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Intravenous thrombolytic therapy for acute ischemic stroke: predictors of favorable neurological outcome

dc.contributor.advisorJovićević, Mirjana
dc.contributor.otherŽivanović, Željko
dc.contributor.otherŽarkov, Marija
dc.contributor.otherJovanović, Dejana
dc.contributor.otherLučić-Prokin, Aleksandra
dc.contributor.otherSimić, Svetlana
dc.creatorRajić, Sonja
dc.date.accessioned2020-07-06T10:11:01Z
dc.date.available2020-02-24T10:11:01Z
dc.date.available2020-07-03T13:23:46Z
dc.date.issued2020-01-09
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/11929
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija156931952450278.pdf?controlNumber=(BISIS)111177&fileName=156931952450278.pdf&id=13503&source=NaRDuS&language=srsr
dc.identifier.urihttps://www.cris.uns.ac.rs/record.jsf?recordId=111177&source=NaRDuS&language=srsr
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije156931953301422.pdf?controlNumber=(BISIS)111177&fileName=156931953301422.pdf&id=13504&source=NaRDuS&language=srsr
dc.description.abstractAkutni ishemijski moždani udar predstavlja jedan od vodećih uzroka morbiditeta i mortaliteta u svetu. Kada dođe do prekida cirkulacije u nekoj od glavnih arterija mozga, moždano tkivo propada velikom brzinom, te je glavni cilj terapije ponovno uspostavljanje krvotoka u ishemijom zahvaćenom tkivu. Intravenska trombolitička terapija uz pomoć tkivnog aktivatora plazminogena je dokazano efikasna i bezbedna, ukoliko se primeni u okviru 4.5 časa od nastanka simptoma i danas predstavlja standarnu terapiju ishemijskog moždanog udara. Postojanje brojnih kontraindikacija za primenu ove terapije je vremenom modifikovano. Pokazano je da mnogi faktori utiču na ishod bolesnika nakon primene intravenske trombolize, a najznačajniji su godine života i težina moždanog udara. Pored njih, čitav niz kliničkih, laboratorijskih i radioloških faktora utiče na krajnji funkcionalni ishod bolesnika. Iako angiografska procena postojanja okluzije arterijskog krvnog suda nije neophoda, utvrđivanje rekanalizacionog statusa u velikoj meri doprinosi evaluaciji efikasnosti ove terapije, kao i uticaju ponovnog uspostavljanja cirkulacije na neurološki ishod. Sagledavanje činilaca koji imaju uticaj na ishod nakon primene trombolitičke terapije, daje nam uvidu u prognozu bolesnika. Za brzu, jednostavnu i objektivnu procenu ishoda, u upotrebi su različiti skoring sistemi, najčešće dostupni u svakodnevnom kliničkom radu. Cilj: Utvrditi prediktore ranog neurološkog poboljšanja nakon 24 sata i povoljnog neurološkog ishoda nakon 3 meseca, kod pacijenata sa AIMU lečenih intravenskom trombolitičkom terapijom. Utvrditi uticaj rekanalizacije prethodno okludiranog krvnog suda na klinički ishod i testirati DRAGON skor u predikciji ishoda. Metode: Istraživanje najvećim delom predstavlja retrospektivnu analizu podataka pacijenata sa akutnim ishemijskim moždanim udarom lečenih intravenskom trombolitičkom terapijom u Kliničkom centru Vojvodine, u desetogodišnjem periodu. Ispitanicima je intravenski aplikovana alteplaza u okviru prva 4.5 časa od nastanka simptoma možanog udara, prema važaćem protokolu. Iz istorija bolesti pacijenata korišteni su relevantni podaci iz anamneze, kao i podaci koji su se odnosili na neurološki i somatski nalaz, zatim laboratorijski parametri i dostupni nalazi neuroimidžinga. Rano neurološko poboljšanje definisano je kao pad NIHSS skora za 40% nakon 24 sata, u odnosu na inicijalnu vrednost. Povoljan neurološki ishod je definisan kao funkcionalna nezavisnost nakon tri meseca (modifikovani Rankinov skor 0-2). Analiza procene uticaja različitih faktora na rano neurološko poboljšanje, uključila je podatke 397 bolesnika, dok je analiza na povoljan neurološki ishod nakon 3 meseca sprovedena je na 379 bolesnika. Za ocenu uticaja faktora na razvoj povoljnog neurološkog ishoda sprovedena je multivarijantna regresiona analiza metodom binarne logističke regresije. Rezultati: Rano neurološko poboljšanje postignuto je kod 36.5% bolesnika. Kao nezavisni prediktori ranog neurološkog poboljšanja izdvojili su se mlađa životna dob, blaži moždani udar i niži ASPECT skor na inicijalnom CT pregledu mozga. Povoljan neurološki ishod je postignut u 54.9% slučajeva. Nezavisni prediktori povojnog tromesečnog ishoda bili su: niže vrednnosti NIHSS skora nakon 24 časa, niže vrednosti prijemne glikemije, mlađi uzrast i kraće trajanje hospitalizacije. Ukupno 87 bolesnika je imalo dostupne podatke o rekanalizacionom statusu, gde je uspešna rekanalizacija zabeležena lod njih 46 (53%). Dobar prognostički znak u smislu postizanja rekanalizacije predstavljaju niži NIHSS skor nakon 2 časa i niže vrednosti triglicerida. DRAGON skor pokazao je visoko statistički značajnu pozitivnu korelaciju srednjeg do visokog intenziteta sa modifikovanim Rankinovim skorom nakon 3 meseca. Vrednosti DRAGON skora manje od 5 predviđaju povoljan ishod (senzitivnost 82%, specifičnost 72%). Zaključak: Utvrđeno je da više od polovine pacijenata sa AIMU, lečenih intravenskom trombolitičkom terapijom, postigne funkcionalnu nezavisnost, tri meseca nakon moždanog udara. Blaži moždani udar, mlađi uzrast i viši ASPECT skor nezavisni su prediktori ranog neurološkog poboljšanja. Veliki broj faktora utiče na tromesečni funkcionalni ishod, a najveći doprinos povoljnom neurološkom ishodu dali su niži NIHSS skor nakon 24 sata, niža prijemna glikemija i mlađi uzrast. Vreme nije imalo prediktivni značaj kod pacijenata koji su lečeni prema protokolu, u okviru 4.5 sata od nastanka simptoma. Uspešna rekanalizacija prethodno okludiranog krvnog suda postignuta je u preko polovine slučajeva i snažno je povezana sa povoljnim funkcionalnim ishodom. DRAGON skor je primenljiv u predikciji ishoda na našoj populaciji. Pacijenti sa nižim vrednostima DRAGON skora imaju veću šansu za povoljan neurološki ishod, u odnosu na one sa višim vrednostima.sr
dc.description.abstractAcute ischemic stroke is one of the leading causes of morbidity and mortality worldwide. A cutoff of circulation in one of the main brain arteries, abruptly leads to brain tissue destruction, so the main goal of the therapy is restitution of the blood flow in the ischemic zone. Intravenous thrombolytic therapy with tissue plasminogen activator is proven efficient and safe if applied 4.5 hours from symptom onset, and today it represents standard therapy of ischemic stroke. Numerous contraindications to this treatment have been modified over time. Multiple factors affect the patient outcome after intravenous thrombolysis, age and stroke severity being the most important. In addition, a range of clinical, laboratory and radiological factors influence the ultimate functional outcome of patients. Although angiographic assessment of artery occlusion is not mandatory, determining recanalization status greatly contributes to the evaluation of therapy effectiveness as well as the impact of re-opening of blood vessel to the neurological outcome. Determining factors that impact outcome after thrombolysis can give us insight into the patient prognosis. For fast, simple and objective estimation of outcome, different prognostic score systems are put to use, usually available in everyday clinical practice. Objective: Determining predictors of early neurological improvement after 24 hours and favorable neurological outcome after 3 months, in patients with acute ischemic stroke treated with intravenous thrombolytic therapy. Determining the impact of recanalization of previously occluded blood vessel on clinical outcome and testing DRAGON score in the prediction of outcome. Methods: The study mainly represents retrospective analysis of data from patients with acute ischemic stroke treated with intravenous thrombolytic therapy in Clinical Centre of Vojvodina, in a ten-year period. All patients were given intravenous alteplase within the 4.5 hours from the symptom onset, in accordance with the protocol. Relevant data from medical history of patients were obtained, including anamnesis, neurological and somatic status, laboratory tests and available neuroimaging findings. Early neurological improvement was defined as improvement by 40% from baseline NIHSS score, after 24 hours. Favorable neurological outcome was defined as functional independence after 3 months (modified Rankin score 0-2). Analysis of the impact of different factors on early neurological improvement included data from 397 patients, whereas analysis on favorable neurological outcome after 3 months included data from 379 patients. To evaluate the influence of factors on the development of favorable neurological outcome, multivariate regression analysis was performed using the binary logistic regression model. Results: Early neurological improvement was achieved in 36.5% of patients. Independent predictors of early neurological improvement were younger age, milder stroke and lower ASPECT score on baseline CT. Favorable neurological outcome was achieved in 54.9% of the cases. Independent predictors of favorable three-month outcome were: lower NIHSS score after 24 hours, lower admission glycemia, younger age and shorter duration of hospitalization. A total of 87 patients underwent recanalization status assessment with successful recanalization being recorded in 46 patients (53%). Good prognostic signs in terms of recanalization were lower NIHSS score after 2 hours and lower levels of triglycerides. DRAGON score showed highly statistically significant positive correlation of medium to high intensity with a modified Rankin score after 3 months. DRAGON score of less than 5 predicts favorable outcome (sensitivity 82%, specificity 72%). Conclusion: We found that more than a half of patients with acute ischemic stroke, treated with intravenous thrombolysis, reach functional independence 3 months after stroke. Milder stroke, younger age and higher ASPECT score are independent predictors of early neurological improvement. Numerous factors affect three-month functional outcome, with lower NIHSS score after 24 hours, lower admission glycemia and younger age contributing the most to favorable neurological outcome. Time did not have predictive value in patients treated according to protocol, within 4.5 hours from symptom onset. Successful recanalization of previously occluded blood vessel has been achieved in over half of cases and is strongly associated with favorable functional outcome. The DRAGON score is applicable in predicting outcome in our population. Patients with lower DRAGON scores are more likely to have favorable neurological outcome than those with higher values.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectmoždana ishemijasr
dc.subjectBrain Ischemiaen
dc.subjectStrokeen
dc.subjectThrombolytic Therapyen
dc.subjectTissue Plasminogen Activatoren
dc.subjectFibrinolytic Agentsen
dc.subjectTreatment Outcomeen
dc.subjectTime-to-Treatmenten
dc.subjectPrognosisen
dc.subjectmoždani udarsr
dc.subjecttrombolitička terapijasr
dc.subjecttkivni aktivator plazminogenasr
dc.subjectfibrinoliticisr
dc.subjectishod terapijesr
dc.subjectvreme do terapijesr
dc.subjectprognozasr
dc.titleIntravenska trombolitička terapija u lečenju akutnog ishemijskog moždanog udara: prediktori povoljnog neurološkog ishodasr
dc.title.alternativeIntravenous thrombolytic therapy for acute ischemic stroke: predictors of favorable neurological outcomeen
dc.typedoctoralThesissr
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/33830/IzvestajKomisije.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/33829/Disertacija.pdf


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