Background: Patients who have suffered an acute ischemic stroke (AIS) and are smokers may have a better outcome following thrombolytic therapy when compared with non-smokers. While this finding is controversial, data on baseline clinical risk factors to predict treatment efficacy of thrombolytic therapy using ambulatory status in patients who suffered AIS and are smokers is not common. Methods: Between 2010 and 2016, retrospective data on patients who have suffered an AIS and received recombinant tissue plasminogen activator (rtPA) were obtained from Greenville health system registry. Assessment of clinical risk factors and the likelihood of an improvement in post-stroke ambulation among smokers and non-smokers was carried out using multivariate logistic regression. Results: Of 1001 patients, 70.8% were smokers and 29.2% non-smokers. Among the smokers and non-smokers, 74.6% and 84.6% improvement in ambulation respectively at discharge. The odds of improved ambulation decrease among smokers as age group increases compared to those below 50 [(60–69 years, aOR, 0.30, 95% C.I, 0.108–0.850, p < 0.05), (70–79 years aOR, 0.27, 95% C.I, 0.096–0.734, p < 0.05), (80+ years aOR, 0.16, 95% C.I, 0.057–0.430, P < 0.01). Patients with National Institute of Health Stroke Scale Score (NIHSS) score > 7 (reference <7) were 91% less likely to have improved ambulation among smokers and non-smokers (aOR, 0.09, 95% C.I, 0.055–0.155, P = 0.01), and (aOR, 0.08, 95% C.I, 0.027–0.214, P = 0.01) respectively. Atrial fibrillation was an independent predictor of decreased improvement in ambulation only among smokers (aOR, 0.58, 95% C.I, 0.356–0.928 P < 0.05). Conclusion: Our findings suggest that elderly smokers with atrial fibrillation would benefit more from aggressive management of atrial fibrillation than non-smokers.

The Georgia Department of Public Health has been engaged in a registry-based quality improvement initiative to monitor and improve the quality of stroke care. It is important to evaluate effectiveness of the quality improvement initiative in order to expand the effort to other sites or disease conditions. The studies, included in this dissertation, addressed whether acute ischemic stroke patients cared for by hospitals participating in the Georgia Coverdell Acute Stroke Registry (GCASR) had a better survival than those treated at other facilities, assessed whether quality of care as measured by nationally accepted ten performance measures is associated with improved patient outcome and evaluated the impact of intravenous alteplase treatment on 1-year mortality. Three data sources – GCASR, Georgia Discharge Data System and the death data – were used for analyses. These data sources were linked applying both a hierarchical deterministic and a probabilistic linkage methods. Survival after stroke incident was analyzed using the extended Cox proportional hazard model. Generalized estimating equation (glimmix procedure) and conditional logistic regression were applied, respectively, to assess the association of quality of care and intravenous alteplase use with 1-year mortality. Acute ischemic stroke patients treated at nonparticipating facilities had a hazard ratio for death of 1.14 (95% confidence interval, 1.03–1.26; p-value = .01) after the first week of admission compared with patients cared for by hospitals participating in the registry. Among patients treated in GCASR-participating hospitals, patients who received the lowest and intermediate quality care respectively had a 3.94 (95%CI: 3.27, 4.75; p-value <0.0001) and a 1.38 (95%CI: 1.12, 1.62; p-value=0.002) times higher odds of dying in one year compared to those who got the best quality stroke care. Patients who were eligible but did not receive IV alteplase had a 1.49 (95%CI: 1.09-2.04; p-value=0.01) times higher odds of dying within one year than those who were treated with the thrombolytic agent. The results strongly suggest that registry-based quality improvement effort has brought significant improvements in ischemic stroke patients’ outcomes. Therefore, it is critical that hospitals adopt a quality improvement strategy to change the process of care delivery for a better patient outcome.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Current stroke imaging protocol at Barrow Neurological Institute calls for a noncontrast computed tomography (NCCT), a computed tomography angiography (CTA), and a computed tomography perfusion (CTP) at the time of presentation to the emergency department (ED), and follow up imaging includes magnetic resonance diffusion weighted imaging (MR‐DWI). This information is used to determine the appropriateness and safety of tissue plasminogen activator (tPA) administration. Previous studies have shown the risk for post‐tPA hemorrhagic conversion rises significantly as the size of the infarct core increases. Thus, it is of great importance to have an accurate method of measuring core infarct size in patients presenting with acute ischemic stroke. The purpose of our study is to determine if CTP correctly identifies the infarct core and if post‐tPA hemorrhagic conversion is related to the size of the infarct core and/or the accuracy of CTP in identifying the infarct core. The ultimate goal is to improve patient outcomes by decreasing the morbidity and mortality associated with tPA administration. This study is a retrospective chart review of all patients who presented to the ED during a one year period with signs and symptoms of acute ischemic stroke who then subsequently received tPA. Imaging was also reviewed, including the NCCT, CTA, CTP, and MRDWI for each patient. In this study, MR‐DWI is used as the gold standard for determining the presence or absence of an infarct core. CTP and MR‐DWI are in agreement of the presence of an infarct core in 7 patients, or 10 percent of the time. Similarly, CTP and MR‐DWI are in agreement of the absence of an infarct core in 31 patients, or 44 percent of the time. In the other 32 patients, CTP and MR‐DWI are in disagreement. The percent correlation between CTP and MR‐DWI was found to be 24 percent with a p‐value < 0.05. As for post‐tPA hemorrhagic conversion, 12 percent of patients had hemorrhagic conversion, and when the hemorrhage rate was compared to the size of the infarct core, the odds of post‐tPA hemorrhagic conversion were 56 times higher in the group of patients with infarct cores larger than one‐third of a vascular territory than in patients with smaller infarct cores with a p‐value < 0.001. Although no significant correlation was found between the accuracy of CTP data and the rate of post‐tPA hemorrhagic conversion, patients with concordant CTP and MR data had a 46% lower likelihood of post‐tPA hemorrhagic conversion than did patients with contradictory CTP and MR‐DWI data. Conclusion: Because patients with infarct cores larger than one‐third of a vascular territory are 56 times more likely to hemorrhage than patients with smaller infarct cores and CTP is less accurate than MR‐DWI in identifying the infarct core in patients presenting with acute ischemic stroke, CTP studies should not be part of the acute stroke imaging protocol. Another imaging modality, such as MR‐DWI, may be preferential in the setting of acute ischemic stroke to identify the infarct core.

Introdução: Diversas condições clínicas podem modificar a resposta ao tratamento trombolítico no acidente vascular isquêmico agudo. O grau de comorbidade dos pacientes medido pelo Índice de Charlson, um índice que mede o grau de comorbidades clínicas em AVC, tem valor prognóstico na incapacidade pós-AVC tanto em populações com acidente vascular do tipo hemorrágico como isquêmico. Objetivo: Avaliar o efeito do grau de comorbidade aferido pelo índice de Charlson na resposta ao tratamento trombolítico no acidente vascular isquêmico e a incapacidade na alta hospitalar. Métodos: Estudo de coorte prospectivo de 96 pacientes tratados com trombólise para o acidente vascular isquêmico, avaliando o impacto das comorbidades clínicas na resposta ao tratamento trombolítico no AVC isquêmico. Os pacientes foram divididos em dois grupos, aqueles com alto ou baixo grau de comorbidades clínicas, conforme o índice de Charlson. A evolução após o tratamento foi aferida pelo escore de gravidade dos sintomas de acordo com a escala do NIHSS medido antes da infusão, imediatamente após o tratamento, 24horas e 7 dias após a trombólise. A incapacidade na alta foi avaliada pela escala modificada de Rankin sendo, considerada boa resposta a pontuação 0-1 e sua frequência comparada entre os dois grupos de pacientes. Resultados: A comparação dos escores médios do NIHSS mostraram diferenças significativas nos diferentes momentos entre os grupos de alta e baixa comorbidade (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Pacientes com índice de comorbidade baixo apresentaram redução do escore do NIHSS de 10.13 para 2.9, enquanto que no grupo com alta comorbidade, o tratamento trombolítico demostrou pouco efeito. Uma boa evolução, definida como incapacidade 0 e 1 na escala modificada de Rankin, foi observada em (73%) dos pacientes com baixo índice de comorbidade, enquanto somente (15%) dos pacientes com alto índice de comorbidade apresentaram essa evolução favorável, uma diferença clinicamente muito significativa (RR 5.62; 95% CI = 2.97 a 10.65; p< 0.001). Conclusão: A presença de comorbidades clínicas medida peloíndice de Charlson foi associada a uma menor resposta neurológica no tratamento trombolítico do AVC isquêmico e a um maior grau de incapacidade funcional na alta. / Background and purpose: Clinical comorbidities modify prognosis in haemorrhagic and ischaemic stroke. Charlson Comorbidity index is a validated and useful tool for evaluating comorbidity in stroke. In this study we evaluated the effect of clinical comorbidities as measured by Charlson Comorbidity Index in the in ischaemic stroke thrombolysis. Methods: Prospective cohort study of 96 thrombolysis treated ischaemic stroke patients. The cohort population was divided in two groups according with severity of Charlson Comorbidity Index. During study, NIHSS score was evaluated four times (pre, post, 24 hours and 7 days after thrombolysis) and lower or higher comorbidities groups were compared using repeated measures ANOVA. Response to thrombolysis in both groups was also analysed with disability modified Rankin scale. Results: We observed differences in evolution of mean NIHSS scores between higher and lower clinical comorbidity groups. Patients with low clinical comorbidities experiencing a significant reduction of NIHSS score that ranged from 10.13 to 2.9 points, while patients in the HIC group had initial NIHSS score of 14.75 and final NIHSS score of 13.78 (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Lack of response to thrombolysis had direct relation with disability at hospital discharge. Better clinical outcome, as evaluated by modified Rankin scale of 0 and 1, was markedly different between groups, with 23 (73%) versus 9 (15%) in low and high clinical comorbidities patients respectively (RR=5.62; 95%CI=2.97 to 10.65; p< 0.001). Conclusion: High level of clinical comorbidities negatively influences response to thrombolysis, attenuating treatment related reduction of stroke symptoms severity and increasing the frequency of disabled patients at discharge.

Introdução: Diversas condições clínicas podem modificar a resposta ao tratamento trombolítico no acidente vascular isquêmico agudo. O grau de comorbidade dos pacientes medido pelo Índice de Charlson, um índice que mede o grau de comorbidades clínicas em AVC, tem valor prognóstico na incapacidade pós-AVC tanto em populações com acidente vascular do tipo hemorrágico como isquêmico. Objetivo: Avaliar o efeito do grau de comorbidade aferido pelo índice de Charlson na resposta ao tratamento trombolítico no acidente vascular isquêmico e a incapacidade na alta hospitalar. Métodos: Estudo de coorte prospectivo de 96 pacientes tratados com trombólise para o acidente vascular isquêmico, avaliando o impacto das comorbidades clínicas na resposta ao tratamento trombolítico no AVC isquêmico. Os pacientes foram divididos em dois grupos, aqueles com alto ou baixo grau de comorbidades clínicas, conforme o índice de Charlson. A evolução após o tratamento foi aferida pelo escore de gravidade dos sintomas de acordo com a escala do NIHSS medido antes da infusão, imediatamente após o tratamento, 24horas e 7 dias após a trombólise. A incapacidade na alta foi avaliada pela escala modificada de Rankin sendo, considerada boa resposta a pontuação 0-1 e sua frequência comparada entre os dois grupos de pacientes. Resultados: A comparação dos escores médios do NIHSS mostraram diferenças significativas nos diferentes momentos entre os grupos de alta e baixa comorbidade (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Pacientes com índice de comorbidade baixo apresentaram redução do escore do NIHSS de 10.13 para 2.9, enquanto que no grupo com alta comorbidade, o tratamento trombolítico demostrou pouco efeito. Uma boa evolução, definida como incapacidade 0 e 1 na escala modificada de Rankin, foi observada em (73%) dos pacientes com baixo índice de comorbidade, enquanto somente (15%) dos pacientes com alto índice de comorbidade apresentaram essa evolução favorável, uma diferença clinicamente muito significativa (RR 5.62; 95% CI = 2.97 a 10.65; p< 0.001). Conclusão: A presença de comorbidades clínicas medida peloíndice de Charlson foi associada a uma menor resposta neurológica no tratamento trombolítico do AVC isquêmico e a um maior grau de incapacidade funcional na alta. / Background and purpose: Clinical comorbidities modify prognosis in haemorrhagic and ischaemic stroke. Charlson Comorbidity index is a validated and useful tool for evaluating comorbidity in stroke. In this study we evaluated the effect of clinical comorbidities as measured by Charlson Comorbidity Index in the in ischaemic stroke thrombolysis. Methods: Prospective cohort study of 96 thrombolysis treated ischaemic stroke patients. The cohort population was divided in two groups according with severity of Charlson Comorbidity Index. During study, NIHSS score was evaluated four times (pre, post, 24 hours and 7 days after thrombolysis) and lower or higher comorbidities groups were compared using repeated measures ANOVA. Response to thrombolysis in both groups was also analysed with disability modified Rankin scale. Results: We observed differences in evolution of mean NIHSS scores between higher and lower clinical comorbidity groups. Patients with low clinical comorbidities experiencing a significant reduction of NIHSS score that ranged from 10.13 to 2.9 points, while patients in the HIC group had initial NIHSS score of 14.75 and final NIHSS score of 13.78 (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Lack of response to thrombolysis had direct relation with disability at hospital discharge. Better clinical outcome, as evaluated by modified Rankin scale of 0 and 1, was markedly different between groups, with 23 (73%) versus 9 (15%) in low and high clinical comorbidities patients respectively (RR=5.62; 95%CI=2.97 to 10.65; p< 0.001). Conclusion: High level of clinical comorbidities negatively influences response to thrombolysis, attenuating treatment related reduction of stroke symptoms severity and increasing the frequency of disabled patients at discharge.

Introdução: Diversas condições clínicas podem modificar a resposta ao tratamento trombolítico no acidente vascular isquêmico agudo. O grau de comorbidade dos pacientes medido pelo Índice de Charlson, um índice que mede o grau de comorbidades clínicas em AVC, tem valor prognóstico na incapacidade pós-AVC tanto em populações com acidente vascular do tipo hemorrágico como isquêmico. Objetivo: Avaliar o efeito do grau de comorbidade aferido pelo índice de Charlson na resposta ao tratamento trombolítico no acidente vascular isquêmico e a incapacidade na alta hospitalar. Métodos: Estudo de coorte prospectivo de 96 pacientes tratados com trombólise para o acidente vascular isquêmico, avaliando o impacto das comorbidades clínicas na resposta ao tratamento trombolítico no AVC isquêmico. Os pacientes foram divididos em dois grupos, aqueles com alto ou baixo grau de comorbidades clínicas, conforme o índice de Charlson. A evolução após o tratamento foi aferida pelo escore de gravidade dos sintomas de acordo com a escala do NIHSS medido antes da infusão, imediatamente após o tratamento, 24horas e 7 dias após a trombólise. A incapacidade na alta foi avaliada pela escala modificada de Rankin sendo, considerada boa resposta a pontuação 0-1 e sua frequência comparada entre os dois grupos de pacientes. Resultados: A comparação dos escores médios do NIHSS mostraram diferenças significativas nos diferentes momentos entre os grupos de alta e baixa comorbidade (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Pacientes com índice de comorbidade baixo apresentaram redução do escore do NIHSS de 10.13 para 2.9, enquanto que no grupo com alta comorbidade, o tratamento trombolítico demostrou pouco efeito. Uma boa evolução, definida como incapacidade 0 e 1 na escala modificada de Rankin, foi observada em (73%) dos pacientes com baixo índice de comorbidade, enquanto somente (15%) dos pacientes com alto índice de comorbidade apresentaram essa evolução favorável, uma diferença clinicamente muito significativa (RR 5.62; 95% CI = 2.97 a 10.65; p< 0.001). Conclusão: A presença de comorbidades clínicas medida peloíndice de Charlson foi associada a uma menor resposta neurológica no tratamento trombolítico do AVC isquêmico e a um maior grau de incapacidade funcional na alta. / Background and purpose: Clinical comorbidities modify prognosis in haemorrhagic and ischaemic stroke. Charlson Comorbidity index is a validated and useful tool for evaluating comorbidity in stroke. In this study we evaluated the effect of clinical comorbidities as measured by Charlson Comorbidity Index in the in ischaemic stroke thrombolysis. Methods: Prospective cohort study of 96 thrombolysis treated ischaemic stroke patients. The cohort population was divided in two groups according with severity of Charlson Comorbidity Index. During study, NIHSS score was evaluated four times (pre, post, 24 hours and 7 days after thrombolysis) and lower or higher comorbidities groups were compared using repeated measures ANOVA. Response to thrombolysis in both groups was also analysed with disability modified Rankin scale. Results: We observed differences in evolution of mean NIHSS scores between higher and lower clinical comorbidity groups. Patients with low clinical comorbidities experiencing a significant reduction of NIHSS score that ranged from 10.13 to 2.9 points, while patients in the HIC group had initial NIHSS score of 14.75 and final NIHSS score of 13.78 (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Lack of response to thrombolysis had direct relation with disability at hospital discharge. Better clinical outcome, as evaluated by modified Rankin scale of 0 and 1, was markedly different between groups, with 23 (73%) versus 9 (15%) in low and high clinical comorbidities patients respectively (RR=5.62; 95%CI=2.97 to 10.65; p< 0.001). Conclusion: High level of clinical comorbidities negatively influences response to thrombolysis, attenuating treatment related reduction of stroke symptoms severity and increasing the frequency of disabled patients at discharge.

Background: Mechanical thrombectomy is the gold standard for treating patients with certain acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, even with major advancements and increasing procedural volumes, acute endovascular therapy remains a high-risk procedure with a considerable 90-day mortality rate, affected by a variety of factors. Purpose: To investigate various clinical and procedural factors associated with 90-day mortality in patients undergoing mechanical thrombectomy for emergent treatment of AIS and determine which of these factors made unique contributions to post-thrombectomy prognosis. Methods: We examined a prospective registry of 323 patients treated with endovascular thrombectomy for AIS between 2016 and 2019 at a high-volume comprehensive stroke center in central Massachusetts. We developed two multivariable logistic regression models adjusting for the contributions of baseline characteristics and recanalization parameters, to identify potential predictors of mortality at 90 days. Results: Among 323 AIS patients treated with mechanical thrombectomy, the overall rate of successful recanalization was 86% and the overall post-procedure mortality rate was 29% by 90 days. After univariate analysis, a baseline multivariable model comprised of: history of stroke (OR 0.28, 95% CI 0.09 – 0.68), pre-stroke modified Rankin Scale (mRS 2: OR 3.75, 95% CI), severe admission National Institutes of Health Stroke Scale (NIHSS 21–42: OR 12.36, 95% CI 1.48 – 103.27), internal carotid artery (ICA) occlusion (OR 2.77, 95% CI 1.18 – 6.55), and posterior circulation occlusion (OR 2.69, 95% CI 1.06 – 6.83) was prognostic of 90-day mortality. A second multivariable model also found the procedural factors of: clot obtained after each pass (OR 0.49, 95% CI 0.24 – 1.00), successful recanalization (OR 0.21, 95% CI 0.06 – 0.8) and symptomatic intracranial hemorrhage (sICH; OR 17.89, 95% CI 5.22 – 61.29) to be identifiable predictors of post-thrombectomy mortality. Conclusion: Death within 90 days after thrombectomy was increased among patients with higher pre-stroke disability, higher stroke severity on admission, ICA or posterior occlusion, and those with sICH complication. A history of stroke, clot extraction after each device pass, and successful recanalization are associated with decreased 90-day mortality. These identifiable contributors may inform patient selection, prognosis evolution, and shared decision-making regarding emergent thrombectomy for treatment of AIS.

No description available.

No description available.

Stroke is the 5th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to include selective intra-arterial pharmacotherapy administration. Using the tandem transient common carotid and middle cerebral artery occlusion (MCAo) model to induce stroke, we threaded micro-angio tubing into the external carotid artery (ECA) towards the bifurcation of the common carotid and internal carotid arteries (CCA/ICA) allowing for the delivery of agents to the site of acute ischemia. Our model was optimized through a flow rate and injection volume study using carbon black ink injected through the intra-arterial model at different flow rates and injection volumes. The purpose of this study was to demonstrate that our injections were arriving at the site of ischemia and to improve injection volumes for future dosing while mitigating systemic side effects by preventing or minimizing systemic distribution. We determined that a flow rate of 2.5 µl/minute and injection volume of 10 µl was optimal. Next, we tested potential neuroprotective compounds nitroglycerin, verapamil, and a combination of verapamil and lubeluzole. Compounds were chosen for drug synergy and to target specific pathways in either an acute or delayed manner. Acute treatments included nitroglycerin and/or verapamil while delayed treatment included lubeluzole. The known mechanism of action for FDA approved nitroglycerin is through vessel dilation that results in increased blood flow to the treated region. A secondary mechanism of nitroglycerin is the production of nitric oxide, which has demonstrated antioxidant and anti-apoptotic effects when processed and released from cells surrounding the blood vessels. Verapamil, a calcium channel blocker, also FDA-approved for cerebral artery vasospasm: is thought to act by blocking the L-type calcium channels on the cell membrane from opening following membrane depolarization after insult. Finally, lubeluzole, also FDA-approved, is proposed to work as an NMDA modulator inhibiting the release of glutamate and nitric oxide synthase and blocking sodium and calcium channels. Through our stroke model we were able to demonstrate that each drug(s) showed a significant decrease in infarct volume and improved functional recovery while simultaneously minimizing potential systemic side effects suggesting that our stroke model may improve the preclinical validation of potential stroke therapies and help bridge the bench to bedside divide in developing new stroke therapies.