Presentasi Kasus Stroke Final

Presentasi KasusPresentasi Kasus

Diajukan oleh : dr. Noegroho HarbaniDiajukan oleh : dr. Noegroho Harbani

Moderator : dr. RM. Hermanu Poespaningrat, SpSModerator : dr. RM. Hermanu Poespaningrat, SpS

Penilai : Prof. DR. dr. Hj. Sri Sutarni , SpS (K)Penilai : Prof. DR. dr. Hj. Sri Sutarni , SpS (K)

dr. Lukman Hakim , SpS dr. Lukman Hakim , SpS

Klaten, 29 April 2009Klaten, 29 April 2009

Identitas

Nama : Tn. S

Pekerjaan : Pensiunan PNS

Umur : 67 tahun

Agama : Islam

MR : 605709

Alamat : Balanharjo, Glagah Wangi, Klaten

Pendidikan : D3

Masuk RS : 31 Maret 2009

ANAMNESIS

Allo anamnesis : diperoleh dari penderita dan istri penderita

(2 April 2009)

Keluhan utama :

Kelemahan anggota gerak kiri

Riwayat Penyakit Sekarang

Lebih kurang 2 Jam SMRS mendadak mengeluh anggota gerak kiri terasa lemah dan berat untuk digerakkan.

Untuk jalan terjatuh, disertai nyeri kepala, bicara pelo, mulut perot dan nyeri kepala .

Riwayat Penyakit Sekarang ( lanj..)

Kelemahan antara tangan dan kaki terjadi bersamaan dengan tingkat kelemahan sama

Selama sakit penderita tidak demam, pandangan kabur, pusing berputar, gangguan menelan, kejang, penurunan kesadaran, kesemutan dan gangguan BAB & BAK

ANAMNESIS

Riwayat Penyakit Dahulu

Riwayat hipertensi sejak tahun 1995 tidak terkontrol

Riwayat merokok (-)

Riwayat kencing manis (-)

Riwayat sakit jantung (-)

Riwayat trauma kepala (-)

Riwayat tumor (-)

Riwayat stroke atau sakit serupa (-)

ANAMNESIS (Lanj.)Riwayat Penyakit Keluarga

Tidak ada keluarga yang menderita sakit serupa

Evaluasi sistem

Sistem serebrospinal : kelemahan anggota gerak kiri, pelo, perot, nyeri kepala bersifat akut

Sistem kardiovaskuler : normal

Sistem Respirasi : normal

Sistem gastrointestinal : normal

Sistem muskuloskeletal : normal

Sistem intugumentum : normal

Sistem urogenital : normal

Resume anamnesis

Laki- laki usia 67 tahun, datang dengan keluhan sejak 2 jam sebelum masuk rumah sakit kelemahan anggota gerak kiri, nyeri kepala, pelo, perot. Tidak ada demam, penurunan kesadaran dan kejang. Tidak ada riwayat trauma, tumor, gangguan penglihatan, sakit gigi, dan infeksi telinga. Riwayat hipertensi sejak 1995 tidak terkontrol.

Diagnosis Sementara

Diagnosis klinis : kelemahan anggota gerak kiri, bicara pelo, dan perot disertai nyeri kepala yang bersifat akut.Diagnosis topik :intraserebral hemisperium dextra, subkortikalDiagnosis etiologi :

1. Stroke hemoragik2. Stroke non hemoragik

Pemeriksaan umum

Keadaan umum : sedang,gizi sedang, compos mentisTanda vital : TD 160/100 mmHg, N : 76x/mnt, RR : 20 x/mnt, t : 36,5 oCStatus internus :Jantung : murmur (-), S1, S2 normal Paru : sonor, vesikular, ronkhi (-)Lever : normalLien : tak terabaStatus psikiatrik : kooperatif, normoaktif, orientasi orang, waktu dan tempat baik

Status neurologis

Kesadaran : compos mentis, GCS 4/5/6kepala : mesocephalMata : pupil isokor, diameter 3 mm, reflek

cahaya +/+, reflek kornea +/+ Leher : kaku kuduk (-), meningeal sign (-)Nervi kraniales : parese NVII dan XII sinistra UMN, Badan : collum vertebra normal, nyeri tekan (-),

refleks dinding perut +/+Sensibilitas : propioseptif : normal

protopatic : normal

Koordinasi dan keseimbangan : sulit dinilai

Fungsi vegetatif : dalam batas normal

Skala Stroke Gadjah Mada : 29

Mini Mental State Examination : 27

Clock Draw Test : 3

Status neurologis

Ekstremitas

B T 555 333 N N

G K Tn

B T 555 333 N N

E E N - +

Tr Rf Rp

E E N - +

Clonus -/-

Status neurologis

Pemeriksaan penunjangLaboratorium (31 - 03 - 2009)

Hb: 11,3AL: 11,7 AT: 260.000 AE: 4,63 Hmt: 35,6 Mono: 5,6 Limf: 1,41 Seg: 7,46 Eos: 0.46GDR : 117 Tot.prot:7,5 Alb:4,46 BUN:18 Creat: 1,2 AST: 16 ALT :27 Na : 142,9 K : 3,08 Cl : 108,6

Laboratorium (11 - 12 - 2008)

Chol: 179TG: 62 HDL: 35,3LDL: 133 Urat: 5,5PTT: 12,4 APTT: 24,8 INR: 0,96

EKG (31 Maret 2009)

Kesan : Normal sinus rhytm (HR:75x/menit)

Pemeriksaan penunjang

Head CT Scan (31 Maret 2009)

Tampak lesi hiperdens di talamus dekstra dan di capsula interna dekstra

Kesan: Intra serebral hemoragi di talamus dan kapsula interna dekstra

Pemeriksaan penunjang

Diagnosis akhir

Diagnosis klinis : hemiparese sinistra cum parese N VII et XII sinistra UMN.

Diagnosis topik : Talamus dan kapsula interna dekstra sesuai dengan vaskularisasi arteri lentrikulostriata cabang arteri serebri media.

Diagnosis etiologis : intraserebral hemoragik

Penatalaksanaan

Umum Airway ,breathing and circulation maintenanceO2 3- L/mntIVFD Ringer asetat 16 tetes/mntCateterFarmakoterapi Anti edema : Manitol 20% 4x125cc inj, tapering offNeuroprotektan : Piracetam inj 3 gr / 6 jam

Citicoline inj 250 mg / 12 jam

Antibiotik : Ceftriaxon 1gr / 12 jam

Prognosis

Death : baik

Disesase : dubia ad bonam

Discomfort : dubia ad bonam

Disability : dubia ad bonam

Dissatisfaction : dubia ad bonma

Destitution : dubia ad malam

Follow up (03/04/2009)S : nyeri kepala (+), sulit tidurO : KU sedang, kes.CM ,GCS E4V5M6, TD 140/90, N 84 x/menit, afebris, RR 20

x/menit, isokor, RC +/+, RK +/+parese N VII & N XII sinistra UMN

- Ekstremitas : G B T K 555 333 RF + RP - +

B T 555 333 + - +

Tn N N Tr E E Cl -- / - N N E E

Sensibilitas : dbnVegetatif : dbn

Tanggal 3/04/09 6/04/09 7/04/09 8/04/09

Keluhan Nyeri kepala +Sulit tidur

Nyeri kepala - Nyeri kepala - Nyeri kepala -

Keadaan umum

Cukup,CME4M6V5

Cukup,CM E4M6V5

Cukup,CM E4M6V5

lCukup,CM E4M6V5

Tanda vital TD : 140/90N: 84,T:37,4

TD : 130/90N: 88,T:36,2

TD : 130/90N: 88,T:36,6

TD : 130/90N: 84,T:36.5

Nn.craniales

Parese NVII&XIIsin UMN

Parese NVII&XIIsin

UMN

Parese NVII&XIIsin

UMN

Parese NVII&XIIsin

UMN

R.fisiologis Meningkat pd ekstremitas kiri

Meningkat pd ekstremitas

kiri


kiri


kiri

R.patologis Positif pd ekstremitas kiri

Positif pd ekstremitas

kiri


kiri


kiri

clonus - / - - / - - / - - / -

Kekuatan

Follow up

555 333

555 333

555 444

555 444

555 444

555 444

555 444

555 444

Definisi StrokeDefinisi Stroke

Stroke adalah gangguan fungsional otak fokal Stroke adalah gangguan fungsional otak fokal maupun global yang terjadi secara akut, berasal maupun global yang terjadi secara akut, berasal dari gangguan aliran darah otak . Termasuk di dari gangguan aliran darah otak . Termasuk di sini perdarahan subarachnoid, perdarahan sini perdarahan subarachnoid, perdarahan intraserebral dan iskemik atau infark serebri. intraserebral dan iskemik atau infark serebri. Tidak termasuk disini gangguan peredaran Tidak termasuk disini gangguan peredaran darah otak sepintas, tumor otak, infeksi atau darah otak sepintas, tumor otak, infeksi atau stroke sekunder karena trauma (WHO, 1986)stroke sekunder karena trauma (WHO, 1986)

• Stroke penyebab kematian ke-3 di berbagai negara

• Stroke didpt pd semua gol. umur ttp terutama pd usia tua dan meningkat dgn tambahnya umur,

• Stroke adl ggn fungsional otak fokal maupun global akut, > 24 jam akibat ggn ADO

• Dibagi 2 : 1. Perdarahan : insiden 15-30 % (Intrakranial

dan subarakhnoid)2. Iskemik : insiden 70-85 %

ALGORITMA STROKE GADJAH MADA

penderita stroke akut

penurunan kes., nyeri kepala, refleks babinski

1 dari ketiganyaada

3 atau 2 dariketiganya ada

tidak adaketiganya

stroke perdarahan stroke iskemik akut(stroke infark)

penurunan kes. ada, nyeri kepaladan refleks babinski tidak ada

ataunyeri kepala ada, penurunan kes.,

dan refleks babinski tidak ada

refleks babinski ada,penurunan kes. dan

nyeri kepala tidak ada

dengan atau tanpa

Risk Factor for StrokeRisk Factor for Stroke

Non modifiableNon modifiable AgeAge GenderGender RasRas HerediterHerediter

ModifiableModifiable Arterial hypertensionArterial hypertension HypercholesterolemiaHypercholesterolemia Cigarette smokingCigarette smoking Diabetes MellitusDiabetes Mellitus HyperhomocysteinemiaHyperhomocysteinemia Alcohol abuseAlcohol abuse Oral contraceptiveOral contraceptive MenopauseMenopause Physical inactivityPhysical inactivity ObesityObesity Atrial FibrillationAtrial Fibrillation HipercoagulabilityHipercoagulability

Kelemahan anggota gerak sesisiKelemahan anggota gerak sesisi

Pelo / cedalPelo / cedal

Perot Perot

Kesulitan menelanKesulitan menelan

VertigoVertigo

Penurunan kesadaranPenurunan kesadaran

Nyeri kepalaNyeri kepala

Cabang arteria carotis internaCabang arteria carotis interna

Cabang arteria vertebralisCabang arteria vertebralis

Gangguan aliran sirkulasi darah dapat Gangguan aliran sirkulasi darah dapat berupa :berupa :

Trombus Trombus

EmbolusEmbolus

Komplikasi StrokeKomplikasi Stroke

DemensiaDemensia

DepresiDepresi

KecacatanKecacatan

EpilepsiEpilepsi

KontrakturKontraktur

Peptic ulcerPeptic ulcer

BronchopneumoniaBronchopneumonia

DeckubitusDeckubitus

SeptikemiaSeptikemia

Trombosis vena Trombosis vena profundaprofunda

Emboli pulmoEmboli pulmo

Ggn keseimbangan Ggn keseimbangan cairancairan

31

ANATOMI OTAKANATOMI OTAK

Anatomy – Stroke. Anatomy – Stroke.

PART OF BRAIN

CONTROL CENTER OF BRAIN

Functional Areas of the Brain

Back

Mungkin sulit dipercaya bahwa di dalam otak Mungkin sulit dipercaya bahwa di dalam otak tersimpan informasi mengenai segala hal yang tersimpan informasi mengenai segala hal yang

mengatur kelangsungan hidup manusiamengatur kelangsungan hidup manusia

38

Corticospinal TractCorticospinal Tract

39

HomunculusHomunculus

Oleh karena ruptur aneurisma, angioma, lesi aterosklerotik

EpidemilogyEpidemilogy

IncidenceIncidence USAUSA

– ICH represents 10-15 percent of all strokes ICH represents 10-15 percent of all strokes (approximately 70,000 new cases each year)(approximately 70,000 new cases each year)11. .

InternationallyInternationally– Asian countries >> incidence of ICH (30%) Asian countries >> incidence of ICH (30%) 22

It is twice as common as subarachnoid hemorrhage It is twice as common as subarachnoid hemorrhage and carries an equally poor prognosis and carries an equally poor prognosis 33

11 Stroke. 1999; 30: 2523-2528. Stroke. 1999; 30: 2523-2528. 22 Strokr.2003;34:2091-2096Strokr.2003;34:2091-2096

33 J Neurosurg. 1993; 78: 188-191.J Neurosurg. 1993; 78: 188-191.

EpidemiologyEpidemiology

MortalityMortality– At 7 days: >20%At 7 days: >20%– At 1 month: >40%At 1 month: >40%– At 1 year: 53%At 1 year: 53%– Correlated with volume of ICH (>30 cc)Correlated with volume of ICH (>30 cc)

Functionally indipendenceFunctionally indipendence– At 1 month: 10%At 1 month: 10%– At 6 months: 20%At 6 months: 20%

Clev Clin J Med 2005;4:341-344Clev Clin J Med 2005;4:341-344

Primary and SecondaryPrimary and SecondaryCauses of Intracerebral HemorrhageCauses of Intracerebral Hemorrhage

Primary Primary SecondarySecondary

HypertensionHypertension

Amyloid angiopathy Amyloid angiopathy

AneurysmsAneurysms

Arteriovenous Arteriovenous malformations malformations

Neoplasms Neoplasms

Trauma Trauma

Anticoagulation Anticoagulation

Use of thrombolytics Use of thrombolytics

Hemorrhagic conversion of Hemorrhagic conversion of ischemic stroke ischemic stroke

HYPERTENSION

OTHER

AV-MALFORMATION

ANEURYSM

Other causes: bleeding into tumor, hypocoagulable state,hemorrhagic infarction, iatrogenic, and trauma

INTRACEREBRAL HEMORRHAGENON TRAUMATIC

Causes of StrokeCauses of Stroke

HipertensiHipertensi

Hipertensi

Akut

Kronis

Pemb.drh kecil Spasme Ensefalopatihipertensif

Pemb drh kecil

Pemb drh sedang

Lipohialinosis

Mikroaneurisma

Trombosis

PIS

Infarklakunar

AterosklerosisTIA,trombosis,Emboli serebri

Faktor resiko lainDM,hiperlipidemi

pecah

Cerebral vascular remodelingCerebral vascular remodeling

Hypertrophy media & narrowing lumenHypertrophy media & narrowing lumen

These changes are protectiveThese changes are protective reduction wall tension reduction wall tension & shifting of autoregulation curve to allow & shifting of autoregulation curve to allow compensation at higher BPcompensation at higher BP

Vasc remodeling accompanied by endothelial Vasc remodeling accompanied by endothelial dysfunction dysfunction impaired relaxation impaired relaxation poor poor compensation of hypoperfusion compensation of hypoperfusion reduced collateral reduced collateral flow flow higher susceptibility to ischemic injury higher susceptibility to ischemic injury

Perdarahan pd hipertensi tjd umumnya pd Perdarahan pd hipertensi tjd umumnya pd tempat yg dalam dari otak spt ganglia tempat yg dalam dari otak spt ganglia basalis dan thalamus krn pemb.darah pd basalis dan thalamus krn pemb.darah pd daerah tsb tertutup dari tekanan yg tingggi daerah tsb tertutup dari tekanan yg tingggi dari the circle of willis.dari the circle of willis.Perdarhan ini lebih sedikit pd Perdarhan ini lebih sedikit pd pons,serebelum atau kortek superfisialpons,serebelum atau kortek superfisial

Studi patologi menunjukkan hiperplasia pd Studi patologi menunjukkan hiperplasia pd dinding arteri media shg tjd reaksi proliferasi sel dinding arteri media shg tjd reaksi proliferasi sel otot polos pd awal hipertensi.otot polos pd awal hipertensi.Hal ini akan membentuk arteriosklerosis Hal ini akan membentuk arteriosklerosis hiperplastik.hiperplastik.Kemungkinan sel otot polos mati dan diganti Kemungkinan sel otot polos mati dan diganti jaringan kolagen yg membuat ddg pemb darah jaringan kolagen yg membuat ddg pemb darah rapuh dan bertanggung jawab pada kebocoran rapuh dan bertanggung jawab pada kebocoran lebih lanjut.lebih lanjut.

Pada hipertensi kronik diduga bahwa Pada hipertensi kronik diduga bahwa fibrinoid necrosis mrp prekursor pdarahan.fibrinoid necrosis mrp prekursor pdarahan.

Cerebral amyloid angiopathy(CAA)Cerebral amyloid angiopathy(CAA)

CAA mrp hasil dari penumpukan peptida CAA mrp hasil dari penumpukan peptida amiloid beta yg tdk larut pd ddg amiloid beta yg tdk larut pd ddg arteri ,arteriola,dan kapiler dari arteri ,arteriola,dan kapiler dari leptomeningeal dan kortek.leptomeningeal dan kortek.

Penggantian sel otot polos pd ddg arteri Penggantian sel otot polos pd ddg arteri oleh peningkatan amiloid beta seiring dg oleh peningkatan amiloid beta seiring dg usia membuat daya lentur arteri bkurang.usia membuat daya lentur arteri bkurang.

Pdarahan yg dihub dg CAA,bhub dg Pdarahan yg dihub dg CAA,bhub dg interaksi dari faktor resiko lain yaitu interaksi dari faktor resiko lain yaitu hipertensi.hipertensi.

Komplikasi vaskulopatik spesifik tjd Komplikasi vaskulopatik spesifik tjd biasanya pd CAA dg pdarahan.biasanya pd CAA dg pdarahan.

Komplikasinya antara lain double barrel Komplikasinya antara lain double barrel appearance,necrosis appearance,necrosis fibrinoid,microaneurisma,stenotik fibrinoid,microaneurisma,stenotik lumen,mikrohemoragik dan cortical lumen,mikrohemoragik dan cortical infarction.infarction.

Ruptur aneurysma : 6-12 per 100000/thRuptur aneurysma : 6-12 per 100000/thWanita : pria = 3:2Wanita : pria = 3:2Umur : sering 40-60 th, jarang anakUmur : sering 40-60 th, jarang anak

> 40 th, wanita > pria> 40 th, wanita > pria < 40 th, pria > wanita< 40 th, pria > wanita

Penyebab : congenital (defect T.media), Penyebab : congenital (defect T.media), atherosclerotik/hipertensi,emboli,infeksi,trauma, dllatherosclerotik/hipertensi,emboli,infeksi,trauma, dllTempat : 20-25% A.cerebri mediaTempat : 20-25% A.cerebri media

10% sirkulasi posterior10% sirkulasi posterior 35-40% A.cerebri anterior35-40% A.cerebri anterior 30% A.carotid interna 30% A.carotid interna

Aneurisma adalah keadaan dimana pemb Aneurisma adalah keadaan dimana pemb darah mjd mbesar scr abnormal atau darah mjd mbesar scr abnormal atau mengembang spt balon yg menonjol mengembang spt balon yg menonjol keluar.keluar.

Sering tjd pd arteri dibasis otak(circulus Sering tjd pd arteri dibasis otak(circulus willisi) dan di aorta.willisi) dan di aorta.

Menyebabkan ruptur dan kematianMenyebabkan ruptur dan kematian

Peningkatan tekanan(hipertensi sistemik) Peningkatan tekanan(hipertensi sistemik) dan meningkatnya ukuran aneurisma dan meningkatnya ukuran aneurisma memicu tekanan pd ddg dan memicu tekanan pd ddg dan meningkatkan resiko rupturmeningkatkan resiko ruptur

Mekanisme aneurismaMekanisme aneurisma

Degradasi proteolitik dari ddg jar ikat aortaDegradasi proteolitik dari ddg jar ikat aorta

Inflamasi dan respon imunInflamasi dan respon imun

Stress biokimiawi pd ddgStress biokimiawi pd ddg

Molekuler genetikMolekuler genetik

Aneurisma terbentuk scr perlahan selama Aneurisma terbentuk scr perlahan selama bbrp tahun dan sering tanpa gejalabbrp tahun dan sering tanpa gejala

Jika aneurisma mengembang scr cepat Jika aneurisma mengembang scr cepat maka tjd ruptur /robekan atau kebocoran maka tjd ruptur /robekan atau kebocoran darah disepanjang ddg pemb darah ,gx darah disepanjang ddg pemb darah ,gx dpt muncul tiba-tibadpt muncul tiba-tiba

Gejala :Gejala :Ruptur (90%) : NK(+),muntah,KK(+),penurunan Ruptur (90%) : NK(+),muntah,KK(+),penurunan

kesadaran,focal sign,kejangkesadaran,focal sign,kejangCompression (7%) : visual defect, Compression (7%) : visual defect,

hipopituitarism, parese anggota gerak, hipopituitarism, parese anggota gerak, optalmoplegi, facial painoptalmoplegi, facial pain

Incidental finding (3%)Incidental finding (3%)

Komplikasi :Komplikasi :Intracranial : rebleeding,cerebral infarctionIntracranial : rebleeding,cerebral infarction

Hidrocephalus,expanding hematom, Hidrocephalus,expanding hematom, kejangkejang

Extracranial : myocard infarc, cardiac Extracranial : myocard infarc, cardiac arrytmia,edema pulmo, stress ulcerarrytmia,edema pulmo, stress ulcer

Cause : anomali vascular intracranialCause : anomali vascular intracranialAVM : Aneurysma = 1:5.3 (US)AVM : Aneurysma = 1:5.3 (US)Gejala : haemorrhage, epilepsy, headache, Gejala : haemorrhage, epilepsy, headache, neurological deficit, cranial bruit,mass effectneurological deficit, cranial bruit,mass effectPenunjang : CT scan, MRI,AngiographyPenunjang : CT scan, MRI,AngiographyIndikasi intervensi :Indikasi intervensi :

Expending haematomaExpending haematomaRisiko perdarahanRisiko perdarahanDefisit neurologic progresifDefisit neurologic progresif

A-V MalformationA-V Malformation

Adalah kelainan kongenital dimana arteri Adalah kelainan kongenital dimana arteri dan vena langsung dihub oleh satu atau dan vena langsung dihub oleh satu atau lebih fistula,hub langsung ini tanpa lebih fistula,hub langsung ini tanpa perantaraan kapiler.perantaraan kapiler.

Lapisan arteri tdk mpy cukup lap muskulerLapisan arteri tdk mpy cukup lap muskuler

Vena sering dilatasi akibat tekanan aliran Vena sering dilatasi akibat tekanan aliran darah yg tinggi mll fistula.darah yg tinggi mll fistula.

MAV mrp sumber stroke pdarahan dan MAV mrp sumber stroke pdarahan dan umumnya pd usia mudaumumnya pd usia muda

Terapi invasif meliputi embolisasi Terapi invasif meliputi embolisasi endovaskuler,reseksi bedah,dan radiasi endovaskuler,reseksi bedah,dan radiasi fokalfokal

PATOFISIOLOGIPATOFISIOLOGI

Perdarahan

PeningkatanTIK

Influks Ca+

NekrosisNeuron

Iskemiaglobal

Pelepasan agenvasokonstriktor

Efek toksikdarah

Influks Ca+

Vasospsme

Iskemia Fokal

Serotonin, Prostaglandin, darah

Proses Vasospasme Pada PerdarahanProses Vasospasme Pada Perdarahan

Pelepasan zat vasokonstriktor dan komponen darah

Influks Ca+ Sel otot polos pembuluh darah

Vasospasmekuat

Iskemik + defisit neurologik

Lumen vasa darah

Vasospasme

Mediate area are insuficiently supplied with blood, and they die

Proses Aterosklerosis

Dimulai luka sel endotel - permukaan tidak mulus lagi – produksi molekul adesi (ICAM) – peningkatan NO - terjadi ketidak seimbangan (Depolarisasi) - ggn tonus vaskuler - aktivasi monosit menjadi makrofag yg mengambil LDL - foam cell

Foam Cell (sel busa) merupakan komponen penting pembentuk struktur masa plak

Aterotrombosis: Trombus Aterotrombosis: Trombus SuperimposedSuperimposed pada Plak Aterosklerotik pada Plak Aterosklerotik

Adapted from Falk E, et al. Circulation. 1995;92:657-671.

A small clot may break off from a larger thrombus and be carried to other places in the bloodstream. When the embolus reaches an artery too narrow to pass through and becomes lodged, blood flow distal to the fragment ceases, resulting in infarction of distal brain tissue due to lack of nutrients and oxygen.As a cause of stroke, embolism accounts for approximately 32% of cases.

Cerebral Embolism Formation

Evolution of the atherosclerotic plaqueEvolution of the atherosclerotic plaque

1. Accumulation of lipoprotein in intima1. Accumulation of lipoprotein in intima 2. Oxidative stress2. Oxidative stress3. Cytokine activation3. Cytokine activation 4. Monocyte penetration4. Monocyte penetration5. Macrophage foam cells5. Macrophage foam cells 6. Smooth muscle cell 6. Smooth muscle cell

migrationmigration7. Extracellular matrix accumulation7. Extracellular matrix accumulation 8. Calcification and fibrosis8. Calcification and fibrosis

GP IIb/IIIa InhibitorsGP IIb/IIIa Inhibitors

1. Platelet Adhesion

2. Platelet Activation

Platelet

GP Ib

Plaque rupture Activated Platelet

GP IIb/IIIa 3. Platelet Agregation

ASA, Clopidogrel

ASA, Clopidogrel

ASA, acetylsalicyclic acid.Cannon and Braunwald, Heart Disease. 2001.

TxA2

Fibrinogen

Role of platelet at trombosis

< 20 : aktifitas listrik hilang< 10 : Gangguan homeostasis

Konsep penumbra

Kebutuhan Kebutuhan GGlukosa lukosa && OOksigenksigen

CBF: CBF: 50 ml / 100 gr jar50 ml / 100 gr jar otak permenit. otak permenit. Oksigen: Oksigen: 6 ml / 100 gr jar6 ml / 100 gr jar otak per menit otak per menit untuk substansia griseauntuk substansia grisea dan dan 2 ml / 100 gr jar2 ml / 100 gr jar otak per menit untuk substansia alba. otak per menit untuk substansia alba. Kebutuhan oksigenKebutuhan oksigen:: 19-23 ml / 100 gr jar 19-23 ml / 100 gr jar otak per menit. otak per menit. Kebutuhan glukosaKebutuhan glukosa: : 4.5 4.5 - - 7 mg / 100 gr jar7 mg / 100 gr jar otak per menit. otak per menit. OtakOtak: : 20% dari seluruh 20% dari seluruh outputoutput jantung, yaitu jantung, yaitu sekitar 800 ml / menitsekitar 800 ml / menit

Proses IskemiProses Iskemi

SumbatanAliran darah Penurunan CBF

Iskemia

ATP, merubah permeabilitas membran

Influks Ca+

berlebihan

Kerusakanmembran

Nekrosis neuron

Cellular Injury During Ischemia

The Ischaemic Cellular Cascade and Targets for Novel Stroke Therapeutic Agents

Cerebral Ischaemia Reperfusion

Neuron depolarisation

Neuronal death

pH Na+ Cl-

adhesion

Glutamate release VGCC open

Intracellular Ca++

PLA2Activation

mitochondria NOS

Organelledamage

Oxidativestress

Tissueresponse

cytokines

molecules

Leukocyteadhesion

inflammation

(1)

Agents stroke iskemik :1. NMDA & AMPA receptor antagonists, Mg+2. Ca A3. NOS inhibitors4. Anti-oxidants5. Adhesion molecule antibodiesVGCC: Voltage gated calcium channelsPLA2 : Fosfolipase A2

(2)

(3)

(4)

(5)

Gadjah Mada Stroke AlgorithmPatient admitted with sudden onset of stroke

Decreasing consciousness +, headache +, Babinski’s reflex +

Decreasing consciousness +, headache +, Babinski’s reflex -

Decreasing consciousness +, headache -, Babinski’s reflex -

Decreasing consciousness +, headache -, Babinski’s reflex +

Decreasing consciousness -, headache +, Babinski’s reflex +

Decreasing consciousness -, headache +, Babinski’s reflex -

Decreasing consciousness -, headache -, Babinski’s reflex +

Decreasing consciousness -, headache -, Babinski’s reflex -

with

No

No

No

No

No

No

No

yes

yes

yes

yes

yes

yes

yes

yes

HS

HS

HS

HS

HS

HS

AIS

AIS

Monroe- Kellie PrincipleMonroe- Kellie Principle

Copied from: Rogers (1996) Textbook of Pediatric Intensive Care p. 646

Brain Blood

CSF MassBone

DISTINGUISHING FEATURES HEMORRHAGIC STROKE VS DISTINGUISHING FEATURES HEMORRHAGIC STROKE VS ISCHEMIC STROKEISCHEMIC STROKE : :

FEATURES SUGGESTING HEMORRHAGIC S.FEATURES SUGGESTING HEMORRHAGIC S. : :• early and prolonged loss of consciousnessearly and prolonged loss of consciousness• prominent headache, nausea and vomitingprominent headache, nausea and vomiting• retinal hemorrhagesretinal hemorrhages• nuchal rigiditynuchal rigidity• focal sign do not fit the anatomic pattern of a single focal sign do not fit the anatomic pattern of a single blood vesselblood vessel

FEATURES SUGGESTING ISCHEMIC STROKE :FEATURES SUGGESTING ISCHEMIC STROKE :• stepwise deterioration or progressive worseningstepwise deterioration or progressive worsening• waxing and waning of findingswaxing and waning of findings• focal neurologic impairments in the pattern of single blood focal neurologic impairments in the pattern of single blood vesselvessel• signs point to a focal cortical or subcortical lessionsigns point to a focal cortical or subcortical lession

(Adams Jr. (Adams Jr. et al., et al., 2002)2002)

SIMPTOMS ICHSIMPTOMS ICH

CLINICAL SIGNS OF INTRACEREBRAL HEMORRHAGE CLINICAL SIGNS OF INTRACEREBRAL HEMORRHAGE (1) (1) (Caplan 1988)(Caplan 1988)

Lesion Pupils/eye movement Motor & sensory deficits

Other

Caudate nucleus

Sometimes ipsilaterally constricted/ conjugate deviation to side of lesion

Contralateral hemiparesis, often transient

Headache, confusion

Putamen (small)

Normal/conjugate deviation to side of lesion

Contralateral hemiparesis & hemisensory loss

Aphasia (if lesion on left side)

Putamen (large)

With herniation, pupil dilated on side of lesion/conjugate deviation to side of lesion

Contralateral hemiparesis & hemisensory loss

Decreased consciousness

Thalamus Constricted poorly reactive to light bilaterally/lids retracted. Eyes down and in. Cannot look up.

Slight contralateral hemiparesis but greater hemisensory loss

Aphasia (if lesion on left side)

CLINICAL SIGNS OF INTRACEREBRAL HEMORRHAGE CLINICAL SIGNS OF INTRACEREBRAL HEMORRHAGE (2) (2) (Caplan 1988)(Caplan 1988)

Lesion Pupils/eye movement Motor & sensory deficits

Other

Occipital lobar white matter

Normal Mild, transient hemiparesis

Contralateral hemianopsia

Pons Constricted reactive to light/no horizontal movements. Vertical movements preserved

Quadriplegia Coma

Cerebellum Constriction on side of lesion/slight deviation to opposite side. Movements to side of lesion impaired or 6th cranial nerve palsy

Ipsilateral limb ataxia. No hemiparesis

Gait ataxia, vomiting

Patogenesis pada hipertensiPatogenesis pada hipertensi

Pembuluh darah px hipertensi mudah Pembuluh darah px hipertensi mudah terlukaterlukaterbentuk trombus dari deposit terbentuk trombus dari deposit lemak,sel darah dan komponen darah lemak,sel darah dan komponen darah lainlainaliran darah kencangaliran darah kencangtrombus terlepas trombus terlepas menyumbat lumen.menyumbat lumen.

Insulin Resistance

FFA production Glucose production

Hyperinsulinemia

Dyslipidemia

T2D

SNS activityAbnormal Na+

handling

HTN

Atherosclerosis

Patogenesis pada DMPatogenesis pada DM

Pembuluh darah px Pembuluh darah px DMDMaterosklerotikaterosklerotikmengganggu autoregulasi mengganggu autoregulasi vaskulervaskulerPasien DMPasien DMautoregulasi menurun sampai 10-autoregulasi menurun sampai 10-15cc/100g/mnt 15cc/100g/mnt penumbrapenumbraPenurunan autoregulasi<10cc/100g/mntPenurunan autoregulasi<10cc/100g/mnt peningkatan Ca ekstrasel dan K peningkatan Ca ekstrasel dan K intraselintraselmerusak retikulum merusak retikulum endoplasmikendoplasmikmitokondria terganggumitokondria tergangguasidosis asidosis dan kematian seldan kematian sel

102

Focal Neurological Impairment (prominent and Focal Neurological Impairment (prominent and suggest location of hemorrhage) #1suggest location of hemorrhage) #1

PutamenPutamen Contralateral hemiparesisContralateral hemiparesis Contralateral sensory lossContralateral sensory loss Contralateral conjugate Contralateral conjugate

gaze paresisgaze paresis Homonymous hemianopiaHomonymous hemianopia Aphasia (dominant) or Aphasia (dominant) or

neglect (non dominant)neglect (non dominant)

ThalamusThalamus Contralateral hemiparesisContralateral hemiparesis Contralateral sensory lossContralateral sensory loss Contralateral or ipsilateral Contralateral or ipsilateral

conjugate gaze paresisconjugate gaze paresis Downward deviation of Downward deviation of

eyeseyes Small sleggish pupilsSmall sleggish pupils Aphasia (dominant)Aphasia (dominant)

103

Cerebral hemisphere Cerebral hemisphere lobar white matterlobar white matter

Contralateral Contralateral hemiparesis or sensory hemiparesis or sensory lossloss

Contralateral conjugate Contralateral conjugate gaze paresisgaze paresis

Contralateral Contralateral homonymous hemianopiahomonymous hemianopia

AbuliaAbulia Aphasia (dominant) or Aphasia (dominant) or

neglect (non dominant)neglect (non dominant)

Brain stem (ussually Brain stem (ussually ponds)ponds)

Quadriparesis or Quadriparesis or hemiparesishemiparesis

Unilateral or bilateral Unilateral or bilateral weaknessweakness

Locked-in syndromesLocked-in syndromes ComaComa Bilateral horizontal gaze Bilateral horizontal gaze

paresisparesis Ocular bobbingOcular bobbing Pinpoint pupilsPinpoint pupils Hyperthermia and Hyperthermia and

hyperventilationhyperventilation

Focal Neurological Impairment (prominent and suggest location of hemorrhage) #2

104

CerebellumCerebellum

Truncal or gait ataxiaTruncal or gait ataxia IpsilateralIpsilateral

Limb ataxiaLimb ataxia Facial weakness and sensory lossFacial weakness and sensory loss Conjugate gaze palsyConjugate gaze palsy Abducent nerve palsyAbducent nerve palsy

Skew deviationSkew deviation Small reactive pupilsSmall reactive pupils Later developmen of coma and bilateral weakness; Later developmen of coma and bilateral weakness;

sensory loss possible sensory loss possible

Focal Neurological Impairment (prominent and suggest location of hemorrhage) #3

105

LocationsLocations

The most common locations for hypertensive The most common locations for hypertensive hemorrhage are:hemorrhage are:PutamenPutamenThalamusThalamusLobar white matter of the cerebral hemispheresLobar white matter of the cerebral hemispheresBrain stem (pons in particular)Brain stem (pons in particular)CerebellumCerebellum

These locations reflect the vascular teerritories of short These locations reflect the vascular teerritories of short penetrating branches (arterioles) arising from the major penetrating branches (arterioles) arising from the major intracranial arteries.intracranial arteries.

106

INTRACEREBRAL HEMORRHAGE

107

PenatalaksanaanPenatalaksanaan

108

Hasil optimal terapi Stroke perdarahan Hasil optimal terapi Stroke perdarahan sampai 96 jamsampai 96 jam setelah onset setelah onset

Puncak vasospasme antara hari ke 5-10)Puncak vasospasme antara hari ke 5-10)

109

ManagementManagement In emergency RoomIn emergency Room

– ABC rulesABC rules– BP continuous monitoringBP continuous monitoring– Continuous ECG monitoringContinuous ECG monitoring– O2 pulse oxymetryO2 pulse oxymetry– 2 IV lines (norma saline only)2 IV lines (norma saline only)– Blood (CBC, SMAC, RBS, PTT, INR)Blood (CBC, SMAC, RBS, PTT, INR)– Save 6 ml of bloodSave 6 ml of blood– Facilitate transfer to the operating room or ICUFacilitate transfer to the operating room or ICU

110

Acute stroke care-General managementAcute stroke care-General management

The mainstay of acute treatment (A,B,C)The mainstay of acute treatment (A,B,C)Treatment and stabilisation of general conditionTreatment and stabilisation of general conditionSpecific therapySpecific therapy– Recanalisation of a vessel occlusionRecanalisation of a vessel occlusion– Preventive of mecanism leading to neuronal death Preventive of mecanism leading to neuronal death

in the ischhemic brainin the ischhemic brain

Early secondary preventionEarly secondary preventionEarly rehabilitationEarly rehabilitationProphylaxis and treatment of complicationsProphylaxis and treatment of complications

(Lamsudin, 2004)

111

Blood pressureBlood pressure– There are adequately sized randomized , controlled There are adequately sized randomized , controlled

study guiding BP mangementstudy guiding BP mangement– Elevated BP (sistolic>200mmHg or diastolic Elevated BP (sistolic>200mmHg or diastolic

>110mmHg0 may tolerated in the acute phase>110mmHg0 may tolerated in the acute phase– Avoid and treat hypotension or drastic reduction BPAvoid and treat hypotension or drastic reduction BP– BP may be lowered if cardiac condition require itBP may be lowered if cardiac condition require it


(Lamsudin, 2004)

112

Blood pressure (BP)Blood pressure (BP)

Indications for immediate AH therapy in acute Indications for immediate AH therapy in acute strokestroke– Intracerebral haemorrhageIntracerebral haemorrhage– Cardic failureCardic failure– Acute coronary syndromeAcute coronary syndrome– Aortic dissectionAortic dissection– Hypertensive enchephalophatyHypertensive enchephalophaty


(Lamsudin, 2004)

113

PENATALAKSANAAN HIPERTENSI PADA PENATALAKSANAAN HIPERTENSI PADA STROKE AKUTSTROKE AKUT

STROKE AKUT

Sistolik > 220 mmHgDiastolik > 140 mmHg

Sistolik > 220 mmHgDiastolik > 121-140 mmHg

Sistolik 180-220 mmHgDiastolik 105-120 mmHg Sistolik < 180 mmHg

Diastolik < 105 mmHg

•Sistolik > 220 mmHg•Diastolik 121-140 mmHg

Ulangi 15'

Perdarahan intraserebralAtau

Ggn end organ

Positif Negatif

Obat antihipertensiparenteral

ObservasiObat antihipertensi oralDiberikan stl hr ke 7-10

(Guidelines Stroke,2007)

Blood Pressure (BP) Management Protocol Blood Pressure (BP) Management Protocol in Acute Strokein Acute Stroke

Antihypertensive treatment should await Antihypertensive treatment should await the spontaneous decline in BP (within 1the spontaneous decline in BP (within 1stst to 10to 10thth days). If increased BP persist after days). If increased BP persist after 7-10 days, start treatment.7-10 days, start treatment.

Patients already on antihypertensive Patients already on antihypertensive medication prior to stroke, drugs should medication prior to stroke, drugs should be held or reduced for 7-10 days (except be held or reduced for 7-10 days (except B-blockers, should be gradually over 5-6 B-blockers, should be gradually over 5-6 days)days)

Treat If:Treat If:1.1. BP is > 220/140 or MAP >130 mmHgBP is > 220/140 or MAP >130 mmHg2.2. Malignant or hypertensive encephalopathyMalignant or hypertensive encephalopathy3.3. Acute MIAcute MI4.4. Aortic dissection is suspectedAortic dissection is suspected5.5. BP is >180/100 and patient is for thrombolytic BP is >180/100 and patient is for thrombolytic

therapytherapy6.6. 24 hours following thrombolytic therapy 24 hours following thrombolytic therapy

(>185/110)(>185/110)

Blood Pressure (BP) Management Protocol in Acute Stroke

The Following medications can be used, if needed:The Following medications can be used, if needed: Esmolol bolus (500 ug/kg IV)Esmolol bolus (500 ug/kg IV) Esmolol infusion (50-150 ug/kg/min) IV, (Body weight x 60 mg of Esmolol infusion (50-150 ug/kg/min) IV, (Body weight x 60 mg of

esmolol diluted in 100 ml of saline, in a rate of 5-15 ml/hour)esmolol diluted in 100 ml of saline, in a rate of 5-15 ml/hour) Labetalol infusion (15-35 ug/kg/ml) IV, (Body weight x 6 mg of Labetalol infusion (15-35 ug/kg/ml) IV, (Body weight x 6 mg of

labetalol diluted in 100 ml of saline, in a rate of 15-35 ml/hour)labetalol diluted in 100 ml of saline, in a rate of 15-35 ml/hour) Labetalol 100-200 mg bid-tid. POLabetalol 100-200 mg bid-tid. PO Analaprilat 1,25-5 mg IV, 6 hourlyAnalaprilat 1,25-5 mg IV, 6 hourly Lasix 20-40 mg iv tid-qidLasix 20-40 mg iv tid-qid Nicardipin 5 mg/hour IVNicardipin 5 mg/hour IV Clonidine 150-300 mg iv bolus (maximum of 750 mg per day)Clonidine 150-300 mg iv bolus (maximum of 750 mg per day) Sodium nitroprusside 0,25-0,5 mg/kg/minSodium nitroprusside 0,25-0,5 mg/kg/min

Avoid the use of calcium channel blockers and Avoid the use of calcium channel blockers and sodium nitropusside as possiblesodium nitropusside as possible

Blood Pressure (BP) Management Protocol in Acute Stroke

Lowering of blood pressure Lowering of blood pressure In acute ischemic stroke ,there is one of:In acute ischemic stroke ,there is one of:

Systolic pressure > 220 mmHgSystolic pressure > 220 mmHg

Diastolic pressure > 120 mmHgDiastolic pressure > 120 mmHg

MAP > 130-140 mm HgMAP > 130-140 mm Hg

with acute infark miocard /heart with acute infark miocard /heart failure or acute kidney failure / failure or acute kidney failure / aorta toracalisaorta toracalis

118

Cushing reflexHaematom as a secondary ICPoxyhemoglobin and bilirubin , causing the intracranial hypertensi and blocking the lcs absorbtionHight catecolamin value

119

NEUROPROTEKTAN

120

Citicholine Citicholine Mechanism (neuronal)Mechanism (neuronal)

– Increase choline formationnd alter degradation Increase choline formationnd alter degradation phosphatydilcholinephosphatydilcholine

– Increase glucose uptake, asetilkholine, Increase glucose uptake, asetilkholine, prevention lipid radicalprevention lipid radical

– Increase glutationIncrease glutation– Decrease lipid peroxidaDecrease lipid peroxida– Na/K ATPase modulationNa/K ATPase modulation

Mechanism (vascular)Mechanism (vascular)– Increase CBFIncrease CBF– Increase O2 consumtionIncrease O2 consumtion– Decrease vasculer resistanceDecrease vasculer resistance (Perdossi, 2004)

Struktur Citicholin (Adibhatla,2002)

Ambilan oleh otak tjd paling awal 30 mnt stl pemberian, kadar puncak stl 6 jam pemberian per oral.Wkt paruh pemberian scr IV adalah 20-30 mnt.

Uptake citicholin eksogen yg diberikan scr IV pada keadaan iskemi, hal ini krn permeabilitas kapiler otak .

Distribusi :hepar,usus,ginjal,paru-paru, otot skelet jtg dan otak (subst.alba>subst. grisea).Krn jml kapiler lbh banyak.

Diekskresi mll urine dg dosis yg sangat kecil.

N

NO

O

H H

OH OH

H

OCH2

NH2

P

OH

OP

C

O

N+CH2CH2O

OCH2

CH2

H2C

CITICHOLINE

Citicholine

HidrolisaCytidine

Cholinediabsorbsi

Otak

Sintesa

PCCT

Citicholine

1-2 DAG

Phosphatidilkolin

Phosphatidilserin

Phosphatidiletanolamin

Phospolipid

Asetilasi

Acetylcholin

BetaineAdo Me

Methionin

S-Adenosyl-L-homocysteinHomocysteinCysteinGlutation

VaskularisasiLokal

Antioksidan

MEMBRAN

REPAIR

PCCT : Cytidine triphosphat – phosphocholine – cytidylyl transferase

1-2 DAG : 1-2 Diasil Gliserol

123

Piracetam Piracetam Mechanism (neuronal)Mechanism (neuronal)

– Repair cell membran fluidityRepair cell membran fluidity– Repair neurotransmissionRepair neurotransmission– Stimulation adenylate kinaseStimulation adenylate kinase

Mechanism (vascular)Mechanism (vascular)– Increase eritrocyte deformabilityIncrease eritrocyte deformability– Decrease platelet hyperagregationDecrease platelet hyperagregation– Repir microcirculationRepir microcirculation

(Perdossi, 2004)

125

Penggunaan Piracetam & Citicoline Pada Stroke & TraumaPenggunaan Piracetam & Citicoline Pada Stroke & Trauma

Perdarahan - Stroke / Trauma )Perdarahan - Stroke / Trauma )

Dapat segera diberikan Dapat segera diberikan walaupun diagnosa belum walaupun diagnosa belum jelasjelas

Dapat mencegah dan Dapat mencegah dan merelaksasi timbulnya merelaksasi timbulnya vasospasmevasospasme

Aman dan dapat diberikan pada Aman dan dapat diberikan pada penderita yang akan dioperasi penderita yang akan dioperasi tanpa meningkatkan risiko tanpa meningkatkan risiko perdarahan ulang perdarahan ulang

Iskemik / Infark( Stroke/Cedera Otak sekunder)

Dapat segera diberikan pada

penderita trauma kepala derajat sedang sampai berat

Dapat mencegah dan mengatasi defisit neurologik iskemik

Dapat menyelamatkan sel neuron penumbra

Mencegah meluasnya infark sel neuron

NON SURGICAL CANDIDATESNON SURGICAL CANDIDATES1. Small hemorrhages (<10 cm3) or minimal neurological deficits.1. Small hemorrhages (<10 cm3) or minimal neurological deficits.2. GCS score 2. GCS score 4. Except for cerebellar hemorrhage with brainstem 4. Except for cerebellar hemorrhage with brainstem

compression for livesaving surgery.compression for livesaving surgery.

SURGICAL CANDIDATESSURGICAL CANDIDATES1. Cerebellar hemorrhage > 3 cm who are neurologically 1. Cerebellar hemorrhage > 3 cm who are neurologically

deteriorating or who have brainstem compression and deteriorating or who have brainstem compression and hydrocepahalus from ventricular obstruction.hydrocepahalus from ventricular obstruction.

2. ICH with structural lesion eg aneurysm, AVM, or cavernous 2. ICH with structural lesion eg aneurysm, AVM, or cavernous angioma.angioma.

3. Young patients with a moderate or large lobar hemorrhage who 3. Young patients with a moderate or large lobar hemorrhage who are clinicallyare clinically deteriorating. deteriorating.

Rekomendasi tindakan pembedahan pada perdarahanRekomendasi tindakan pembedahan pada perdarahanintreaserebralintreaserebral

Ismail S, 2008

128

FINAL RESULTS OF THE INTERNATIONAL SURGICAL TRIAL IN ICH FINAL RESULTS OF THE INTERNATIONAL SURGICAL TRIAL IN ICH (ISTICH)(ISTICH)

(Mendelow WSC 2004)(Mendelow WSC 2004)

1033 patients with spontaneous supratentorial ICH 1033 patients with spontaneous supratentorial ICH 107 centers in 27 countries.107 centers in 27 countries.

23.8% favourable outcome in “early conse23.8% favourable outcome in “early conserrvative vative treatment” vs 26.1% in “early surgery” (NS).treatment” vs 26.1% in “early surgery” (NS).

Mortality 63.7 % vs 62.6 % (NS); Rankin score Mortality 63.7 % vs 62.6 % (NS); Rankin score 28.1% vs 32.8% (NS); Barthel 22.6% vs 26.7% 28.1% vs 32.8% (NS); Barthel 22.6% vs 26.7% (NS).(NS).

Superficial location (<1cm from surface) favour Superficial location (<1cm from surface) favour early surgery. early surgery.

129

MannitolMannitol

1.1. Lowering ICP : Lowering ICP : Immediate plasma expansionImmediate plasma expansion : reduce : reduce the hematocrit and blood viscosity (improved the hematocrit and blood viscosity (improved rheology) which increases CBF and Orheology) which increases CBF and O22 delivery. delivery. Osmotic effectOsmotic effect : increased serum tonicity draws : increased serum tonicity draws edema fluid from cerebral parenchyma.edema fluid from cerebral parenchyma.

2.2. Supports the microcirculation by improving blood Supports the microcirculation by improving blood rheologyrheology

3.3. Possible free scavengingPossible free scavenging(Greenberg,2000)(Greenberg,2000)

Dose : 0,5 – 1,0 g/kg body weight Dose : 0,5 – 1,0 g/kg body weight (Adam,et al., 2001)(Adam,et al., 2001)

Iv bolus 100 ml of 20 % mannitol over 15 minutes Iv bolus 100 ml of 20 % mannitol over 15 minutes (Lindsay, et (Lindsay, et al., 1997)al., 1997)

Management penurunan tekanan intrakranialManagement penurunan tekanan intrakranial

131

PROGNOSISPROGNOSIS

Pouratian 2003Pouratian 2003

Volume of the hematomaVolume of the hematoma ( (≥ 30 cc)≥ 30 cc)

Neurologic status (GCS scoreNeurologic status (GCS score ≤ 8≤ 8))

Intraventricular extension of the clotIntraventricular extension of the clot

HydrocephalusHydrocephalus

Subarachnoid extensionSubarachnoid extension

Anticoagulation agentsAnticoagulation agents

Relative edema Relative edema

Davis WSC 2004Davis WSC 2004

● ● Infratentorial lesionInfratentorial lesion

● ● Coronary heart diseaseCoronary heart disease

● ● HyperthermiaHyperthermia

133

REHABILITATIONREHABILITATION

Rekomendasi pencegahan stroke Rekomendasi pencegahan stroke perdarahanperdarahan

Ismail S, 2008

DefinisiDefinisi

Rehabilitasi (WHO): Tindakan bertujuan Rehabilitasi (WHO): Tindakan bertujuan mengurangi dampak disabilitas/handicap agar mengurangi dampak disabilitas/handicap agar dapat berintegrasi dg masyarakat.dapat berintegrasi dg masyarakat.

Fisioterapi mrp sub instalasi rehabilitasiFisioterapi mrp sub instalasi rehabilitasitx tx okupasi,ortotik prostetik,terapi wicara,psikologi okupasi,ortotik prostetik,terapi wicara,psikologi dan sosial medikdan sosial medik

TujuanTujuan

Memperbaiki fungsi Memperbaiki fungsi motorik,wicara,kognitif,dan fungsi lain motorik,wicara,kognitif,dan fungsi lain yang tergangguyang terganggu

Readaptasi sosial dan mental untuk Readaptasi sosial dan mental untuk memulihkan hubungan interpersonal dan memulihkan hubungan interpersonal dan aktivitas sosialaktivitas sosial

Dapat melaksanakan aktivitas kehidupan Dapat melaksanakan aktivitas kehidupan sehari-harisehari-hari

lanjutanlanjutan

Prinsip rehabilitasi strokePrinsip rehabilitasi stroke penderita tidak penderita tidak tergantung pada orang laintergantung pada orang lain

Keberhasilan bukan dari banyaknya jiwa Keberhasilan bukan dari banyaknya jiwa yg tertolong tp berapa banyak penderita yg tertolong tp berapa banyak penderita berfx lagi dimasyarakatberfx lagi dimasyarakat

138

RehabilitationRehabilitation

EUSI RecommendationsEUSI Recommendations1. Rehabilitation should be initiated early after 1. Rehabilitation should be initiated early after

stroke stroke (Level I)(Level I)

2. Every patient should have access to evaluation 2. Every patient should have access to evaluation for rehabilitation for rehabilitation (Level III)(Level III)

3. Rehabilitation services should be provided by a 3. Rehabilitation services should be provided by a multidisciplinary team multidisciplinary team (Level III)(Level III)

139

Rehabilitation Program : Rehabilitation Program :

Physical therapy :Physical therapy :•MobilizationMobilization•WalkingWalking•Major motor or sensory impairment of the Major motor or sensory impairment of the

limbslimbs•Prescription of devices, such as a cane or Prescription of devices, such as a cane or

walkerwalker

Occupational Therapy :Occupational Therapy :•Fine movements of the handFine movements of the hand•Arm function Arm function •Utilization of toolsUtilization of tools•Assistive devicesAssistive devices•Ability to function independentlyAbility to function independently

140

Speech TherapySpeech Therapy : :

• Disorders of languageDisorders of language

• Disorders of articulationDisorders of articulation

• Disorders of swallowingDisorders of swallowing

Faktor yang berpengaruh pada Faktor yang berpengaruh pada hasil akhir rehabilitasihasil akhir rehabilitasi

Penyebab strokePenyebab strokeBeratnya strokeBeratnya strokeLokasi strokeLokasi strokeUsia penderitaUsia penderitaMotivasi penderita,kepribadian premorbit dan moodMotivasi penderita,kepribadian premorbit dan moodKeluarga penderitaKeluarga penderitaSistem sosio ekonomi penderita dan keluargaSistem sosio ekonomi penderita dan keluargaDefisit neurologi yang khususDefisit neurologi yang khususWaktu,awal,lamanya dan intensitas pemberian terapi Waktu,awal,lamanya dan intensitas pemberian terapi rehabilitasirehabilitasiTim rehabilitasiTim rehabilitasi

142

Komplikasi StrokeKomplikasi Stroke

DemensiaDemensia

DepresiDepresi

KecacatanKecacatan

EpilepsiEpilepsi

KontrakturKontraktur

Peptic ulcerPeptic ulcer

BronchopneumoniaBronchopneumonia

DekubitusDekubitus

SeptikemiaSeptikemia

Trombosis vena Trombosis vena profundaprofunda

Emboli pulmoEmboli pulmo

Ggn keseimbangan Ggn keseimbangan cairancairan

143

Risk of Stroke RecurrenceRisk of Stroke Recurrence(percentage experiencing (percentage experiencing stroke)stroke)

After TIAAfter TIA After StrokeAfter Stroke

30 days 4-8% 3-10%30 days 4-8% 3-10%

1 Year 12-13% 10-14%1 Year 12-13% 10-14%

5 Years 24-29% 25-40%5 Years 24-29% 25-40%

Source: Sacco RL, Wolf PA, Gorelick PB. Source: Sacco RL, Wolf PA, Gorelick PB. Neurology 1999; 53 (supp 4): S15-S24.Neurology 1999; 53 (supp 4): S15-S24.

144

Sindrom ArteriSindrom Arteri

145

Middle Cerebral Artery.Middle Cerebral Artery.

Largest branch of Internal Largest branch of Internal Carotid.Carotid.

Supplies portion of frontal Supplies portion of frontal lobe and lateral surface of lobe and lateral surface of Temporal and Parietal Temporal and Parietal lobes.lobes.

Primary Motor and Sensory Primary Motor and Sensory areas for face, throat , hand areas for face, throat , hand and arm.and arm.

Dominant hemisphere, Dominant hemisphere, supplies area controlling supplies area controlling speech.speech.

Is the Artery most often Is the Artery most often occluded in stroke.occluded in stroke.

146

The MCA proceeds laterally into the lateral sulcus The MCA proceeds laterally into the lateral sulcus and spreads to supply virtually the entire lateral and spreads to supply virtually the entire lateral surface of the cerebral hemiphere, where most of surface of the cerebral hemiphere, where most of the precentral and postcentral gyri are located.the precentral and postcentral gyri are located.

Included in this region are the motor speech of Included in this region are the motor speech of area Broca and the sensory language area of area Broca and the sensory language area of Wernickle.Wernickle.

MCA also supply the putamen, part of the caudate MCA also supply the putamen, part of the caudate nucleus, the outer globus pallidus, the posterior nucleus, the outer globus pallidus, the posterior limb of the internal capsule and the corona limb of the internal capsule and the corona radiata.radiata.

Middle Cerebral Artery.

147

MIDDLE CEREBRAL ARTERY (MCA)MIDDLE CEREBRAL ARTERY (MCA)

Characterized by weakness of the Characterized by weakness of the contralateral face with hemianopsia and a contralateral face with hemianopsia and a preference of the eyes and head toward preference of the eyes and head toward the side of the involved hemisperethe side of the involved hemispere

Aphasia in dominant hemisphere injuryAphasia in dominant hemisphere injury HemineglectHemineglect Involvement restricted to branches of the Involvement restricted to branches of the

MCA may produces fragment of this MCA may produces fragment of this syndrome sparing of leg strenghsyndrome sparing of leg strengh

148

Stroke SyndromesStroke SyndromesMiddle cerebral artery - completeMiddle cerebral artery - complete

Weakness - upper and lower extremity (C)Weakness - upper and lower extremity (C) Weakness - face - lower half (C)Weakness - face - lower half (C) Hemisensory loss - upper and lower extremity (C)Hemisensory loss - upper and lower extremity (C) Sensory loss - face - all modalities (C)Sensory loss - face - all modalities (C) Aphasia – receptive (D)Aphasia – receptive (D) Aphasia – expressive (D)Aphasia – expressive (D) Hemineglect (ND)Hemineglect (ND) Lateral gaze weakness (C)Lateral gaze weakness (C) Gaze preference (C)Gaze preference (C) Visual loss - homonymous hemianopia (C)Visual loss - homonymous hemianopia (C)

(AHA Stroke Center, 2004)

149

Stroke SyndromesStroke SyndromesMiddle cerebral artery – superior divisionMiddle cerebral artery – superior division

Weakness - upper and lower extremity (C)Weakness - upper and lower extremity (C) Weakness - face - lower half (C)Weakness - face - lower half (C) Hemisensory loss - upper and lower extremity (C)Hemisensory loss - upper and lower extremity (C) Sensory loss - face - all modalities (C)Sensory loss - face - all modalities (C) Hemineglect (ND)Hemineglect (ND) Aphasia – expressive (D)Aphasia – expressive (D)

(AHA Stroke Center, 2004)

150

Visual loss - homonymous hemianopia Visual loss - homonymous hemianopia (C)(C)

Visual loss - upper quadrant anopsia Visual loss - upper quadrant anopsia (C)(C)

Constructional apraxia (ND)Constructional apraxia (ND) Aphasia – receptive (D)Aphasia – receptive (D)

Stroke SyndromesStroke SyndromesMiddle cerebral artery – inferior divisionMiddle cerebral artery – inferior division

( AHA Stroke center, 2004)

151

Anterior Cerebral ArteryAnterior Cerebral Artery

152

The ACA follow the corpus callosum The ACA follow the corpus callosum supplying the anterior four fifths of supplying the anterior four fifths of the corpus callosum and medial the corpus callosum and medial aspect of the frontal and parietal aspect of the frontal and parietal lobes. Deep branches, arising near lobes. Deep branches, arising near the circle of Willis, supply the anterior the circle of Willis, supply the anterior limb of the internal capsule, the limb of the internal capsule, the inferior head of caudate nucleus and inferior head of caudate nucleus and the anterior part of the globus the anterior part of the globus pallidus.pallidus.

Anterior Cerebral Artery

153

ANTERIOR CEREBRAL ARTERY (ACA)ANTERIOR CEREBRAL ARTERY (ACA)

Much rarerMuch rarer The classic presentation is proximal arm/leg The classic presentation is proximal arm/leg

weakness with present of distal strength, the weakness with present of distal strength, the so-called “man in a barrel”so-called “man in a barrel”

ACA occlusions cause contralateral motor and ACA occlusions cause contralateral motor and somatosensory deficits, primarily of the lower somatosensory deficits, primarily of the lower extremities.extremities.

In addition, apraxia, mental and personal In addition, apraxia, mental and personal changes, primitiv reflexes and bowel and changes, primitiv reflexes and bowel and bladder incontinence often ptresentbladder incontinence often ptresent

154

Posterior Cerebral ArteryPosterior Cerebral Artery

155

POSTERIOR CEREBRAL ARTERY (PCA)POSTERIOR CEREBRAL ARTERY (PCA)

Involves the brainstem, cerebellum, thalamus Involves the brainstem, cerebellum, thalamus & occipital lobes& occipital lobes

Present with bilateral limb weakness or sensory Present with bilateral limb weakness or sensory disturbances, cranial nerve defisit, ataxia, disturbances, cranial nerve defisit, ataxia, nausea, and vomiting or comanausea, and vomiting or coma

occlusion of the basilar artery trunk : Present occlusion of the basilar artery trunk : Present with hemianopia, memory disturbance, mild with hemianopia, memory disturbance, mild personality disturbancepersonality disturbance

Rarely; bilateral thalamus : a state of Rarely; bilateral thalamus : a state of decreased responsiveness and apathy without decreased responsiveness and apathy without motor, sensory or visual impairmentmotor, sensory or visual impairment

156

AFASIAAFASIA

157

AFASIAAFASIAAfasia adalah:Afasia adalah:

gangguan kemampuan berbahasa gangguan kemampuan berbahasa seseorang yang disebabkan oleh seseorang yang disebabkan oleh kerusakan otak akibat suatu kerusakan otak akibat suatu stroke(gangguan peredaran darah di otak)stroke(gangguan peredaran darah di otak)(Dharmaperwira prins,1993)(Dharmaperwira prins,1993)

158

Penyebab AfasiaPenyebab AfasiaGPDO(gangguan peredaran darah di GPDO(gangguan peredaran darah di otak),(trombosis,emboli,perdarahan otak)otak),(trombosis,emboli,perdarahan otak)

Tumor otakTumor otak

InfeksiInfeksi

TraumaTrauma

Afasia progresifAfasia progresif

159

Sindrom-sindrom AfasiaSindrom-sindrom AfasiaAfasia GlobalAfasia GlobalAfasia BroccaAfasia BroccaAfasia Transkortikal motorisAfasia Transkortikal motorisAfasia Transkortikal sensorikAfasia Transkortikal sensorikAfasia Transkortikal campuranAfasia Transkortikal campuranAfasia WernickeAfasia WernickeAfasia KonduksiAfasia KonduksiAfasia AnomikAfasia Anomik

AfasiaAfasiaNoNo JenisJenis Bicara Bicara

spontanspontanPenamaPenamaanan

PemahaPemahamanman

pengulanpengulangangan

membacmembacaa

menulismenulis

11 BrocaBroca -- -- ++ -- ++ --

22 WernickeWernicke ++ -- -- -- -- --

33 GlobalGlobal -- -- -- -- -- --

44 KonduksiKonduksi ++ +/-+/- ++ -- ++ ++

55 AnomikAnomik ++ -- ++ ++ ++ ++

66 Transkortikal Transkortikal motorikmotorik

-- +/-+/- ++ ++ ++ ++

77 Transkortikal Transkortikal sensoriksensorik

++ -- ++ ++ -- +/-+/-

161

Afasia BroccaAfasia BroccaNama lain:afasia motoris,afasia Nama lain:afasia motoris,afasia ekspresif,afasia motoris eferenekspresif,afasia motoris eferen

Lokasi lesi:frontoparietal hemisfer kiriLokasi lesi:frontoparietal hemisfer kiri

Emboli pada arteri candelabra sinistra yng Emboli pada arteri candelabra sinistra yng memvaskularisasi operkulummemvaskularisasi operkulum

162

Afasia wernickeAfasia wernickeNama lain: afasia sensorik,afasia Nama lain: afasia sensorik,afasia reseptif,afasia akustisreseptif,afasia akustis

Lokasi lesi: bagian posterior girus temporal Lokasi lesi: bagian posterior girus temporal atas hemisfer kiriatas hemisfer kiri

Kelainan pada arteri temporalis posteriorKelainan pada arteri temporalis posterior

163

Afasia KonduksiAfasia KonduksiNama lain: afasia sentral,afasia aferen Nama lain: afasia sentral,afasia aferen motorismotoris

Lokasi lesi: bagian posterior fasikulus Lokasi lesi: bagian posterior fasikulus arkuatus hemisfer kiriarkuatus hemisfer kiri

Gangguan pada arteri parietalis posteriorGangguan pada arteri parietalis posterior

164

Afasia GlobalAfasia GlobalLokasi lesi: daerah fronto temporoparietal Lokasi lesi: daerah fronto temporoparietal perisylvis di hemisfer kiriperisylvis di hemisfer kiri

Semua aspek bahasa & bicara tergangguSemua aspek bahasa & bicara terganggu

Sumbatan pada bagian depan arteri Sumbatan pada bagian depan arteri serebri media,bisa juga karena hematom serebri media,bisa juga karena hematom yang luasyang luas

165

Afasia Transkortikal motorisAfasia Transkortikal motoris

Nama lain: sindrom isolasi anterior,afasia Nama lain: sindrom isolasi anterior,afasia dinamisdinamis

Lokasi lesi:frontal hemisfer kiriLokasi lesi:frontal hemisfer kiri

Gangguan pada arteri orbitofrontolateral dan Gangguan pada arteri orbitofrontolateral dan cabang terminal arteri serebri anteriorcabang terminal arteri serebri anterior

166

Afasia Transkortikal SensorisAfasia Transkortikal SensorisLokasi lesi: temporoparieto oksipital kiri.Lokasi lesi: temporoparieto oksipital kiri.

Kerusakan di area border zone parietalis Kerusakan di area border zone parietalis temporalis oleh arteri serebri media dan temporalis oleh arteri serebri media dan arteri serebri posteriorarteri serebri posterior

167

Afasia AnomikAfasia AnomikNama lain: afasia nominal, afasia amnestisNama lain: afasia nominal, afasia amnestis

Broca’s Aphasia

• Damage to Broca’s area alone is not enough to produce Broca’s aphasia

• Usually involves Broca’s area + surrounding areas including M1 & insula.

Wernicke’s Aphasia

• Damage to Wernicke’s area alone is not enough to produce Wernicke’s aphasia

• Usually involves Wernicke’s area + surrounding areas including MTG & angular gyrus.

Conduction Aphasia

• Damage to the arcuate fasciculus has not been associated with conduction aphasia

• Usually two lesion patterns: posterior STG (wernicke’s areas) and/or SMG

Common area?

Transcortical Sensory Aphasia

• Variable lesion patterns, mostly posterior to Wernicke’s area

• Deficit tends to be transient evolving into anomic aphasia

Common area?

Transcortical Motor Aphasia

• Damage often anterior and/or superior to Broca’s area

Global Aphasia

• Tend to be large “peri-Sylvian” lesions• But smaller lesions can also cause global aphasia

Tx. APHASIATx. APHASIAPiracetam had a potential effect on cognitive Piracetam had a potential effect on cognitive functions functions used in the treatment of aphasia (4.8 g daily used in the treatment of aphasia (4.8 g daily over 6 to12 weeks) but the mechanism over 6 to12 weeks) but the mechanism remained a matter of speculation.remained a matter of speculation.

Piracetam as an Piracetam as an adjuvant to speech therapyadjuvant to speech therapy improves recoveryimproves recovery of various language functions, of various language functions, and this effect is accompanied by a significant and this effect is accompanied by a significant increase of task-related flow activation in eloquent increase of task-related flow activation in eloquent areas of the left hemisphere. areas of the left hemisphere.

(Kessler (Kessler et al.,et al., 2000) 2000)

179

Speech Tx and AphasiaSpeech Tx and Aphasia

The efficacy of The efficacy of speech therapyspeech therapy is is still controversialstill controversial, , with several randomized controlled trials yielding no with several randomized controlled trials yielding no difference in outcome between treated and nontreated difference in outcome between treated and nontreated groups. groups.

(Ferro (Ferro et al. cit et al. cit Kessler Kessler et alet al., 2000) ., 2000)

On the other hand, most author assume a beneficial On the other hand, most author assume a beneficial specific effect of speech therapy particularly when it is specific effect of speech therapy particularly when it is intense and starts earlyintense and starts early. .

(Musso (Musso et al.et al., 1999), 1999)

RECOVERY FROM APHASIARECOVERY FROM APHASIA

Two mechanismsTwo mechanisms for recovery from aphasia, for recovery from aphasia, repair of damaged repair of damaged language networkslanguage networks and and activation of compensatory areas. activation of compensatory areas.

Recovery must involve regions Recovery must involve regions outside the morphologically damaged outside the morphologically damaged areaarea that regain or take over language functions lost in acute stroke. that regain or take over language functions lost in acute stroke.

The The restoration of left hemisphere language networksrestoration of left hemisphere language networks is associated is associated with better recovery and inversely related to activity in the with better recovery and inversely related to activity in the compensated compensated

or recruited areas of the right hemisphere. or recruited areas of the right hemisphere.

(Cao (Cao et alet al., 1999 and Kessler ., 1999 and Kessler et al.,et al., 2000) 2000)

PROGNOSISPROGNOSIS

Most of the Most of the spontaneous recoveryspontaneous recovery in linguistic function in linguistic function occurs in the occurs in the first weeksfirst weeks after stroke and is after stroke and is completed by completed by

the end of the first yearthe end of the first year, although reports exist of , although reports exist of improvements occurring as a result of improvements occurring as a result of long-term therapylong-term therapy of of

patients with chronic aphasia patients with chronic aphasia

(Pulvermuller (Pulvermuller et alet al., 2001).., 2001).

182

Faktor –Faktor PrognosisFaktor –Faktor Prognosis

Luas cederaLuas cedera

Letak cederaLetak cedera

Keparahan afasiaKeparahan afasia

UmurUmur

Intelegensi dan PendidikanIntelegensi dan Pendidikan

LateralisasiLateralisasi

KepribadianKepribadian

183

TADIRTADIR

TES AFASIATES AFASIA

UNTUKUNTUK

DIAGNOSISDIAGNOSIS

INFORMASIINFORMASI

REHABILITASIREHABILITASI

184

Tujuan TADIRTujuan TADIR

Membuat diagnosis afasia /bukan afasiaMembuat diagnosis afasia /bukan afasia

Membuat diagnosis sindrom afasia manaMembuat diagnosis sindrom afasia mana

Memberi informasi kepada pasien, Memberi informasi kepada pasien, lingkungannya dan orang ketiga lainlingkungannya dan orang ketiga lain

Menjadi titik tolak untuk penangananMenjadi titik tolak untuk penanganan

rehabilitasirehabilitasi

185

Perbedaan khasPerbedaan khas

AfasiaAfasia: kesulitan penemuan kata(verbal & : kesulitan penemuan kata(verbal & tulis jelek,visual bagus)tulis jelek,visual bagus)DisartriDisartri: Kesulitan mengucapkan kata: Kesulitan mengucapkan kataDemensiaDemensia: Kesalahan memberi : Kesalahan memberi nama(persepsi visual jelek)nama(persepsi visual jelek)

Jk tdpt perekaman normal ke ingatan dr Jk tdpt perekaman normal ke ingatan dr gambar tidak ada demensiagambar tidak ada demensia

(Dharmaperwira Prins,1993(Dharmaperwira Prins,1993

Hounsfield Unit(HU)Hounsfield Unit(HU) +1000+1000 BoneBone +100+100 CalsificationsCalsifications +70+70

HemorrhagesHemorrhages +50+50

Grey matterGrey matter +35+35

White matterWhite matter +25+25

Edema/necrosisEdema/necrosis +10+10

Cerebrospinal fluidCerebrospinal fluid +5+5 00 WaterWater -10-10

Fatty structureFatty structure -100-100 -1000-1000 AirAir

AstutiAstutiNeurologist Neurologist

RSUP DR SARDJITO/FK UGMRSUP DR SARDJITO/FK UGMYOGYAKARTAYOGYAKARTA

16 Februari 200816 Februari 2008

Role of Mecobalamin CNSPrevention, therapy

TARGET

PATOMEKANISMEHOMOSISTEIN

FAKTOR RISIKO INDEPENDEN YANG PENTING UNTUK PENYAKIT SEREBRO DAN

KARDIOVASKULER DAN PENYAKIT PERIFERAL

FAKTOR RISIKO OSTEOPOROSIS KOMPLIKASI STROKE

transmetilasi........increases nucleic acid synthesis in nerve cells

Scot JM, et al.: Lancet 1981, 337

remetilasi........ increases lecithin synthesis, major component of myelin sheath

Tashiro S, et al.: Hakkone Symposium,”The Nervous System and Methyl B12,” 1981, p-30

Improves Lecithin Synthesis

Nakazawa et.al. International Symposium on Neuropathy, Japan. 1983

Hyperhomocysteinemia is a risk factor for both

ischemic stroke and

osteoporotic fractures in elderly men and women

Pernodjo Dahlan, Pernodjo Dahlan, Astuti*,Astuti*,20052005

THE BENEFIT OF THE BENEFIT OF MEASUREMENT OF MEASUREMENT OF

CORRELATION BETWEEN CORRELATION BETWEEN HOMOCYSTEINE AND HOMOCYSTEINE AND ANTIOXIDANT STATUS ANTIOXIDANT STATUS TO MALONDIALDEHIDE TO MALONDIALDEHIDE

LEVEL IN VASCULAR LEVEL IN VASCULAR DEMENTIADEMENTIA

61 native Javanese patients 61 native Javanese patients were eligiblewere eligible

We found 22 subjects (36 %) We found 22 subjects (36 %) with with hyperhomocysteinemia, hyperhomocysteinemia, which is mild which is mild hyperhomocysteinemia (21 hyperhomocysteinemia (21 subject /34,4 %) subject /34,4 %)

There were 22 patients (36 There were 22 patients (36 %) with %) with hyperhomocysteinemia, and hyperhomocysteinemia, and most of them had mild most of them had mild hyperhomocysteinemia (hyperhomocysteinemia ( 15 – 30 15 – 30 mol/L) (21 patients mol/L) (21 patients or 34,4 %) with or 34,4 %) with meanmean homocysteine 19,60 homocysteine 19,60 3,08. 3,08.

TheThe prevalence of prevalence of hyperhomcysteinemia is still hyperhomcysteinemia is still high in vascular dementiahigh in vascular dementia

Result of studies on Homocysteine in Indonesia

N Mean tHcy (mmol/L)

Tugasworo 30 Stroke 14.34±5.45(33% Hyper Hcy)

Meta-analyses of 27 clinical studies Elevation in risk associated with

5 µM increment in tHcy

Cerebrovasc.dis. M/F1.9

(1.6-2.3)(11 studies)

Boushey et al, JAMA 1995

Stroke Stroke increases the increases the

risk of risk of subsequent hip subsequent hip fracture by 2 to fracture by 2 to

4 times.4 times.

Increased fracture risk is a Increased fracture risk is a recognized complication recognized complication followingfollowing strokestroke. Bone loss . Bone loss following a hemiplegic following a hemiplegic strokestroke has been proposed has been proposed

as a major risk factor for as a major risk factor for post-post-strokestroke hip fracture, hip fracture, with awith a recent focus on the recent focus on the development of novel development of novel therapeutic measurestherapeutic measures to to prevent bone loss and prevent bone loss and fractures after fractures after strokestroke. We . We brieflybriefly review the literature review the literature on the epidemiology and on the epidemiology and pathophysiologypathophysiology of bone of bone loss and hip fracture after loss and hip fracture after strokestroke, and then critically, and then critically

review recent studies on review recent studies on preventive strategies.preventive strategies.

Hip fractures after stroke and their preventionP.K. Myint1,2, K.E.S. Poole3 and E.A. Warburton1

Increased Increased Osteoclast Activity Osteoclast Activity in the Presence of in the Presence of Increased Increased Homocysteine Homocysteine ConcentrationsConcentrations

may be an may be an independent risk independent risk factor for osteoporotic factor for osteoporotic fractures and fractures and therefore may also therefore may also adversely affect bone adversely affect bone metabolism.metabolism.Markus Herrmann,1 Thomas Widmann,2 Graziana Markus Herrmann,1 Thomas Widmann,2 Graziana

Colaianni,3 Silvia Colucci,3 Colaianni,3 Silvia Colucci,3 Alberta Zallone,3 and Alberta Zallone,3 and Wolfgang Herrmann1*Wolfgang Herrmann1*Clinical Chemistry 51, No. 12, Clinical Chemistry 51, No. 12, 200200

Increased plasma homocysteine (Hcys)

Several studies found that Several studies found that cobalamin and cobalamin and

folate status are related to folate status are related to bone mineral density (BMD) bone mineral density (BMD)

and fracture riskand fracture risk

Markus Herrmann,1 Thomas Widmann,2 Graziana Markus Herrmann,1 Thomas Widmann,2 Graziana Colaianni,3 Silvia Colucci,3 Colaianni,3 Silvia Colucci,3 Alberta Zallone,3 and Alberta Zallone,3 and Wolfgang Herrmann1*Wolfgang Herrmann1*Clinical Chemistry 51, No. 12, 200Clinical Chemistry 51, No. 12, 200

In a 2-year prospective, placebo-controlled, double-blind trial, Sato et al. (29 ) observed a strong reductionin fracture incidence in stroke patients who received high doses of folate and vitamin B12.

In addition, low cobalamin status has been shown to reduce osteoblast activity Nothing is known, however, about osteoclast (OC) function in the presence of increased HCY or low B vitamin concentrations.

It has been suggested that disturbed crosslinking of collagen fibrils and reduced fibrillin-1 and -2 deposition lead to a disturbed architecture of bone matrix in homocystinuric patients.

> The impact of intermolecular collagen cross-links in bone has been adduced, in part, from studies of lathyrism The sweet pea (Lathyrus odoratus) compound -aminopropionitrile irreversibly inhibits lysyl oxidase and blocks initial collagen cross-link formation. This effect could lead to reduced bone quality and might be an alternative explanation for an increased fracture risk in hyperhomocysteinemic patients.

SEDIAAN

active form CH3 (methyl - )

Jenis Vitamin B12 dan manfaatnya

B12

TIDAK AKTIF

AKTIF

CN

Co Vitamin B komplekB1, B6, B12

Vit B kompleksB1, B6, B12

OH

Co

OHOH

CH2

Co

Dalam Liver

Hycobal

Dalam Serum

CH3

Co

Memperbaiki neuropatimelalui sintesis asam nukleat,protein dan fosfolipid

CH3

Co

Neuropatiperifer

Neuropatiperifer

Memperbaiki anemiamelalui sintesis heme

Anemia dan neuropati akibat defisiensi dan Metabolisme abnormal vit. B1 B6 B12




Memperbaiki Defisiensi cobalamin

Memperbaiki Defisiensi cobalamin

Kadar Homosistein me

Faktor Risiko gangguan Serebrovaskuler

koroner, peny. Pembuluh darah tepiTrombosis vena

KADAR DALAM

SERUM & LCS

highly concentration in CSF and serum

ditransportasikan dengan kadar yang ditransportasikan dengan kadar yang tinggi tinggi

ke dalam organel sel – sel sarafke dalam organel sel – sel saraf

0.9%

CN-B12

OH-B12

DBCC

CH3- B12

8.1%

0.7%

Serum Cairanserebrospinal

91.2%

73.2%

25.9%

Uchino et. al.Vitamins 1970; 42(3): 198

Keterangan:CH3-B12, Mecobalamin ( Methycobal )CN-B12, CyanocobalaminDBCC, DeoxyadenosylcobalaminOH-B12, Hydroxocobalamin

Inada et al: Hakone symposium” the Nervous System and Vitamin B12, 23-29(1981)MBL-0680

Bagaimana MECOBALAMIN memperbaiki kerusakan saraf ?

Objective: Evaluate Methycobal

transport to human C.S.F.Method : CH3-B12 - 1,000ug

: CN -B12 - 1,000ug

Nabuo Tanaka, et al.: Hakone Symp.”Nervous Sys. & Vit. B12”, p5, 1981

One I.M. inj.

A double-blind, randomized A double-blind, randomized controlled study of 628controlled study of 628

consecutive patients aged 65 consecutive patients aged 65 years or older with residual years or older with residual hemiplegia at least 1 yearhemiplegia at least 1 year

following first ischemic stroke, following first ischemic stroke, who were recruited from a who were recruited from a single Japanese hospital fromsingle Japanese hospital from

April 1, 2000, to May 31, April 1, 2000, to May 31, 2001. Patients were assigned 2001. Patients were assigned to daily oral treatment with to daily oral treatment with 5mg of folate and 1500 μg of 5mg of folate and 1500 μg of mecobalamin, or double mecobalamin, or double placebo; 559 completed theplacebo; 559 completed the

2-year follow-up.2-year follow-up.

Yoshihiro Sato, MDYoshihiro Sato, MD

Yoshiaki Honda, MDYoshiaki Honda, MD

Jun Iwamoto, MDJun Iwamoto, MD

Tomohiro Kanoko, PhDTomohiro Kanoko, PhD

Kei Satoh, MDKei Satoh, MD

In this Japanese population with a In this Japanese population with a high baseline fracture risk, high baseline fracture risk, combinedcombined

treatment with folate treatment with folate and vitamin B12 is and vitamin B12 is safe and effective in safe and effective in reducing the risk of a reducing the risk of a hip fracture in elderly hip fracture in elderly patients following patients following stroke.stroke.

JAMA. 2005;293:1082-JAMA. 2005;293:1082-10881088

Yoshihiro Sato, MD, Yoshiaki Honda, MD; Yoshihiro Sato, MD, Yoshiaki Honda, MD; Jun Iwamoto, MD; Tomohiro Kanoko, Jun Iwamoto, MD; Tomohiro Kanoko, PhD; Kei Satoh, MDPhD; Kei Satoh, MD

JAMA, March 2, 2005—Vol 293, No. 9JAMA, March 2, 2005—Vol 293, No. 9

Treatment with folate and Treatment with folate and mecobalaminmecobalamin

was effective in reducing was effective in reducing the risk of the serious the risk of the serious

post stroke complication post stroke complication ofof

fractures.fractures.

Effect of Folate and Effect of Folate and Mecobalamin on Hip Mecobalamin on Hip Fractures in Patients Fractures in Patients

With Stroke With Stroke A Randomized Controlled A Randomized Controlled

TrialTrial demonstrated a demonstrated a reduction in reduction in

plasma plasma homocysteine homocysteine

levels by levels by combination combination

therapy with therapy with folate and vitamin folate and vitamin

B12 B12

in patients with in patients with ischemic stroke.ischemic stroke.

Yoshihiro Sato, MD, Yoshiaki Yoshihiro Sato, MD, Yoshiaki Honda, MD; Jun Iwamoto, MD; Honda, MD; Jun Iwamoto, MD; Tomohiro Kanoko, PhD; Kei Tomohiro Kanoko, PhD; Kei Satoh, MDSatoh, MDJAMA, March 2, 2005—Vol 293, JAMA, March 2, 2005—Vol 293, No. 9No. 9

Amelioration by Amelioration by mecobalamin of subclinical mecobalamin of subclinical

carpal tunnel syndrome carpal tunnel syndrome involving unaffected limbs in involving unaffected limbs in

stroke patientsstroke patientsThe purpose of this study was to evaluate the effects of the The purpose of this study was to evaluate the effects of the orally administered orally administered mecobalaminmecobalamin, an analogue of vitamin B12, , an analogue of vitamin B12, for carpal tunnel syndrome (CTS) in the nonparetic side in for carpal tunnel syndrome (CTS) in the nonparetic side in patients following patients following strokestroke. In a randomized open label and . In a randomized open label and prospective study of prospective study of strokestroke patients, 67 received of 1500 mug patients, 67 received of 1500 mug mecobalaminmecobalamin daily for 2 years, and the remaining 68 daily for 2 years, and the remaining 68 (untreated group) did not. At baseline, sensory nerve conduction (untreated group) did not. At baseline, sensory nerve conduction velocity, motor nerve conduction velocity, sensory nerve action velocity, motor nerve conduction velocity, sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency, palm-to-wrist SNAP, motor nerve conduction velocity latency, palm-to-wrist SNAP, motor nerve conduction velocity compound motor action potentials, and distal motor latency of compound motor action potentials, and distal motor latency of median nerve were significantly more abnormal on the median nerve were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. nonparetic side than on the hemiparetic side or in controls. Before the treatment 21 patients (31%) of untreated and 20 Before the treatment 21 patients (31%) of untreated and 20 patients (30%) of treated group met electrophysiologic criteria patients (30%) of treated group met electrophysiologic criteria for CTS. Sensory impairment of the nonparetic side had for CTS. Sensory impairment of the nonparetic side had lessened in the treated group. After 2 years, all lessened in the treated group. After 2 years, all electrophysiologic indices of nonparetic side were significantly electrophysiologic indices of nonparetic side were significantly improved in the treated group compared with those in the improved in the treated group compared with those in the untreated group. The improvement from baseline of untreated group. The improvement from baseline of electrophysiologic parameters in sensory nerve in the treated electrophysiologic parameters in sensory nerve in the treated group was greater than the improvement measured in motor group was greater than the improvement measured in motor nerve. There were no side effects. Oral nerve. There were no side effects. Oral mecobalaminmecobalamin treatment is a safe and potentially beneficial treatment is a safe and potentially beneficial therapytherapy for CTS in for CTS in strokestroke patients. patients.

Department of Neurology, Mitate Hospital, 3237 Department of Neurology, Mitate Hospital, 3237 Yugeta, Tagawa 826-0041, Japan. y-Yugeta, Tagawa 826-0041, Japan. [email protected]@ktarn.or.jp

overuse of the non paretic hand and wrist of the nonparetic side following stroke result in significantly more abnormal on the nonparetic side than on the hemiparetic side in terms of electrophysiologic indices of median nerve function.

An active form of cobalaminAn active form of cobalamin

Participates in transmethylationParticipates in transmethylation

Improves synthesis of proteins, nucleicImproves synthesis of proteins, nucleic

acids and phospholipids which are needed acids and phospholipids which are needed in in

the repair of damaged nerves.the repair of damaged nerves.

Farmakokinetik

1. AbsorpsiB12 yang terdapat dalam makanan akan berikatan dengan Faktor Intrinsik(FI) dalam lambung dan diabsorpsi oleh usus. B12 tidak dapat diabsorpsi tanpa FI. Sehingga pada pasien lanjut usia, yang terinfeksi Helicobacter pylori atau gangguan gastrointestinal lainnya beresiko mengalami defisiensi B12. Bahkan pada pasien yang diangkat lambungnya (seperti pada ulkus dan kanker) maka absorpsi B12 dari makanan adalah nol.

Tetapi, jika B12 diberikan dalam dosis farmakologi(yang berarti dipakai sebagai obat dalam bentuk tablet atau kapsul), maka FI tidak dibutuhkan untuk absorpsinya

2. DistribusiSetelah vitamin B12 diabsorpsi oleh aliran darah, vitamin B12 berikatan dengan transcobalamin II (pembawa protein). Kompleks B12-transcobalamin II ditransportasikan ke dalam sel kemudian dihidrolisa. Nasib B12 selanjutnya adalah berperan dalam proses transmetilasi atau disimpan sebagai adenosilcobalamin.

Hidroksocobalamin akan menghasilkan bentuk antibodi dari transcobalamin II-B12 kompleks (menginaktifkan kompleks). Sehingga penggunaan hidroksocobalamin tidak direkomendasikan.

Methylcobalamin merupakan sediaan yang sudah dalam bentuk aktif untuk perbaikan kerusakan saraf (neuropati)

Cyanocobalamin di dalam liver tidak diubah menjadi methylcobalamin sehingga tidak dapat dimanfaatkan untuk proses perbaikan kerusakan saraf (Ide H, 1987)

3. EkskresiKarena Methycobal sifatnya larut dalam air, maka ia diekskresikan melalui urin.

4. Waktu yang dibutuhkan untuk mencapai kadar puncak dalam serum plasma darah:Oral (kapsul) : 1 jamInjeksi: Intra Muskular = 3 – 5 jam; Intra Vena = 3 menit

5. Konsentrasi dalam darah setelah pemakaian jangka panjangOral (kapsul) : 2 – 2,7 kali normalInjeksi :

- Intra Muskular : 15 – 30 kali normal- Intra vena : 15 – 30 kali normal

PREVALEPREVALENSINSI

DEFISIENSI COBALAMINDEFISIENSI COBALAMIN

USA : 300.000 – 3 JutaUSA : 300.000 – 3 Juta EROPA & INDIA : 1.6 – 10 % EROPA & INDIA : 1.6 – 10 %

POPULASIPOPULASI INDONESIA : ?INDONESIA : ?

BANYAK BANYAK

UMUR: 40 – 70 Th.UMUR: 40 – 70 Th.

DEFISIENSI COBALAMINDEFISIENSI COBALAMIN

USA : 300.000 – 3 JutaUSA : 300.000 – 3 Juta EROPA & INDIA : 1.6 – 10 % EROPA & INDIA : 1.6 – 10 %

POPULASIPOPULASI INDONESIA : ?INDONESIA : ?

BANYAK BANYAK

UMUR: 40 – 70 Th.UMUR: 40 – 70 Th.

MekanisMekanismeme

Defisiensi cobalaminDefisiensi cobalamin

? ?

Gangguan pd sarafGangguan pd sarafDemielinisasiDemielinisasi

S-adenosylmethionine (SAM)

HIPOTESIS :

Kadar methylmalonat acid (MMA)

Merusak rantai as.lemak sel neuron

neurotoksik

Paradigma Baru

Defisiensi cobalamin

Gangguan pd jaringan sitokin & growth factors di CNS

TNF-alpha; NGF (Nerve Growth Factor); IL-6 dan EGF (Epidermal Growth Factor)

Neurotropik

Defisiensi Defisiensi CobalamiCobalami

nn

Dalam darahDalam darah

&&

LcsLcs

Kadar EGF

Kadar TNF-alphaKadar homosistein

Up-regulation sitokinneurotoksik

Down regulation Faktor-faktor neurotropik

Kerusakan sel neuron

PERAN NITRIC OXYDE (N0)PERAN NITRIC OXYDE (N0)

Defisiensi Cobalamin

MENGOKSIDASI INTI COBALT DARI COBALAMIN

PERUBAHAN HOMOSISTEIN METHIONINESuplai SAM

TERPUTUS

TERHAMBAT

•inform them of the risks and to recommend a healthy lifestyle. •A healthy lifestyle not only will lower tHcy levels but, more importantly, will promote health irrespective of whether homocysteine is a cause or a marker of disease.

change in lifestyle will also change the tHcy levels

Raised tHcy levels are related to a poor lifestyle

Green T.J., McMahon, J.A., Skeaff, C.M., Williams, S.M., and Whiting S.J. Am J Clin Nutr 2007;85:460–4.

Total Homocysteine concentrations are strongly dependent on

folate and vitamin B-12 status,

results of randomized controlled trials show that supplementation with folic acid and

vitamins B-12 and B-6 is an effective way of lowering homocysteine.

Green T.J., McMahon, J.A., Skeaff, C.M., Williams, S.M., and Whiting S.J. Am J Clin Nutr 2007;85:460–4.

MECOBALAMINMECOBALAMIN

Vitamin B12 (cobalamin) is an essential cofactor for methionine synthase and N5-

methyltetrahydrofolate serves as the methyl donor.

Yoshihiro Sato, MD, Yoshiaki Honda, MD; Jun Iwamoto, MD; Tomohiro Kanoko, PhD; Kei Satoh, MDJAMA, March 2, 2005—Vol 293, No. 9

there are close relationships between plasma homocysteine and cobalamin and folate.

•A close association between plasma homocysteine and risk of ischemi stroke has been reported and plasma homocysteine levels are higher in patients with ischemic stroke in both acute and convalescent phases.

• In patients with homocysteinuria, a rare autosomal recessive biochemical abnormality, there is an increased prevalence of skeletal abnormalities, including osteoporosis, a primary risk factor for hip fracture. Thus, elevated plasma homocysteine concentrations may be associated with osteoporosis and increase the risk of a hip fracture.

• An increased homocysteine level appears to be a strong and independent risk factor for an osteoporotic fracture of the bones, including the hip, in older men and women.

Homocysteine before and after treatment of 8 weeks

8.8

11.1 11.2 11.5

8.89.9

8.77.1

02468

101214

Control Methycobal Folic asid Methycobal +Folic acid

Pre Post Methycobal:1500ug/ day Folic acid:5mg/ day

n 72 63 6464

umol/ l

Hyperhomocysteinemia in Patients with ConvalescentStage Ischemic Stroke: Effect of Combined Therapy with Folic

Acid and Methycobal

Y. Sato. Journal of the Neurological Sciences.2002 202, 65-68

Methycobal gro group CH3B12 1500µg/day up CH3B12 1500µg/day

Methycobal acts as a cofactor in the remethylation of homocysteine.

Role of Methycobal

METHYLENE-TETRAHYDROFOLATE

METHYLTETRA-HYDROFOLATE

Methyl-cobalamin

THF

MethionineMethionine

Methionine synthase

Re-methylation

HomocysteineHomocysteine

AdoMetAdoMet

AdoHcyAdoHcy

Homocysteine is essential in the bodyHomocysteine is essential in the body

Homocysteine participates in three processes: In the transsulfuration pathway to synthesize

cystathionine, cysteine and glutathione. The Catabolism of betaine and choline The recycling of the intracellular folate.

Homocysteine controls growth and support bone and tissue formation.

Why Homocysteine is HarmfulWhy Homocysteine is Harmful

Elevated Elevated HomocysteineHomocysteine

Elevated Elevated HomocysteineHomocysteine

Atherosclerosis and thrombosisMyocardial Infarction

StrokePheripheral vascular

Disease

Birth defects like neural

tube defects

Homocysteine Homocysteine Thiolactone

Protein damage, loss of function, Formation of extensively modified protein

Venous thrombosisVenous

thromboembolism

When associated withDiabetes it increasesthe risk of angiopathy

Alzheimer’s DiseaseOther types of cognitive Loss due to disturbed

transmethylation

Stroke

definisialgoritmafaktor resikoanatomi otak

Stroke perdarahanetiologi

hipertensianeurismaA-V malformasi

patofisiologisimtomtanda klinisdiagnosis lokasi perdarahantatalaksanakontrol tekanan darahPrognosisRehabilitasiKomplikasi

Neuroprotektanciticholinepiracetammannitol

Sindrom ArteriArteri serebri mediaArteri serebri anteriorArteri serebri posterior

Afasiadefinisisindrom afasiaprognosis afasiadiagnosis afasia (TADIR)

Mecobalamin (dr. Astuti)

Documents

Presentasi Kasus Stroke Final