gejala awal stroke biasanya berupa:1. Hilangnya keseimbangan (vertigo)2. Tidak mampu mengenali bagian tubuh3. Penglihatan ganda (pandangan kabur)4. Kelumpuhan di satu sisi tubuh yang sifatnya semntara5. Gangguan bicara

Serangan kecil atau serangan awal stroke biasanya diawali dengan daya ingat menurun dan sering kebingungan secara tiba-tiba dan kemudian menghilang dalam waktu 24 jam selain itu tanda dan gejala stroke dapat diamati dari beberapa hal :

1. Adanya serangan neurologis fokal berupa kelemahan atau kelumpuhan lengan, tungkai atau salah satu sisi tubuh

2. Melemahnya otot (hemiplegia), kaku dan menurunnya fungsi sensorik3. Hilangnya rasa atau adanya sensasi abnormal pada lengan atau tungkai atau salah satu sisi

tubuh seperti baal, mati rasa sebelah badan, terasa kesemutan, perih bahakan seperti rasa terbakar dibagian bawah kulit

4. Gangguan penglihatan seperti hanya dapat melihat secara parsial ataupun tidak dapat melihat keseluruhan karena penglihatan gelap dan pandangan ganda sesaat

5. Menurunnya kemampuan mencium bau dan mengecap6. Berjalan menjadi sulit dan langkahnya tertatih-tatih bahkan terkadang mengalami kelumpuhan

total7. Hilangnya kendali terhadap kandung kemih sehingga sering kencing tanpa disadari8. Kehilangan keseimbangan, gerakan tubuh tidak terkoordinasi dengan baik9. Tidak memahami pembicaraan orang lain, tidak mampu membaca, menulis dan berhitung

dengan baik10. Adanya gangguan dan kesulitan dalam menelan makanan ataupun minuman (cenderung

keselek)11. Adanya gangguan bicara dan sulit berbahasa yang ditunjukkan dengan bicara tidak jelas (rero),

sengau, pelo, gagap dan berbicara haya sepatah kata bahkan sulit memikirkan atau mengucapkan kata-kata yang tepat

12. Menjadi Pelupa (Dimensia) dan tidak mampu mengenali bagian tubuh13. Vertigo (pusing, puyeng) atau perasaan berputar yang menetap saat tidak beraktifitas14. Kelopak mata sulit dibuka15. Menjadi lebih sensitif, mudah menangis ataupun tertawa16. Banyak tidur dan selalu ingin tidur17. Gangguan kesadaran, pingsan sampai tak sadarkan diri

Penyebab Penyakit StrokeAda dua faktor yang merupakan penyebab stroke yaitu resiko medis dan resiko perilaku

Faktor resiko medis yang menyebabkan atau memperparah stroke antara lain hipertensi (penyakit tekanan darah tinggi), kolesterol, arteriosklerosis (pengerasan pembuluh darah), gangguan jantung, diabetes, riwayat stroke dalam keluarga (faktor keturnan) dan migren (sakit kepelah sebelah). Menurut data statistik 80% pemicu stroke adalah hipertensi dan arteriosklerosis

Faktor resiko perilaku disebakan oleh gaya hidup dan pola makan yang tidak sehat seperti kebiasaan merokok, menkonsumsi minuman bersoda dan beralkohol gemar mengkonsumsi makanan cepat saji (fast food dan junk food). Faktor resiko perilaku lainnya adalah kurangnya aktifitas gerak / olah raga dan obesitas. Salah satu pemicunya juga adalah susasana hati yang tidak nyaman seperti sering marah tanpa alasan yang jelas.

Stroke[1] (bahasa Inggris: stroke, cerebrovascular accident, CVA) adalah suatu kondisi yang terjadi ketika pasokan darah ke suatu bagian otak tiba-tiba terganggu. Dalam jaringan otak, kurangnya aliran darah menyebabkan serangkaian reaksi biokimia, yang dapat merusakkan atau mematikan sel-sel saraf di otak. Kematian jaringan otak dapat menyebabkan hilangnya fungsi yang dikendalikan oleh jaringan itu. Stroke adalah penyebab kematian yang ketiga di Amerika Serikat dan banyak negara industri di Eropa (Jauch, 2005). Bila dapat diselamatkan, kadang-kadang penderita mengalami kelumpuhan di anggota badannya, hilangnya sebagian ingatan atau kemampuan bicaranya. Beberapa tahun belakangan ini makin populer istilah serangan otak. Istilah ini berpadanan dengan istilah yang sudah dikenal luas, "serangan jantung".Stroke terjadi karena cabang pembuluh darah terhambat oleh emboli. Emboli bisa berupa kolesterol atau udara.[sunting] KlasifikasiStroke dibagi menjadi dua jenis yaitu stroke iskemik maupun stroke hemorragik. Sebuah prognosis hasil sebuah penelitian di Korea menyatakan bahwa,[2] 75,2% stroke iskemik diderita oleh kaum pria dengan prevalensi berupa hipertensi, kebiasaan merokok dan konsumsi alkohol. Berdasarkan sistem TOAST, komposisi terbagi menjadi 20,8% LAAS, 17,4% LAC, 18,1% CEI, 16,8% UDE dan 26,8% ODE.[sunting] Stroke hemorragikDalam stroke hemorragik, pembuluh darah pecah sehingga menghambat aliran darah yang normal dan darah merembes ke dalam suatu daerah di otak dan merusaknya. Pendarahan dapat terjadi di seluruh bagian otak seperti caudate putamen; talamus; hipokampus; frontal, parietal, dan occipital cortex; hipotalamus; area suprakiasmatik; cerebellum; pons; dan midbrain.[3] Hampir 70 persen kasus stroke hemorrhagik menyerang penderita hipertensi.[4]

Stroke hemorragik terbagi menjadi subtipe intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH),[5] cerebral venous thrombosis, dan spinal cord stroke.[6] ICH lebih lanjut terbagi menjadi parenchymal hemorrhage, hemorrhagic infarction, dan punctate hemorrhage.[3]

[sunting] Stroke iskemikDalam stroke iskemik, penyumbatan bisa terjadi di sepanjang jalur pembuluh darah arteri yang menuju ke otak. Darah ke otak disuplai oleh dua arteria karotis interna dan dua arteri vertebralis. Arteri-arteri ini merupakan cabang dari lengkung aorta jantung (arcus aorta).[sunting] Sistem klasifikasi etiologisBeberapa sistem klasifikasi yang didasarkan kepada pertimbangan etiologi telah diterapkan kepada stroke iskemik.[7] Beberapa sistem tersebut gagal mengikuti perkembangan jaman dan tidak lagi dipergunakan, beberapa sistem yang lain masih dapat diterima oleh sebagian masyarakat dan dipergunakan dalam lingkup yang terbatas. Berikut adalah sistem klasifikasi yang paling mutakhir dan paling banyak digunakan.[sunting] Sistem TOASTSistem TOAST (bahasa Inggris: Trial of ORG 10172 in Acute Stroke Treatment) pertama kali dikembangkan kepada terapi stroke iskemik akut pada awal tahun 1990. Sistem ini didasarkan kepada sebagian besar fitur klinis namun tetap mempertimbangkan informasi diagnostik dari CT, MRI, transthoracic echocardiography, extracranial carotid ultrasonography, dan jika memungkinkan, cerebral angiography.Sistem TOAST membagi stroke menjadi 5 subtipe yaitu,[8][9] large artery atherosclerosis (LAAS), cardiaoembolic infarct (CEI), small artery occlusion/lacunar infarct (LAC), stroke of another determined cause/origin (ODE), dan stroke of an undetermined cause/origin (UDE).[sunting] Sistem CCSKlasifikasi sistem CCS (bahasa Inggris: Causative Classification of Stroke System) mirip dengan sistem TOAST dengan perbedaan dalam subtipe large artery atherosclerosis dibedakan menjadi occlusive dan stenotic. Sebagai contoh, penurunan diameter ≥ 50%, atau penurunan diameter <50% disertai plaque

ulceration atau trombosis. Dan subtipe undetermined cause dibedakan lebih lanjut menjadi unknown, incomplete evaluation, unclassified stroke (more than one etiology), dan cryptogenic embolism.[sunting] Sistem ASCOASCO merupakan akronim dari atherothrombosis, small vessel disease, cardiac causes, and other uncommon causes. Sistem ASCO merupakan klasifikasi berdasarkan sistem fenotipe. Tiap fenotipe masih terbagi menjadi jenjang 0, 1, 2, 3 atau 9. Jenjang 0 berarti disease is completely absent, 1 berarti definitely a potential cause of the index stroke, 2 untuk causality uncertain dan 3 untuk unlikely a direct cause of the index stroke (but disease is present), 9 bagi grading is not possible due to insufficient work-up.[10]

Dalam sistem ini, penderita dapat dikategorikan menjadi lebih dari satu subtipe etiologis, misalnya, penderita dengan ateroma karotid yang menyebabkan stenosis 50% dan fibrilasi atrial dengan aterosklerosis dan emboli kardiak, atau dijabarkan menjadi seperti A1-S9-C0-O3.[sunting] Sistem UCSD Stroke DataBankSistem UCSD mengklasifikan stroke iskemik menjadi large-vessel stenotic, large-vessel occlusive, Small-vessel stenotic, small-vessel occlusive, embolic dan unknown cause. Sedangkan klasifikasi stroke hemorragik terbagi menjadi subtipe yang sama yaitu tipe intracerebral dan subarachnoid.[sunting] Sistem HCSRSistem HCSR (bahasa Inggris: Harvard Cooperative Stroke Registry) membuat klasifikasi menjadi subtipe stroke yang disertai trombosis di arteri atau dengan infark lakunar, cerebral embolism, intracerebral hematoma, subarachnoid hemorrhage dari malformasi aneurysm atau arteriovenous.[11]

[sunting] Sistem NINCDS Stroke Data BankDalam Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke memklasifikasi menjadi subtipe diagnostik berdasarkan riwayat klinis penderita, pemeriksaan, test laborat meliputi tomografi, noninvasive vascular imaging, dan saat memungkinkan dan relevan, angiografi. Dari diagnosa tersebut subtipe infarcts of undetermined cause (IUC) dapat diklasifikasi ulang menjadi subtipe embolisme idiopatik, stenosis atau trombosis di pembuluh nadi, infark lakunar, infarksi superfisial dan sindrom nonlakunar.[12]

[sunting] Sistem lainBeberapa ahli lain mempertimbangan klasifikasi berdasarkan fenotipe seperti keberadaan internal carotid artery plaque, intima-media thickness, leukoaraiosis, cerebral microbleeds (CMB), atau multiple lacunae.[6]

CMB adalah deposit hemosiderin intraserebral yang terdapat di ruang pervaskular.[13] Ekspresi CMB sangat tinggi di infark lakunar dan infark aterotrombotik, dan berekspresi rendah di infarksi kardioembolik. CMB dan leukoaraiosis sangat berkaitan erat. Hasil prognosis menunjukkan bahwa CMB ditemukan dalam 47-80% kasus primary intracerebral haemorrhage dan 0-78% dalam kasus ischaemic cerebrovascular disease.[14]

[sunting] PatofisiologiHingga saat ini patofisiologi stroke merupakan studi yang sebagian besar didasarkan kepada serangkaian penelitian,[15] terhadap berbagai proses yang saling terkait, meliputi kegagalan energi, hilangnya homeostasis ion sel, asidosis, peningkatan kadar Ca 2+ sitosolik, eksitotoksisitas, toksisitas dengan radikal bebas, produksi asam arakidonat, sitotoksisitas dengan sitokina, aktivasi sistem komplemen, disrupsi sawar darah otak, aktivasi sel glial dan infiltrasi leukosit.[16]

Pusat area otak besar yang terpapar iskemia akan mengalami penurunan aliran darah yang dramatis, menjadi cedera dan memicu jenjang reaksi seperti lintasan eksitotoksisitas yang berujung kepada nekrosis yang menjadi pusat area infark dikelilingi oleh penumbra/zona peri-infarksi. Menurut morfologi, nekrosis merupakan bengkak selular akibat disrupsi inti sel, organel, membran plasma, dan disintegrasi struktur inti dan sitoskeleton.

Di area penumbra, apoptosis neural akan berusaha dihambat oleh kedua mekanisme eksitotoksik dan peradangan,[17] oleh karena sel otak yang masih normal akan menginduksi sistem kekebalan turunan untuk meningkatkan toleransi jaringan otak terhadap kondisi iskemia, agar tetap dapat melakukan aktivitas metabolisme. Protein khas CNS seperti pancortin-2 akan berinteraksi dengan protein modulator aktin, Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE-1) dan Bcl-xL akan membentuk kompleks protein mitokondrial untuk proses penghambatan tersebut.Riset terkini menunjukkan bahwa banyak neuron di area penumbra dapat mengalami apoptosis setelah beberapa jam/hari sebagai bagian dari proses pemulihan jaringan pasca stroke dengan 2 lintasan, yaitu lintasan ekstrinsik dan lintasan intrinsik.Iskemia tidak hanya mempengaruhi jaringan parenkima otak, namun berdampak pula kepada sistem ekstrakranial. Oleh karena itu, stroke akan menginduksi imunosupresi yang dramatis melalui aktivasi berlebih sistem saraf simpatetik, sehingga memungkinkan terjadinya infeksi bakterial seperti pneumonia.[sunting] Eksitotoksisitas asam glutamatAsam glutamat merupakan asam amino neurotransmiter eksitatorial utama di otak, akan menumpuk di ruang ekstraselular dan mengaktivasi pencerapnya.[16] Aktivasi pencerap glutamat akan mempengaruhi konsentrasi ion intraselular, terutama ion Na + dan Ca 2+ . Peningkatan influx ion Na+ dapat membuat sel menjadi cedera pada awal mula terjadinya iskemia, namun riset menunjukkan bahwa sebagian besar kerusakan sel yang ditimbulkan oleh toksisitas asam glutamat saat terjadi iskemia lebih disebabkan oleh peningkatan berlebih influx ion kalsium intraselular yang kemudian menimbulkan efek toksik.[sunting] Stres oksidatifSepanjang proses stroke, terjadi peningkatan radikal bebas seperti anion superoksida, radikal hidroksil dan NO. Sumber utama senyawa radikal bebas turunan oksigen yang biasa disebut spesi oksigen reaktif dalam proses iskemia adalah mitokondria. Sedangkan produksi senyawa superoksida saat pasca iskemia adalah metabolisme asam arakidonat melalui lintasan siklo-oksigenase dan lipo-oksigenase. Radikal bebas juga dapat diproduksi oleh sel mikroglia yang teraktivasi dan leukosit melalui sistem NADPH oksidase segera setelah terjadi reperfusi di jaringan iskemik. Oksidasi tersebut akan menyebabkan kerusakan lebih lanjut di jaringan dan merupakan molekul yang penting untuk memicu apoptosis setelah stroke iskemik.NO umumnya dihasilkan dari L-arginina dengan salah satu isoform NO sintase, dan merupakan kluster diferensiasi neuron di seluruh bagian otak dengan sebutan nNOS. Aktivasi nNOS memerlukan kalsium/kalmodulin. Di sisi lain, ekspresi iNOS (bahasa Inggris: inducible NOS) terdapat di sel radang seperti sel mikroglia dan monosit. Kedua isoform nNOS dan iNOS memiliki peran yang merusak otak pada rentang waktu iskemia. Namun isoform yang ketiga eNOS (bahasa Inggris: endothelial NOS) memiliki efek vasodilasi dan tidak bersifat merusak.Aktivasi pencerap NMDA saat iskemia akan menstimulasi produksi NO oleh nNOS. NO yang terbentuk akan masuk ke dalam sitoplasma dan bereaksi dengan superoksida dan menghasilkan sejenis spesi oksigen yang sangat reaktif yaitu peroksinitrita (ONOO-).Pasca iskemia, kedua jenis spesi oksigen reaktif dan spesi nitrogen reaktif kemudian berperan untuk mengaktivasi beberapa lintasan metabolisme seperti radang, apoptosis, dan penurunan pasokan oksigen yang berdampak kepada peningkatan asam laktat melalui glikolisis anaerobik atau asidosis. Selain itu, akan tampak ekspresi gen iNOS di sel vaskular maupun sel yang mengalami peradangan dan ekspresi gen COX-2 di sel saraf di area antara infark dan penumbra. Kedua gen radang ini akan meningkatkan kerusakan iskemik.[18]

[sunting] Peroksidasi lipidSelain menghasilkan berbagai senyawa ROS, lintasan asidosis juga turut serta dalam proses sintesis protein intraselular. Peroksidasi lipid di membran sel yang menginduksi apoptosis terhadap neuron,

akan menghasilkan senyawa aldehida yang disebut 4-hidroksinonenal (4-HNE) yang akan bereaksi dengan transporter membran seperti Na+/K+ ATPase, transporter glutamat dan transporter glukosa.Kerusakan di transporter membran, yang menyebabkan influx berlebih ion Ca 2+ dan radikal bebas, lebih lanjut akan mengaktivasi faktor transkripsi neuroprotektif seperti NF-κB, HIF-1 dan IRF-1. Aktivasi faktor transkripsi ini akan menginduksi produksi sitokina radang seperti IL-1, IL-6, TNF-α, kemokina seperti IL-8, MCP-1, molekul adhesi sel seperti selektin, ICAM-1, VCAM-1 dan gen pro-radang lainnya seperti IIP-10.[sunting] Disfungsi sawar darah otakSawar darah otak yang merupakan jaringan endotelium di otak akan merespon kondisi cedera akibat stroke dengan meningkatkan permeabilitas dan menurunkan fungsi sawarnya, bersamaan dengan degradasi lamina basal di dinding pembuluhnya. Oleh sebab itu, pada kondisi akut, stroke akan meningkatkan interaksi antara sel endotelial otak dengan sel ekstravaskular seperti astrosit, mikroglia, neuron, dengan sel intravaskular seperti keping darah, leukosit; dan memberikan kontribusi lebih lanjut pada proses peradangan, disamping perubahan sirkulasi kadar ICAM-1, trombomodulin, faktor jaringan dan tissue factor pathway inhibitor.[19] Disfungsi endotelial yang menyebabkan defisiensi sawar darah otak, impaired cerebral autoregulation dan perubahan protrombotik dipercaya merupakan penyebab cerebral small vessel disease (SVD). Penderita (SVD) dapat mengalami infark lakunar, atau dengan disertai leukoaraiosis.Dari 594 penderita stroke, leukoaraiosis ditemukan dalam 55,4% cerebral large vessel disease (LVD) atau ateroskeloris, 30,3% dalam SVD dan 14,3% dalam cardioembolic disease. Dalam pronosis LVD, leukoaraiosis memiliki kecenderungan ke arah grup stenosis intrakranial dengan 40,3% untuk grup intrakranial, 26,9% untuk grup ekstrakranial dan 45,5% untuk grup kombinasi keduanya. Tidak ditemukan korelasi antara leukoaraiosis dengan diabetes mellitus, hiperlipidemia, merokok, hipertensi dan penyakit jantung.[20]

[sunting] Infiltrasi leukositDi jaringan otak terdapat beberapa populasi sel dengan kapasitas untuk mensekresi sitokina setelah terjadi stimulasi iskemia, yaitu sel endotelial, astrosit, sel mikroglia dan neuron.Peran respon peradangan pasca iskemia dilakukan oleh sel mikroglia, terutama di area penumbra dengan sekresi sitokina pro-radang, metabolit dan enzim toksik. Selain itu, sel mikroglia dan astrosit juga mensekresi faktor neuroprotektif seperti eritropoietin, TGFβ1, dan metalotionein-2.Terdapat banyak bukti yang menunjukkan peran leukosit terhadap patogenesis cedera akibat stroke seperti cedera di jaringan akibat reperfusi dan disfungsi mikrovaskular. Bukti-bukti tersebut dapat diklasifikasikan menjadi 3 bagian pokok yaitu,

terjadi akumulasi leukosit pasca iskemia hingga terjadi cedera jaringan simtoma iskemia direspon dengan peningkatan neutrofil.[21] Dalam percobaan dengan tikus,

rendahnya populasi neutrofil dalam sirkulasi darah menunjukkan volume infark yang lebih kecil. pencegahan adhesi sel antara leukosit dengan sel endotelial pada sawar darah otak, dengan

antibodi monoklonal terbukti dapat memberikan perlindungan terhadap cedera akibat stroke.Akumulasi sel T terjadi pasca iskemia,[21] dan diperkirakan merupakan penyebab terjadinya reperfusi. Sel T CD8 dapat menginduksi cedera otak dengan molekul dari granula sitotoksik. Sel TH1 CD4+ dengan sekresi sitokina pro-radang termasuk IL-2, IL-12, IFN-γ dan TNF-α dapat memperburuk efek yang ditimbulkan stroke, sedangkan Sel TH2 CD4+ dengan sitokina anti-radang seperti IL-4, IL-5, IL-10 dan IL-13 lebih mempunyai peran protektif.[sunting] PendarahanPada percobaan terhadap hewan kelinci, setidaknya sitokina TNF-α atau antibodinya berperan atas terjadinya pendarahan setelah terjadi stroke iskemik yang diinduksi oleh klot.[22] Dalam hal ini terjadi peningkatan prognosis terjadinya pendarahan dari 18,5% menjadi 53,3% dan peningkatan volume pendarahan hingga 87%. Disamping itu, penggunaan tissue plasminogen activator (tPA) dengan dosis standar 3,3 mg/kg akan meningkatkan kemungkinan pendarahan dari 18,5% menjadi 76,5%, efek tPA ini

dapat diredam dengan penggunaan antibodi anti-TNFα. Pemberian EPO setelah 6 jam serangan stroke akan memperburuk pendarahan yang diinduksi tPA dengan mediasi MMP-9, NF-κB dan interleukin-1 receptor-associated kinase-1 (IRAK-1).[23]

Pada hewan tikus, TNF-α akan menginduksi ekspresi MMP-9 yang menurunkan kadar protein dalam sawar darah otak seperti okludin,[24] dan meningkatkan permeabilitas pada pembuluh kapiler otak.[25]

MMP-9 kemudian memodulasi,[26] Gelatinase A untuk membuka sawar darah otak. Pendarahan yang terjadi kemudian direspon tubuh dengan memproduksi urokinase-type plasminogen activator (uPA). Ekspresi MMP-9 juga dapat diinduksi oleh lipopolisakarida.[27]

[sunting] Faktor risiko Merokok Alkohol Diet tingginya kadar kolesterol Riwayat keluarga [28]

[sunting] HipertensiHipertensi akan merangsang pembentukan plak aterosklerotik di pembuluh arteri dan arteriol dalam otak, serta menginduksi lintasan lipohialinosis di pembuluh ganglia basal, hingga menyebabkankan infark lakunar atau pendarahan otak.[29]

[sunting] Fibrilasi atrialFibrilasi atrial merupakan indikasi terjadinya kardioembolisme, sedangkan kardioembolisme merupakan 20% penyebab stok iskemik.[30] Kardioembolisme terjadi akibat kurangnya kontraksi otot jantung di bilik kiri, disebut stasis, yang terjadi oleh penumpukan konsentrasi fibrinogen, D-dimer dan faktor von Willebrand.[31] Hal ini merupakan indikasi status protrombotik dengan infark miokardial, yang pada gilirannya, akan melepaskan trombus yang terbentuk, dengan konsekuensi peningkatan risiko embolisasi di otak. Sekitar 2,5% penderita infark miokardial akut akan mengalami stroke dalam kurun waktu 2 hingga 4 minggu, 8% pria dan 11% wanita akan mengalami stroke iskemik dalam waktu 6 tahun, oleh karena disfungsi dan aneurysm bilik kiri jantung.[sunting] AterosklerosisPenelitian mengenai lintasan aterogenesis yang memicu aterosklerosis selama ini terfokus kepada pembuluh nadi koroner, namun proses serupa juga terjadi di otak dan menyebabkan stroke iskemik. [32]

Aterosklerosis dapat menyerang pembuluh nadi otak seperti pembuluh karotid, pembuluh nadi di otak tengah, dan pembuluh basilar, atau kepada pembuluh arteriol otak seperti pembuluh lenticulostriate, basilar penetrating, dan medullary. Beberapa riset menunjukkan bahwa mekanisme aterosklerosis yang menyerang pembuluh nadi dapat sedikit berbeda dengan mekanisme kepada pembuluh arteriol.Aterosklerosis intrakranial dianggap sebagai kondisi yang sangat jarang terjadi. Hasil otopsi infark otak dari 339 penderita stroke yang meninggal akibat aterosklerosis intrakranial, ditemukan 62,2% plak intrakranial dan 43,2% stenosis intrakranial.[33] Hasil otopsi oleh National Cardiovascular Center, Osaka, Jepang terhadap 142 penderita stroke yang meninggal dalam waktu 30 hari sejak terhitung sejak terjadi serangan iskemia, menunjukkan bahwa kedua jenis trombus yang kaya akan keping darah dan yang kaya akan fibrin berkembang di culprit plaque di dalam pembuluh nadi otak merupakan faktor utama penyebab stroke aterotrombotik.[34] 70% kasus stroke kardioembolik menunjukkan keberadaan trombus sebagai sumber potensial terbentuknya emboli di jantung atau pembuluh balik terhadap penderita patent foramen ovale dan tetralogy of Fallot. Umumnya trombus yang kaya akan keping darah yang mengendap di pembuluh balik jantung, akan terlepas dan membentuk emboli di pembuluh nadi otak.[sunting] Diabetes mellitusBerdasarkan studi hasil otopsi, penderita diabetes mellitus rentan terhadap infark lakunar dan cerebral small vessel disease. Studi epidemiologi menunjukkan bahwa diabetes merupakan faktor risiko bagi stroke iskemik. Patogenesis stroke yang dipicu tampaknya dimulai dari reasi berlebih glikasi dan oksidasi,

disfungsi endotelial, peningkatan agregasi keping darah, defisiensi fibrinolisis dan resistansi insulin.[35]

Dalam hewan tikus, stroke iskemik yang terjadi dalam diabetes mellitus akan memicu stroke hemorragik yang disertai dengan peningkatan enzim MMP-9 di otak yang memperburuk kondisi leukoaraiosis.[36]

[sunting] Transient Ischemic Attack (TIA)Transient ischemic attack (TIA), disebut juga acute cerebrovascular syndrome (ACVS),[37] adalah salah satu faktor risiko dari stroke iskemik.[38]

TIA dapat dijabarkan sebagai episode singkat disfungsi neurologis yang biasanya terjadi akibat gangguan vaskular,[39] berupa simtoma iskemia di otak atau retina yang berlangsung kurang dari 24 jam, atau kurang dari 1 jam,[40] tanpa meninggalkan bekas berupa infark serebral[41] akut.[42]

Dari sudut pandang lain, oleh karena stroke merupakan defisiensi neurologis akibat perubahan aliran darah di jaringan otak, maka TIA dapat dikatakan sebagai indikasi atau simtoma yang ditimbulkan dari perubahan aliran darah otak yang tidak dapat dideteksi secara klinis dalam waktu 24 jam.[43]

TIA tidak selalu menjadi indikasi akan terjadinya stroke di kemudian hari, dan jarang sekali dikaitkan dengan stroke hemorragik primer. Dalam populasi manusia yang telah beranjak tua, TIA diinduksi oleh terhalangnya aliran darah di pembuluh darah besar terutama akibat aterotrombosis, namun dalam penderita yang berusia di bawah 45 tahun TIA umumnya disebabkan oleh robeknya pembuluh darah (bahasa Inggris: arterial dissection), migrain dan obat-obatan sympathomimetic. TIA juga dapat disebabkan oleh :

Large artery atherothrombosis with distal flow reduction Arteriosklerosis di pembuluh darah kecil ("lacunar TiAs") Emboli Kardiogenic dan emboli antar-arteri Vasospasma Vaskulitis Sludging-polycythemia. sickle cell anemia. Trombositemia dan sejenisnya Hypercoaguable states-puerperium. oral contraceptive use. 'sticky platelet syndrome" dan

sejenisnya Meningitis Cortical vein thrombosis-dehydration. Puerperium. Infection. Neoplasma dan sejenisnya Displasia fibromuskular Sindrom Moyamoya Arteritis Takayasu

Namun beberapa kondisi lain dapat menimbulkan gejala yang sangat serupa dengan TIA, seperti focal seizure activity, migraine (?"spreading depression"), compressive mononeuropathies (carpal tunnel syndrome. ulnar elbow compression and so forth), sindrom Adams-Stokes, tumor otak dengan gejala neurologik transien, hematoma subdural, Demyelinating disease, hipoglisemia, hiperglisemia, primary ocular disease-glaucoma, vitreal hemorrhage. floaters and the like, functional disorders-conversion hysteria, malingering, hiperventilasi.[sunting] Cardiac papillary fibroelastoma (CPF)Dari 725 kasus CPF, 55% merupakan penderita pria dengan lokasi tumor, umumnya, ditemukan di permukaan valvular, terutama di katup trikuspidalis aortik, selain katup mitralis. Tumor juga ditemukan di permukaan non-valvular, seperti di bilik kiri. Ukuran tumor bervariasi dari 2 mm hingga 70 mm.[44]

Manifestasi klinis CPF meliputi stroke, infark miokardial, emboli paru, gagal jantung congestive dan serangan jantung mendadak.[45] Meskipun demikian, tidak semua penderita menunjukkan simtoma demikian.[sunting] Cryptogenic cerebral infarction (CCI)CCI paling banyak ditemukan dalam penderita patent foramen ovale baik yang disertai maupun tidak disertai septal aneurysm.[46][47] Sejak tahun 1989, CCI merupakan penyebab 40% kasus stroke iskemik. 4,9% pria dan 2,4% wanita mengalami mutasi genetik galaktosidase-alfa yang merupakan indikasi

penyakit Fabry, sedangkan studi lain menunjukkan keterkaitan dengan trombofilia.[48] Lintasan patogenesis CCI diperkirakan meliputi aterosklerosis di pembuluh nadi otak, baik yang bersifat intrakranial seperti moderate middle cerebral artery stenosis, ekstrakranial seperti vertebral artery origin stenosis atau proksimal seperti thick plaques in the aortic arch yang selama ini dianggap tidak berkaitan dengan patogenesis stroke.[49]

[sunting] Patent foramen ovale (PFO)Sindrom platipnea-ortodeoksia merupakan kondisi yang jarang terjadi dengan simtoma berupa dispnea dan desaturasi arterial. PFO merupakan salah satu bentuk sindrom platipnea-ortodeoksia dengan peningkatan ortostatik di area defisiensi atrial septal.[50] Hasil diagnosa PFO yang sering ditemukan pada CCI dan migrain, juga diperkirakan sebagai penyebab emboli pada penderita tromboembolisme arterial.[sunting] DiagnosisDiagnosis stroke adalah secara klinis beserta pemeriksaan penunjang. Pemeriksaan penunjang yang dapat dilakukan antara lain CT scan kepala, MRI. Untuk menilai kesadaran penderita stroke dapat digunakan Skala Koma Glasgow. Untuk membedakan jenis stroke dapat digunakan berbagai sistem skor, seperti Skor Stroke Siriraj, Algoritma Stroke Gajah Mada, atau Algoritma Junaedi.[sunting] Simtoma klinisFitur stroke iskemik yang sangat umum, menurut Uniformed Services University of the Health Sciences, masih berdasar kepada banyaknya hasil diagnosis pemeriksaan fisik terhadap penderita yang dirangkum dalam satu kurun waktu. USUHS merangkumnya menjadi tabel berikut agar dapat digunakan masyarakat awam untuk mengenali gejala klinis stroke sedini mungkin. Dan bagi tenaga medis profesional, The National Institute of Health telah membuat tabel skala strok sebagai panduan guna melakukan diagnosis dalam waktu kurang dari sekitar 5 hingga 10 menit.[sunting] Simtoma paraklinisBeberapa senyawa biokimiawi di dalam serum darah yang dapat dijadikan dasar diagnosis dan prognosis terjadinya nekrosis otak antara lain:[51]

[sunting] S100-βS100-β adalah peptida yang disekresi astrosit pada saat terjadi cedera otak, proses neurodegenerasi dan kelainan psikiatrik. S100-β merupakan senyawa pengikat kalsium, secara in vitro, pada kadar rendah, interaksi dengan sistem kekebalan di otak akan meningkatkan kelangsungan hidup bagi neuron yang sedang berkembang, namun, pada kadar yang lebih tinggi, S100-β akan menstimulasi produksi sitokina pro-peradangan dan apoptosis.Studi terhadap hewan menunjukkan efek neuroprotektif S100-β dengan teraktivasinya proses selular di neuron yang menahan eksitotoksisitas yang diinduksi NMDA. Peningkatan serum S100-β selalu terjadi pada stroke iskemik, dan terjadi pula pada kondisi yang lain seperti traumatic brain injury (TBI), Alzheimer dan schizophrenia.Saat terjadi stroke iskemik, konsentrasi serum S100-β mencapai titik maksimum pada hari ke-2 hingga 4. Nilai konsentrasi maksimum S100-β berkaitan dengan skala stroke NIH, ukuran dan patofisiologi infark, sehingga semakin tinggi nilai maksimum S100-β, semakin tinggi pula risiko terjadinya transformasi hemorragik. Peningkatan S100-β juga ditemukan dalam stroke hemorragik primer, yang menunjukkan volume hematoma awal.Peningkatan kadar S100-β tidak harus terjadi dengan cepat, dan masih banyak sel selain astrosit dan sel Schwann yang menhasilkan S100-β, sehingga penggunaan nilai serum S100-β sebagai salah satu dasar diagnosis stroke masih cukup rentan. Namun beberapa studi telah menunjukkan bahwa serum S100-β lebih terkait dengan kondisi integritas sawar darah otak.[sunting] Glial fibrillary-associated protein (GFAP)GFAP merupakan monomeric intermediate filament protein yang terdapat di astrosit dan sel ependimal otak yang berfungsi sebagai bagian sitoskeleton. Kadar serum S100-β dan GFAP akan meningkat tajam pada hari 1-2 sesuai dengan ukuran infark, dan kembali normal sekitar 3 minggu kemudian.

Serum GFAP merupakan indikator yang lebih peka daripada S100-β pada stroke minor maupun guratan kecil, namun waktu tunda peningkatan serum ini membuat aplikasi diagnostiknya menjadi terbatas.[sunting] Myelin basic protein (MBP)MBP adalah protein hidrofilik penting bagi struktur selubung mielin. Kadar MBP dalam CSF sering digunakan sebagai indikasi aktivitas patogen dalam sklerosis multipel. Stroke juga disertai dengan peningkatan kadar MBP dalam CSF sekitar 1 minggu setelah terjadinya serangan, dan kembali normal setelah minggu ketiga.[sunting] Fatty acid-binding proteins (FABPs)FABP adalah kelompok molekul intraselular yang berperan dalam menyangga dan sebagai transportasi asam lemak berantai panjang, yang akan segera disekresi ke dalam sirkulasi darah sesaat setelah terjadi kerusakan sel. Di tubuh manusia terdapat 9 jenis FABP yang tersebar dalam masing-masing jenis jaringan yang berbeda. Empat jenis FABP terdapat di sistem saraf, dua diantaranya hanya ditemukan di sistem saraf pusat orang dewasa, yaitu brain-type (B-FABP) di glia dan heart-type (H-FABP) di neuron.Ditemukannya H-FABP dalam berbagai jenis jaringan merupakan tanda-tanda infak miokardial akut. B-FABP berada dalam jaringan di dalam sistem saraf pusat dan tidak dapat dideteksi dalam serum darah manusia sehat. Serum H-FABP dan B-FABP akan tajam dalam 2-3 jam sejak terjadi serangan stroke. B-FABP merupakan indikasi yang sangat peka terhadap infark lakunar dan infark subkortikal, namun tidak menunjukkan tingkat kerusakan yang terjadi di neuron, dan bukan merupakan indikasi spesifik terjadinya stroke. Sebaliknya peningkatan H-FABP berbanding lurus dengan ukuran infark dan tingkat kerusakan saraf.[sunting] Neuron-specific enolase (NSE)NSE merupakan salah satu dari tiga bentuk enolase, sebuah enzim yang terdapat di lintasan glikolisis. Walaupun cukup spesifik di neuron, NSE juga dapat ditemukan di kultur sel neuroendokrin dan bentuk sel kanker terkait. Konsentrasi NSE di dalam CSF akan meningkat seiring terjadinya stroke iskemik dan sejumlah cedera otak lain seperti subarachnoid hemorrhage, ICH, dan lain-lain, hingga mulai dapat dideteksi setelah 4-8 jam setelah terjadinya serangan. Konsentrasi tertinggi setelah terjadi stroke iskemik memiliki korelasi dengan nilai pada skala stroke NIH.[sunting] Protein tau (TP)Otak memiliki 6 isomer TP yang memungkinkan terbentuknya mikrotubula dengan interaksi tubulin. Peningkatan kadar TP terjadi dengan sangat lambat dan hanya 27% total konsentrasi yang mengalami peningkatan di luar batas atas ambang normal dalam waktu 24 jam setelah serangan stroke iskemik, namun nilai konsentrasi ini menunjukkan ukuran infark dan strata serangan stroke. Peningkatan kadar TP dalam CSF pasca stroke juga merupakan indikasi ukuran infark. Akan tetapi stroke tidak mempengaruhi kadar β-amyloid, ApoE dan klusterin dalam CSF.[sunting] PenangananPenderita stroke akut biasanya diberikan SM-20302,[52] atau microplasmin,[53] oksigen, dipasang infus untuk memasukkan cairan dan zat makanan, kemudian diberikan manitol atau kortikosteroid untuk mengurangi pembengkakan dan tekanan di dalam otak,[54] akibat infiltrasi sel darah putih. Penelitian terakhir menunjukkan bahwa kelumpuhan dan gejala lainnya bisa dicegah atau dipulihkan jika recombinan tissue plasminogen activator (rtPA) atau streptokinase yang berfungsi menghancurkan emboli diberikan dalam waktu 3 jam,[55] setelah timbulnya stroke. Trombolisis dengan rtPA terbukti bermanfaat pada manajemen stroke akut, walaupun dapat meningkatkan risiko pendarahan otak, [56]

terutama pada area sawar darah otak yang terbuka.[57]

Beberapa senyawa yang diberikan bersamaan dengan rtPA untuk mengurangi risiko tersebut antara lain batimastat (BB-94) dan marimastat (BB-2516),[58] yang menghambat enzim MMP, senyawa spin trap agent seperti alpha-phenyl-N-t-butylnitrone (PBN) dan disodium- [tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059),[59] dan senyawa anti-ICAM-1.[60]

Metode perawatan hemodilusi dengan menggunakan albumin masih kontroversial,[61] namun penelitian oleh The Amsterdam Stroke Study memberikan prognosis berupa penurunan angka kematian dari 27% menjadi 16%, peningkatan kemandirian aktivitas dari 35% menjadi 48%, saat 3 bulan sejak terjadi serangan stroke akut.[sunting] PemulihanSerangan stroke terkait dengan keterbatasan pulihnya fungsi otak, meskipun area peri-infark menjadi lebih bersifat neuroplastik sehingga memungkinkan perbaikan fungsi sensorimotorik melakukan pemetaan ulang di area otak yang mengalami kerusakan. Di tingkat selular, terjadi dua proses regenerasi dalam korteks peri-infark, akson akan mengalami perubahan fenotipe dari neurotransmiter ke dalam status regeneratif,[62] dan menjulurkan tangkainya untuk membuat koneksi baru di bawah pengaruh trombospondin,[63], laminin, dan NGF hasil sekresi sel Schwann,[64] dan terjadi migrasi sel progenitor neuron ke dalam korteks peri-infark.[65] Hampir sepanjang 1 bulan sejak terjadi serangan stroke, daerah peri-infark akan mengalami penurunan molekul penghambat pertumbuhan. Pada rentang waktu ini, neuron akan mengaktivasi gen yang menstimulasi pertumbuhan, dalam ritme yang bergelombang. Neurogenesis saling terkait dengan angiogenesis juga terjadi bergelombang yang diawali dengan migrasi neuroblas dengan ekspresi GFAP,[66] yang berada dalam zona subventrikular ke dalam korteks peri-infark. Migrasi ini dimediasi oleh beberapa senyawa antara lain eritropoietin,[67] stromal-derived factor 1 (SDF-1) dan angiopoietin-1, hingga menghasilkan neuroblas dengan jarak tempuh migrasi yang lebih panjang dan rentang waktu sitokinesis yang lebih pendek.[68]

Terhambatnya fungsi pencerap GABA ekstrasinaptik di area peri-infark yang terjadi akibat oleh disfungsi transporter GABA GAT-3/GAT-4, dalam hewan tikus, dapat dipulihkan dengan pemberian benzodiazepina.[69]

[sunting] PencegahanDalam manusia tanpa faktor risiko stroke dengan umur di bawah 65 tahun, risiko terjadinya serangan stroke dalam 1 tahun berkisar pada angka 1%.[70] Setelah terjadinya serangan stroke ringan atau TIA, penggunaan senyawa anti-koagulan seperti warfarin, salah satu obat yang digunakan untuk penderita fibrilasi atrial,[71] akan menurunkan risiko serangan stroke dari 12% menjadi 4% dalam satu tahun. Sedangkan penggunaan senyawa anti-keping darah seperti aspirin, umumnya pada dosis harian sekitar 30 mg atau lebih, hanya akan memberikan perlindungan dengan penurunan risiko menjadi 10,4%. [72]

Kombinasi aspirin dengan dipyridamole memberikan perlindungan lebih jauh dengan penurunan risiko tahunan menjadi 9,3%.Cara yang terbaik untuk mencegah terjadinya stroke adalah dengan mengidentifikasi orang-orang yang berisiko tinggi dan mengendalikan faktor risiko stroke sebanyak mungkin, seperti kebiasaan merokok, hipertensi, dan stenosis di pembuluh karotid,[73] mengatur pola makan yang sehat dan menghindari makanan yang mengandung kolesterol jahat (LDL), serta olaraga secara teratur. Stenosis merupakan efek vasodilasi endotelium yang umumnya disebabkan oleh turunnya sekresi NO oleh sel endotelial, dapat diredam asam askorbat yang meningkatkan sekresi NO oleh sel endotelial melalui lintasan NO sintase atau siklase guanilat, mereduksi nitrita menjadi NO dan menghambat oksidasi LDL [74] di lintasan aterosklerosis.Beberapa institusi kesehatan seperti American Heart Association atau American Stroke Association Council, Council on Cardiovascular Radiology and Intervention memberikan panduan pencegahan yang dimulai dengan penanganan seksama berbagai penyakit yang dapat ditimbulkan oleh aterosklerosis, penggunaan senyawa anti-trombotik untuk kardioembolisme dan senyawa anti-keping darah bagi kasus non-kardioembolisme,[75] diikuti dengan pengendalian faktor risiko seperti arterial dissection, patent foramen ovale, hiperhomosisteinemia, hypercoagulable states, sickle cell disease; cerebral venous sinus thrombosis; stroke saat kehamilan, stroke akibat penggunaan hormon pasca menopause, penggunaan senyawa anti-koagulan setelah terjadinya cerebral hemorrhage; hipertensi,[76] hipertensi, kebiasaan merokok, diabetes, fibrilasi atrial, dislipidemia, stenosis karotid, obesitas, sindrom metabolisme,

konsumsi alkohol berlebihan, konsumsi obat-obatan berlebihan, konsumsi obat kontrasepsi, mendengkur, migrain, peningkatan lipoprotein dan fosfolipase.

A stroke, previously known medically as a cerebrovascular accident (CVA), is the rapidly developing loss of brain function(s) due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood flow) caused by blockage (thrombosis, arterial embolism), or a hemorrhage (leakage of blood).[1] As a result, the affected area of the brain is unable to function, which might result in an inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field.[2]

A stroke is a medical emergency and can cause permanent neurological damage, complications, and death. It is the leading cause of adult disability in the United States and Europe and the second leading cause of death worldwide.[3] Risk factors for stroke include old age, hypertension (high blood pressure), previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, cigarette smoking and atrial fibrillation.[2] High blood pressure is the most important modifiable risk factor of stroke.[2]

A silent stroke is a stroke that does not have any outward symptoms, and the patients are typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain, and places the patient at increased risk for both transient ischemic attack and major stroke in the future. Conversely, those who have suffered a major stroke are at risk of having silent strokes.[4] In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. Silent strokes are estimated to occur at five times the rate of symptomatic strokes.[5][6] The risk of silent stroke increases with age, but may also affect younger adults and children, especially those with acute anemia.[5][7]

An ischemic stroke is occasionally treated in a hospital with thrombolysis (also known as a "clot buster"), and some hemorrhagic strokes benefit from neurosurgery. Treatment to recover any lost function is termed stroke rehabilitation, ideally in a stroke unit and involving health professions such as speech and language therapy, physical therapy and occupational therapy. Prevention of recurrence may involve the administration of antiplatelet drugs such as aspirin and dipyridamole, control and reduction of hypertension, and the use of statins. Selected patients may benefit from carotid endarterectomy and the use of anticoagulants.[2]

[edit] DefinitionThe traditional definition of stroke, devised by the World Health Organization in the 1970s,[8] is a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours". This definition was supposed to reflect the reversibility of tissue damage and was devised for the purpose, with the time frame of 24 hours being chosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack, which is a related syndrome of stroke symptoms that resolve completely within 24 hours.[2] With the availability of treatments that, when given early, can reduce stroke severity, many now prefer alternative concepts, such as brain attack and acute ischemic cerebrovascular syndrome (modeled after heart attack and acute coronary syndrome, respectively), that reflect the urgency of stroke symptoms and the need to act swiftly.[9]

[edit] ClassificationA slice of brain from the autopsy of a person who suffered an acute middle cerebral artery (MCA) strokeStrokes can be classified into two major categories: ischemic and hemorrhagic. [10] Ischemic strokes are those that are caused by interruption of the blood supply, while hemorrhagic strokes are the ones which result from rupture of a blood vessel or an abnormal vascular structure. About 87% of strokes are caused by ischemia, and the remainder by hemorrhage. Some hemorrhages develop inside areas of

ischemia ("hemorrhagic transformation"). It is unknown how many hemorrhages actually start as ischemic stroke.[2]

[edit] IschemicMain articles: Cerebral infarction and Brain ischemiaIn an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. There are four reasons why this might happen:

1. Thrombosis (obstruction of a blood vessel by a blood clot forming locally)2. Embolism (obstruction due to an embolus from elsewhere in the body, see below),[2]

3. Systemic hypoperfusion (general decrease in blood supply, e.g., in shock)[11]

4. Venous thrombosis .[12]

Stroke without an obvious explanation is termed "cryptogenic" (of unknown origin); this constitutes 30-40% of all ischemic strokes.[2][13]

There are various classification systems for acute ischemic stroke. The Oxford Community Stroke Project classification (OCSP, also known as the Bamford or Oxford classification) relies primarily on the initial symptoms; based on the extent of the symptoms, the stroke episode is classified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of the stroke, the area of the brain affected, the underlying cause, and the prognosis.[14][15] The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinical symptoms as well as results of further investigations; on this basis, a stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) embolism of cardiac origin, (3) occlusion of a small blood vessel, (4) other determined cause, (5) undetermined cause (two possible causes, no cause identified, or incomplete investigation).[2][16]

[edit] HemorrhagicMain articles: Intracranial hemorrhage and intracerebral hemorrhageAn intraparenchymal bleed (bottom arrow) with surrounding edema (top arrow)Intracranial hemorrhage is the accumulation of blood anywhere within the skull vault. A distinction is made between intra-axial hemorrhage (blood inside the brain) and extra-axial hemorrhage (blood inside the skull but outside the brain). Intra-axial hemorrhage is due to intraparenchymal hemorrhage or intraventricular hemorrhage (blood in the ventricular system). The main types of extra-axial hemorrhage are epidural hematoma (bleeding between the dura mater and the skull), subdural hematoma (in the subdural space) and subarachnoid hemorrhage (between the arachnoid mater and pia mater). Most of the hemorrhagic stroke syndromes have specific symptoms (e.g., headache, previous head injury).[edit] Signs and symptomsStroke symptoms typically start suddenly, over seconds to minutes, and in most cases do not progress further. The symptoms depend on the area of the brain affected. The more extensive the area of brain affected, the more functions that are likely to be lost. Some forms of stroke can cause additional symptoms. For example, in intracranial hemorrhage, the affected area may compress other structures. Most forms of stroke are not associated with headache, apart from subarachnoid hemorrhage and cerebral venous thrombosis and occasionally intracerebral hemorrhage.[edit] Early recognitionVarious systems have been proposed to increase recognition of stroke by patients, relatives and emergency first responders. A systematic review, updating a previous systematic review from 1994, looked at a number of trials to evaluate how well different physical examination findings are able to predict the presence or absence of stroke. It was found that sudden-onset face weakness, arm drift (i.e., if a person, when asked to raise both arms, involuntarily lets one arm drift downward) and abnormal speech are the findings most likely to lead to the correct identification of a case of stroke (+ likelihood ratio of 5.5 when at least one of these is present). Similarly, when all three of these are absent, the likelihood of stroke is significantly decreased (– likelihood ratio of 0.39).[17] While these findings are not

perfect for diagnosing stroke, the fact that they can be evaluated relatively rapidly and easily make them very valuable in the acute setting.Proposed systems include FAST (stroke) (face, arm, speech, and time),[18] as advocated by the Department of Health (United Kingdom) and The Stroke Association, the American Stroke Association (www.strokeassociation.org) , National Stroke Association (US www.stroke.org), the Los Angeles Prehospital Stroke Screen (LAPSS)[19] and the Cincinnati Prehospital Stroke Scale (CPSS).[20] Use of these scales is recommended by professional guidelines.[21]

For people referred to the emergency room, early recognition of stroke is deemed important as this can expedite diagnostic tests and treatments. A scoring system called ROSIER (recognition of stroke in the emergency room) is recommended for this purpose; it is based on features from the medical history and physical examination.[21][22]

[edit] SubtypesIf the area of the brain affected contains one of the three prominent central nervous system pathways—the spinothalamic tract, corticospinal tract, and dorsal column (medial lemniscus), symptoms may include:

hemiplegia and muscle weakness of the face numbness reduction in sensory or vibratory sensation initial flaccidity (hypotonicity), replaced by spasticity (hypertonicity), hyperreflexia, and

obligatory synergies.[23]

In most cases, the symptoms affect only one side of the body (unilateral). Depending on the part of the brain affected, the defect in the brain is usually on the opposite side of the body. However, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms, the presence of any one of these symptoms does not necessarily indicate a stroke.In addition to the above CNS pathways, the brainstem give rise to most of the twelve cranial nerves. A stroke affecting the brain stem and brain therefore can produce symptoms relating to deficits in these cranial nerves:

altered smell, taste, hearing, or vision (total or partial) drooping of eyelid (ptosis) and weakness of ocular muscles decreased reflexes: gag, swallow, pupil reactivity to light decreased sensation and muscle weakness of the face balance problems and nystagmus altered breathing and heart rate weakness in sternocleidomastoid muscle with inability to turn head to one side weakness in tongue (inability to protrude and/or move from side to side)

If the cerebral cortex is involved, the CNS pathways can again be affected, but also can produce the following symptoms:

aphasia (difficulty with verbal expression, auditory comprehension, reading and/or writing Broca's or Wernicke's area typically involved)

dysarthria (motor speech disorder resulting from neurological injury) apraxia (altered voluntary movements) visual field defect memory deficits (involvement of temporal lobe) hemineglect (involvement of parietal lobe) disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe) anosognosia (persistent denial of the existence of a, usually stroke-related, deficit)

If the cerebellum is involved, the patient may have the following:

trouble walking altered movement coordination vertigo and or disequilibrium

[edit] Associated symptomsLoss of consciousness, headache, and vomiting usually occurs more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing the brain.If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke.[edit] Causes

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Thrombotic strokeIn thrombotic stroke a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. A thrombus itself (even if non-occluding) can lead to an embolic stroke (see below) if the thrombus breaks off, at which point it is called an "embolus." Two types of thrombosis can cause stroke:

Large vessel disease involves the common and internal carotids, vertebral, and the Circle of Willis. Diseases that may form thrombi in the large vessels include (in descending incidence): atherosclerosis, vasoconstriction (tightening of the artery), aortic, carotid or vertebral artery dissection, various inflammatory diseases of the blood vessel wall (Takayasu arteritis, giant cell arteritis, vasculitis), noninflammatory vasculopathy, Moyamoya disease and fibromuscular dysplasia.

Small vessel disease involves the smaller arteries inside the brain: branches of the circle of Willis, middle cerebral artery, stem, and arteries arising from the distal vertebral and basilar artery. Diseases that may form thrombi in the small vessels include (in descending incidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as a result of high blood pressure and aging) and fibrinoid degeneration (stroke involving these vessels are known as lacunar infarcts) and microatheroma (small atherosclerotic plaques).[24]

Sickle cell anemia, which can cause blood cells to clump up and block blood vessels, can also lead to stroke. A stroke is the second leading killer of people under 20 who suffer from sickle-cell anemia.[25]

Embolic strokeAn embolic stroke refers to the blockage of an artery by an arterial embolus, a travelling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectious endocarditis).Because an embolus arises from elsewhere, local therapy solves the problem only temporarily. Thus, the source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms usually are maximal at start. Also, symptoms may be transient as the embolus is partially resorbed and moves to a different location or dissipates altogether.Emboli most commonly arise from the heart (especially in atrial fibrillation) but may originate from elsewhere in the arterial tree. In paradoxical embolism, a deep vein thrombosis embolises through an atrial or ventricular septal defect in the heart into the brain.Cardiac causes can be distinguished between high and low-risk:[26]

High risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of the mitral or aortic valve disease, artificial heart valves, known cardiac thrombus of the atrium or ventricle, sick sinus syndrome, sustained atrial flutter, recent myocardial infarction, chronic myocardial infarction together with ejection fraction <28 percent, symptomatic congestive heart failure

with ejection fraction <30 percent, dilated cardiomyopathy, Libman-Sacks endocarditis, Marantic endocarditis, infective endocarditis, papillary fibroelastoma, left atrial myxoma and coronary artery bypass graft (CABG) surgery

Low risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramen ovale (PFO), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale, left ventricular aneurysm without thrombus, isolated left atrial "smoke" on echocardiography (no mitral stenosis or atrial fibrillation), complex atheroma in the ascending aorta or proximal arch

Systemic hypoperfusionSystemic hypoperfusion is the reduction of blood flow to all parts of the body. It is most commonly due to cardiac pump failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially "watershed" areas - border zone regions supplied by the major cerebral arteries. A watershed stroke refers to the condition when blood supply to these areas is compromised. Blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur. This phenomenon is also referred to as "last meadow" to point to the fact that in irrigation the last meadow receives the least amount of water.Venous thrombosisCerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds the pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke.[12]

Intracerebral hemorrhageIt generally occurs in small arteries or arterioles and is commonly due to hypertension, intracranial vascular malformations (including cavernous angiomas or arteriovenous malformations), cerebral amyloid angiopathy, or infarcts into which secondary haemorrhage has occurred.[2] Other potential causes are trauma, bleeding disorders, amyloid angiopathy, illicit drug use (e.g., amphetamines or cocaine). The hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into the ventricular system, CSF or the pial surface. A third of intracerebral bleed is into the brain's ventricles. ICH has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoid hemorrhage (which technically may also be classified as a type of stroke[2]).[edit] Pathophysiology[edit] Ischemic

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Micrograph showing cortical pseudolaminar necrosis, a finding seen in strokes on medical imaging and at autopsy. H&E-LFB stain.Micrograph of the superficial cerebral cortex showing neuron loss and reactive astrocytes in a person that suffered a stroke. H&E-LFB stain.Ischemic stroke occurs because of a loss of blood supply to part of the brain, initiating the ischemic cascade.[27] Brain tissue ceases to function if deprived of oxygen for more than 60 to 90 seconds and after approximately three hours, will suffer irreversible injury possibly leading to death of the tissue, i.e., infarction. (This is why TPAs (e.g., Streptokinase, Alteplase) are given only until three hours since the onset of the stroke.) Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow, by causing the formation of blood clots within the vessel, or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a

consequence of atrial fibrillation, or in the carotid arteries, break off, enter the cerebral circulation, then lodge in and occlude brain blood vessels. Since blood vessels in the brain are now occluded, the brain becomes low in energy, and thus it resorts into using anaerobic respiration within the region of brain tissue affected by ischemia. Unfortunately, this kind of respiration produces less adenosine triphosphate (ATP) but releases a by-product called lactic acid. Lactic acid is an irritant which could potentially destroy cells since it is an acid and disrupts the normal acid-base balance in the brain. The ischemia area is referred to as the "ischemic penumbra".[28]

Then, as oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy phosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. A major cause of neuronal injury is release of the excitatory neurotransmitter glutamate. The concentration of glutamate outside the cells of the nervous system is normally kept low by so-called uptake carriers, which are powered by the concentration gradients of ions (mainly Na+) across the cell membrane. However, stroke cuts off the supply of oxygen and glucose which powers the ion pumps maintaining these gradients. As a result the transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing glutamate into the extracellular space. Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx of calcium which activates enzymes that digest the cells' proteins, lipids and nuclear material. Calcium influx can also lead to the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to apoptosis.Ischemia also induces production of oxygen free radicals and other reactive oxygen species. These react with and damage a number of cellular and extracellular elements. Damage to the blood vessel lining or endothelium is particularly important. In fact, many antioxidant neuroprotectants such as uric acid and NXY-059 work at the level of the endothelium and not in the brain per se. Free radicals also directly initiate elements of the apoptosis cascade by means of redox signaling.[25]

These processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs.Brain tissue survival can be improved to some extent if one or more of these processes is inhibited. Drugs that scavenge reactive oxygen species, inhibit apoptosis, or inhibit excitatory neurotransmitters, for example, have been shown experimentally to reduce tissue injury caused by ischemia. Agents that work in this way are referred to as being neuroprotective. Until recently, human clinical trials with neuroprotective agents have failed, with the probable exception of deep barbiturate coma. However, more recently NXY-059, the disulfonyl derivative of the radical-scavenging spintrap phenylbutylnitrone, is reported to be neuroprotective in stroke.[29] This agent appears to work at the level of the blood vessel lining or endothelium. Unfortunately, after producing favorable results in one large-scale clinical trial, a second trial failed to show favorable results.[25]

In addition to injurious effects on brain cells, ischemia and infarction can result in loss of structural integrity of brain tissue and blood vessels, partly through the release of matrix metalloproteases, which are zinc- and calcium-dependent enzymes that break down collagen, hyaluronic acid, and other elements of connective tissue. Other proteases also contribute to this process. The loss of vascular structural integrity results in a breakdown of the protective blood brain barrier that contributes to cerebral edema, which can cause secondary progression of the brain injury.As is the case with any type of brain injury, the immune system is activated by cerebral infarction and may under some circumstances exacerbate the injury caused by the infarction. Inhibition of the inflammatory response has been shown experimentally to reduce tissue injury due to cerebral infarction, but this has not proved out in clinical studies.[edit] Hemorrhagic

Hemorrhagic strokes result in tissue injury by causing compression of tissue from an expanding hematoma or hematomas. This can distort and injure tissue. In addition, the pressure may lead to a loss of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on brain tissue and vasculature.[25]

[edit] DiagnosisA CT showing early signs of a middle cerebral artery stroke with loss of definition of the gyri and grey white boundaryStroke is diagnosed through several techniques: a neurological examination (such as the Nihss), CT scans (most often without contrast enhancements) or MRI scans, Doppler ultrasound, and arteriography. The diagnosis of stroke itself is clinical, with assistance from the imaging techniques. Imaging techniques also assist in determining the subtypes and cause of stroke. There is yet no commonly used blood test for the stroke diagnosis itself, though blood tests may be of help in finding out the likely cause of stroke.[30]

[edit] Physical examinationA physical examination, including taking a medical history of the symptoms and a neurological status, helps giving an evaluation of the location and severity of a stroke. It can give a standard score on e.g., the NIH stroke scale.[edit] ImagingFor diagnosing ischemic stroke in the emergency setting:[31]

CT scans (without contrast enhancements)sensitivity= 16%specificity= 96%

MRI scansensitivity= 83%specificity= 98%

For diagnosing hemorrhagic stroke in the emergency setting: CT scans (without contrast enhancements)

sensitivity= 89%specificity= 100%

MRI scansensitivity= 81%specificity= 100%

For detecting chronic hemorrhages, MRI scan is more sensitive.[32]

For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may be helpful. SPECT documents cerebral blood flow and PET with FDG isotope the metabolic activity of the neurons.[edit] Underlying etiologyWhen a stroke has been diagnosed, various other studies may be performed to determine the underlying etiology. With the current treatment and diagnosis options available, it is of particular importance to determine whether there is a peripheral source of emboli. Test selection may vary, since the cause of stroke varies with age, comorbidity and the clinical presentation. Commonly used techniques include:

an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis) or dissection of the precerebral arteries

an electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultant clots in the heart which may spread to the brain vessels through the bloodstream)

a Holter monitor study to identify intermittent arrhythmias an angiogram of the cerebral vasculature (if a bleed is thought to have originated from an

aneurysm or arteriovenous malformation)

blood tests to determine hypercholesterolemia, bleeding diathesis and some rarer causes such as homocysteinuria

[edit] PreventionGiven the disease burden of strokes, prevention is an important public health concern.[33] Primary prevention is less effective than secondary prevention (as judged by the number needed to treat to prevent one stroke per year).[33] Recent guidelines detail the evidence for primary prevention in stroke.[34] Because stroke may indicate underlying atherosclerosis, it is important to determine the patient's risk for other cardiovascular diseases such as coronary heart disease. Conversely, aspirin confers some protection against first stroke in patients who have suffered a myocardial infarction or patients with a high cardiovascular risk.[35][36]

[edit] Risk factorsThe most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation (although magnitude of this effect is small: the evidence from the Medical Research Council trials is that 833 patients have to be treated for 1 year to prevent one stroke [37][38]). Other modifiable risk factors include high blood cholesterol levels, diabetes, cigarette smoking[39][40] (active and passive), heavy alcohol consumption [41] and drug use,[42] lack of physical activity, obesity, red meat consumption[43] and unhealthy diet.[44] Alcohol use could predispose to ischemic stroke, and intracerebral and subarachnoid hemorrhage via multiple mechanisms (for example via hypertension, atrial fibrillation, rebound thrombocytosis and platelet aggregation and clotting disturbances).[45] The drugs most commonly associated with stroke are cocaine, amphetamines causing hemorrhagic stroke, but also over-the-counter cough and cold drugs containing sympathomimetics.[46][47]

No high quality studies have shown the effectiveness of interventions aimed at weight reduction, promotion of regular exercise, reducing alcohol consumption or smoking cessation.[48] Nonetheless, given the large body of circumstantial evidence, best medical management for stroke includes advice on diet, exercise, smoking and alcohol use.[49] Medication or drug therapy is the most common method of stroke prevention; carotid endarterectomy can be a useful surgical method of preventing stroke.[edit] Blood pressureHypertension accounts for 35-50% of stroke risk.[50] Epidemiological studies suggest that even a small blood pressure reduction (5 to 6 mmHg systolic, 2 to 3 mmHg diastolic) would result in 40% fewer strokes.[51] Lowering blood pressure has been conclusively shown to prevent both ischemic and hemorrhagic strokes.[52][53] It is equally important in secondary prevention.[54] Even patients older than 80 years and those with isolated systolic hypertension benefit from antihypertensive therapy.[55][56][57]

Studies show that intensive antihypertensive therapy results in a greater risk reduction. [58] The available evidence does not show large differences in stroke prevention between antihypertensive drugs —therefore, other factors such as protection against other forms of cardiovascular disease should be considered and cost.[58][59]

[edit] Atrial fibrillationPatients with atrial fibrillation have a risk of 5% each year to develop stroke, and this risk is even higher in those with valvular atrial fibrillation.[60] Depending on the stroke risk, anticoagulation with medications such as coumarins or aspirin is warranted for stroke prevention.[61]

[edit] Blood lipidsHigh cholesterol levels have been inconsistently associated with (ischemic) stroke. [53][62] Statins have been shown to reduce the risk of stroke by about 15%. [63] Since earlier meta-analyses of other lipid-lowering drugs did not show a decreased risk,[64] statins might exert their effect through mechanisms other than their lipid-lowering effects.[63]

[edit] Diabetes mellitusPatients with diabetes mellitus are 2 to 3 times more likely to develop stroke, and they commonly have hypertension and hyperlipidemia. Intensive disease control has been shown to reduce microvascular

complications such as nephropathy and retinopathy but not macrovascular complications such as stroke.[65][66]

[edit] Anticoagulation drugsOral anticoagulants such as warfarin have been the mainstay of stroke prevention for over 50 years. However, several studies have shown that aspirin and antiplatelet drugs are highly effective in secondary prevention after a stroke or transient ischemic attack.[35] Low doses of aspirin (for example 75–150 mg) are as effective as high doses but have fewer side effects; the lowest effective dose remains unknown.[67] Thienopyridines (clopidogrel, ticlopidine) "might be slightly more effective" than aspirin and have a decreased risk of gastrointestinal bleeding, but they are more expensive.[68] Their exact role remains controversial. Ticlopidine has more skin rash, diarrhea, neutropenia and thrombotic thrombocytopenic purpura.[68] Dipyridamole can be added to aspirin therapy to provide a small additional benefit, even though headache is a common side effect. [69] Low-dose aspirin is also effective for stroke prevention after sustaining a myocardial infarction.[36] Except for in atrial fibrillation, oral anticoagulants are not advised for stroke prevention —any benefit is offset by bleeding risk.[70]

In primary prevention however, antiplatelet drugs did not reduce the risk of ischemic stroke while increasing the risk of major bleeding.[71][72] Further studies are needed to investigate a possible protective effect of aspirin against ischemic stroke in women.[73][74]

[edit] SurgerySurgical procedures such as carotid endarterectomy or carotid angioplasty can be used to remove significant atherosclerotic narrowing (stenosis) of the carotid artery, which supplies blood to the brain. There is a large body of evidence supporting this procedure in selected cases. [49] Endarterectomy for a significant stenosis has been shown to be useful in the secondary prevention after a previous symptomatic stroke.[75] Carotid artery stenting has not been shown to be equally useful. [76][77] Patients are selected for surgery based on age, gender, degree of stenosis, time since symptoms and patients' preferences.[49] Surgery is most efficient when not delayed too long —the risk of recurrent stroke in a patient who has a 50% or greater stenosis is up to 20% after 5 years, but endarterectomy reduces this risk to around 5%. The number of procedures needed to cure one patient was 5 for early surgery (within two weeks after the initial stroke), but 125 if delayed longer than 12 weeks.[78][79]

Screening for carotid artery narrowing has not been shown to be a useful screening test in the general population.[80] Studies of surgical intervention for carotid artery stenosis without symptoms have shown only a small decrease in the risk of stroke.[81][82] To be beneficial, the complication rate of the surgery should be kept below 4%. Even then, for 100 surgeries, 5 patients will benefit by avoiding stroke, 3 will develop stroke despite surgery, 3 will develop stroke or die due to the surgery itself, and 89 will remain stroke-free but would also have done so without intervention.[49]

[edit] Nutritional and metabolic interventionsNutrition, specifically the Mediterranean-style diet, has the potential of more than halving stroke risk.[83]

With regard to lowering homocysteine, a meta-analysis of previous trials has concluded that lowering homocysteine with folic acid and other supplements may reduce stroke risk.[84] However, the two largest randomized controlled trials included in the meta-analysis had conflicting results. One reported positive results;[85] whereas the other was negative.[86]

The European Society of Cardiology and the European Association for Cardiovascular Prevention and Rehabilitation have developed an interactive tool for prediction and managing the risk of heart attack and stroke in Europe. HeartScore is aimed at supporting clinicians in optimising individual cardiovascular risk reduction. The Heartscore Programme is available in 12 languages and offers web based or PC version.[87]

[edit] Treatment[edit] Stroke unit

Ideally, people who have had a stroke are admitted to a "stroke unit", a ward or dedicated area in hospital staffed by nurses and therapists with experience in stroke treatment. It has been shown that people admitted to a stroke unit have a higher chance of surviving than those admitted elsewhere in hospital, even if they are being cared for by doctors without experience in stroke.[2]

When an acute stroke is suspected by history and physical examination, the goal of early assessment is to determine the cause. Treatment varies according to the underlying cause of the stroke, thromboembolic (ischemic) or hemorrhagic. A non-contrast head CT scan can rapidly identify a hemorrhagic stroke by imaging bleeding in or around the brain. If no bleeding is seen, a presumptive diagnosis of ischemic stroke is made.[edit] Treatment of ischemic strokeAn ischemic stroke is caused by a thrombus (blood clot) occluding blood flow to an artery supplying the brain. Definitive therapy is aimed at removing the blockage by breaking the clot down ( thrombolysis), or by removing it mechanically (thrombectomy). The more rapidly blood flow is restored to the brain, the fewer brain cells die.[88]

Other medical therapies are aimed at minimizing clot enlargement or preventing new clots from forming. To this end, treatment with medications such as aspirin, clopidogrel and dipyridamole may be given to prevent platelets from aggregating.[35]

Tight control of blood sugars in the first few hours does not improve outcomes and may cause harm. [89]

High blood pressure is also not typically lowered as this has not been found to be helpful.[edit] ThrombolysisIn an increasing number of primary stroke centers, pharmacologic thrombolysis ("clot busting") with the drug tissue plasminogen activator (tPA), is used to dissolve the clot and unblock the artery. However, the use of tPA in acute stroke is controversial. On one hand, it is endorsed by the American Heart Association and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are not other contraindications (such as abnormal lab values, high blood pressure, or recent surgery). This position for tPA is based upon the findings of two studies by one group of investigators[90] which showed that tPA improves the chances for a good neurological outcome. When administered within the first three hours thrombolysis improves functional outcome without affecting mortality.[91] A recent study using alteplase for thrombolysis in ischemic stroke suggests clinical benefit with administration 3 to 4.5 hours after stroke onset. [92]

However, in the NINDS trial 6.4% of patients with large strokes developed substantial brain hemorrhage as a complication from being given tPA. A recent study found the mortality to be higher among patients receiving tPA versus those who did not.[93] Additionally, it is the position of the American Academy of Emergency Medicine that objective evidence regarding the efficacy, safety, and applicability of tPA for acute ischemic stroke is insufficient to warrant its classification as standard of care.[94] Intra-arterial fibrinolysis, where a catherter is passed up an artery into the brain and the medication is injected at the site of thrombosis, has been found to improve outcomes in people with acute ischemic stroke.[95]

[edit] Mechanical thrombectomyMerci Retriever L5.Another intervention for acute ischemic stroke is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. Mechanical embolectomy devices have been demonstrated effective at restoring blood flow in patients who were unable to receive thrombolytic drugs or for whom the drugs were ineffective,[96][97][98][99]

though no differences have been found between newer and older versions of the devices. [100] The devices have only been tested on patients treated with mechanical clot embolectomy within eight hours of the onset of symptoms.

[edit] Angioplasty and stentingAngioplasty and stenting have begun to be looked at as possible viable options in treatment of acute ischemic stroke. In a systematic review of six uncontrolled, single-center trials, involving a total of 300 patients, of intra-cranial stenting in symptomatic intracranial arterial stenosis, the rate of technical success (reduction to stenosis of <50%) ranged from 90-98%, and the rate of major peri-procedural complications ranged from 4-10%. The rates of restenosis and/or stroke following the treatment were also favorable.[101] This data suggests that a large, randomized controlled trial is needed to more completely evaluate the possible therapeutic advantage of this treatment.[edit] Secondary prevention of ischemic strokeAnticoagulation can prevent recurrent stroke. Among patients with nonvalvular atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. [102]

However, a recent meta-analysis suggests harm from anti-coagulation started early after an embolic stroke.[103] Stroke prevention treatment for atrial fibrillation is determined according to the CHADS/CHADS2 system. The most widely used anticoagulant to prevent thromboembolic stroke in patients with nonvalvular atrial fibrillation is the oral agent Warfarin while dabigatran is a new alternative which does not require prothrombin time monitoring.If studies show carotid stenosis, and the patient has residual function in the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after stroke.[edit] Treatment of hemorrhagic strokePatients with intracerebral hemorrhage require neurosurgical evaluation to detect and treat the cause of the bleeding, although many may not need surgery. Anticoagulants and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are monitored for changes in the level of consciousness, and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.[edit] Care and rehabilitationStroke rehabilitation is the process by which patients with disabling strokes undergo treatment to help them return to normal life as much as possible by regaining and relearning the skills of everyday living. It also aims to help the survivor understand and adapt to difficulties, prevent secondary complications and educate family members to play a supporting role.A rehabilitation team is usually multidisciplinary as it involves staff with different skills working together to help the patient. These include nursing staff, physiotherapy, occupational therapy, speech and language therapy, and usually a physician trained in rehabilitation medicine. Some teams may also include psychologists, social workers, and pharmacists since at least one third of the patients manifest post stroke depression. Validated instruments such as the Barthel scale may be used to assess the likelihood of a stroke patient being able to manage at home with or without support subsequent to discharge from hospital.Good nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, and monitoring vital signs such as temperature, pulse, and blood pressure. Stroke rehabilitation begins almost immediately.For most stroke patients, physical therapy (PT), occupational therapy (OT) and speech-language pathology (SLP) are the cornerstones of the rehabilitation process. Often, assistive technology such as a wheelchair, walkers, canes, and orthosis may be beneficial. PT and OT have overlapping areas of working but their main attention fields are; PT focuses on joint range of motion and strength by performing exercises and re-learning functional tasks such as bed mobility, transferring, walking and other gross motor functions. Physiotherapists can also work with patients to improve awareness and use of the hemiplegic side. Rehabilitation involves working on the ability to produce strong movements or the ability to perform tasks using normal patterns. Emphasis is often concentrated on functional tasks and

patient’s goals. One example physiotherapists employ to promote motor learning involves constraint-induced movement therapy. Through continuous practice the patient relearns to use and adapt the hemiplegic limb during functional activities to create lasting permanent changes. [104] OT is involved in training to help relearn everyday activities known as the Activities of daily living (ADLs) such as eating, drinking, dressing, bathing, cooking, reading and writing, and toileting. Speech and language therapy is appropriate for patients with the speech production disorders: dysarthria and apraxia of speech, aphasia, cognitive-communication impairments and/or dysphagia (problems with swallowing).Patients may have particular problems, such as dysphagia , which can cause swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly into the stomach. If swallowing is still deemed unsafe, then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remain indefinitely.Treatment of spasticity related to stroke often involves early mobilisations, commonly performed by a physiotherapist, combined with elongation of spastic muscles and sustained stretching through various positioning.[23] Gaining initial improvements in range of motion is often achieved through rhythmic rotational patterns associated with the affected limb.[23] After full range has been achieved by the therapist, the limb should be positioned in the lengthened positions to prevent against further contractures, skin breakdown, and disuse of the limb with the use of splints or other tools to stabilize the joint.[23] Cold in the form of ice wraps or ice packs have been proven to briefly reduce spasticity by temporarily dampening neural firing rates.[23] Electrical stimulation to the antagonist muscles or vibrations has also been used with some success.[23]

Stroke rehabilitation should be started as quickly as possible and can last anywhere from a few days to over a year. Most return of function is seen in the first few months, and then improvement falls off with the "window" considered officially by U.S. state rehabilitation units and others to be closed after six months, with little chance of further improvement. However, patients have been known to continue to improve for years, regaining and strengthening abilities like writing, walking, running, and talking. Daily rehabilitation exercises should continue to be part of the stroke patient's routine. Complete recovery is unusual but not impossible and most patients will improve to some extent: proper diet and exercise are known to help the brain to recover.Some current and future therapy methods include the use of virtual reality and video games for rehabilitation. These forms of rehabilitation offer potential for motivating patients to perform specific therapy tasks that many other forms do not.[105] Many clinics and hospitals are adopting the use of these off-the-shelf devices for exercise, social interaction and rehabilitation because they are affordable, accessible and can be used within the clinic and home.[105]

[edit] PrognosisThis section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (September 2008)

Disability affects 75% of stroke survivors enough to decrease their employability. [106] Stroke can affect patients physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on size and location of the lesion.[107] Dysfunctions correspond to areas in the brain that have been damaged.Some of the physical disabilities that can result from stroke include muscle weakness, numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learned movements), difficulties carrying out daily activities, appetite loss, speech loss, vision loss, and pain. If the stroke is severe enough, or in a certain location such as parts of the brainstem, coma or death can result.

Emotional problems resulting from stroke can result from direct damage to emotional centers in the brain or from frustration and difficulty adapting to new limitations. Post-stroke emotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions), mania, apathy, and psychosis.30 to 50% of stroke survivors suffer post stroke depression, which is characterized by lethargy, irritability, sleep disturbances, lowered self esteem, and withdrawal.[108] Depression can reduce motivation and worsen outcome, but can be treated with antidepressants.Emotional lability, another consequence of stroke, causes the patient to switch quickly between emotional highs and lows and to express emotions inappropriately, for instance with an excess of laughing or crying with little or no provocation. While these expressions of emotion usually correspond to the patient's actual emotions, a more severe form of emotional lability causes patients to laugh and cry pathologically, without regard to context or emotion.[106] Some patients show the opposite of what they feel, for example crying when they are happy.[109] Emotional lability occurs in about 20% of stroke patients.Cognitive deficits resulting from stroke include perceptual disorders, speech problems, dementia, and problems with attention and memory. A stroke sufferer may be unaware of his or her own disabilities, a condition called anosognosia. In a condition called hemispatial neglect, a patient is unable to attend to anything on the side of space opposite to the damaged hemisphere.Up to 10% of all stroke patients develop seizures, most commonly in the week subsequent to the event; the severity of the stroke increases the likelihood of a seizure.[110][111]

[edit] EpidemiologyStroke could soon be the most common cause of death worldwide. [112] Stroke is currently the second leading cause of death in the Western world, ranking after heart disease and before cancer,[2] and causes 10% of deaths worldwide.[113] Geographic disparities in stroke incidence have been observed, including the existence of a "stroke belt" in the southeastern United States, but causes of these disparities have not been explained.The incidence of stroke increases exponentially from 30 years of age, and etiology varies by age.[114]

Advanced age is one of the most significant stroke risk factors. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65.[108][25] A person's risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in childhood.Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Higher levels of Von Willebrand factor are more common amongst people who have had ischemic stroke for the first time.[115] The results of this study found that the only significant genetic factor was the person's blood type. Having had a stroke in the past greatly increases one's risk of future strokes.Men are 25% more likely to suffer strokes than women,[25] yet 60% of deaths from stroke occur in women.[109] Since women live longer, they are older on average when they have their strokes and thus more often killed (NIMH 2002).[25] Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause and the treatment thereof (HRT).

Pengobatan Stroke dan Perawatan PASCA Stroke

Stroke adalah penyakit otak yang paling destruktif dengan konsekuensi berat. Stroke tidak hanya akan menimbulkan kecacatan yang dapat membebani seumur hidup tapi juga ancaman kematian bagi pasien.

Jika mengalami serangan stroke, segera dilakukan pemeriksaan untuk menentukan apakah penyebabnya bekuan darah atau perdarahan yang tidak bisa diatasi dengan obat penghancur bekuan darah.

Penelitian terakhir menunjukkan bahwa kelumpuhan dan gejala lainnya bisa dicegah atau dipulihkan jika obat stroke yang berfungsi menghancurkan bekuan darah disuntikkan kurang dari tiga jam sejak serangan (periode emas).

Obat yang diberikan biasanya diberikan berdasarkan penyebab stroke , dan akibat yang ditimbulkan oleh stroke tersebut, seperti obat depresi (untuk mengatasi gangguan psikis), dan memerlukan respirator (alat bantu nafas).

Salah satu penyebab stroke adalah kolesterol yang meningkatkan risiko penyumbatan pembuluh darah akibat bekuan darah, sehingga obat stroke yang biasa diberikan obat pengencer darah dan obat penurun kadar kolesterol.

Antikoagulan (anti penggumpalan) tidak diberikan kepada penderita tekanan darah tinggi dan tidak pernah diberikan kepada penderita dengan perdarahan otak karena akan menambah risiko terjadinya perdarahan ke dalam otak.

Perawatan Paska Stroke

Sekali terkena serangan stroke tidak membuat Anda terbebas dari stroke. Di samping dampak menimbulkan kecacatan, masih ada kemungkinan dapat terserang kembali di kemudian hari.

Pasca stroke biasanya penderita memerlukan rehabilitasi serta terapi psikis seperti terapi fisik, terapi okupasi, terapi wicara, dan penyediaan alat bantu di unit orthotik prostetik. Juga penanganan psikologis pasien, seperti berbagi rasa, terapi wisata, dan sebagainya.

Selain itu, juga dilakukan community based rehabilitation (rehabilitasi bersumberdaya masyarakat) dengan melakukan penyuluhan dan pelatihan masyarakat di lingkungan pasien agar mampu menolong, setidaknya bersikap tepat terhadap penderita. Hal ini akan meningkatkan pemulihan dan integrasi dengan masyarakat.

Bahaya yang menghantui penderita stroke adalah serangan stroke berulang yang dapat fatal atau kualitas hidup yang lebih buruk dari serangan pertama.

Bahkan ada pasien yang mengalami serangan stroke sebanyak 6-7 kali. Hal ini disebabkan pasien tersebut tidak mengendalikan faktor risiko stroke.

Bagi mereka yang sudah pernah terkena serangan stroke, Gaya hidup sehat haruslah jadi pilihan agar tidak kembali diserang stroke, seperti: berhenti merokok, diet rendah lemak atau kolesterol dan tinggi serat, berolahraga teratur 3 X seminggu (30-45 menit), makan secukupnya, dengan memenuhi kebutuhan gizi seimbang, menjaga berat badan jangan sampai kelebihan berat badan, berhenti minum alkohol dan atasi stres.