sinus runs between the meninges and is the primary vein draining the cranial vasculature

Algorithm for the symptomatic and prophylactic treatment of migraine headache

(adapted from Capobianco13).

Rami Burstein uses a brush to check skin sensitivity.

www.ncbi.nlm.nih.gov/genemap

DNA to protein

http://cellbio.utmb.edu/cellbio/ribosome.htm

Poly A site choice and alternative splicing produce either Calcitonin or CGRP (Calcitonin Gene Related Peptide) (hormones) in the calcitonin gene transcript from rats depending on

tissue type:

Amino acid sequences of human and -CGRP

Endocrine Reviews; 1996

Endocrine Reviews; 1996

Endocrine Reviews; 1996

PENATALAKSANAAN MIGREN:

Terapi abortif Terapi preventif

menghilangkan nyeri kepala serta gejala-gejala yang menyertai ketika serangan migren sedang berlangsung

(1) mengurangi frekuensi, durasi, dan intensitas serangan;

(2) memperbaiki reaksi terhadap pengobatan akut;

(3) memperbaiki fungsi dan mengurangi disabilitas.

Silberstein, 2000; American Academy of Neurology

Obat Mekanisme kerja - asetaminofen

 

- aspirin

-Ergot (ergotamine tartrate, dihydroergotamine)

-Opioid

-triptans (sumatriptan, rizatriptan, zolmitriptan)

 

-steroid

- beta bloker (propanolol, timolol)

 

-Ca channel antagonis (nimodipin, flunarisin)

-Antikonvulsan :

- Asam divalproat

 

  - Gabapentin

- Inhibisi sintesa prostaglandin di CNS, inhibisi aktifitas nosiseptif via reseptor 5HT

-    Inhibisi sintesa prostaglandin

-  Selektif arterial konstriktor yang kuat dan mempunyai daya ikat yang kuat pd otot dinding arteri

-    Stimulasi reseptor opioid endogen

-  Berikatan dengan reseptor 5HT1B, 5HT 1D, 5HT 1F, menginhibisi

neuronal dengan cara blokade sensoris pada n. trigeminal, blokade pelepasan vasoaktif peptide dan juga proses inflamasi neurovaskuler di dura maupun meningen.

-    Anti inflamasi-Inhibisi pelepasan NE dg cara blokade prejunctional beta bloker reseptor, efek agonis pada 5HT1 reseptor, efek antagonis pada 5HT2

- Mempengaruhi Ca influks dalam mencegah vasokonstriksi dan pelepasan SP

-  Menambah kadar GABA di sinap, menghambat enzin GABA di otak, menambah konduktansi kalium yang memberi hiperpolarisasi neuronal, menghentikan letupan dari neuron 5HT dari nukleus raphe dorsalis.

- Merubah aktivitas glutamic acid decarboxylase sehingga mampu meningkatkan GABA, menghambat pelepasan monoamin neurotransmiter (termasuk noradrenalin, dopamin dan serotonin)

Silberstein, 2001;Headache Council Philippne Neurological Association, 2000

Wagner, 2005

British Journal of Pharmacology (2000) 129, 420-423

(Olesen et al., 2004)

(Olesen et al., 2004)

(Olesen et al., 2004)

(Olesen et al., 2004)

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Silberstein, 2000; American Academy of Neurology

Goadsby et al., 2002

Indications for Hospitalization When outpatient treatment has been unsuccessful, hospitalization may be necessary for:

•Severe dehydration, for which inpatient parenteral therapy may be necessary •Diagnostic suspicion (confirmed by appropriate diagnostic testing) of organic etiology, such as:

1.infectious disorder involving the CNS (ie, brain abscess or meningitis) 2.acute vascular compromise (ie, aneurysm, subarachnoid hemorrhage) 3.structural disorder with accompanying symptoms (ie, brain tumor)

1.Prolonged, unrelenting headache with associated symptoms, such as nausea and vomiting, which, if allowed to continue, would pose a further threat to the patient's welfare 2.Status migraine, or dependence on analgesics, ergots, opiates, barbiturates, or tranquilizers 3.Pain that is accompanied by serious adverse reactions or complications from therapy continued use of such therapy aggravates or induces further illness 4.Pain that occurs in the presence of significant medical disease -- but appropriate treatment of headache symptoms aggravates or induces further illness 5.Failed outpatient detoxification, for which inpatient pain and psychiatric management may be necessary 6.Intractable and chronic cluster headache, for which inpatient administration of histamine or dihydroergotamine may be necessary 7.Treatment requiring co-pharmacy with drugs that may cause a drug interaction, thus necessitating careful observation (monoamine oxidase inhibitors and ß-blockers)

Drug Benefit Trends, 1999

Jenis migren karakteristik

Typical aura with migraine headache

Migren dg aura spt tanda-tanda:

-aura visual : (+):chy kilat, berkedip, bintik2/ garis2. (-) : gelap

-aura sensorik: (+) : spt ditusuk jarum, (-): parestesi

Gradual > 5 mnt; < 1 jam, reversibel; diikuti NK yg memenuhi kriteria migren WO aura

Typical aura with non-migraine headache

diikuti NK yg tidak memenuhi kriteria migren WO aura

Familial hemiplegic migraine (FHM)

-bersifat autosomal, dominan

-Sergn.di t/ oleh NK jns migren dg foto/ fonopobia, N,V

-Didahului/ disertai hemiparesis bbrp mnt-mgg, membaik tanpa g/ sisa.

-Tjd sergn.awal masa kanak-kanak, atau < 30 th

-20% keluarga dg FHM

Cyclical vomiting N,V, episodik, berulang, pucat, lethargi

Abdominal migraine Nyeri di tengah abdomen, episodik, berulang, selama 1-72 jam, diikuti N,V, dg masa diantara serangan pasien dlm kead. Normal

Benign paroxysmal vertigo of childhood

Sergn. Vertigo tiba2 saat interval anak sehat

Multipel, tiba2, gangg.keseimb(+), nistagmus, muntah, Pem.Neuro(N), EEG (N)

Chronic migraine NK migren t/ aura selama 15 hr/> per-bulan; selama 3 bln/ > tanpa ada tanda-tanda overdosis obat

Persistent aura without infarction

Gejala aura menetao selama > 1 minggu, tanpa ada kelainan infark pada rontgen

Migrainous infarction Gjl aura 1 atau lebih sehubungan dg lesi iskemik otak sesuai dg teritori daerahnya pd pem. Imaging

Migraine-triggered seizure

Timbulnya kejang yg dipicu oleh adanya aura migren

Probable migraine Serangan migren yg disertai/ tdk NK dimn tdk adanya salah satu gjl, shg tdk memenuhi kriteria migren yg sebenarnya; baik migren dg/ tanpa aura

Kaplan et.al., 1997

Kaplan et.al., 1997

Kaplan et.al .,1997

Serotonin ReceptorsClassClass LocalizationLocalization Synaptic ActionSynaptic Action Signalling Signalling

MechanismMechanism5-HT1A Raphe nuclei

Hippocampus

Inhibition (↑ K+) ↓ cAMP

Direct K+ open

5-HT1B Cranial Blood Vessels

Cerebral vasoconstriction ↓ cAMP

5-HT1D Cranial Blood Vessels

Autoreceptor-mediated ↓ 5-HT release

↓ cAMP

5-HT1E/F Cortex

Striatum

↓ cAMP

5-HT2A Platelets

Smooth Muscle

Cerebral Cortex

Platelet aggregation

Contraction

Excitation (↓ K+)

IP3 production