Study evaluates adenosine, which is used as an adjunct to conventional reperfusion therapy (percutaneous coronary intervention, i.e. PCI), role in reducing the infarct size and preserving the left ventricular function in patients with acute myocardial infarction. During the study we examined patients with the left ventricular anterior wall acute myocardial infarction (AMI), when PCI and stenting were used for infarct-related artery (IRA) re-opening. Study evaluates influence of complementary use of adenosine in reducing the myocardial ischemic-reperfusion injury, the manifestation of slow-reflow or no-reflow phenomenon. The results of reperfusion therapy with adjunctive adenosine and without adenosine were analyzed in two homogeneous patient groups. By using new non-invasive imaging methods (single photon emission computer tomography, transthoracic Doppler echocardiography, dobutamine stress echocardiography) it was estimated, that adenosine preserves myocardial contractility and coronary flow reserve during the acute phase of myocardial infarction, reduces the final infarct size, improves the recovery of left ventricular global and segmental contractile function at five months follow-up. Those results are achieved due to adenosine impact on improving blood flow restoration not only in major coronary arteries, but also at microcirculatory level and ensuring of adequate and effective myocardial reperfusion. / Tyrime analizuojama adenozino, kuriuo papildoma įprastinė reperfuzinė terapija (perkutaninė koronarinė intervencija), įtaka mažinant infarkto dydį ir išsaugant kairiojo skilvelio funkciją pacientams, sergantiems ūminiu miokardo infarktu. Tyrimo metu siekta įvertinti PKI ir stentavimo būdu atveriant priekinės nusileidžiančios šakos spindį, kurio okliuzija sąlygojo kairiojo skilvelio priekinės sienelės ūminį miokardo infarktą, papildomai naudojamo adenozino įtaką mažinant miokardo išeminį-reperfuzinį pažeidimą, lėtos ar nutrūkusios tėkmės fenomeno pasireiškimą ir išplitimą. Reperfuzinės terapijos (PKI naudojant adenoziną ir PKI be adenozino) rezultatų ypatumai ir skirtumai palyginti dviejose homogeniškose pagal kontrolinius kintamuosius pacientų grupėse. Pasitelkus naujausius neinvazinius vaizdinimo metodus (miokardo perfuzijos radionuklidinę kompiuterinę tomografiją, transtorakalinę doplerinę echokardiografiją, dobutamino krūvio echokardiografiją) nustatyta, kad adenozinas, gerindamas kraujo tėkmės atstatymą ne tik stambiosiose vainikinėse arterijose, bet ir mikrocirkuliacijos grandyje, užtikrindamas adekvačią bei efektyvią miokardo reperfuziją, išsaugo miokardo kontraktilinį bei koronarinės tėkmės rezervus ūminio miokardo infarkto metu, mažina galutinį infarkto dydį, gerina bendrosios ir segmentinės kairiojo skilvelio kontraktilinės funkcijos atsistatymą praėjus 5 mėn. po reperfuzinio miokardo infarkto gydymo.

Tyrime analizuojama adenozino, kuriuo papildoma įprastinė reperfuzinė terapija (perkutaninė koronarinė intervencija), įtaka mažinant infarkto dydį ir išsaugant kairiojo skilvelio funkciją pacientams, sergantiems ūminiu miokardo infarktu. Tyrimo metu siekta įvertinti PKI ir stentavimo būdu atveriant priekinės nusileidžiančios šakos spindį, kurio okliuzija sąlygojo kairiojo skilvelio priekinės sienelės ūminį miokardo infarktą, papildomai naudojamo adenozino įtaką mažinant miokardo išeminį-reperfuzinį pažeidimą, lėtos ar nutrūkusios tėkmės fenomeno pasireiškimą ir išplitimą. Reperfuzinės terapijos (PKI naudojant adenoziną ir PKI be adenozino) rezultatų ypatumai ir skirtumai palyginti dviejose homogeniškose pagal kontrolinius kintamuosius pacientų grupėse. Pasitelkus naujausius neinvazinius vaizdinimo metodus (miokardo perfuzijos radionuklidinę kompiuterinę tomografiją, transtorakalinę doplerinę echokardiografiją, dobutamino krūvio echokardiografiją) nustatyta, kad adenozinas, gerindamas kraujo tėkmės atstatymą ne tik stambiosiose vainikinėse arterijose, bet ir mikrocirkuliacijos grandyje, užtikrindamas adekvačią bei efektyvią miokardo reperfuziją, išsaugo miokardo kontraktilinį bei koronarinės tėkmės rezervus ūminio miokardo infarkto metu, mažina galutinį infarkto dydį, gerina bendrosios ir segmentinės kairiojo skilvelio kontraktilinės funkcijos atsistatymą praėjus 5 mėn. po reperfuzinio miokardo infarkto gydymo. / Study evaluates adenosine, which is used as an adjunct to conventional reperfusion therapy (percutaneous coronary intervention, i.e. PCI), role in reducing the infarct size and preserving the left ventricular function in patients with acute myocardial infarction. During the study we examined patients with the left ventricular anterior wall acute myocardial infarction (AMI), when PCI and stenting were used for infarct-related artery (IRA) re-opening. Study evaluates influence of complementary use of adenosine in reducing the myocardial ischemic-reperfusion injury, the manifestation of slow-reflow or no-reflow phenomenon. The results of reperfusion therapy with adjunctive adenosine and without adenosine were analyzed in two homogeneous patient groups. By using new non-invasive imaging methods (single photon emission computer tomography, transthoracic Doppler echocardiography, dobutamine stress echocardiography) it was estimated, that adenosine preserves myocardial contractility and coronary flow reserve during the acute phase of myocardial infarction, reduces the final infarct size, improves the recovery of left ventricular global and segmental contractile function at five months follow-up. Those results are achieved due to adenosine impact on improving blood flow restoration not only in major coronary arteries, but also at microcirculatory level and ensuring of adequate and effective myocardial reperfusion.

En så tidig reperfusionsbehandling som möjligt hos patienter med ST-höjningsinfarkt förbättrar prognosen både gällande kardiell status och minskad dödlighet. Arbetet runt patienten måste ske skyndsamt men samtidigt med hög kompetens. Trots tydliga riktlinjer och tidsmål för reperfusionsbehandling uppfylls inte alltid dessa. Med ökad förståelse för faktorer som påverkar tidsflödet från första vårdkontakt till reperfusionsbehandling skapas förutsättningar för ett mer tidseffektivt och därmed säkrare omhändertagande av patienter som drabbade av ST-höjningsinfarkt. Syftet var att identifiera faktorer som påverkar tidsflödet från första vårdkontakt till reperfusionsbehandling vid det akuta omhändertagandet av patienter med ST-höjningsinfarkt. Metoden var en icke systematisk litteraturöversikt. Totalt inkluderades 15 artiklar både av kvantitativ- och kvalitativ ansats. Artiklarna som inkluderades i resultatet kvalitetsgranskades utifrån Sophiahemmets bedömningsunderlag för att klassificera och kvalitetsbedöma de vetenskapliga artiklarna. Artiklarna analyserades med integrerad analysmetod där likheter och olikheter mellan artiklarna identifierades, sammanställdes och delades in i underrubriker samt kategorier. I resultatet framkom fyra huvudkategorier; “Patientrelaterade faktorer”, “System-och organisatoriska faktorer”, “Vårdpersonalens inflytande” och “Kommunikation”. Resultatet från litteraturöversikten visar faktorer som hade både positiv och negativ inverkan på tidsåtgången från första vårdkontakt till reperfusionsbehandling. Faktorer som associerades med förlängd tidsåtgång var: prehospitalt långa transporttider, ospecifika symtom och otillgängligt Percutant Coronar Interventions-lab (PCI-lab). Faktorerna som associerades med tidssparande effekt var: prehospitalt EKG, när patienten transporterades direkt till PCI-lab utan att gå via akuten, prehospital notifikation, fungerande teamarbete, standardiserade arbetssätt och protokoll, organisatoriskt engagemang med regelbunden feedback till personalen samt kompetensutbildning. Slutsatsen är att faktorer som associerades med förlängd tidsåtgång var prehospitalt långa transportavstånd, ospecifika symtom och otillgängligt PCI-lab. Faktorerna som associerades med tidssparande effekt var prehospitalt EKG, direkt transport till PCI-lab utan att passera akutmottagningen, fungerande teamarbete med god kommunikation, standardiserade arbetssätt, organisatoriskt engagemang med regelbunden feedback och utvärdering samt kompetensutbildning för berörd personal. För att identifiera faktorer som är tidsvinnande och skapa nya strategier krävs engagemang och samarbete från samtliga professioner som möter patienten. / As early reperfusion therapy as possible in patients with ST-elevation infarction, the prognosis improves both in terms of cardiac status and reduced mortality. The care around the patient must be done quickly but at the same time with high knowledge precision. Despite clear guidelines and goals for reperfusion, not everyone lives up to them. With an increased understanding of factors that affect the flow of time from initial care contact to reperfusion treatment, conditions are created for more time-efficient and safer care of patients suffering from ST-elevation myocardial infarction. The aim was to identify factors that affect the time flow from first medical contact to reperfusion therapy in the acute care of patients with ST-elevation myocardial infarction. The method was a literature study with a systematic search strategy. A total of 15 articles were included which were both quantitative and qualitative. The articles that were included in the results section were read through several times by both authors and quality reviewed with assessment data for literature studies. The articles were analyzed with an integrated analysis method and divided into subheadings and categories. The results revealed four main categories; "Patient-related factors", "System and organizational factors", "Influence of care staff" and "Communication". The results from the literature review show factors that had both a positive and negative impact on the time required from first medical contact to reperfusion therapy. Factors associated with prolonged time consumption were: prehospital transport times, nonspecific symptoms, and unavailable Percutaneous Coronary Intervention-lab (PCI-lab). The factors associated with the timesaving effect were: prehospital ECG, when the patient was transported directly to the PCI-lab without going through the emergency room, prehospital notification, functioning teamwork, standardized working methods and protocols, organizational commitment with regular feedback to staff and skills training The conclusion is that factors associated with prolonged time consumption were prehospital long transport distances, nonspecific symptoms and unavailable PCI lab. The factors associated with time-saving effect were prehospital ECG, direct transport to PCI-lab without passing the emergency room, functioning teamwork with good communication, standardized working methods, organizational commitment with regular feedback and evaluation and competence training for relevant staff. Identifying factors that are time-saving and creating new strategies requires commitment and cooperation from all professionals who meet the patient.

Base teórica: O Acidente Vascular Cerebral (AVC) é a causa mais comum de novos diagnósticos de epilepsia no idoso. Embora a epilepsia pós-AVC seja um fenômeno clínico reconhecido há muito tempo, seguem muitas questões não resolvidas. Além disso, nas últimas duas décadas, o tratamento do AVC isquêmico sofreu mudanças radicais com a introdução da trombólise e da hemicraniectomia descompressiva (HD) para o tratamento do infarto maligno de artéria cerebral média (ACM). As consequências destas duas novas abordagens terapêuticas nas características da epilepsia pós-AVC ainda são pouco exploradas. Objetivo: Estudar as características e estimar fatores de risco para as crises epilépticas ou a epilepsia pós-AVC em pacientes submetidos ao tratamento agudo (Estudo 1) ou HD para infarto maligno de ACM (Estudo 2). Métodos: O estudo 1 é uma coorte de 153 pacientes submetidos a trombólise. Variáveis estudadas incluiram fatores de risco para o AVC e variáveis associadas ao AVC isquêmico agudo e trombólise. Utilizamos a análise de regressão de Cox para o estudo das variáveis que se associaram de forma independente com crises epilépticas, epilepsia pós-AVC e o desfecho do AVC. O estudo 2 é também uma coorte que retrospectivamente avaliou 36 pacientes com infarto maligno de ACM tratados com HD. Tempo, incidência e fatores de risco para crises epilépticas e desenvolvimento de epilepsia foram analisados. Resultados: Estudo 1: 74 pacientes (48,4%) eram mulheres; média de idade foi 67,2 anos (DP=13,1). Média do NIHSS na chegada foi 10,95 (DP=6,25) e 2,09 (DP=3,55) após 3 meses. Transformação hemorrágica ocorreu em 22 (14,4%) dos pacientes. Foi considerado desfecho bom classificação na escala modificada de Rankin (mRS) 0-1, sendo encontrado em 87 (56,9%) dos pacientes. Vinte e um pacientes (13,7%) tiveram crises epilépticas e 15 (9,8%) desenvolveram epilepsia após a trombólise. Crises epilépticas foram associadas de forma independente com transformação hemorrágica e desfecho não favorável (mRS ≥ 2) em três meses após o AVC. Transformação hemorrágica e mRS ≥ 2 avaliados em 3 meses, associaram-se de forma independente com epilepsia pós-AVC. Crises epilépticas surgiram como um fator de risco independente para desfecho pobre. Estudo 2. A média de seguimento dos pacientes foi de 1.086 (DP= 1.172) dias. Nove pacientes morreram antes de receberem alta hospitalar e no período de um ano, 11 pacientes haviam morrido. Quase 60% alcançaram mRS ≤ 4. Treze pacientes desenvolveram crises dentro da primeira semana após o AVC. No total, crises epilépticas ocorreram em 22 (61%) dos 36 pacientes. Dezenove pacientes (56%) dos 34, sobreviveram ao período agudo e desenvolveram epilepsia após infarto da ACM e HD. Questionamos aos pacientes ou responsáveis se eles se arrependeram de terem autorizado a HD no momento do AVC. Também foi perguntado se eles autorizariam a HD novamente. Trinta e dois (89%) não se arrependeram de ter autorizado a HD no momento do infarto agudo da ACM, e autorizaria novamente em retrospecto. Conclusão: Confirmamos que as frequências de crises ou epilepsia pós-AVC e trombolítico são comparáveis com as frequências das décadas da era pré-trombólise e confirmamos a alta incidência de crises epilépticas e epilepsia após infartos malignos de ACM submetidos a HD. Em nosso estudo, as crises epilépticas associaram-se de forma independente com pior prognóstico após terapia trombolítica. / Background: The most common cause of newly diagnosed epilepsies in the elderly is stroke. Although post-stroke epilepsy is a well-studied stroke complication, many questions remain unsolved. In addition, during the past two decades, the treatment of stroke has changed dramatically with the introduction of thrombolysis for treatment of acute ischemic stroke (AIS) and decompressive hemicraniectomy (DHC) for malignant middle cerebral artery infarction (MCA). The consequences of these two new therapeutic approaches for characteristics of post-stroke epilepsy remains poorly explored. Objective: To study characteristics and estimate risk factors for acute seizures or post-stroke epilepsy in patients submitted to thrombolysis for treatment of acute stroke (Study 1) or DHC for malignant MCA infarction. Methods: Study 1 is a cohort study of 153 patients submitted to thrombolysis. Variables studied included risk factors for stroke, and variables related to acute stroke and thrombolysis. Variables independently associated with seizures, pos-stroke epilepsy or stroke outcome were defined using Cox regression analysis. Study 2 is also a cohort study that retrospectively assessed 36 patients with malignant stroke of the MCA submitted to DHC. Timing, incidence and plausible risk factors for seizure and epilepsy development were analyzed in these patients. Results: Study 1. Seventy-four patients (48.4%) were female; mean age of patients was 67.2 years-old (SD=13.1). Initial NIHSS mean score was 10.95 (SD=6.25) and 2.09 (SD=3.55) after three months. Hemorrhagic transformation occurred in 22 (14.4%) patients. A good outcome, as defined by a modified Rankin Scale (mRS) of 0-1, was observed in 87 (56.9%) patients. Twenty one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation and with mRS ≥ 2 three months after stroke. Hemorrhagic transformation and unfavorable outcome, as measured by mRS ≥ 2 after three months, were variables independently associated with post-stroke epilepsy. Seizures emerged as an independent factor for poor outcome in stroke thrombolysis. Study 2. Mean patient follow-up time was of 1.086 (SD=1.172) days. Nine patients died before being discharged and after one year eleven patients died. Almost 60% had the modified Rankin score ≤ 4. Thirteen patients developed seizures within the first week after stroke. In total, seizures occurred in 22 (61%) of 36 patients. Nineteen patients (56%) out of 34 patients who survived the acute period developed epilepsy after MCA infarcts and DHC. Also, we asked patients or the person responsible for them whether they regretted, in retrospect, having authorized DHC at the time of the stroke. It was also asked whether they would authorize DHC again. Thirty- two (89%) did not regret having authorized DHC at the time of acute MCA infarct, and would authorize DHC again in retrospect. Conclusion: We confirm that seizures or post-stroke epilepsy rates after thrombolysis are comparable with rates from pre-thrombolysis decades and a high incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC. In our study, seizures were an independent risk factor associated with worst outcome after thrombolysis therapy.

Base teórica: O Acidente Vascular Cerebral (AVC) é a causa mais comum de novos diagnósticos de epilepsia no idoso. Embora a epilepsia pós-AVC seja um fenômeno clínico reconhecido há muito tempo, seguem muitas questões não resolvidas. Além disso, nas últimas duas décadas, o tratamento do AVC isquêmico sofreu mudanças radicais com a introdução da trombólise e da hemicraniectomia descompressiva (HD) para o tratamento do infarto maligno de artéria cerebral média (ACM). As consequências destas duas novas abordagens terapêuticas nas características da epilepsia pós-AVC ainda são pouco exploradas. Objetivo: Estudar as características e estimar fatores de risco para as crises epilépticas ou a epilepsia pós-AVC em pacientes submetidos ao tratamento agudo (Estudo 1) ou HD para infarto maligno de ACM (Estudo 2). Métodos: O estudo 1 é uma coorte de 153 pacientes submetidos a trombólise. Variáveis estudadas incluiram fatores de risco para o AVC e variáveis associadas ao AVC isquêmico agudo e trombólise. Utilizamos a análise de regressão de Cox para o estudo das variáveis que se associaram de forma independente com crises epilépticas, epilepsia pós-AVC e o desfecho do AVC. O estudo 2 é também uma coorte que retrospectivamente avaliou 36 pacientes com infarto maligno de ACM tratados com HD. Tempo, incidência e fatores de risco para crises epilépticas e desenvolvimento de epilepsia foram analisados. Resultados: Estudo 1: 74 pacientes (48,4%) eram mulheres; média de idade foi 67,2 anos (DP=13,1). Média do NIHSS na chegada foi 10,95 (DP=6,25) e 2,09 (DP=3,55) após 3 meses. Transformação hemorrágica ocorreu em 22 (14,4%) dos pacientes. Foi considerado desfecho bom classificação na escala modificada de Rankin (mRS) 0-1, sendo encontrado em 87 (56,9%) dos pacientes. Vinte e um pacientes (13,7%) tiveram crises epilépticas e 15 (9,8%) desenvolveram epilepsia após a trombólise. Crises epilépticas foram associadas de forma independente com transformação hemorrágica e desfecho não favorável (mRS ≥ 2) em três meses após o AVC. Transformação hemorrágica e mRS ≥ 2 avaliados em 3 meses, associaram-se de forma independente com epilepsia pós-AVC. Crises epilépticas surgiram como um fator de risco independente para desfecho pobre. Estudo 2. A média de seguimento dos pacientes foi de 1.086 (DP= 1.172) dias. Nove pacientes morreram antes de receberem alta hospitalar e no período de um ano, 11 pacientes haviam morrido. Quase 60% alcançaram mRS ≤ 4. Treze pacientes desenvolveram crises dentro da primeira semana após o AVC. No total, crises epilépticas ocorreram em 22 (61%) dos 36 pacientes. Dezenove pacientes (56%) dos 34, sobreviveram ao período agudo e desenvolveram epilepsia após infarto da ACM e HD. Questionamos aos pacientes ou responsáveis se eles se arrependeram de terem autorizado a HD no momento do AVC. Também foi perguntado se eles autorizariam a HD novamente. Trinta e dois (89%) não se arrependeram de ter autorizado a HD no momento do infarto agudo da ACM, e autorizaria novamente em retrospecto. Conclusão: Confirmamos que as frequências de crises ou epilepsia pós-AVC e trombolítico são comparáveis com as frequências das décadas da era pré-trombólise e confirmamos a alta incidência de crises epilépticas e epilepsia após infartos malignos de ACM submetidos a HD. Em nosso estudo, as crises epilépticas associaram-se de forma independente com pior prognóstico após terapia trombolítica. / Background: The most common cause of newly diagnosed epilepsies in the elderly is stroke. Although post-stroke epilepsy is a well-studied stroke complication, many questions remain unsolved. In addition, during the past two decades, the treatment of stroke has changed dramatically with the introduction of thrombolysis for treatment of acute ischemic stroke (AIS) and decompressive hemicraniectomy (DHC) for malignant middle cerebral artery infarction (MCA). The consequences of these two new therapeutic approaches for characteristics of post-stroke epilepsy remains poorly explored. Objective: To study characteristics and estimate risk factors for acute seizures or post-stroke epilepsy in patients submitted to thrombolysis for treatment of acute stroke (Study 1) or DHC for malignant MCA infarction. Methods: Study 1 is a cohort study of 153 patients submitted to thrombolysis. Variables studied included risk factors for stroke, and variables related to acute stroke and thrombolysis. Variables independently associated with seizures, pos-stroke epilepsy or stroke outcome were defined using Cox regression analysis. Study 2 is also a cohort study that retrospectively assessed 36 patients with malignant stroke of the MCA submitted to DHC. Timing, incidence and plausible risk factors for seizure and epilepsy development were analyzed in these patients. Results: Study 1. Seventy-four patients (48.4%) were female; mean age of patients was 67.2 years-old (SD=13.1). Initial NIHSS mean score was 10.95 (SD=6.25) and 2.09 (SD=3.55) after three months. Hemorrhagic transformation occurred in 22 (14.4%) patients. A good outcome, as defined by a modified Rankin Scale (mRS) of 0-1, was observed in 87 (56.9%) patients. Twenty one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation and with mRS ≥ 2 three months after stroke. Hemorrhagic transformation and unfavorable outcome, as measured by mRS ≥ 2 after three months, were variables independently associated with post-stroke epilepsy. Seizures emerged as an independent factor for poor outcome in stroke thrombolysis. Study 2. Mean patient follow-up time was of 1.086 (SD=1.172) days. Nine patients died before being discharged and after one year eleven patients died. Almost 60% had the modified Rankin score ≤ 4. Thirteen patients developed seizures within the first week after stroke. In total, seizures occurred in 22 (61%) of 36 patients. Nineteen patients (56%) out of 34 patients who survived the acute period developed epilepsy after MCA infarcts and DHC. Also, we asked patients or the person responsible for them whether they regretted, in retrospect, having authorized DHC at the time of the stroke. It was also asked whether they would authorize DHC again. Thirty- two (89%) did not regret having authorized DHC at the time of acute MCA infarct, and would authorize DHC again in retrospect. Conclusion: We confirm that seizures or post-stroke epilepsy rates after thrombolysis are comparable with rates from pre-thrombolysis decades and a high incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC. In our study, seizures were an independent risk factor associated with worst outcome after thrombolysis therapy.

Base teórica: O Acidente Vascular Cerebral (AVC) é a causa mais comum de novos diagnósticos de epilepsia no idoso. Embora a epilepsia pós-AVC seja um fenômeno clínico reconhecido há muito tempo, seguem muitas questões não resolvidas. Além disso, nas últimas duas décadas, o tratamento do AVC isquêmico sofreu mudanças radicais com a introdução da trombólise e da hemicraniectomia descompressiva (HD) para o tratamento do infarto maligno de artéria cerebral média (ACM). As consequências destas duas novas abordagens terapêuticas nas características da epilepsia pós-AVC ainda são pouco exploradas. Objetivo: Estudar as características e estimar fatores de risco para as crises epilépticas ou a epilepsia pós-AVC em pacientes submetidos ao tratamento agudo (Estudo 1) ou HD para infarto maligno de ACM (Estudo 2). Métodos: O estudo 1 é uma coorte de 153 pacientes submetidos a trombólise. Variáveis estudadas incluiram fatores de risco para o AVC e variáveis associadas ao AVC isquêmico agudo e trombólise. Utilizamos a análise de regressão de Cox para o estudo das variáveis que se associaram de forma independente com crises epilépticas, epilepsia pós-AVC e o desfecho do AVC. O estudo 2 é também uma coorte que retrospectivamente avaliou 36 pacientes com infarto maligno de ACM tratados com HD. Tempo, incidência e fatores de risco para crises epilépticas e desenvolvimento de epilepsia foram analisados. Resultados: Estudo 1: 74 pacientes (48,4%) eram mulheres; média de idade foi 67,2 anos (DP=13,1). Média do NIHSS na chegada foi 10,95 (DP=6,25) e 2,09 (DP=3,55) após 3 meses. Transformação hemorrágica ocorreu em 22 (14,4%) dos pacientes. Foi considerado desfecho bom classificação na escala modificada de Rankin (mRS) 0-1, sendo encontrado em 87 (56,9%) dos pacientes. Vinte e um pacientes (13,7%) tiveram crises epilépticas e 15 (9,8%) desenvolveram epilepsia após a trombólise. Crises epilépticas foram associadas de forma independente com transformação hemorrágica e desfecho não favorável (mRS ≥ 2) em três meses após o AVC. Transformação hemorrágica e mRS ≥ 2 avaliados em 3 meses, associaram-se de forma independente com epilepsia pós-AVC. Crises epilépticas surgiram como um fator de risco independente para desfecho pobre. Estudo 2. A média de seguimento dos pacientes foi de 1.086 (DP= 1.172) dias. Nove pacientes morreram antes de receberem alta hospitalar e no período de um ano, 11 pacientes haviam morrido. Quase 60% alcançaram mRS ≤ 4. Treze pacientes desenvolveram crises dentro da primeira semana após o AVC. No total, crises epilépticas ocorreram em 22 (61%) dos 36 pacientes. Dezenove pacientes (56%) dos 34, sobreviveram ao período agudo e desenvolveram epilepsia após infarto da ACM e HD. Questionamos aos pacientes ou responsáveis se eles se arrependeram de terem autorizado a HD no momento do AVC. Também foi perguntado se eles autorizariam a HD novamente. Trinta e dois (89%) não se arrependeram de ter autorizado a HD no momento do infarto agudo da ACM, e autorizaria novamente em retrospecto. Conclusão: Confirmamos que as frequências de crises ou epilepsia pós-AVC e trombolítico são comparáveis com as frequências das décadas da era pré-trombólise e confirmamos a alta incidência de crises epilépticas e epilepsia após infartos malignos de ACM submetidos a HD. Em nosso estudo, as crises epilépticas associaram-se de forma independente com pior prognóstico após terapia trombolítica. / Background: The most common cause of newly diagnosed epilepsies in the elderly is stroke. Although post-stroke epilepsy is a well-studied stroke complication, many questions remain unsolved. In addition, during the past two decades, the treatment of stroke has changed dramatically with the introduction of thrombolysis for treatment of acute ischemic stroke (AIS) and decompressive hemicraniectomy (DHC) for malignant middle cerebral artery infarction (MCA). The consequences of these two new therapeutic approaches for characteristics of post-stroke epilepsy remains poorly explored. Objective: To study characteristics and estimate risk factors for acute seizures or post-stroke epilepsy in patients submitted to thrombolysis for treatment of acute stroke (Study 1) or DHC for malignant MCA infarction. Methods: Study 1 is a cohort study of 153 patients submitted to thrombolysis. Variables studied included risk factors for stroke, and variables related to acute stroke and thrombolysis. Variables independently associated with seizures, pos-stroke epilepsy or stroke outcome were defined using Cox regression analysis. Study 2 is also a cohort study that retrospectively assessed 36 patients with malignant stroke of the MCA submitted to DHC. Timing, incidence and plausible risk factors for seizure and epilepsy development were analyzed in these patients. Results: Study 1. Seventy-four patients (48.4%) were female; mean age of patients was 67.2 years-old (SD=13.1). Initial NIHSS mean score was 10.95 (SD=6.25) and 2.09 (SD=3.55) after three months. Hemorrhagic transformation occurred in 22 (14.4%) patients. A good outcome, as defined by a modified Rankin Scale (mRS) of 0-1, was observed in 87 (56.9%) patients. Twenty one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation and with mRS ≥ 2 three months after stroke. Hemorrhagic transformation and unfavorable outcome, as measured by mRS ≥ 2 after three months, were variables independently associated with post-stroke epilepsy. Seizures emerged as an independent factor for poor outcome in stroke thrombolysis. Study 2. Mean patient follow-up time was of 1.086 (SD=1.172) days. Nine patients died before being discharged and after one year eleven patients died. Almost 60% had the modified Rankin score ≤ 4. Thirteen patients developed seizures within the first week after stroke. In total, seizures occurred in 22 (61%) of 36 patients. Nineteen patients (56%) out of 34 patients who survived the acute period developed epilepsy after MCA infarcts and DHC. Also, we asked patients or the person responsible for them whether they regretted, in retrospect, having authorized DHC at the time of the stroke. It was also asked whether they would authorize DHC again. Thirty- two (89%) did not regret having authorized DHC at the time of acute MCA infarct, and would authorize DHC again in retrospect. Conclusion: We confirm that seizures or post-stroke epilepsy rates after thrombolysis are comparable with rates from pre-thrombolysis decades and a high incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC. In our study, seizures were an independent risk factor associated with worst outcome after thrombolysis therapy.

Contexte L’occlusion d’une artère du cœur cause un syndrome coronarien aigu (SCA) soit avec une élévation du segment ST (IAMEST) ou sans élévation du segment ST (1). Le traitement des patients avec un IAMEST requiert soit une intervention coronarienne d’urgence (ICP primaire) ou une thérapie fibrinolytique (FL). La thérapie FL peut être administrée soit dans un contexte pré-hospitalier (PHL) ou à l’hôpital. Une prise en charge précoce des patients avec SCA peut être améliorée par un simple indice de risque. Objectifs Les objectifs de cette thèse étaient de : 1) comparer l’ICP primaire et la thérapie FL (2); décrire plusieurs systèmes internationaux de PHL; (3) développer et valider un indice de risque simplifié pour une stratification précoce des patients avec SCA. Méthodes Nous complétons des méta-analyses, de type hiérarchique Bayésiennes portant sur l’effet de la randomisation, d’études randomisées et observationnelles; complétons également un sondage sur des systèmes internationaux de PHL; développons et validons un nouvel indice de risque pour ACS (le C-ACS). Résultats Dans les études observationnelles, l’ICP primaire, comparée à la thérapie FL, est associée à une plus grande réduction de la mortalité à court-terme; mais ce sans bénéfices concluants à long terme. La FL pré-hospitalière peut être administrée par des professionnels de la santé possédant diverses expertises. Le C-ACS a des bonnes propriétés discriminatoires et pourrait être utilisé dans la stratification des patients avec SCA. Conclusion Nous avons comblé plusieurs lacunes importantes au niveau de la connaissance actuelle. Cette thèse de doctorat contribuera à améliorer l’accès à des soins de qualité élevée pour les patients ayant un SCA. / Background Acute occlusion of an artery of the heart results in acute coronary syndromes (ACS), either with ST-segment elevation (STEMI) or without ST-segment elevation (1). STEMI requires urgent treatment to restore coronary artery flow either by primary percutaneous coronary intervention (PCI) or fibrinolytic therapy (FL) (2). Although several randomized controlled trials (RCTs) demonstrate the superiority of primary PCI in reducing mortality compared to FL (2), the benefit of primary PCI over FL remains uncertain in unselected “real-life” patients (3,4). FL can be administered either in the pre-hospital setting (i.e., pre-hospital FL (PHL)) or at the hospital. PHL is rarely available outside Europe (5,6). Insights into the organization of PHL systems of care may promote more widespread use of PHL. Risk stratification of ACS patients should be prompt to ensure timely PCI for high-risk patients and to avoid unnecessary intervention in low-risk patients (7). Despite the availability of numerous ACS risk scores, there is still no simple risk score that can be easily applied in the initial management of ACS patients (8). Objectives The objectives of this doctoral dissertation were to address these current knowledge gaps in the optimal management of ACS. The objectives were to: 1) evaluate the efficacy, effectiveness, and safety of primary PCI and FL, (2) describe the infrastructure, processes and outcomes of several international PHL systems; and (3) develop and validate a novel clinical risk score for early risk stratification of ACS patients. Methods To address these objectives, I completed Bayesian hierarchical random-effects meta-analyses of published RCTs and observational studies which compare primary PCI and FL in patients with STEMI. I undertook a survey of the infrastructure, processes and outcomes of PHL in several European and North American pre-hospital emergency systems. Finally, I developed and validated an ACS risk score called the Canadian ACS (C-ACS). Results Primary PCI was superior to FL in reducing short-term mortality in RCTs and observational studies. However, the long-term survival benefit of primary PCI was noted only in RCTs, and not in the observational studies. PHL can be effectively delivered by health care professionals with variable levels of expertise. The new risk score, C-ACS, has good discriminant properties for short- and long-term mortality in patients with ACS. Conclusions The first manuscript of this dissertation has been recognized as one of the most valuable recent publications in STEMI management and has contributed to reorganization of STEMI care in Ontario. The other two manuscripts in this dissertation provide practical information and tools for health professionals caring for patients with ACS. In summary, this doctoral dissertation has and will continue to contribute to improve access to high quality care for patients with ACS.

Contexte L’occlusion d’une artère du cœur cause un syndrome coronarien aigu (SCA) soit avec une élévation du segment ST (IAMEST) ou sans élévation du segment ST (1). Le traitement des patients avec un IAMEST requiert soit une intervention coronarienne d’urgence (ICP primaire) ou une thérapie fibrinolytique (FL). La thérapie FL peut être administrée soit dans un contexte pré-hospitalier (PHL) ou à l’hôpital. Une prise en charge précoce des patients avec SCA peut être améliorée par un simple indice de risque. Objectifs Les objectifs de cette thèse étaient de : 1) comparer l’ICP primaire et la thérapie FL (2); décrire plusieurs systèmes internationaux de PHL; (3) développer et valider un indice de risque simplifié pour une stratification précoce des patients avec SCA. Méthodes Nous complétons des méta-analyses, de type hiérarchique Bayésiennes portant sur l’effet de la randomisation, d’études randomisées et observationnelles; complétons également un sondage sur des systèmes internationaux de PHL; développons et validons un nouvel indice de risque pour ACS (le C-ACS). Résultats Dans les études observationnelles, l’ICP primaire, comparée à la thérapie FL, est associée à une plus grande réduction de la mortalité à court-terme; mais ce sans bénéfices concluants à long terme. La FL pré-hospitalière peut être administrée par des professionnels de la santé possédant diverses expertises. Le C-ACS a des bonnes propriétés discriminatoires et pourrait être utilisé dans la stratification des patients avec SCA. Conclusion Nous avons comblé plusieurs lacunes importantes au niveau de la connaissance actuelle. Cette thèse de doctorat contribuera à améliorer l’accès à des soins de qualité élevée pour les patients ayant un SCA. / Background Acute occlusion of an artery of the heart results in acute coronary syndromes (ACS), either with ST-segment elevation (STEMI) or without ST-segment elevation (1). STEMI requires urgent treatment to restore coronary artery flow either by primary percutaneous coronary intervention (PCI) or fibrinolytic therapy (FL) (2). Although several randomized controlled trials (RCTs) demonstrate the superiority of primary PCI in reducing mortality compared to FL (2), the benefit of primary PCI over FL remains uncertain in unselected “real-life” patients (3,4). FL can be administered either in the pre-hospital setting (i.e., pre-hospital FL (PHL)) or at the hospital. PHL is rarely available outside Europe (5,6). Insights into the organization of PHL systems of care may promote more widespread use of PHL. Risk stratification of ACS patients should be prompt to ensure timely PCI for high-risk patients and to avoid unnecessary intervention in low-risk patients (7). Despite the availability of numerous ACS risk scores, there is still no simple risk score that can be easily applied in the initial management of ACS patients (8). Objectives The objectives of this doctoral dissertation were to address these current knowledge gaps in the optimal management of ACS. The objectives were to: 1) evaluate the efficacy, effectiveness, and safety of primary PCI and FL, (2) describe the infrastructure, processes and outcomes of several international PHL systems; and (3) develop and validate a novel clinical risk score for early risk stratification of ACS patients. Methods To address these objectives, I completed Bayesian hierarchical random-effects meta-analyses of published RCTs and observational studies which compare primary PCI and FL in patients with STEMI. I undertook a survey of the infrastructure, processes and outcomes of PHL in several European and North American pre-hospital emergency systems. Finally, I developed and validated an ACS risk score called the Canadian ACS (C-ACS). Results Primary PCI was superior to FL in reducing short-term mortality in RCTs and observational studies. However, the long-term survival benefit of primary PCI was noted only in RCTs, and not in the observational studies. PHL can be effectively delivered by health care professionals with variable levels of expertise. The new risk score, C-ACS, has good discriminant properties for short- and long-term mortality in patients with ACS. Conclusions The first manuscript of this dissertation has been recognized as one of the most valuable recent publications in STEMI management and has contributed to reorganization of STEMI care in Ontario. The other two manuscripts in this dissertation provide practical information and tools for health professionals caring for patients with ACS. In summary, this doctoral dissertation has and will continue to contribute to improve access to high quality care for patients with ACS.