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BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Trombectomia , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento , Infarto da Artéria Cerebral Média/complicações , Doenças das Artérias Carótidas/complicações , Recuperação de Função Fisiológica , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/etiologiaRESUMO
OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024;96:582-590.
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Fibrinolíticos , AVC Isquêmico , Terapia Trombolítica , Tempo para o Tratamento , Humanos , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica/métodos , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Administração Intravenosa , Resultado do Tratamento , Fatores de TempoRESUMO
Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024.
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OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.
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Edema Encefálico , Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Edema Encefálico/etiologia , Edema Encefálico/complicações , Resultado do Tratamento , Estudos Prospectivos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/terapia , Infarto Cerebral/complicações , Reperfusão/métodos , Procedimentos Endovasculares/métodosRESUMO
BACKGROUND: The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS: We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS: Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS: More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.
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Edema Encefálico , Hipertensão Intracraniana , Hemorragia Subaracnóidea , Humanos , Hipertensão Intracraniana/diagnóstico por imagem , Hipertensão Intracraniana/etiologia , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Pressão IntracranianaRESUMO
OBJECTIVE/AIM: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. RESULTS: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. CONCLUSIONS: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.
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AVC Isquêmico , Hemorragia Subaracnóidea , Humanos , Trombectomia/efeitos adversos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/etiologia , Hemorragia Cerebral/diagnóstico por imagemRESUMO
OBJECTIVES: To characterize and compare the stability of cortical potentials evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) across the naïve, parkinsonian, and pharmacologically treated parkinsonian states. To advance cortical potentials as possible biomarkers for DBS programming. MATERIALS AND METHODS: Serial electrocorticographic (ECoG) recordings were made more than nine months from a single non-human primate instrumented with bilateral ECoG grids spanning anterior parietal to prefrontal cortex. Cortical evoked potentials (CEPs) were generated through time-lock averaging of the ECoG recordings to DBS pulses delivered unilaterally in the STN region using a chronically implanted, six-contact, scaled DBS lead. Recordings were made across the naïve followed by mild and moderate parkinsonian conditions achieved by staged injections of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin. In addition to characterizing the spatial distribution and stability of the response within each state, changes in the amplitude and latency of CEP components as well as in the frequency content were examined in relation to parkinsonian severity and dopamine replacement. RESULTS: In the naïve state, the STN DBS CEP presented as a multiphase response maximal over M1 cortex, with components attributable to physiological activity distinguishable from stimulus artifact as early as 0.45-0.75 msec poststimulation. When delivered using therapeutically effective parameters in the parkinsonian state, the CEP was highly stable across multiple recording sessions within each behavioral state. Across states, significant differences were present with respect to both the latency and amplitude of individual response components, with greater differences present for longer-latency components (all p < 0.05). Power spectral density analysis revealed a high-beta peak within the evoked response, with significant changes in power between disease states across multiple frequency bands. CONCLUSIONS: Our findings underscore the spatiotemporal specificity and relative stability of the DBS-CEP associated with different disease states and with therapeutic benefit. DBS-CEP may be a viable biomarker for therapeutic programming.
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Estimulação Encefálica Profunda , Núcleo Subtalâmico , Animais , Estimulação Encefálica Profunda/métodos , Potenciais Evocados/fisiologia , Núcleo Subtalâmico/fisiologiaRESUMO
OBJECTIVES: Mobile stroke unit (MSU) has been shown to rapidly provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSU encounters neurological disorders other than AIS that require emergent treatment. METHODS/MATERIALS: We obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 221 consecutive MSU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSU, the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and likely stroke mimics was made. RESULTS: From July 2014 to April 2015, 221 patients were treated on MSU. 78 (35%) patients had initial clinical diagnosis of definite/probable AIS or TIA, 69 (31%) were diagnosed as possible AIS or TIA, 15 (7%) had intracranial hemorrhage while 59 patients (27%) were diagnosed as likely stroke mimics. Stroke mimics encountered included 13 (6%) metabolic encephalopathy, 11 (5%) seizures, 9 (4%) migraines, 3 (1%) substance abuse, 2 (1%) CNS tumor, 3 (1%) infectious etiology and 3 (1%) hypoglycemia. Fifty-four (24%) patients received non-thrombolytic treatments on MSU CONCLUSION: About one third of MSU encounters were not AIS initially, including intracranial hemorrhage and stroke mimics. MSU can be utilized to provide pre-hospital treatments in emergent neurological conditions other than AIS.
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Serviços Médicos de Emergência , AVC Isquêmico/diagnóstico por imagem , Unidades Móveis de Saúde , Neuroimagem , Idoso , Bases de Dados Factuais , Diagnóstico Diferencial , Feminino , Humanos , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Terapia Trombolítica , Fatores de Tempo , Tempo para o TratamentoRESUMO
BACKGROUND AND PURPOSE: We aimed to investigate the acute stroke presentations during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The data were obtained from a health system with 19 emergency departments in northeast Ohio in the United States. Baseline period from January 1 to March 8, 2020, was compared with the COVID period from March 9, to April 2, 2020. The variables included were total daily stroke alerts across the hospital emergency departments, thrombolysis, time to presentation, stroke severity, time from door-to-imaging, time from door-to-needle in thrombolysis, and time from door-to-puncture in thrombectomy. The 2 time periods were compared using nonparametric statistics and Poisson regression. RESULTS: Nine hundred two stroke alerts during the period across the emergency departments were analyzed. Total daily stroke alerts decreased from median, 10 (interquartile range, 8-13) during baseline period to median, 8 (interquartile range, 4-10, P=0.001) during COVID period. Time to presentation, stroke severity, and time to treatment were unchanged. COVID period was associated with decrease in stroke alerts with rate ratio of 0.70 (95% CI, 0.60-0.28). Thrombolysis also decreased with rate ratio, 0.52 (95% CI, 0.28-0.97) but thrombectomy remained unchanged rate ratio, 0.93 (95% CI, 0.52-1.62) Conclusions: We observed a significant decrease in acute stroke presentations by ≈30% across emergency departments at the time of surge of COVID-19 cases. This observation could be attributed to true decline in stroke incidence or patients not seeking medical attention for emergencies during the pandemic.
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Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Isquemia Encefálica/epidemiologia , COVID-19 , Serviço Hospitalar de Emergência , Humanos , Ohio/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica/estatística & dados numéricos , Tempo para o TratamentoRESUMO
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.
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Betacoronavirus/patogenicidade , Encéfalo/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Encefalite Viral/fisiopatologia , Pneumonia Viral/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/metabolismo , Coagulação Sanguínea , Encéfalo/metabolismo , Encéfalo/virologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Encefalite Viral/epidemiologia , Encefalite Viral/metabolismo , Encefalite Viral/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Mediadores da Inflamação/metabolismo , Estresse Oxidativo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina , SARS-CoV-2 , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/metabolismo , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/virologia , Vasodilatação , VirulênciaRESUMO
PURPOSE: Blood blister-like aneurysms (BBA) are small, friable, broad-based aneurysms that represent high risk for rerupture. Treatment of BBA is challenging, and may include surgical wrapping, clipping, multiple overlapping stents, and/or coiling. Flow diversion is a rapidly evolving treatment strategy for intracranial aneurysms, but the evidence for its use in cases of BBA is scarce. METHODS: A retrospective review of flow-diverter-treated, ruptured BBA cases at our tertiary care institution was undertaken. Clinical, imaging, procedural, and mid-term follow-up data on the patients were collected. RESULTS: Eight patients underwent flow-diverter stent treatment for ruptured BBA. Median age at time of treatment was 49 years (interquartile range [IQR] 42-57) with five females (62.5%). The most common location of the BBA was the supraclinoid segment of the internal carotid artery. The median Hunt-Hess score was 2 (IQR 1.7-3.2). All patients were treated with dual anti-platelet therapy. Good clinical outcomes (modified Rankin score 0-2) were seen in 6/7 (85.7%) patients with available follow-up at 1 year. Complete occlusion of the aneurysm on latest angiogram (7) or MRI (1) was seen in 6/8 (75%) patients (at a median of 8 months). No patient had rerupture, retreatment, or recurrence of the aneurysm. CONCLUSION: Flow-diverter stents may be a feasible treatment option for BBAs. They offer high occlusion and low retreatment rates with good mid-term outcomes, but the long-term efficacy remains unknown. Also, dual anti-platelet therapy in the acute ruptured setting can be challenging.
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Aneurisma Roto/terapia , Vesícula/terapia , Aneurisma Intracraniano/terapia , Stents , Adulto , Aneurisma Roto/diagnóstico por imagem , Vesícula/diagnóstico por imagem , Angiografia Cerebral , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The American Heart Association/American Stroke Association guidelines recommend all patients presenting to emergency departments (EDs) with a potential stroke be seen within 10 minutes of arrival, although this may not be achieved in all patients. We sought to identify factors associated with delayed evaluation of ED patients with potential stroke. METHODS: Using the National Hospital Ambulatory Medical Care Survey, we identified all patient ED visits from 2003 to 2010 and further identified those patients with strokes or stroke-like symptoms using International Classification of Disease, Ninth Revision codes. Visits were classified as those evaluated within 10 minutes of ED arrival or those where evaluation by the treating provider was 10 minutes or greater (delayed evaluation). We stratified visits, compared proportions, and calculated the unadjusted and adjusted odds ratios (ORs) in a multivariable model. RESULTS: We identified 743 cases in the database representing an estimated 2.3 million ED visits for patients with strokes. Of these, 600000 were seen within 10 minutes and 1.7 million visits with delayed evaluation. Visits at nonmetropolitan statistical area hospitals were associated with decreased odds of delayed evaluation (OR, 0.41 [95% confidence interval, 0.26-0.64]; P < .001). Being triaged to a less urgent emergency severity index category was associated with increased odds of delayed evaluation (OR 3.08 (95% CI 1.94-4.89) p < 0.001). Other factors were not associated with delayed evaluation. CONCLUSION: In this national sample of patients presenting with strokes to US EDs, patient visits to metropolitan statistical area hospitals and those triaged to less urgent categories were associated with delayed evaluation.
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Eficiência Organizacional , Serviço Hospitalar de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/normas , Acidente Vascular Cerebral/diagnóstico , Triagem/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. METHODS: Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. RESULTS: A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. CONCLUSIONS: Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.
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Isquemia Encefálica/metabolismo , Líquido Cefalorraquidiano/metabolismo , Ferro/metabolismo , Hemorragia Subaracnóidea/metabolismo , Vasoespasmo Intracraniano/metabolismo , Idoso , Isquemia Encefálica/etiologia , Ceruloplasmina/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologiaRESUMO
Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.
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Stroke is a leading cause of death, long-term disability, and socioeconomic costs, highlighting the urgent need for effective treatment. During acute phase, intravenous administration of recombinant tissue plasminogen activator (tPA), a thrombolytic agent, and endovascular thrombectomy (EVT), a mechanical intervention to retrieve clots, are the only FDA-approved treatments to re-establish cerebral blood flow. Due to a short therapeutic time window and high potential risk of cerebral hemorrhage, a limited number of acute stroke patients benefit from tPA treatment. EVT can be performed within an extended time window, but such intervention is performed only in patients with occlusion in a larger, anatomically more proximal vasculature and is carried out at specialty centers. Regardless of the method, in case of successful recanalization, ischemia-reperfusion injury represents an additional challenge. Further, tPA disrupts the blood-brain barrier integrity and is neurotoxic, aggravating reperfusion injury. Nanoparticle-based approaches have the potential to circumvent some of the above issues and develop a thrombolytic agent that can be administered safely beyond the time window for tPA treatment. Different attributes of nanoparticles are also being explored to develop a multifunctional thrombolytic agent that, in addition to a thrombolytic agent, can contain therapeutics such as an anti-inflammatory, antioxidant, neuro/vasoprotective, or imaging agent, i.e., a theragnostic agent. The focus of this review is to highlight these advances as they relate to cerebrovascular conditions to improve clinical outcomes in stroke patients.
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BACKGROUND: Multiple trials have shown that mechanical thrombectomy (MT) is superior to medical therapy. However, no robust evidence is available regarding MT beyond 24 h. In this study, we aimed to determine the safety and efficacy of endovascular stroke therapy in this late window. METHODS: We conducted a retrospective study of prospectively collected data of patients who met extended window trial criteria, but underwent MT beyond 24 h. Safety and efficacy outcomes included symptomatic intracerebral hemorrhage (sICH), procedural complications, number of passes, successful recanalization (mTICI 2b - 3), delta (Δ) NIHSS (baseline-discharge), and favorable outcomes (mRS 0-2 at 90 days). RESULTS: A total of 39 patients were included with a median age of 69 years (IQR 61.5, 73.5); 54% were females. Hypertension was present in 76% of patients; 23% were smokers. Half of the patients had M1 occlusion (48.7%). Median preprocedural NIHSS was 11 (IQR 7.0, 19.5). Successful revascularization was achieved in 87%; median number of passes was 2 (IQR 1.0, 3.0). Median ΔNIHSS was 3.0 (IQR -1.5, 8.0). Favorable outcome was achieved in 49% (95% CI: 34%-64%), and 95% were free of complications. A total of 3 patients (7.7%) had sICH. In an exploratory analysis, posterior circulation occlusion was associated with higher mRS at 90 days (OR: 14.7, p = 0.016). Favorable discharge facility was associated with lower mRS at 90 days (OR: 0.11, p = 0.004). CONCLUSIONS: Our study showed comparable clinical outcomes of MT beyond 24 h compared to MT trials within 24 h in patients with favorable imaging profile, especially in anterior circulation occlusions.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Estudos Retrospectivos , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Hemorragia Cerebral , Resultado do Tratamento , Isquemia Encefálica/terapiaRESUMO
BACKGROUND: Early thrombolysis for acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) is associated with better clinical outcome. This is thought to be due to greater tissue salvage with earlier recanalization. We explored whether ultra-early administration of intravenous tissue plasminogen activator (IV tPA) within 60 min (Golden Hour) of symptom onset for AIS due to ELVO is associated with a higher rate of recanalization. METHODS: We performed a retrospective analysis of recanalization rates and clinical outcomes in patients with AIS due to ELVO treated with IV tPA, comparing patients who received IV tPA within 60 min of stroke symptom onset with those treated beyond 60 min. RESULTS: Between January 2013 and December 2016, 158 patients with AIS due to ELVO were treated with IV tPA. Of these, 25 (15.8%) patients received IV tPA within 60 min of stroke symptom onset, while the remaining 133 (84.2%) patients received IV tPA beyond 60 min. The ultra-early treatment group was found to have a higher rate of complete recanalization (28.0% vs 6.8%, 95% CI 1.78-16.63), better chance of early neurological improvement (76.0% vs 50.4%, 95% CI 1.16-8.65), favorable clinical outcomes (mRS ≤ 2 or return to premorbid mRS) (65.0% vs 36.8%, 95% CI 1.42-9.34), and lower mortality (5% vs 31.1%, 95% CI 0.01-0.74) at 90-day follow-up compared to the later treatment group. CONCLUSION: Our data suggest that ultra-early administration of IV tPA significantly improves recanalization rates and clinical outcomes in patients with AIS due to ELVO.
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Isquemia Encefálica , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do TratamentoRESUMO
INTRODUCTION: Mobile stroke units have recently been introduced in the care of patients suspected of having an acute stroke, leading to shortening in the time to thrombolytics. We aimed to compare the clinical effectiveness in terms of functional outcome and survival among patients treated in mobile stroke unit and/or conventional care. METHODS: A systematic search of electronic databases, comparing the clinical outcomes among patients with acute stroke in the same study was conducted from 1990 to 2019. Pooled and subgroup analysis were performed using the random- and fixed-effect model based upon the I2 heterogeneity. RESULTS: A total of 21,297 patients from 11 publications (seven randomized controlled trials and four non-randomized controlled trials including prospective cohort studies) were retrieved. This included 6065 (n = 28.4%) of the patients treated in the mobile stroke unit and 71.6% (n = 15,232) of the patients managed in the conventional care. The mean age at clinical presentation (70.1 ± 14.5 vs. 71.05 ± 15.8) and National Institute Health Stroke Scale (9.8 ± 1.7 vs. 8.4 ± 1.5) was comparable (p > 0.05) in patients treated with mobile stroke unit and conventional care, respectively. The mean time-to-treatment window was significantly shorter among the patients treated in mobile stroke unit compared to conventional care (62.0 min vs. 75.0 min; p = 0.03, respectively). The pooled analysis of clinical outcome at day 7 indicated that patients treated in mobile stroke unit had 1.46-folds higher likelihood of better clinical outcome (modified Rankin scale 0-2) than those in the hospital (odds ratio: 1.46, 95% confidence interval: 1.306-2.03, p = 0.02). However, there was no significant difference in terms of mortality (odds ratio: 0.98, 95% confidence interval: 0.81-1.18, p = 0.80), stroke-related neurological deficits (odds ratio: 1.37, 95% confidence interval: 0.81-2.32, p = 0.24), and other serious adverse events (odds ratio: 0.69, 95% confidence interval: 0.39-1.20, p = 0.19) among patients treated in mobile stroke unit versus conventional care. CONCLUSION: Our results corroborate that patients treated in mobile stroke unit lead to short-term recovery following acute stroke without influencing the mortality rate. Further prospective studies are needed to validate our results.
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Acidente Vascular Cerebral , Fibrinolíticos , Humanos , Unidades Móveis de Saúde , Estudos Prospectivos , Acidente Vascular Cerebral/terapia , Tempo para o TratamentoRESUMO
BACKGROUND AND PURPOSE: We sought to validate ultrasound as a reliable means of assessing vessel stenosis of vertebral artery origins. METHODS: We reviewed 1,135 patient charts with ultrasound of the posterior circulation performed in 2008-2015 in a single hospital. Inclusion criteria for native vessels consisted of ultrasound and digital subtraction angiography (DSA) performed within 3 months. Patients with indwelling stents were analyzed separately from native vessels. Using DSA as the gold standard, we determined sensitivity and specificity of ultrasound in detecting occlusion at vertebral artery origin. All patients with nonoccluded native vertebral artery origins were evaluated for degree of stenosis on DSA, and compared to mean flow velocity (MFV), peak systolic velocity (PSV), and end-diastolic velocity (EDV) on ultrasound. RESULTS: Among 218 vertebral artery origins in 139 patients evaluated, ultrasound showed sensitivity of 85.7% (95% confidence interval (CI): 69.7-95.2%) for occlusion and specificity of 99.5% (95%CI: 96.9-99.9%). Among 126 arteries without occlusion, <50% stenosis had average MFV (39 ± 19 cm/s), 50-69% stenosis had average MFV (68 ± 35 cm/s), and severe (70-99%) stenosis had average MFV (120 ± 93 cm/s) (P < .001). MFV cutoff value of 44 cm/s corresponded to 77% sensitivity and 70% specificity to detect vertebral artery origin stenosis >50% (C-statistic: .81). PSV value of 97 cm/s corresponded with 72% sensitivity and 70% specificity to detect >50% stenosis (C-statistic: .77). MFV cutoff value of 60 cm/s corresponded with 70% sensitivity and 82% specificity to predict 70-99% stenosis (C-statistic: .83). PSV cutoff value of 110 cm/s corresponded with 80% sensitivity and 72% specificity to predict 70-99% stenosis (C-statistic: .84). CONCLUSION: Ultrasound has good sensitivity and excellent specificity for detecting vertebral origin occlusion. Flow velocity can be used to screen for severe stenosis of vertebral artery at origin.
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Velocidade do Fluxo Sanguíneo/fisiologia , Ultrassonografia/métodos , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem , Idoso , Angiografia Digital , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Artéria Vertebral/fisiopatologia , Insuficiência Vertebrobasilar/fisiopatologiaRESUMO
BACKGROUND: Prospective evidence to support mechanical thrombectomy (MT) for mild ischemic stroke with large vessel occlusion (LVO) is lacking. There is uncertainty about using an invasive procedure in patients with mild symptoms. OBJECTIVE: To evaluate the safety and feasibility of MT in patients with mild symptoms and LVO. METHODS: Our single-arm prospective pilot study recruited patients with LVO and initial National Institute of Health Stroke Scale (NIHSS) <6, who underwent standard MT. Primary safety endpoints were symptomatic intracerebral hemorrhage (sICH), and/or worsening NIHSS by ≥4 points. Secondary endpoints included angiographic recanalization, NIHSS change, final infarct volume, and modified Rankin score (mRS). RESULTS: We enrolled 20 patients (mean age 65.6 ± 12.3 yr; 45% females). Thrombolysis in Cerebral Ischemia 2B/3 thrombectomy was achieved in 95%. No patients suffered sICH. One patient (5%) had neurologic worsening within 24 h because of underlying intracranial stenosis. No other complications or safety concerns were identified. Median NIHSS was significantly better at discharge (0.5, P = .007) and at last follow-up (0, P < .001) than before treatment (3). Mean post vs preintervention infarct volumes were small without significant difference (1.2 ml, P = .434). Most patients (85%) were discharged directly home. Excellent clinical outcome (mRS 0-1) at last follow-up was seen in 95% of patients. CONCLUSION: This is one of the first specifically designed prospective studies showing that MT is safe and feasible in patients with low NIHSS and LVO. Chronic underlying vasculopathy may be a challenging dilemma. We observed excellent clinical and radiographic outcomes, but randomized controlled trials are needed to demonstrate the efficacy of MT in this unique cohort.